2006 - Novel Approaches To The Diagnosis and Treatment of Posttraumatic Stress Disorder - Roy

NOVEL APPROACHES TO THE DIAGNOSIS AND
TREATMENT OF POSTTRAUMATIC STRESS

DISORDER
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Sub-Series E: Human and Societal Dynamics – Vol. 6 ISSN: 1574-5597

Novel Approaches to the Diagnosis
and Treatment of Posttraumatic
Stress Disorder
Edited by
Michael J. Roy
Division of Military Internal Medicine, Uniformed Services
University of the Health Sciences, Bethesda, Maryland, USA
Amsterdam • Berlin • Oxford • Tokyo • Washington, DC

Published in cooperation with NATO Public Diplomacy Division
Proceedings of the NATO Advanced Research Workshop on Novel Approaches to the Diagnosis
and Treatment of Posttraumatic Stress Disorder
Cavtat, Croatia
13–16 June 2005
© 2006 IOS Press.
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Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder v
M.J. Roy (Ed.)
IOS Press, 2006
© 2006 IOS Press. All rights reserved.
Preface
We believe that this Advanced Research Workshop has given participants an opportu-
nity to foster essential international collaborative research on the diagnosis and treat-
ment of posttraumatic stress disorder, a common and disabling consequence of war,
terrorism, and natural disasters. As a result, it represents an important piece in efforts to
help soldiers and civilians of NATO and partner nations in the face of future interna-
tional conflicts.
This publication contains the full papers corresponding to the relevant presenta-
tions provided at the workshop.
This text is organized so as to provide a coherent picture of the work and thoughts
of participants in the ARW, rather than necessarily following the exact order of the
presentations as they were provided in Cavtat, although this summary conveys to the
reader the manner in which presentations and working groups were conducted.
Appropriate financial support was vital for the successful organization and imple-
mentation of the workshop. Grateful acknowledgments for generosity go to the primary
sponsor, the NATO Security through Science Programme, as well as to a number of
Croatian donors, who recognized the importance of this event. As a token of our appre-
ciation, the logos of all sponsors are included here.
The workshop was organized and this accompanying publication was assembled
by joint dedication and efforts from the members of Uniformed Services University of
the Health Sciences (USUHS), Bethesda, MD, and University of Zagreb, Faculty
of Electrical Engineering and Computing (FEEC), Croatia. Professor Michael Roy of
USUHS, the NATO-country program co-director and organizing co-director, conceived
the overall design of the workshop, and with the assistance of his research assistant
Patricia Kraus, wrote and submitted an application to NATO. Dr. Roy selected and
invited the majority of the speakers and participants, and he and Ms. Kraus edited each
of the chapters incorporated in this publication. Professor Kresimir Cosic, the organiz-
ing co-director and a member of FEEC, coordinated financial aspects of the ARW,
solicited additional funding from Croatian donors, invited representatives of the Gov-
ernment of Croatia, and promoted the workshop within international politico-military
circles. He coordinated coverage of the workshop with Croatian Radiotelevision, and
organized meals as well as a boat trip to Dubrovnik for participants. Professor Dragica
Kozaric Kovacic, the partner-country program co-director and a member of University
Hospital Dubrava in Zagreb, Croatia, extended invitations to several international
speakers, further improving the quality of the workshop. Assistant Professor Miroslav
Slamic, a member of FEEC, handled accreditations, the purchase of consumable sup-
plies, and designed such items as the workshop poster, program cover, and the appear-
ance of compact disks (CDs) of presentations and pictures for participants. He was also
the workshop photographer. Sinisa Popovic, a member of FEEC, was the “glue” that
held together the planning and smooth running of the workshop, coordinating travel,
lodging and meal arrangements, precise estimation of expenses, assembling of work-
shop materials, and other arrangements with the conference site. Marko Cosic designed
vi
the gala dinner menu and coupons, and assisted Mr. Popovic with local arrangements
and assembling of workshop materials, handled some on-site financial matters, etc.
Workshop CDs were made possible through the joint efforts of Miroslav Slamic, Sinisa
Popovic, Marko Cosic, and Patricia Kraus.
Dr. Roy also gratefully acknowledges the many hours of assistance Ms. Kraus
provided in reviewing the manuscripts for this text.
vii
Program Co-directors
Michael Roy, USA Dragica Kozaric Kovacic, Croatia
Organizing Co-directors
Kresimir Cosic, Croatia Michael Roy, USA
Speakers
Amy Adler, USA Mariano Alcaniz, Spain
Randy Boddam, Canada Cristina Botella, Spain
Tim Brennen, Norway Gianluca Castelnuovo, Italy
Kresimir Cosic, Croatia JoAnn Difede, USA
Paul Emmelkamp, The Netherlands Azucena Garcia Palacios, Spain
Elke Geraerts, The Netherlands John Gruzelier, UK
Jamie Hacker Hughes, UK Neven Henigsberg, Croatia
Louis Jehel, France Naomi Josman, Israel
Tanja Jovanovic, Croatia Ivica Klapan, Croatia
Ivica Kostovic, Croatia Dragica Kozaric Kovacic, Croatia
David Lam, USA George Naneishvili, Georgia
Nela Pivac, Croatia Sinisa Popovic, Croatia
Ronald Poropatich, USA Albert “Skip” Rizzo, USA
Barbara Rothbaum, USA Michael Roy, USA
Charles van der Mast, The Netherlands Zoltan Vekerdi, Hungary
Brenda Wiederhold, USA Joseph Zohar, Israel
Publicity
Michael Roy, USA Kresimir Cosic, Croatia
Dragica Kozaric Kovacic, Croatia
Local Arrangements and Social Events

Kresimir Cosic, Croatia Sinisa Popovic, Croatia
Marko Cosic, Croatia
Finances
Michael Roy, USA Kresimir Cosic, Croatia
Sinisa Popovic, Croatia Marko Cosic, Croatia
Publication
Michael Roy, USA Patricia Kraus, USA
Sinisa Popovic, Croatia Miroslav Slamic, Croatia
Workshop Materials and CDs

Miroslav Slamic, Croatia Sinisa Popovic, Croatia
Marko Cosic, Croatia Patricia Kraus, USA
Secretary
Sinisa Popovic, Croatia
Photographer
Miroslav Slamic, Croatia
viii
Croatian Radiotelevision Reportage Guests

Kresimir Cosic, Croatia David Lam, USA
Barbara Rothbaum, USA JoAnn Difede, USA
Michael J. Roy, USA
Organizers
General Sponsor
Sponsors
ix
Key Speakers
CANADA
Randy Boddam
Psychiatry and Mental Health, Rm 406, Health Care Centre, 1745 Alta Vista
Drive, Ottawa, Ontario, Canada, K1A 0K6
CROATIA
Kresimir Cosic
University of Zagreb, Faculty of Electrical Engineering and Computing,
Unska 3, 10000 Zagreb, Croatia
Neven Henigsberg
Department of Psychopharmacology, Croatian Institute for Brain Research,
Medical School, University of Zagreb, Salata 12, HR-10000, Zagreb, Croatia
Tanja Jovanovic
Department of Psychiatry & Behavioral Sciences, Emory University School of
Medicine, 1365 Clifton Road, Atlanta, GA 30322, USA
Ivo Klapan
Zagreb University School of Medicine, and Croatian Telemedicine Society of
the Croatian Medical Association, HR-10000 Zagreb, Croatia
Ivica Kostovic
Croatian Institute for Brain Research, School of Medicine, Zagreb University
Hospital Center Gojka Suska 12, HR-10000 Zagreb, Croatia
Dragica Kozaric-Kovacic, MD, PhD
University Hospital Dubrava, Department of Psychiatry, Referral Centre for the
Stress-Related Disorders of the Ministry of Health of the Republic of Croatia
Avenija Gojka Suska 6, 10000 Zagreb, Croatia
Nela Pivac
Division of Molecular Medicine, Rudjer Boskovic Institute, POBox 180,
HR-10002 Zagreb, Croatia
Sinisa Popovic
FRANCE
Louis Jehel
Psychotraumatologiy Unit, Tenon, University Hospital, Ap-HP, Paris France, 4,
rue de la Chine75020, Paris, France
GEORGIA
George Naneishvili
M.Asatiani Research Institute of Psychiatry, 10 Asatiani St., Tbilisi 0177,
Georgia
x
HUNGARY
Zoltan Vekerdi
Operational Division, Medical Command, Hungarian Defence Forces, 1885
Budapest PO Box 25, Hungary
ISRAEL
Naomi Josman
Department of Occupational therapy, University of Haifa, Mount Carmel,
Haifa, 31905 Israel
Joseph Zohar
Chaim Sheba Medical Center
Division of Psychiatry
Tel-Hashomer, 52621 Israel
ITALY
Gianluca Castelnuova
Applied Technology for Neuro-Psychology Istituto Auxologico Italiano,
Casello Postale 1-2892, Intra (Verbania), Italy
NORWAY
Tim Brennen
Department of Psychology, University of Oslo
Box 1094 Blindern, Oslo 0317, Norway
SPAIN
Mariano Alcaniz
Medical Image Computing Laboratory. Technical University of Valencia.
Camino vera s/n. 46022 Valencia, Spain
Cristina Botella
Department of Psychology, Universitat Jaume I, Campus de Riu Sec, Avda. Sos
Baynat s/n, 12071 Castellon, Spain
Azucena Garcia-Palacios
Department of Psychology, Universitat Jaume I, Campus de Riu Sec, Avda. Sos
Baynat s/n, 12071 Castellon, Spain
THE NETHERLANDS
Paul Emmelkamp
Department of Clinical Psychology, Roetersstraat 15, 1018 WB Amsterdam,
The Netherlands
Elke Geraerts
Department of Experimental Psychology, Maastricht University, PO Box 616,
6200 MD, Maastricht, The Netherlands
Charles van der Mast
Delft University of Technology, Mekelweg 4, 2628 CD Delft, The Netherlands
xi
THE UNITED KINGDOM

John Gruzelier
Division of Neuroscience & Mental Health, Faculty of Medicine, Imperial
College room 10 L17 Charing Cross Campus St., Dunstan’s Road, London,
W6 8RP, England
Jamie Hacker Hughes
ACDMH, King’s College London, Weston Education Centre, 10 Cutcombe
Road, London, England
UNITED STATES
Amy Adler
US Army Medical Research Unit – Europe
Nachrichten Kaserne, Karlsruher str. 144
Heidelberg 69126, Germany
JoAnn Difede
Department of Psychiatry, Weill Cornell Medical College 525 East 68th Street
Box 200, New York, New York 10021, USA
David Lam
University of Maryland Medical School and U.S. Army Telemedicine and
Advanced Technology Research Center
PSC 79, BOX 145
APO AE 09714, USA
Ronald Poropatich
US Army Medical Research & Materiel Command
504 Scott Street
Fort Detrick
Maryland 21702-5012, USA
Albert Skip Rizzo
University of Southern California Institute for Creative Technologies
13274 Fiji Way, Marina Del Rey, California 90292, USA
Barbara Rothbaum
Department of Psychiatry, Emory University School of Medicine, 1365 Clifton
Road, Atlanta, Georgia 30322, USA
Michael Roy
Department of Medicine, Uniformed Services University, 4301 Jones Bridge
Road, A3062, Bethesda, Maryland 20814, USA
Brenda Wiederhold
Interactive Media Institute, 6160 Cornerstone Court East, Suite 161, San Diego,
CA 92121, USA
xii
Participants
CROATIA
Mirjana Grubisic-Ilic
University Hospital Dubrava, Department of Psychiatry, Referral Centre for
Stress-related Disorders of the Ministry of Health of the Republic of Croatia
Avenija Gojka Suska 6
10 000 Zagreb, Croatia
Tihana Jendricko
University Hospital Dubrava, Department of Psychiatry, Referral Centre for
Stress-related Disorders of the Ministry of Health of the Republic of Croatia
Avenija Gojka Suska 6
10 000 Zagreb, Croatia
Zeljka Mihajlovic
University of Zagreb, Faculty of Electrical Engineering and Computing
Department of Electronics, Microelectronics, Computer and Intelligent Systems
Unska 3
10000 Zagreb, Croatia
Dorotea Muck-Seler
Division of Molecular Medicine, Ruđer Bošković Institute, PO Box 180,
HR-10002 Zagreb, Croatia
Miroslav Slamic
CZECH REPUBLIC
Pavel Kral
Central Military Hospital Prague
U Vojenske nemocnice 1200
169 02, Praha 6
Czech Republic
Vlastimil Tichy
Central Military Hospital Prague
U Vojenske nemocnice 1200
169 02, Praha 6
Czech Republic
SLOVENIA
Robert Donicar
NATO COMEDS WG MP
ZDRAVSTVENI CENTER MORS, STULA B.S.
1000 Ljubljana, Slovenia
Zdravko Strnisa
OPK-H. Bracica 2
2000 Maribor, Slovenia
xiii
UNITED STATES
Patricia Kraus
Department of Medicine, Uniformed Services University of the Health
Sciences, 4301 Jones Bridge Road, A3056, Bethesda, Maryland 20814, USA
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xv
Novel Approaches to the Diagnosis and

Treatment of Posttraumatic Stress Disorder
Michael J. ROY, MD, MPH, FACP 1
Director, Division of Military Internal Medicine, Professor of Medicine
Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
Background
Terrorist events, natural and man-made disasters, and intra- and international conflicts
over the past 10–15 years have led to increased attention to the prevalence and adverse
health consequences of posttraumatic stress disorder (PTSD). PTSD has an esti-
mated 2–5% point prevalence and 8–12% lifetime prevalence in the general population,
with higher rates in primary care settings, and even more so in combat veterans [1–9].
It is especially common after terrorism and natural disasters: for example, 60% of those
who sought care after terrorist sarin release still met PTSD criteria 6 months later [10],
as did 41% of victims of a terrorist bombing in a Paris subway [11]. Likewise, 43% of
earthquake survivors in Turkey were diagnosed with PTSD [12]. With 24-hour televi-
sion news coverage, such events impact an entire society; after the terrorist attacks in
the U.S. on September 11, 2001, one in six adults nationwide had persistent distress
2 months later, and this was associated with poorer function at work, avoiding public
places, greater worries, and greater use of alcohol and drugs. [13–14] Persistent PTSD
has in turn been implicated in reduced societal resistance, delayed communal recovery,
and lesser income earned by the individuals with PTSD [15–18]. Preventing persis-
tence of PTSD may help to alleviate these symptoms of distress that impact every cor-
ner of a society after war, terrorism, or disasters, and should materially increase the
speed of societal recovery from these insults.
PTSD unfortunately often goes undiagnosed, and available diagnostic instruments
tend to be either cumbersome and time-consuming, or insensitive. PTSD is associated
with a variety of somatic symptoms, markedly higher rates of depression and other
psychological conditions, poorer physical health, missing work, impaired function at
work and at home, and significantly higher healthcare costs. [15–18] PTSD is not only
associated with significant adverse impact on quality of life, but it has also proven to be
relatively persistent, and it has been difficult to produce durable, full responses to ther-
apy. Selective serotonin reuptake inhibitors result in improvement for many individu-
als, but remission is sometimes only partial, and there is a sizeable percentage of pa-
tients who do not respond or do not continue with pharmacotherapy due to side effects.
Cognitive behavioral therapy that incorporates imaginal exposure elements has been
found to be effective in multiple clinical trials, and recent expert consensus treatment
guidelines characterize it as the non-pharmacologic treatment of choice. [19–20] Re-
1
Corresponding Author: LTC Michael Roy. Uniformed Services University of the Health Sciences, De-
partment of Medicine, 4301 Jones Bridge Road, A3062. Bethesda, Maryland, 20814, USA. Telephone:
(301) 295 9601; Fax: (301) 295 3557; Email: mroy@usuhs.mil.
xvi
cent technologic advances make it possible for virtual reality (VR) scenarios to be real-
istic enough to effectively confront individuals with stimuli associated with their trau-
matic experience through progressively more intense exposure, neutralizing behavioral
cues. In recent years, virtual reality technology has been utilized to help patients over-
come a variety of phobias, anxiety disorders and PTSD. In uncontrolled studies, small
numbers of Vietnam War veterans and World Trade Center survivors with PTSD have
each been reported to improve through the use of progressively more realistic and in-
tense virtual reality exposures. Investigators in multiple nations have published case
reports, as well as trials comparing therapeutic approaches that incorporate VR with
usual care or waiting list controls, describing success with the use of VR to treat a vari-
ety of psychiatric disorders. There have not yet been studies that clearly define the
added benefit that VR might provide when used in addition to pharmacotherapy or
other approaches with demonstrable efficacy but still large numbers who have inade-
quate or incomplete responses.
PTSD was first defined in veterans of the Vietnam War, but the symptoms that
constitute this disorder have been reported from many nations through centuries of
warfare. PTSD and other psychologic sequelae often persist long after physical wounds
have healed, preventing the return of sizeable numbers of military service members to
the battlefield, and thus impairing readiness. Moreover, persistent PTSD often evolves
into, or is accompanied by, depression and other psychiatric conditions, resulting in
lower response rates once treatment is initiated, and consequently greater morbidity.
Undiagnosed and/or untreated PTSD impairs the resilience of military service members
both while they remain on active duty, and when they return to society at large.
In 1998, the annual cost of PTSD and related anxiety disorders was estimated at
$63 billion dollars (50 billion Euros), in the United States alone, with PTSD represent-
ing the most significant healthcare utilization and work limitations of all the anxiety
disorders. [21–22]
1. Cavtat, June 13–16, 2005
In June, 2005, in the town of Cavtat on the Adriatic coast of Croatia, we brought to-
gether many of the leading researchers in the use of VR therapy in psychological disor-
ders. The purpose of this NATO-sponsored Advanced Research Workshop (ARW) was
to give these groundbreaking researchers an opportunity to share their experiences and
expertise, to achieve consensus on the best methods for incorporating VR in the treat-
ment of veterans of war and terrorism, and to foster multinational collaborative studies
in this regard. To achieve this, invited experts shared the most salient findings of recent
research with which they have been involved. We then divided all workshop partici-
pants into working groups to focus on four key elements of the challenges faced in util-
izing VR and other new technologies in the treatment of PTSD:
• Diagnostic and epidemiologic concerns with PTSD
• Technological challenges in the use of VR
• Integration of cognitive behavioral therapy and virtual reality approaches
• Outcomes measurement and issues in follow up
Each working group drafted a consensus document, which the group leader then
presented to all ARW attendees. Feedback was solicited to ensure a general consensus
xvii
and the working group leaders incorporated this into the documents that comprise the
final four chapters of this book.
The workshop opened with a welcome from several Croatian hosts, including Dr.
Dragica Kozaric-Kovacic, Professor Kresimir Cosic, and Deputy Prime Minister Jad-
ranka Kosor. Among other things, they emphasized the magnitude of the problem that
PTSD poses for Croatia. The best estimates are that there are 10,000 Croatian Home-
land War veterans with PTSD, another 1500 veterans have committed suicide, and
since the war was fought on their own soil, countless civilians also have been trauma-
tized by the war. It is estimated that 15–40% of Croatian Homeland War veterans have
PTSD, and that 50–90% of them have comorbid psychiatric conditions such as depres-
sion. Deputy Prime Minister Kosor emphasized that it is also well-recognized that
many veterans have delayed manifestations of disability, which is why the Croatian
Parliament agreed to render compensation available to those veterans displaying effects
within 10 years after the end of the war.
Dr. John Gruzelier of Imperial College, London, reviewed the significance of theta
waves on electro-encephalograms (EEGs), emphasizing their association with survival
behavior, memory, and anatomical areas of the brain that are thought to be of particular
importance in PTSD, such as the hippocampus. He also noted the significance of theta
waves in autobiographical positive memories as well as flashbacks. Later in the first
day of the conference, Dr. Kostovic, Director of the Croatian Institute for Brain Re-
search, expanded upon this to detail the central role of the amygdala and limbic system
in pathways that are central in PTSD. In addition, Dr. Nela Pivac from the Rudjer
Boskovic Insitute in Croatia reviewed work on the neurobiologic basis for PTSD, par-
ticularly associated changes in various neurotransmitter levels.
Dr. Dragica Kozaric-Kovacic, Professor of Psychiatry, Director of the Referral
Center for Stress-Related Disorders at the University of Zagreb School of Medicine,
Croatia, documented that up to 40% of Croatian Homeland War veterans with PTSD
had psychotic symptoms. These symptoms were quite well-circumscribed, representing
hallucinations specifically related to their combat exposure, rather than the more bi-
zarre hallucinations characteristic of schizophrenia. She also noted that Croatian veter-
ans completing the Minnesota Multiphasic Personality Inventory, Version 2 (MMPI-2)
had their highest average scores on scale 8, unofficially known as the “schizophrenia”
scale. She believes that those with psychotic symptoms represent a more severe form of
PTSD, and it is her experience that treatment with antipsychotic medication is benefi-
cial to these individuals. Finally, Dr. Kozaric also emphasized the high rate of comor-
bid psychiatric conditions, upwards of 60%, in those with PTSD; alcohol abuse was the
single most common comorbid condition.
Dr. Tim Brennen, professor of psychology at the University of Norway, and Elke
Geraerts, a doctoral candidate at the University of Maastricht in the Netherlands, re-
viewed their work on the cognitive processes underlying PTSD, as well as their efforts
to model what occurs cognitively after traumatization. They described some fascinating
work on the effects of PTSD on memory, utilizing lists of words that included both
trauma-related and unrelated terms, then asking PTSD and control patients what they
were able to remember. Dr. Brennen documented that those with PTSD have greater
difficulty forgetting words associated with their trauma, even when asked to try to do
so. He also reported that combat veterans with PTSD are more likely than controls to
think they heard trauma-related words that were not on the list, but there was no differ-
ence for unrelated words. Ms. Geraerts reported similar findings with women victims
of sexual assault.
xviii
Dr. Ronald Poropatich, Senior Advisor to the Telemedicine and Advanced Tech-
nology Research Center at the US Army Medical Research and Materiel Command,
and Dr. Ivica Klapan, Professor of Otorhinolaryngology at the University of Zagreb,
each discussed various applications of new technologies. Dr. Poropatich delineated the
potential use of personal digital assistants, “smart dog tags” and other digital formats
for storing and transmitting medical records information. He also displayed the wide
range of applications for robotics to decrease the exposure of soldiers—including
medical personnel—in far-forward areas of the battlefield, from detecting chemical
weapons to performing surgery at distant sites. Since his talk was tangential to the sub-
ject of PTSD, Dr. Poropatich’s presentation is not covered in this book. Dr. Klapan
discussed the application of three-dimensional modelling to increase the level of infor-
mation available pre-operatively, improving surgical approaches.
Dr. Michael Roy, Professor of Medicine at Uniformed Services University, pro-
vided vivid examples of the face of PTSD in primary care, drawing upon patients he
has seen over the years at Walter Reed Army Medical Center. He outlined the chal-
lenges in faced in making the diagnosis in primary care, from competing demands to
stigmatization, while emphasizing that similar issues are relevant to combat veterans.
Dr. Roy noted the lack of validated diagnostic tools for PTSD in primary care, and the
need to conduct studies to establish effective screening measures. In addition, he out-
lined plans to use the “Virtual Iraq” environment described later in the meeting by
Dr. Rizzo, integrated with a cognitive behavioral therapy approach as described by
Dr. Difede, to assess the added benefit of CBT/VR to pharmacotherapy in combat vet-
erans. Provided that commensurate funding is obtained, current plans are for this study
to begin in both Washington and Zagreb in late 2005, enrolling Operation Iraqi Free-
dom veterans in Washington, and Homeland War veterans in Zagreb.
Mr. Sinisa Popovic of the University of Zagreb provided a presentation on behalf
of collaboration with Drs. Kresimir Cosic and Miroslav Slamic. He focused on efforts
to integrate physiologic measures of subjects, as well as Subjective Units of Distress
(SUDs) scales, into software programs to facilitate guided progression of VR expo-
sures, easing the pressure on the therapist to do so.
Dr. Tanja Jovanovic of the University of Zagreb described psychophysiologic
measures that could prove useful in supplementing or corroborating responses to ques-
tionnaires in diagnosing PTSD. These include cardiovascular (heart rate, heart rate
variability, blood pressure) measures, respiratory rate, electromyography, electroe-
ncephalography, and skin conductance. Each measure adds something different in
terms of the rapidity, duration, or other characteristics of the response, and they can be
used to distinguish those with PTSD, in addition to later value in directing the progres-
sion of therapy.
Dr. Louis Jehel reviewed the diagnostic instruments available for PTSD. He noted
that the established gold standard, the Clinician Administered PTSD Scale (CAPS) is
too lengthy and time-consuming to be used as a broad screening measure. An optimal
cut-off score that has high sensitivity and specificity has not yet been established for
the 17-item PTSD Checklist (PCL). Other available instruments still lack validation
and/or have limitations.
Dr. Brenda Wiederhold, Director of the Virtual Reality Medical Center in San
Diego, California reviewed the track record of success that VR has had in treating
anxiety disorders. She emphasized that one particular strength of VR is that it does not
depend on patients’ ability to imagine scenarios, instead directly confronting the patient
with the environment, which is especially valuable in conditions such as PTSD, where
xix
avoidance is a primary feature of the disorder. Dr. Wiederhold noted that the incorpora-
tion of VR into a CBT approach has been shown to result in 33% faster response rates
in the treatment of agoraphobia, for example. She also discussed the use of VR to con-
duct stress inoculation training (SIT), drawing parallels between SIT and treatment,
with the former addressing peak performers while the latter focuses on the impaired.
Dr. Azucena Garcia-Palacios of Valencia, Spain, expanded upon the data favoring
the use of VR in phobias and related disorders. She emphasized the advantage of being
able to provide exposures under controlled circumstances without the risks inherent in
actual in vivo exposures. In fact, she reported data demonstrating that 81% of patients
preferred VR over in vivo exposures. For social phobia and panic with agoraphobia, the
medical literature documents superiority for VR over waiting list controls, and compa-
rability with in vivo exposures. Dr. Garcia-Palacios also described more recent applica-
tions of VR in eating disorders, addictions, pathological grief, autism, and ADHD. She
was followed by her colleague, Dr. Cristina Botella, who reviewed the experience of
VR in the treatment of PTSD. Dr. Botella noted that therapists have historically under-
utilized the exposure component in the conduct of CBT, with one study indicating that
only 17% of therapists were using it. She reviewed the historical precedents for VR,
based upon PIE—proximity, immediacy, and expectancy, developed during and subse-
quent to the two world wars; this policy was based upon the belief that soldiers would
have better outcomes with prompt return to combat, the exposure that was responsible
for their symptoms. Dr. Botella also described the EMMA project, a computer-based
interactive therapy modality that enables the patient to incorporate their own elements
into the virtual environment, with both visual and auditory elements.
Dr. Giancarlo Castelnuovo of Milan reviewed the experience of the VEPSY Up-
dated project in the treatment of anxiety disorders, obesity and other eating disorders,
and male sexual disorders. He reported that more than 50,000 individuals have ac-
cessed the open, free virtual environment they made available on the internet, and
over 500 patients have been enrolled in certified controlled clinical trials. The VEPSY
Updated project has made considerable gains in identifying the most effective treat-
ment model for a variety of psychiatric disorders.
Dr. Barbara Rothbaum from Emory University in Atlanta, Georgia emphasized
that the problem with PTSD is one of extinction—trauma has an effect on everyone
initially, but it wears off over the ensuing weeks for most, while it becomes disabling
for those with PTSD. VR for the latter individuals provides the opportunity to relive the
trauma under therapeutic circumstances until it is no longer traumatic. Dr. Rothbaum
also reported some promising initial results with d-cycloserine in the augmentation of
VR.
Dr. Joann Difede of Weill Medical College at Cornell University in New York
City described her use of CBT/VR with firefighters responding to the World Trade
Center site on September 11, 2001. Dr. Difede reported that nearly 10% of firefighters
met full criteria for PTSD, with almost 25% having subsyndromal PTSD. She then
outlined the novel therapeutic approach that was initially used in those firemen who
had difficulty complying with imaginal exposure in the course of CBT. A virtual envi-
ronment was developed that incorporated computer-generated images of planes hitting
the World Trade Centers with actual audio from newscasts from 9/11. After four ses-
sions in which therapists used a CBT approach including psychoeducational efforts and
the introduction of ujayi breathing techniques, VR was introduced and used over the
course of another half-dozen or more 75-minute sessions. The use of VR in this manner
had an impressively large effect size in comparison to waitlist controls.
xx
Dr. Naomi Josman of the University of Haifa, Israel, reviewed the added value of
occupational therapy with virtual reality exposure therapy, with an examination of oc-
cupational performance before and after therapy. She also discussed the significance of
“presence” as a measure of the investment of the patient in VR.
Dr. Skip Rizzo of the Institute for Creative Technology at the University of South-
ern California reinforced Dr. Wiederhold’s comments regarding the ability of VR to
ensure that those with PTSD are confronted with their virtual environment, so that they
can not avoid it, as those with this disorder are often inclined to do. He emphasized the
need for inter-institutional collaboration, and highlighted a series of additional investi-
gators using VR in the treatment of PTSD, including Beck at the University of Buffalo
for survivors of motor vehicle accidents, and researchers in Portugal treating combat
veterans of wars in former Portuguese colonies in Africa in the 1970’s. In addition, Dr.
Rizzo described the importance of sensory input other than vision in VR, noting the
well-delineated importance of auditory input, as well as the added value of vibration
through the use of a platform, and more recent work incorporating smells. He also in-
troduced the concept of using exposure to a virtual environment as a screening tool
after military deployment, identifying those with strong physiologic responses as indi-
viduals who might benefit from intervention.
2. Working Groups
These presentations set the stage for the four working groups described earlier. All
ARW attendees actively participated in the deliberations of the working groups, which
were held for an entire afternoon on the second day of the ARW. Group leader presen-
tations ensued the following morning, with active feedback provided from other ARW
participants.
3. Special Presentation
The following morning, a special presentation was provided by Dr. Joseph Zohar, a
researcher with years of experience in the evaluation of PTSD in Israeli combat veter-
ans, who reviewed the results of a large case-control study in which PTSD patients
were compared to matched controls with regard to demographic and pre-draft cognitive
and behavioral testing. In general, while some of these measures were successful in
predicting whether one might develop schizophrenia, they were not useful predictors of
the development of PTSD. However, those who appeared to have less resources, as
evidenced by such measures as having less education, more siblings, reservist status,
and immigrant status, were more likely to seek help for PTSD symptoms on the battle-
front rather than waiting until after deployment. While their overall prognosis did not
appear different, this information can prove useful in making appropriate resources
available.
4. PTSD and NATO Operations
The ARW was closed out by a special session examining PTSD and NATO operations.
This was opened by a graphic presentation from Dr. Zoltan Vekerdi of the Hungarian
xxi
Defense Force. Dr. Vekerdi detailed his eye-witness account of “Black Sunday” in Ka-
bul in 2003, when four Germans and 2 Afghans were killed, while another 35 required
medical treatment of injuries—the result of the suicide bombing of a German motor-
cade which had been headed to the airport to depart the country after completing a tour
of duty.
Dr. Amy Adler, a psychologist with the US Army Medical Research Unit—
Europe, described the results of psychological screening of soldiers returning from de-
ployment to Afghanistan and Iraq. Their results indicated that the 4-question screen
known as the PC-PTSD performed as well in this population as the 17-item PTSD
Checklist for Military Populations (PCL-M). The PC-PTSD was more desirable on the
basis of its brevity, and it has been incorporated in a U.S. Department of Defense form
that is routinely used to screen soldiers after deployment. Dr. Adler also highlighted
data that indicate screening should be done at 3–6 months after deployment since many
do not develop symptoms until that point, rather than immediately upon return.
Dr. Randy Boddam, Chief of Psychiatry for the Canadian Defence Force, reiter-
ated the importance of screening at the 3–6 month period, noting the “honeymoon”
phenomenon that is associated with improved mood and other symptoms upon imme-
diate return home. He also noted the value of taking care of family members, identify-
ing a strong correlation between problems with family members at home and those of
deployed soldiers. Dr. Boddam detailed the Canadian approach to the management of
operational stress, which makes a significant attempt to be proactive, beginning with
the recruitment process, and including an algorithm that addresses diagnosis and treat-
ment.
Dr. Jamie Hacker Hughes of Kings College in London described the workings of
the NATO Research and Technology Group (RTG)-20. Their objective is to develop
guidelines for military leaders on stress and psychological support to enhance effec-
tiveness in modern military operations. They developed a report to describe fundamen-
tal areas of agreement between NATO members that addresses pre-, during, and post-
deployment periods. Among the items agreed upon are that all military service mem-
bers are responsible for monitoring their own mental health, and that the mental health
of the unit will enhance—or detract from—the ability of the unit to carry out their mis-
sion. They are also conducting a survey of military line unit leaders to determine what
they perceive their needs to be with regard to mental health support.
Dr. David Lam ended the meeting on a positive note by describing NATO’s Secu-
rity through Science Program, and the variety of potential funding categories available
to researchers through this program. Since this information is available on the NATO
website, it has not been included in this volume.
5. Summary
This was an effective, valuable meeting, enabling many of the leading researchers in
the application of VR to the treatment of PTSD to come together to share their experi-
ences and ideas. It will undoubtedly spur greater international collaboration to further
improve the diagnosis and treatment of this challenging disorder that continues to af-
flict more soldiers from NATO member nations on a daily basis. VR has tremendous
potential that is only beginning to be realized, and it is critical to maintain international
collaboration as valuable research is being conducted at many different sites. The his-
torical response rate of PTSD to conventional therapy is poor enough to warrant the
xxii
earliest application of novel therapies as they are proven to provide added value. Future
meetings should build upon the spirit of collaboration that was fostered in Cavtat in
order to further improve the health of those who defend our nations’ borders.
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xxiii
Contents
Preface v
Key Speakers ix
Participants xii
Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress
Disorder xv
Michael J. Roy
Section I. Epidemiology and Pathophysiology of PTSD
Biological Markers in Croatian War Veterans with Combat Related

Posttraumatic Stress Disorder 3
Nela Pivac, Dragica Kozarić-Kovačić and Dorotea Mück-Šeler
Theta Synchronisation of Hippocampal and Long Distance Circuitry in the Brain:
Implications for EEG-Neurofeedback and Hypnosis in the Treatment of PTSD 13
John Gruzelier
Limbic Circuitry and Posttraumatic Stress Disorder 23
Ivica Kostović and Miloš Judaš
Investigating Cognitive Abnormalities in Posttraumatic Stress Disorder 31
Elke Geraerts and Tim Brennen
Psychotic Features of Combat Related Chronic Posttraumatic Stress Disorder
and Antipsychotic Treatment 42
Dragica Kozarić-Kovačić and Nela Pivac
Section II. Diagnosis and Screening
Efforts to Improve the Diagnosis and Treatment of Posttraumatic Stress

Disorder 59
Michael J. Roy and Patricia L. Kraus
Assessment of Available Diagnostic Instruments for Posttraumatic Stress
Disorder 67
Louis Jehel and Kathleen Dullea
Psychological Screening Validation with Soldiers Returning from Combat 78
Paul D. Bliese, Kathleen M. Wright, Amy B. Adler and Jeffrey L. Thomas
Psychophysiological Responses to Trauma-Related Stimuli in PTSD:
Potential for Scenario Adaptation in VR Exposure Therapy 87
Tanja Jovanović, Sinisa Popović and Dragica Kozarić-Kovačić
xxiv
Section III. Management of Posttraumatic Stress Disorder
Pharmacotherapy Research in Posttraumatic Stress Disorder 101

Neven Henigsberg
Canadian Forces Approach to the Identification and Management of
Operational Stress Injuries 111
Randy Boddam
“Stress and Psychological Support in Modern Military Operations”
NATO Human Factors and Medicine HFM081 Research Task Group RTG020
History, Status, Objectives and Achievements to Date 121
Jamie G.H. Hacker Hughes, Amy Adler, Vlastimil Tichy and Yves Cuvelier
Section IV. Virtual Reality Therapy in the Treatment of Posttraumatic Stress

Disorder and Related Psychiatric Conditions
Scenario Self-Adaptation in Virtual Reality Exposure Therapy for

Posttraumatic Stress Disorder 135
Sinisa Popovic, Miroslav Slamic and Kresimir Cosic
Advanced Technologies in Military Medicine 148
Brenda K. Wiederhold, Alex H. Bullinger and Mark D. Wiederhold
Indications Provided by the Eating Disorder Module of the VEPSY Updated
Project: Towards a New Generation of Virtual Environments for Clinical
Applications 161
Gianluca Castelnuovo, Gianluca Cesa, Andrea Gaggioli,
Fabrizia Mantovani, Mauro Manzoni, Enrico Molinari and Giuseppe Riva
Treatment of Mental Disorders with Virtual Reality 170
Azucena Garcia-Palacios, Cristina Botella, Hunter Hoffman,
Rosa M. Baños, Jorge Osma, Verónica Guillén and Conxa Perpina
Clinical Issues in the Application of Virtual Reality to Treatment of PTSD 183
Cristina Botella, Soledad Quero, Nuria Lasso de la Vega, Rosa Baños,
Verónica Guillén, Azucena García-Palacios and Diana Castilla
Virtual Reality in the Treatment of Survivors of Terrorism in Israel 196
Naomi Josman, Azucena Garcia-Palacios, Ayelet Reisberg, Eli Somer,
Patrice L. (Tamar) Weiss and Hunter Hoffman
Virtual Vietnam: Virtual Reality Exposure Therapy 205
Barbara Olasov Rothbaum
Developing a Virtual Reality Treatment Protocol for Posttraumatic Stress
Disorder Following the World Trade Center Attack 219
JoAnn Difede, Judith Cukor, Nimali Jayasinghe and Hunter Hoffman
A Virtual Reality Exposure Therapy Application for Iraq War Military
Personnel with Post Traumatic Stress Disorder: From Training to Toy to
Treatment 235
Albert Rizzo, Jarrell Pair, Ken Graap, Brian Manson, Peter J. McNerney,
Brenda Wiederhold, Mark Wiederhold and James Spira
xxv
Section V. Other Aspects of Military Healthcare
Advanced 3D Computer-Assisted Technologies in Improving Patient Telecare 251

Ivica Klapan, Ljubimko Šimičić and Sven Lončarić
War Related Stress 264
George Naneishvili, Nino Okribelashvili and Ketevan Gigolashvili
PTSD – Hungarian Lessons Learned in Afghanistan and Iraq 268
Zoltan Vekerdi and Laszlo Schandl
Section VI. Working Groups
Posttraumatic Stress Disorder --- Diagnostic and Epidemiological Concerns 279

G. Naneishvili
Technological Challenges in the Use of Virtual Reality Exposure Therapy 286
Charles van der Mast, Sinisa Popovic, Dave Lam, Gianluca Castelnuovo,
Pavel Kral and Zeljka Mihajlovic
Novel Approaches for the Integration of Behavioural Therapy and Virtual Reality 296
Mariano R. Alcañiz, Carmen L. Juan, Beatriz S. Rey
and José Antonio Q. Lozano
Posttraumatic Stress Disorder: Assessment and Follow-Up 309
Paul M.G. Emmelkamp
Author Index 321

Section I
Epidemiology and Pathophysiology of PTSD
Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder 3
M.J. Roy (Ed.)
IOS Press, 2006
Biological Markers in Croatian War

Veterans with Combat Related
Posttraumatic Stress Disorder
Nela PIVAC a,1 , Dragica KOZARIû-KOVAýIû b and Dorotea MÜCK-ŠELER a
a,1
Division of Molecular Medicine, Ruÿer Boškoviü Institute, Zagreb, Croatia
b
Referral Centre for the Stress Related Disorders of the Ministry of Health of the
Republic of Croatia, Department of Psychiatry, Dubrava University Hospital,
Zagreb, Croatia
Abstract. Posttraumatic stress disorder (PTSD) is a severe psychiatric illness

associated with disturbances in diverse neurobiological systems. The evaluation of
a variety of biomarkers might facilitate a goal of modern medicine, a proper
treatment for an individual patient at a given stage of disease. This is especially
important in PTSD, a disorder with a complex clinical picture, diverse symptoms,
and frequent comorbidities. Biological markers (platelet serotonin, platelet
monoamine oxidase, plasma lipid levels, plasma dopamine beta hydroxylase,
plasma cortisol and serum levels of thyroid hormones) were determined, and
clinical symptoms were evaluated, in 93 male war veterans with chronic combat
related PTSD, using the Clinician Administrated PTSD Scale, Positive and
Negative Syndrome Scale, and the Hamilton Rating scales for Depression and
Anxiety. Platelet serotonin concentration and plasma dopamine beta hydroxylase
activity were similar in PTSD subjects and healthy controls. Platelet monoamine
oxidase activity, and plasma/serum levels of total and free triiodothyronine and
cortisol were increased in war veterans with PTSD compared to controls,
indicating that these biomarkers might be used as the trait markers in PTSD. Since
a great proportion of our war veterans with chronic combat related PTSD had a
severe form of PTSD, complicated with the presence of psychotic or depressive
symptoms, further studies are underway to elucidate the association between
biological markers and particular symptoms occurring in PTSD.
Keywords. Combat related Posttraumatic Stress Disorder, War veterans, Blood

Platelets, Serotonin, Monoamine Oxidase, Plasma Lipid Levels, Dopamine Beta
Hydroxylase, Plasma Cortisol Levels, Free and Total Triiodothyronine
Introduction
Posttraumatic stress disorder (PTSD) is a severe psychiatric disorder, classified as an

anxiety disorder that occurs in some individuals exposed to a life-threatening traumatic
event. PTSD is characterized by specific clusters of symptoms: reexperiencing the
1
Corresponding Author: Nela PIVAC, Division of Molecular Medicine, Rudjer Boškoviü Institute, POBox
180, HR-10002 Zagreb, Croatia, E-mail: npivac@irb.hr
4 N. Pivac et al. / Biological Markers in Croatian War Veterans with Combat Related PTSD
trauma, numbing of responsiveness and avoidance, and hyperarousal. War trauma and
combat experience result in a high prevalence of PTSD. The disorder is often chronic,
frequently complicated with comorbid psychiatric diagnoses such as major depressive
disorder, anxiety, mood and substance use disorders. Socio-cultural but also
geographically specific comorbidities have been proposed [1,2]. In extensive studies
using an ethnically homogenous population of Croatian war veterans with combat-
related PTSD [3], a high prevalence of comorbid diagnoses were found [4]. The most
frequent comorbidities were depression, alcohol and drug abuse, panic disorder and
phobia, psychosomatic disorder, psychotic disorders, and dementia [5,6]. Recent
studies identified a specific, severe, psychotic subtype of PTSD, unresponsive to
antidepressant treatment [5-10].
Biomarkers might be used for preclinical screening, diagnosis, disease staging, and
monitoring of treatment, and their utility becomes especially important in PTSD, a
disorder with a complex clinical picture, diverse symptoms, and variable course, that is
complicated by various comorbidities. Disturbances in multiple neurobiological
systems (e.g., GABA, glutamate, noradrenalin, dopamine, serotonin, acetylcholine,
opioids, and the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-
thyroid (HPT) axes), are responsible for the diverse clinical symptoms (avoidance,
anxiety, flashbacks, nightmares, hyperarousal, numbing, anger, impulsivity,
aggression) occurring in PTSD [11-14].
In the studies evaluating biological markers in Croatian war veterans with combat
related PTSD, we investigated platelet serotonergic markers, i.e. platelet serotonin (5-
hydroxytryptamine, 5-HT) concentration [15,16], platelet monoamine oxidase (MAO)
activity [16,17], plasma lipid levels [18], plasma dopamine beta hydroxylase (DBH)
activity [19], plasma cortisol levels [20], and serum thyroid hormones [21].
1. Materials and methods
1. 1. Participants
Ninety three subjects with combat related PTSD participated in the study. All
participants were Croatian male war veterans, aged 28-48 years, all Caucasians, who
were hospitalized at the Referral Centre for the Stress Related Disorders of the Ministry
of Health of the Republic of Croatia, Regional Center for Psychotrauma, in the
University Hospital Dubrava, Zagreb, Croatia, from 1999 to 2002. The diagnosis of
current and chronic PTSD was conducted according to the Structured Clinical
Interview based on DSM-IV(SCID). The subjects were asked to describe their
traumatic experiences and were given enough time to talk about these and other
psychiatric disturbances. Different clinical symptoms (trauma-related, psychotic, and
depressive), occurring in this cadre of war veterans were assessed with the CAPS, the
Positive and Negative Syndrome Scale (PANSS), and the Hamilton Rating Scales for
Depression (HAM-D) and Anxiety (HAM-A). All patients were war veterans who had
been on active duty in the Croatian armed forces (range of 1-4 years, most with 3 years
of continuous combat experience), had similar social and cultural backgrounds, and the
great majority were married. All were screened with a comprehensive multidisciplinary
evaluation (conducted by 2 psychiatrists and a psychologist) prior to entry into
inpatient treatment. Subjects were excluded from the study if they had a positive family
N. Pivac et al. / Biological Markers in Croatian War Veterans with Combat Related PTSD 5
history of psychosis, or a history of schizophrenia, schizoaffective disorder or bipolar

disorder, a serious concomitant medical condition, a history of seizures or misuse of
alcohol or drugs (recent use of any psychotropic drugs within one month of baseline),
clinically significant abnormalities in electrocardiogram or laboratory findings, or a
serious risk of suicide. Combat-related symptoms included intrusive images of
screaming soldiers, fire, bombing, rocketing, etc. Individuals taking cholesterol-
lowering drugs were excluded. The procedures were fully explained and written
informed consent was obtained from all patients. The local Ethics committee approved
this protocol.
The control group consisted of 124 healthy male volunteers, with no personal or
family history of psychopathology, and receiving no medical treatment. None of the
healthy subjects were receiving psychiatric or related treatment before the samples were
selected. Groups were matched on age, gender, smoking, and other socio-demographic
characteristics. The control subjects agreed, and provided written informed consent, to
participate in the study and to provide a blood sample.
1.2. Biochemical determination
A forearm vein was cannulated for blood sampling at 08.00 a.m., after an overnight
fasting. Blood samples (8 ml) were drawn in a plastic syringe with 2 ml of acid citrate
dextrose anticoagulant. Platelet-rich-plasma (PRP) was obtained by centrifugation (935
x g) for 70 s at room temperature. Platelets were sedimented by further centrifugation
of PRP at 10,000 x g for 5 min. The platelet pellet was washed with saline and
centrifuged again. Platelet 5-HT concentration was determined by the
spectrofluorimetric method, as previously described [15,16,22]. Platelet MAO activity
was determined spectrofluorimetrically using kynuramine as a substrate, as previously
described [16]. Platelet protein levels were measured by the method of Lowry et al.
[23]. Serum lipid levels—total cholesterol, high-density lipoprotein (HDL), and
triglycerides (TG) levels—were determined by enzymatic color test, while serum low-
density lipoprotein (LDL) levels were measured using an enzymatic clearance assay.
Serum thyroid hormones: total and free triiodothyronine (T3) levels were assayed using
an luminoimmunochemical assay kit (Johnson and Johnson Clinical Diagnostic
Products, Amersham, UK). Plasma DBH activity was determined by a photometric
assay, using tyramine as a substrate, by the method of Nagatsu and Udenfriend [24].
Cortisol levels were determined using a commercially available radioimmunoassay kit
from Diagnostic Products Cooperation, CA, USA.
1.3. Data analysis
All data (expressed as mean ± S.D.) were evaluated by one-way analysis of variance
(ANOVA), followed by Tukey’s multiple comparison test. The level of significance
was p<0.05.
2. Results
The mean scores on the CAPS, PANSS, HAM-D and HAM-A scales are shown in
Table 1 for war veterans with combat related PTSD. No significant difference
(F=0.704, df=1,165 p>0.05, one way ANOVA) was found between the age of war
veterans (39.7 ± 8.5 years) and control subjects (38.4 ± 11.9 years).
Table 1. Mean scores in CAPS, PANSS, HAMD and HAMA scales and subscales in 93 war veterans with
chronic combat related PTSD
Measures Scores (mean r SD)

CAPS total 81.2 r 13.1
PANSS total 84.3 r 20.9
PANSS positive 16.9 r 6.5
PANSS negative 12.4 r 5.1
PANSS general psychopathology 45.8 r 9.5
PANSS supplementary items 9.2 r 2.4
HAMD 21.5 r 4.8
HAMA 24.4 r 6.4
Platelet 5-HT concentration did not differ significantly (F=0.069, df=1,152

p=0.079, one way ANOVA) between war veterans with PTSD and control subjects
(Figure 1).
Plasma cortisol levels differed significantly between groups (Table 2). Plasma
cortisol levels were significantly higher (p<0.05, Tukey’s test) in war veterans with
PTSD than in control subjects (Table 2).
Table 2. Plasma cortisol levels in 55 male Croatian war veterans with chronic combat related PTSD and in
42 male control subjects
Groups Plasma cortisol (nmol/)

PTSD 577.0 r 185.3
Control group 465.6 r 204.8*
One-way ANOVA F=7.835; df=1,95; p<0.006
Figure 1. Platelet 5-HT concentration in war veterans with PTSD and control subjects
Figure 2: Platelet MAO activity in war veterans with PTSD and control subjects
Platelet MAO activity differed significantly (F=18.903; df=1,208; p<0.001, one-

way ANOVA) between war veterans with PTSD and control subjects. The enzyme
activity in war veterans with PTSD was significantly (p<0.05, Tukey’s test) higher than
MAO activity in platelets of control subjects (Figure 2).
There were significant differences in serum total T3 levels (F=6.28; df=1,68;
p<0.001, one way ANOVA) and serum free T3 levels (F=2.27; df=1,68; p<0.02, one
way ANOVA) between war veterans with combat related PTSD and healthy control
subjects. Serum total T3 levels were 32% higher in war veterans with combat related
PTSD than in healthy control subjects, while serum free T3 levels were slightly but still
significantly increased by 8% in war veterans with combat related PTSD when
compared to control subjects.
Plasma DBH activity was not significantly (F=0.29; df=1,78; p=0.593, one-way
ANOVA) different between war veterans with PTSD and control subjects (Figure 3).
Figure 3. Plasma DBH activity in war veterans with PTSD and control subjects
Plasma lipid levels differed significantly (evaluated by one-way ANOVAs)

between war veterans with PTSD and control subjects. War veterans with PTSD had
significantly (p<0.05, Tukey’s test) higher serum cholesterol and triglycerides levels,
and significantly (p<0.05, Tukey’s test) lower HDL levels than the control group
(Table 3). War veterans with PTSD and control subjects had similar values of serum
LDL levels (Table 3).
Table 3. Serum cholesterol, triglycerides, HDL and LDL in 37 Croatian war veterans with chronic combat
related PTSD and in 33 control subjects.
Groups Cholesterol Triglycerides HDL LDL (mmol/L)

(mmol/L) (mmol/L) (mmol/L)
PTSD 5.79 r 1.09 2.48 r 1.18 0.89 r 0.30 3.41 r 0.82
Control 4.96 r 1.06* 1.29 r 0.94* 1.18 r 0.21* 3.21 r 0.88
ANOVA F=3.22; F=4.69; F=4.75; F=0.98; p>0.10
df=1,68 p<0.001 p<0.001 p<0.001
3. Discussion
In PTSD, a disorder with a complex clinical picture, diverse symptoms, and different
comorbidities, the evaluation of complex biological signals might be used to improve
the characterization of the baseline group characteristics, to predict a suicidal risk, to
differentiate particular symptoms or syndromes, and to improve the understanding of
the underlying neurobiology of PTSD.
The rationale for the use of blood platelets as a limited peripheral model for the
central 5-HT synaptosomes lies in the similar pharmacodynamics of 5-HT with central
5-HT neurons [25,26]. Recent reports suggest that platelet 5-HT concentration [27,28],
and platelet MAO activity [17,29,30] might serve as biological or trait markers for
particular mental disturbances. The hypothesis of a deficit of the serotonergic system in
PTSD is based on data showing disturbed 5-HT function in PTSD [14]. Serotonergic
alterations might contribute to the cognitive disturbances and deficits in the memory
systems occurring in PTSD [14], and platelet 5-HT has been reported to be altered in
aggression [25] and impulsivity [31]. In line with previous reports [15,16,32], our data
indicate that platelet 5-HT concentration is not altered in war veterans with PTSD.
Since biological markers have been proposed to be more closely related to basic
psychopathological characteristics, i.e. trait markers [26,31], than to nosological entities
(such as PTSD), our data confirm this presumption. This finding supports the hypothesis
that platelet 5-HT is more related to particular trait markers, such as aggression [25],
impulsivity [31], or to particular symptoms [27,28], suicidal behaviour [26-28], than to
state characteristics [26,27].
Platelet MAO shares similar biochemical and pharmacological characteristics, and
identical amino acid sequences, with brain MAO-B [33], and was proposed to represent
a genetic marker for the size or functional capacity of the central monoamine systems
and serotonergic system [28]. We have found increased platelet MAO activity in
Croatian war veterans with PTSD, in contrast to previous data [16,17,34]. The
discrepancies between studies might be explained by the differences in the time course
of PTSD (i.e. acute PTSD in the studies [16,17] vs. chronic PTSD in the present study),
and the lack of alcohol comorbidity in the present group when compared to the
previous study [34]. Our data, showing increased platelet MAO values in the large
numbers of war veterans with combat related PTSD, agree with the altered platelet
MAO in different personality and temperamental traits, such as sensation seeking and
impulsivity [29,30], and impulse and affect dysregulation [35]. Smoking decreases
platelet MAO activity [29,30,36], but after controlling for the effect of smoking, the
activity of the enzyme remained elevated (data not shown) in our Croatian war veterans
with PTSD.
The noradrenergic system is hyperactive in PTSD, and increased noradrenergic

markers, both in cerebrospinal fluid and in plasma and urine, were observed in PTSD
patients [11,14]. Noradrenergic neurons arise from the locus ceruleus and project to
diverse structures involved in learning and memory (prefrontal cortex, amygdala and
hippocampus), and stress response (hypothalamus). These brain regions modulate
stress/fear response and emotional memory [11,14]. DBH is an enzyme that catalyzes
the conversion of dopamine to noradrenalin. War veterans with chronic combat related
PTSD in our study had similar plasma DBH values as healthy subjects. The lack of
changes in plasma DBH in our sample might suggest that plasma DBH is not a suitable
biological marker of the altered noradrenergic activity in PTSD, or that DBH is altered
only in the psychotic subtype of PTSD, as suggested before [37]. To elucidate this
relationship, the studies evaluating the relationship of DBH with psychotic PTSD are
underway.
The altered plasma levels of cortisol, T3, thyroxin (T4) and thyroid-stimulating
hormone (TSH) reflect the dysregulated HPA and/or HPT axis activity in stress-related
disorders [11]. The concept of a hyperactive HPT axis, with consequent elevation of
total and free T3 in PTSD patients, agrees with our data [21], and confirms the link
between stress and clinical hyperthyroidism [11]. Hypersecretion of corticosteroids for
prolonged periods can harm cognitive processes that are disturbed in PTSD [14]. Our
data [20] show increased plasma cortisol levels in war veterans with combat related
PTSD, adding to the contradictory findings regarding the status of basal and stimulated
cortisol levels in PTSD patients. Since noradrenergic and HPA systems act
synergistically in response to acute or prolonged stressful stimuli, disturbances in
noradrenergic and HPA axis systems would elicit a cascade of events and disrupt the
regulatory mechanisms modulating response to trauma, and add to the development of
PTSD symptoms.
In line with the data showing altered plasma lipid levels in PTSD [38], we have
shown that war veterans with PTSD have increased levels of serum cholesterol, and
triglycerides, decreased levels of HDL [18], and unaltered levels of LDL. Since
increased serum cholesterol is a risk factor for cardiovascular disease in PTSD patients,
these findings call for dietary modification for war veterans with PTSD.
The great proportion of our war veterans with chronic combat related PTSD had a
severe form of PTSD, complicated with the presence of psychotic or depressive
symptoms. Therefore, further studies are underway to elucidate the association between
biological markers and particular symptoms occurring in PTSD, and to facilitate the
identification of the specific form or subtype of PTSD, disease staging, and monitoring
of treatment.
The research of biological markers, which reflect the activity of the central
neurotransmitter and/or neuroendocrine systems, should focus on efforts to integrate
the data, and to explain the multiple interactions among these neurobiological systems
in PTSD, in order to achieve a goal of modern medicine, a tailored pharmacological
and non-pharmacological treatment for an individual patient with PTSD at an
appropriate point in the course of the disorder.
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M.J. Roy (Ed.)
IOS Press, 2006
Theta Synchronisation of Hippocampal and

Long Distance Circuitry in the Brain:
Implications for EEG-Neurofeedback and
Hypnosis in the Treatment of PTSD
John GRUZELIER Ph.D1
Division of Neuroscience & Mental Health, Faculty of Medicine, Imperial College London, UK
Abstract. The significance of the brain’s theta rhythm is considered for its role in
synchronising electrical activity in the hippocampus and over widely distributed
brain regions, circuitry which is of cardinal importance for post traumatic stress
disorder (PTSD). This circuitry is involved in memory retrieval, survival
behaviour, navigation including virtual reality tracking, wellbeing, and the
integration of emotion and cognition. These processes are all implicated in the
cognitive neuroscience of PTSD. Two modalities of treatment are outlined that
have been found effective in contributing to the treatment of PTSD - hypnosis and
EEG-neurofeedback. Both elevate the brain’s theta rhythm, and both warrant
further study in contributing to the treatment of PTSD, and the nascent potential of
virtual reality (VR) exposure. E-mail contact: j.gruzelier@imperial.ac.uk
Keywords. Theta rhythm, hippocampus, brain circuitry, PTSD, hypnosis, EEG-

neurofeedback.
1. The Theta Rhythm
1.1. Survival Behaviour and the Hippocampus
Theta activity is a brain rhythm that oscillates between 4 and 8 cycles per second and is positioned
in the EEG spectrum between the slower delta rhythm and the faster alpha rhythm. In animals it
spans a wider band (4 – 12 Hz) and is termed “rhythmic slow activity” (RSA). It has been
historically linked with the hippocampus [1] and behaviourally with locomotion and exploratory
activity, or a spatial map [2], all categorised as “species-specific survival” behaviour, and thought
to be adaptively reprocessed in memory during REM sleep [3,4]. Place cells were first discovered
1
Corresponding author: John GRUZELIER. Division of Neuroscience & Mental Health, Faculty of
Medicine, Imperial College Room 10L17, Charing Cross Campus St Dunstan's Road London W6 8RP,
England Tel: + 44 20 8846 7246 Fax: + 44 20 8846 1670
14 J. Gruzelier / Theta Synchronisation of Hippocampal and Long Distance Circuitry in the Brain
in the hippocampus by Petsche [5], and recently “theta-modulated place-by-direction” cells have
been discovered in rodents [6]. Now through intracerebral EEG recording, place cells in epileptic
patients have been shown to resonate at theta frequencies in virtual reality studies [7], with theta
augmented by active navigation when compared with passive navigation [8].
1.2. Entrainment of Circuitry for Integrating Cognition and Emotion
The hippocampus is involved in circuitry synchronised by the theta rhythm. Non-rhythmic

neuronal impulses of brain stem origin, once they have been relayed to the septum, are converted
into rhythmic theta bursts and are transmitted to the hippocampus and then to the cortex (and so
are detectable by scalp electrodes). These are maintained via feedback loops [3]. Recent
research extends the domain to other limbic structures. This includes a recurrent network
involving the hippocampus, medial mammilliary bodies, anterior thalamus, post cingulated
entorhinal cortex and subiculum, and then back to the hippocampus. There is in addition an
ascending modulatory circuit from the supramammillary nucleus of the hypothalamus which
contains cells determining the frequency of the theta rhythm. This circuit can act independently
of the hippocampus, and via reciprocal connections can modulate the hippocampus, infralimbic
cortex and prefrontal cortex [9]. Therefore circuitry is available for the integration of cognition
and emotion. This occurs through topographically specific connections from neocortex and
ascending connections from the brainstem.
1.3. Long Range, Top-Down Connectivity
Theta synchronisation extends beyond this circuitry. It has a fundamental role in all long distance
regional connectivity in the brain. Long range connectivity is essential to navigation, the historical
signature of theta in animals. Furthermore Bland and Oddie [10] have proposed that theta
oscillations coordinate activity in brain regions involved in updating motor plans on the basis of
sensory input. In other words theta is the conduit for sensory-motor integration, where afferent
sensory input is organised and directed to regions orchestrating a motor plan and allowing for a
motivated navigational response. Similarly, during a virtual movement, taxi driver navigational
task, theta oscillations were recorded from intra cranial electrodes in epileptic patients [11]; with
searching distinguished from goal seeking behaviour by the frequency and distribution of theta.
A similar coordinating role for theta is inherent in Miller’s [3] theory of resonant self
organising loops that orchestrate representations of the salient memory “context” against which
sensory input is compared. Here theta entrainment is seen to strengthen the connection weights of
hippocampal-cortical loops phase-locked to the theta rhythm. These loops are widely dispersed to
distal parts of the brain.
In a landmark study Von Stein et al [12] on the basis of empirical studies proposed an inverse
relation between the frequency of the EEG oscillation and the scale and range of functional
synchrony. Synchronisation of the fast gamma frequencies involved in perception and encoding,
or “bottom up” processing, was local in extent, whereas long range synchronisation, connecting
distal parts of the brain was mediated by the slow theta and alpha frequencies involved in internal
mental processes such as visual imagery and working-memory.
This “top down” processing role of theta has been exemplified by a mental calculation study
combining EEG with fMRI [13]. Theta oscillations were associated with the fMRI blood
oxygenation signals representing both activation and deactivation. The process of mental
calculation disclosed theta synchronisation of a network distributed through frontal, temporal and
parietal cortices.
J. Gruzelier / Theta Synchronisation of Hippocampal and Long Distance Circuitry in the Brain 15
Therefore, of the waking EEG frequencies, theta has a special role in synchronising the
circuitry that is widely distributed in the brain, circuitry especially brought into play by top-down
internalised processing.
1.4. Consciousness
Theta activity has long been associated with altered states of consciousness, including dreaming,
meditation, hypnosis, and hypnogogia - the border between waking and sleeping.
Relations between theta and normal consciousness have now been affirmed through studies
of working memory, becoming popularised through considerations of theta as the electrical
signature of the hippocampus in animals and the role of the hippocampus in encoding and
retrieval of episodic memory in man. To mention three studies, Burgess and Gruzelier [14] found
that theta power increased with the conscious recognition of words, while Klimesch et al [15]
showed that aside from theta accompanying the recognition process itself, during encoding only
the words that were later to be recognised were accompanied by increases in theta power. When
contrasting reports of remembering when there was a clear conscious recollection, versus reports
of knowing without recollection, both were found to be accompanied by increases in theta when
compared with “ no awareness” reports, however, these qualitatively different conscious
judgements were distinguished by the time course of the increase in theta, occurring later and
longer for remembered judgements [16].
A recent meditation study comparing long versus short term meditators practising Sahaja
Yoga underscores the fundamental roles of theta not only in meditation, but also in wellbeing, and
in top down and long range connectivity [17]. When instructed through internalised attention to
meditate to achieve a state of bliss, long term meditators were best distinguished from novices by
theta activity in anterior and midline regions. Subjective ratings of bliss also correlated positively
with theta activity. The synchronisation of theta disclosed a locus in the left prefrontal region, and
from this locus synchronisation was widely distributed, extending to posterior association cortices
bilaterally. It is noteworthy that the left prefrontal locus has before been associated with both the
expression of positive affect and with internalised attention.
1.5. Summary of the Functional Implications of Theta
• Theta has long been regarded as a signature of hippocampal function,

modulating place cells and having associations with comparator memory
functions such as orienting and survival behaviour and involving integration
of both cognitive and affective contexts.
• Theta is augmented in conscious memory judgements.
• Theta is involved in top-down internalised processing exemplified by visual
imagery, working memory and meditation.
• Theta is associated with positive emotion.
• Theta synchronises hippocampal circuits which organise sensory input and
orchestrate a motor plan, and which coordinate cognition and emotion.
• Theta is involved in long range circuitry in the brain and facilitates
connectivity.
2. Neurophysiology of PTSD
There are a number of resonances between the functional significance of theta and contemporary
understandings of the neurophysiology of PTSD.
2.1. The Hippocampus
Considering first the hippocampus, this has been implicated in PTSD through its role in episodic
memory retrieval, as well its susceptibility to stress [18]. A reduction in hippocampal volume has
been reported in a majority of studies of PTSD [19]. This may be reversible, for following
antidepressant treatment evidence was found of hippocampal neurogenesis and an increase in
volume in PTSD, along with alleviation of stress [20].
2.2. Brain Circuitry
Regarding circuitry and connectivity, recall of traumatic events involves neural circuitry involving
limbic structures such as the hippocampus, paralimbic structures such as the anterior cingulated
and orbitofrontal cortex, as well as prefrontal structures such as the left inferior prefrontal cortex
and Broca’s area. Putatively abnormal functional connectivity has been reported in a standard
working memory task in a mixed group of PTSD patients [21]. Whereas bilateral parietal areas
and the left precentral gyrus were more activated in PTSD than in controls, other areas were less
activated and these included the inferior medial frontal lobe, bilateral middle frontal gyri and right
inferior temporal gyrus. This was interpreted as reflecting disconnectivity of working memory
functional networks in keeping with the patients’ dependence on nonverbal memory.
Lannis et al [22] took this hypothesis further by examining the memory circuits involved in
the recall of traumatic events which were provoked by scripts and compared with the recall of
neutral events. Comparisons were made between trauma patients with PTSD who experienced the
recall as flashbacks (flashbacks which were accompanied by raised heart rate), PTSD patients
without flashbacks and non-PTSD control patients. In support of dependency on nonverbal
episodic memory with PTSD there was a striking laterality effect. Whereas in patient controls a
left hemispheric circuit underpinned autobiographical memory retrieval, in both PTSD groups the
right hemisphere was activated in line with image-based retrieval. Furthermore in patients with
PTSD without flashbacks, interpreted as exhibiting a dissociative response to trauma, circuitry
was consistent with the evocation of heightened awareness of bodily sensations [23].
2.3 Electrophysiology
EEG recordings in PTSD are sparse. Considering first the EEG spectrum, Begic and colleagues
[24, 25] have conducted two studies with Croatian war veterans, replicating an elevation in fast
wave beta activity which was found to be widely distributed. Elevated beta activity is consistent
with raised levels of anxiety. Similarly in a study which examined EEG asymmetry in PTSD,
right parietal activation was found associated with an anxious arousal syndrome. The right
lateralised effect supported the right hemispheric involvement reported in functional imaging
studies [22].
Regarding EEG connectivity, Chae et al [26] examined an EEG measure called nonlinear
dynamical complexity which has been interpreted as indexing connectivity of neuronal cell
assemblies and the integration of sensory input with ongoing neuronal activity [27]. The higher
the complexity, the higher the connectivity. Patients had suffered PTSD for an average of 6 years
due to motor accidents, assault or witnessing trauma, and were medication-free for two weeks.
Lower complexity, an index of reduced connectivity, was disclosed in patients in over half of the
16 derivations recorded, and while these included the 4 temporal lobe electrodes the effects were
more widely distributed. Similarly, in a conference abstract Leiberg et al [28] report EEG
coherence patterns of motor accident survivors recorded while viewing trauma relevant pictures.
Reduced coherence (connectivity) was disclosed between temporal, centroparietal and frontal
areas.
2.4. Summary of the Neurophysiology of PTSD and Implications for Theta and Hippocampal
Circuits.
• Hippocampal processes involved in PTSD include survival behaviour such as conscious

retrieval of traumatic episodic memories, the comparator process which underpins
orienting/startle and susceptibility to stress, and all involving theta synchronisation.
• There are abnormalities of circuitry in PTSD widely distributed in the brain and with a
limbic locus, in keeping with both abnormal integration and with evidence of reduced
complexity (connectivity).
• In PTSD there is atypical right hemispheric circuitry, in keeping with image-based
retrieval which is dissociated from left hemispheric narrative processes, and associated
with anxious arousal.
• In PTSD there is EEG evidence of elevated fast frequency activity and right parietal
activity in keeping with an anxious arousal syndrome.
3. Hypnosis and EEG-Neurofeedback Theta Training
3.1. Neurophysiology of Hypnosis
EEG studies have consistently associated theta activity with hypnosis [29], perhaps assisted by
the mentally relaxing effects of hypnosis [30]. Functional imaging studies show that hypnotizable
subjects following hypnosis may alter their perceptual abilities in line with instructions, as would
follow from increased cognitive and physiological flexibility and mental efficiency [29, 31].
Neural circuitry is altered and there is evidence of an uncoupling of lateral left frontal functions
[31], hypothesized to facilitate the orchestration of behaviour by the therapist [32].
Theoretically hypnosis has obvious affinities with the symptoms of PTSD. In fact trauma
may be viewed as an hypnotizing agent, for trauma can trigger responses with hypnotic features
such as amnesia, identity distortion, dissociation, numbing, verbal stupor and stupor [33]. Spiegel
[34] has articulated three clusters of symptoms of PTSD in parallel with hypnosis as follows:
intrusive flashbacks and nightmares with hypnotic absorption; dissociation with hypnotic
dissociation; exaggerated response to disturbing stimuli with hypnotic automaticity. Hypnosis can
enable the access of these symptoms and facilitate their reprocessing. High hypnotisability has
often been found to be a characteristic of patients who suffer from PTSD [35].
3.1.1. Hypnotherapy and PTSD

Hypnosis has been widely used as a treatment for PTSD for over a century [36], but there are few
controlled studies or systematic case studies [37]. In a meta analysis of Flammer and Bongartz
[38] only one controlled study [39] was cited and this involved a successful brief intervention
with 52 patients. Since then Bryant et al [40] reported a controlled study with civilian trauma
survivors randomly assigned to six sessions of either cognitive-behavioural therapy (CBT)
consisting of exposure, cognitive restructuring and anxiety management, to the same CBT
package coupled with hypnosis, or to counseling. At 6 month follow-up counseling was less
successful than the other approaches, with CBT when combined with hypnosis the more
successful in reducing the reexperiencing of symptoms.
In a single case study Degun-Mather [41] effectively treated a Korean war veteran who 40
years later presented with depression and was unable to further contain PTSD with dissociative
fugues. This will be presented in some detail to provide a flavour of the hypnotic approach. Hers
was a multimodal treatment approach designed in three phases. The first stage involved
stabilization through education and CBT with hypnosis. The second was grounded in hypnotic
reprocessing of traumatic memories through a safe-remembering method and hypnotic dreams,
along with cognitive reevaluation of traumatic events to resolve negative affect. The third
involved further memory integration aided by dream elaboration with and without hypnosis, and
rehabilitation. The hypnotherapy process she conceptualized, after Brende [42], as follows: 1)
Stabilizing and grounding the patient through anxiety reduction using ‘special place’ and ‘anchor’
techniques, post hypnotic suggestion, and self-hypnosis training for relaxation and identification
of triggers. 2) An uncovering technique facilitating recall of fragmented memories through re
evoking the state in which the events occurred, and talking through and integrating fragmented
memories into a narrative. 3) Re-associating with dissociated feelings. 4) Client led re-evaluation
of traumatic events by utilizing ideomotor responses and at a pace that could rapidly shift to a
calmer state facilitating reappraisal. 5) Post-hypnotic dream suggestions and hypnotic dream
elaboration with written narratives that the patient experienced with an automatic hypnotic quality.
6) Reintegrating the dissociated psyche using ego-state therapy, and introducing an older self to a
younger self both in hypnosis and through posthypnotic suggestion.
3.2. Elevating the Theta/Alpha Ratio
Elevating the theta/alpha ratio is a widely used clinical and optimal performance EEG-
neurofeedback protocol which we have recently validated [43]. It was originally developed to
produce an hypnogogic state for the purposes of enhancing creativity when benefits were found in
enhanced wellbeing and psychic integration [44]. Subsequently it was effective as one part of a
multimodality approach along with temperature biofeedback, visualization, systematic
desensitization, rhythmic breathing and autogenic training in the treatment of veterans with
alcoholism and alcoholism with depression [45-47], and importantly war veterans with PTSD [48].
The protocol aims to facilitate a rise in levels of theta (4-8 Hz) over alpha (8-12 Hz) in a state
of eyes-closed relaxation. Normally on closure of the eyes and onset of relaxation the EEG
displays high amplitude rhythmic alpha activity. With further deactivation alpha activity slowly
subsides and slower theta activity gradually becomes predominant. The point in time when theta
activity supersedes alpha activity, the so-called theta/alpha “crossover”, is commonly associated
with loss of consciousness and the onset of early sleep stages. By teaching participants to raise
theta over alpha activity while not falling asleep, the alpha/theta protocol aims to produce
consciously a state of deep relaxation and deactivation, apparently resembling a meditative state
that would normally be unconscious.
Until our studies, though widely practiced by EEG-neurofeedback practitioners, this
apparently promising approach lacked validation, though an accumulation of results with other
EEG protocols in the field of ADHD through small scale controlled studies [49] suggested that
therapeutic claims may well be of promise. We first provided evidence of operant control of the
theta/alpha ratio [50] and demonstrated that this was highly effective in enhancing artistic aspects
of music performance in replicable results with conservatory students [51]. This was in
comparison with training elevations in the faster oscillations including the 12-14 HZ “SMR” band
and the beta 1 band, and in comparison with other approaches including aerobic fitness, mental
skills training, the Alexander technique which is universally applied in music conservatories to
relieve somatic stress and improve posture, as well as in comparison with standby controls. We
went on to demonstrate mood enhancement in socially anxious medical students when compared
with a mock feedback control [52], and to extend the music results to ballroom dance performance
[53].
The advantages of theta training for the performing arts went beyond anxiety reduction and
relaxation training [43, 50, 51]. The order of magnitude of the benefits for theta training were of
professional significance, were replicable, and by their nature - the enhancing of artistic aspects of
music performance - were consistent with associations between the hypnogogic state and
creativity [52]. These effects can best be understood through both the cognitive and affective
effects of theta. Cognitive effects are the result of memory enhancement synchronizing properties,
and sensory-motor integration via theta’s long range network,, whereas affective influences
operate by enhancing well being.
3.3 Summary of the Relevance of Hypnosis and Theta Training for PTSD
• Hypnosis is associated with elevated theta, in keeping with internalized top-down

processing including visual imagery and memory retrieval, and deep relaxation.
• Trauma may trigger responses with hypnotic features and shared processes such as
absorption, dissociation and automaticity.
• Hypnotherapy has been used successfully to treat PTSD alone or as an adjunct to CBT.
• PTSD patients are characterized by hypnotic susceptibility.
• Hypnotherapy assists in memory revivification and the integration of fragmented
episodic memories, against a background of anxiety reduction, empowerment and
psychic integration.
• Theta training has been found effective in treating PTSD as part of a multimodal
programme.
• Theta training has elevated mood and empowerment.
4. Future Directions
This NATO workshop has disclosed that VR holds promise of substituting for, or replacing, in
vivo exposure procedures in the CBT treatment of PTSD. As hypnosis has been shown in
controlled studies to benefit PTSD, integration with VR would be of interest, as would integration
of VR with EEG-neurofeedback training to enhance the theta/alpha ratio, training which has also
been found efficacious with PTSD. Other EEG-neurofeedback protocols such as elevation of the
12-14 Hz “sensory motor rhythm” band may also assist with the anxious arousal PTSD syndrome,
for this protocol provides mental relaxation [53], a relaxed attentional focus [54, 55], has been
efficacious in treating ADHD [49], and has been found to improve verbal working memory [55].
From the evolving neuroscience of PTSD, abnormalities of circuitry have been inferred.
Therefore, techniques such as theta training and hypnosis, which through the elevation of theta
facilitate the synchrony of long distance connectivity in the brain, are likely to provide a valuable
adjunct to CBT approaches. Finally, the advent of wireless bluetooth EEG recording has potential
in providing important ongoing feedback to help guide the therapist in the choice of VR scenarios
and CBT strategies.
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M.J. Roy (Ed.)
IOS Press, 2006
Limbic Circuitry and Posttraumatic Stress

Disorder
Ivica KOSTOVIû 1 and Miloš JUDAŠ,
Croatian Institute for Brain Research,
School of Medicine, University of Zagreb, Croatia
Abstract: The objective of this review is to outline problems which should be

considered in trying to define PTSD as neurobiological disorder with abnormal
neuronal circuitry. The amygdala is the central neuronal structure for expression of fear
memory and fear conditioning (emotional function). Due to the prominent connections
with the cingulate and prefrontal cortex and hypothalamus, the amygdala can be
considered as a part of the limbic circuitry. For regulation of contextual stimulus
(cognitive function), the amygdala interacts with the memory circuit of the hippocampal
cortex. Limbic circuitry, which incorporates structures of the great limbic lobe,
prefrontal cortex and cingulate cortex, conveys impulses to the hypothalamus, which is
the main executive structure for the interaction with endocrine pituitary and brainstem
tegmental autonomic and transmitter (neuromodulatory) functions. Human stress-
related changes of emotional functions show specificities related to phylogenetic
specialization of the human cortex and developmental differences related to the
prolonged developmental vulnerability throughout childhood and adolescence.
Keywords: amygdala, limbic system, stress, emotional brain
1. The Limbic Lobe and Limbic «System»
Recent scientific studies provide evidence that PTSD is a brain disorder with biological
underpinnings [1,2]. For contemporary neuroscience it is a challenging task to disclose the
psychobiological mechanisms of PTSD. The crucial question is to determine abnormalities
of neuronal circuitry which underlie the cascade of biological and psychological responses
following the activation of fear-related neuronal systems. Functional and structural changes
in the so-called «limbic» circuitry and limbic structures are frequently associated with
PTSD. Although many researchers suggest the rather poorly defined term and concept of
limbic circuitry should be abandoned from use [3], the concept of the limbic system is still
1
Corresponding Author: Ivica Kostovic. School of Medicine, Zagreb University Hospital Center Gojka
Šuška 12, HR-10000 Zagreb, Croatia
24 I. Kostović and M. Judaš / Limbic Circuitry and Posttraumatic Stress Disorder
frequently used in the current literature, and the term «limbic» is often associated with the
«emotional» brain.
We believe that the topographical and structural characteristics of the so-called limbic
structures, as well as their predominant connections, justify the use of the term «limbic» in
certain well-defined contexts. The following arguments can be used in support of this
approach:
The limbic structures form the great limbic lobe of Broca, in a topographically specific
manner (limbus means margin) closely associated with two subcortical structures – the
amygdala and the septum.
The limbic cortices such as the hippocampus and anterior cingulate cortex, together
with subcortical structures such as the amygdala, are frequently altered in individuals with
PTSD.
The amygdala, which is responsible for fear reactions [4,5,2,3], is closely associated
with two regions, namely the frontal cortex and hypothalamus, which were included in the
limbic system according to the concept presented by Nauta [6].
The hypothalamus, extensively connected to the limbic cortical and subcortical
structures, can be considered as the executive part of the limbic circuitry, receiving input
from the hippocampus, amygdala and frontal lobe, and conveying impulses to the
periaqueductal gray (part of the limbic midbrain area) and the pituitary gland. Through the
hypothalamus, limbic structures can regulate autonomic and endocrine responses following
stress.
For a long time, limbic emotional functions were considered to be separate from
cognitive-memory functions. Today we know that contextual stimulus (cognitive function)
and fear conditioning (emotional function) form the so-called contextual fear conditioning,
and require both the amygdala and hippocampus [3]. Thus, through fear conditioning,
emotional and cognitive function of limbic structures in the primate brain work together
and their function seems to be disturbed in PTSD.
2. Abnormalities Of Neuronal Circuitry in Ptsd
At the moment, the exact abnormalities of the neuronal circuitry underlying PTSD are
not known. The significant changes observed in PTSD patients in the anterior cingulate
cortex and hippocampus with neuroimaging techniques does not necessarily mean causal
relationship. Thus, it is not known whether these are just consequences of abnormal brain
function at the level of different chemical-transmitter pathways throughout the prolonged
period. The chemically identified transmitter pathways which innervate the limbic cortex
(Figure 1) and subcortical structures (frontal cortex, anterior cingulate cortex, amygdala)
are affected in different mental disorders and are not specific for PTSD. Dopaminergic,
serotonergic, noradrenergic and cholinergic pathways which modulate emotional behavior
and cognitive functions were reported to be affected in PTSD [2] but also in other mental
disorders.
I. Kostović and M. Judaš / Limbic Circuitry and Posttraumatic Stress Disorder 25
An additional problem in the analysis of transmitter systems is that certain transmitters

may display different levels and regulation acutely after exposure to stress than they do
later when PTSD develops. Therefore, it is better to analyze transmitter dysregulation.
Figure 1. The midbrain limbic area is the source of noradrenergic (shown) and dopaminergic-serotonergic-
cholinergic (not shown) pathways which innervate the limbic cortex and the amygdala.
Another problem in the interpretation of transmitter changes in the neuronal circuitry

are interindividual (probably at least partly genome-based) differences in response to stress.
Sex and gender differences in organization of emotional circuitry are probably an additional
confounding factor influencing abnormalities of transmitters in PTSD. For example, it was
recently reported [7] that the activity of the amygdala on the left side of the brain relates to
memory for emotional material in women. In men, however, memory for the same
emotional material relates to the activity of the amygdala on the right side of the brain.
Furthermore, women activate a smaller network involving the left amygdala, but
demonstrate greater overlap between brain areas involved in ongoing emotional processing
and memory, which might explain why women tend to have stronger emotional memories
than men.
Figure 2. Papez's circuit connects the limbic cortex of the hippocampus and the cingulate gyrus with the
hypothalamus and thalamus.
3. Limbic Circuitry
One of the most famous limbic circuits is Papez's circuit, initially described in 1937 as
a hypothetical circuit for emotional functions. At the time, it was unclear where emotional
reactions were integrated, but Papez selected the great limbic lobe of Broca as the most
likely candidate structure for those functions. Subsequent intensive studies of visceral and
emotional brain regions [8] in fact confirmed that some components of Papez' circuit are
involved in different aspects of emotional behavior, namely autonomic, motor and
hormonal responses. Papez' circuit (Figure 2) connects the hippocampus, its prominent
projections to the hypothalamus (mammillary body), the «limbic» anterior thalamic
nucleus, and the cingular frontal cortex which projects along the cingulum bundle to the
entorhinal area, which sends short perforant and alveolar pathways back to the
hippocampus. One portion of that circuit, which connects the hippocampus, is today known
as the memory circuit.
Figure 3. Topographical position and connections of amygdala. Note the afferent connections from the auditory
cortex and efferent connections to the hypothalamus (stria terminalis) and cortex.
Subsequent findings on the connectivity of the limbic cortex and associated subcortical
nuclei (amygdala, septum) have enlarged the extent of limbic circuitry. Thanks to modern
tracing techniques, it was shown that most of the pathways streaming to the limbic cortex
and out of the limbic cortex pass through the lateral hypothalamus (i.e. medial forebrain
bundle), and connect the midbrain tegmentum which is rich in dopaminergic, cholinergic,
noradrenergic, and serotonergic nuclei projecting to the limbic cortex through the lateral
hypothalamus. In addition, it has been shown that the prefrontal cortex also projects to the
hypothalamus and receives various limbic projections. The projections of the orbitofrontal
cortex to the amygdala and hypothalamus represent an additional reason why the
orbitofrontal cortex was considered to be important for different aspects of emotional
behavior.
Altogether, limbic circuitry involves classical limbic structures, the hypothalamus, and
prefrontal and cingulate cortices. Through the hypothalamus, all endocrine functions of the
hypophysis can be controlled; the projection to periaqueductal gray matter provides control
of autonomic functions, while the presence of steroid receptors provides feedback
mechanisms for the effects of adrenal and steroid hormones.
Figure 4. Schematic representation of connections between the cortex, amygdala and hypothalamus. Note the
central position of the amygdala and key executive position of the hypothalamus.
4. The Amygdala
The amygdala is definitively a central structure in the regulation of expression of fear

memory (Figure 3). In order to provide this function, especially fear conditioning, the
amygdala receives massive projections from sensory cortices (Figure 4). The afferent
projections required for auditory provoked conditioning originate from primary and
associative auditory cortex, but there is also input from the medial geniculate nucleus [3,9].
For the processing of visually conditioned stimuli and the well-known function of the
amygdala in negative emotions related to the recognition of faces [4,5], more complex
cortical processing is needed between primary and associative visual areas of the
occipitotemporal lobe. These sensory driven inputs terminate in the lateral nucleus of the
amygdala. From the lateral nucleus, there are extremely elaborate intra-amygdaloid
connections [9,3,10,11] to the central nucleus of the amygdala (Figure 4). In order to
convey amygdala output, several crucial pathways exist which can explain different
functions of amygdala. Brainstem projections to the periaqueductal gray matter are
involved in autonomic expression of fear responses, with participation from the lateral
hypothalamus. For neuroendocrine control, there are well defined projections through the
bundle known as stria terminalis, which terminates in the hypothalamic nucleus, the so-
called bed nucleus of the stria terminalis. The stria terminalis is also known as the
neuroendocrine pathway of the amygdala. These projections are also crucial for control of
pituitary functions. However, the most massive projection is the amygdalofugal pathway to
orbitofrontal and medial frontal cortex, essential for interactions of fear memory and
working memory.
5. Phylogenetic Specializations of The Limbic Circuitry in The Human Brain
In considering experimental data on stress-related changes of brain function, one must

consider that human limbic circuitry is composed of a number of phylogenetically
specialized areas. First of all, the prefrontal cortex which is the granular cortex, is the most
developed part of the cortex in the human brain, which has a greater number of processing
modules and greater diversity of inputs than in other anthropoid apes. The anterior
cingulate area, which represents the anterior attention system of the brain, believed to have
a central role in PTSD, contains special corkscrew giant neurons [11] which are not found
in monkeys. It has been demonstrated that the anterior cingulate cortex contains spindle-
shaped corkscrew cells which can be activated during emotional tasks and the entire area
containing these cells can be called an affective division of the cingulate cortex [11].
6. Developmental Differences in Response of Limbic Circuitry
Many PTSD investigators note that there are many differences in frequency,
presentation and response to stressors between children, adolescents and adults. In addition,
it is clear that persons who were abused in childhood more frequently develop PTSD after
traumatic events [2]. From a neurobiological point of view, this is expected. First of all, all
transmitters involved in the innervation of limbic areas—and known to change in PTSD—
show significant developmental shifts. The most notable is the development of
dopaminergic innervation in the frontal cortex [12]. Second, it is known that pyramidal
neurons of the frontal cortex mature relatively late [13] and that synaptogenesis in the
limbic cortex shows significant changes throughout childhood and adolescence [14].
During the early postnatal months, there is a significant reorganization of cortical pathways
[15], which implies significant plasticity of the developing brain. This is evidence that
limbic circuitry is different in children in comparison to adults, in terms of the number of
synapses, the position of growing axons, the presence of trophic factors, and maturation of
pyramidal and nonpyramidal neurons.
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M.J. Roy (Ed.)
IOS Press, 2006
Investigating Cognitive Abnormalities in

Posttraumatic Stress Disorder
Elke GERAERTS a, 1 and Tim BRENNEN b

a
Department of Experimental Psychology, Maastricht University, The Netherlands
b
Department of Psychology, University of Oslo, Norway
Abstract. Over the past decade, researchers have increasingly drawn upon concepts and
methods developed in cognitive psychology to reveal cognitive processes underlying
symptoms of Posttraumatic Stress Disorder (PTSD). These studies have shown that
individuals with PTSD display difficulties retrieving specific autobiographical
memories in response to cue words, instead recalling overgeneral memories. Moreover,
they exhibit difficulty forgetting trauma-related words during directed forgetting, and
exhibit enhanced false memory effects for trauma-related material. Such findings
suggest that experimental methods can supplement conventional self-report inventories
to elucidate cognitive abnormalities underlying PTSD symptomatology. However, to
reach a better understanding of the phenomenon, one should also take symptom
overreporting into account.
Keywords. Posttraumatic Stress Disorder, cognitive processes, false memories,

malingering
Introduction
Some people who are exposed to terrible events persist in reexperiencing these events in
flashbacks, nightmares, and intrusive recollections, often qualifying for a diagnosis of
Posttraumatic Stress Disorder (PTSD). Other people exposed to equally shocking events
1
Corresponding Author: Elke Geraerts, Department of Experimental Psychology, Maastricht
University, PO Box 616, 6200 MD, Maastricht, The Netherlands. Tel.: +31-433882468; fax: +31-
433884196. E-mail: E.Geraerts@Psychology.Unimaas.NL.
32 E. Geraerts and T. Brennen / Investigating Cognitive Abnormalities in PTSD
only show this distress for a short period of time, after which they recall these experiences
in a relatively normal manner. This diversity in response to trauma entails that people differ
in the way they process these incidents. The continuing involuntary and intrusive cognitive
phenomena imply dysfunctions in the mechanisms of memory.
Indeed, among the anxiety syndromes, PTSD is the one that can most correctly be
characterised as a disorder of memory [1]. That is why, during the last decade, researchers
have begun to employ paradigms of cognitive psychology to characterise mental
abnormalities in PTSD patients. Besides this line of research, increasingly sophisticated
theories have been developed that endeavored to keep pace with new findings while at the
same time remaining anchored in basic psychological research [2].
The aim of this chapter is to describe how cognitive processes underlying PTSD
symptoms can be revealed, by providing a review of prior research and focusing on
recently conducted studies with survivors of war and childhood sexual abuse. Finally, we
will discuss topics related to the overreporting of PTSD symptoms.
1. Prior Research
1.1. PTSD and Autobiographical Memory
Since it has recently been argued that PTSD can be seen as a disorder of memory, several
studies have explored the connection between PTSD symptoms and memory processes. For
instance, a series of studies has shown a connection between overgeneral memory and
PTSD [3-4]. In one study, Vietnam combat veterans with PTSD, relative to healthy combat
veterans, had difficulty recalling specific personal memories in response to cue words with
either a positive (e.g., kindness), negative (e.g., panic) or neutral (e.g., appearance) meaning
[3]. Despite having been trained to retrieve specific autobiographical memories, PTSD
participants tended to slide back into an overgeneral retrieval style during the experiment.
Patients with PTSD who had been emotionally primed by viewing a combat-related
videotape, had more difficulties accessing specific memories than those who had viewed a
videotape related to a neutral theme (i.e., furniture).
In a further study [4], Vietnam combat veterans with and without PTSD were asked to
retrieve specific personal memories illustrating traits indicated by positive (e.g., loyal) and
negative (e.g., guilty) cue words. Veterans with PTSD, relative to healthy veterans,
exhibited difficulties retrieving specific autobiographical memories, especially in response
to positive cue words. That is, while PTSD patients showed equivalent rates of specific
memory retrieval for positive and negative cues, healthy veterans found it easier to think of
episodes when they had exhibited positive traits than when they had exhibited negative
traits.
1.2. PTSD and Directed Forgetting

E. Geraerts and T. Brennen / Investigating Cognitive Abnormalities in PTSD 33
Besides research concerning autobiographical memory, cognitive psychologists have tested

controversial hypotheses by using traumatised populations. Some authors state that certain
experiences may be so traumatic that victims deal with them in an avoidant-dissociative
way [5]. For instance, this style would enable survivors of childhood sexual abuse (CSA) to
disengage attention from threatening stimuli and would result in impoverished, i.e.
repressed or dissociated, autobiographical memories of traumatic events [6]. Although
possibly adaptive under the circumstances of chronic abuse, this encoding style presumably
puts people at risk for developing subsequent psychiatric problems.
McNally and colleagues [7] reasoned that a particular variant of directed forgetting
paradigm would be well-suited to testing whether psychiatrically impaired adults with
histories of childhood sexual abuse are indeed characterised by an avoidant encoding style.
In an item-specific directed forgetting paradigm, participants are presented with words one
at a time. Immediately after each word appeared, participants are instructed either to
remember or to forget that particular word. After this encoding phase, memory for both the
to-be-remembered (TBR) and the to-be-forgotten (TBF) words is tested, and the standard
result in this paradigm is that when participants are given a surprise recall of the entire set
of stimuli, they recall fewer TBF words than TBR words [8]. The key mechanism behind
this directed forgetting effect is presumed to be encoding activities, because better recall of
TBR words can be explained by the fact that participants terminate encoding and rehearsal
processes as soon as the forget instruction follows a TBF word [9]. Accordingly, if
psychiatrically impaired survivors of childhood sexual abuse develop an ability to avoid
encoding trauma-related material, they should show memory deficits for trauma-related
TBR words relative to neutral and positive TBR words. Put another way, for such a group,
directed forgetting ought to be observed only for neutral (e.g., mailbox) and positive (e.g.,
celebrate) material but not for trauma-related material (e.g., incest). McNally et al. tested
this with three groups of participants: The first group comprised women reporting histories
of childhood sexual abuse and who were diagnosed with PTSD; the second group
comprised women with similar abuse histories but no PTSD. Finally, the third group
included women without abuse histories and without PTSD. Contrary to the avoidant
encoding hypothesis, participants with PTSD only displayed overall memory deficits
compared to the other groups for neutral and positive words, which they were supposed to
remember equally well. Additionally, they remembered trauma-related words very well,
including those they were instructed to forget. In contrast, healthy survivors and
participants with no history of childhood abuse recalled TBR words better than TBF words,
irrespective of word valence. Taken together, these data imply that individuals with PTSD
easily encode and recall trauma-related material, and that persistent trauma-related thoughts
may undermine the encoding of material that is not related to the trauma.
It can be seen that cognitive research on PTSD has depicted cognitive processes that
may figure in the source of certain symptoms of the disorder. Results of the studies
described above can be clearly linked to classic symptoms of PTSD like intrusions and
avoidance. Studies imply, for example, that enhanced accessibility and failure of inhibition
are candidates for the mechanism underlying the phenomenon of intrusive recollection.
This evident link between PTSD symptoms and underlying cognitive deficits displayed in
these studies, underlines the importance of research investigating the cognitive patterns in
PTSD patients and trauma-exposed controls.
2. Cognitive Models of PTSD
Besides research exploring these cognitive abnormalities underlying PTSD, several models
of cognitive functioning in PTSD have been proposed [10-12]. The model of Ehlers and
Clark [12], for example, describes a network of cognitive processes, including strategies
that the person chooses to use that lead from the traumatic situation itself to the
maintenance of persistent PTSD. The model reflects the notion that strategies with which
the person attempts to keep unpleasant mental intrusions to a minimum may paradoxically
make their elimination more difficult. Implicit in this and other models is that trauma
exposure per se is not enough to produce and maintain PTSD: amongst other variables,
particular cognitive strategies that only arise in a subset of trauma-exposed people are
necessary to produce that. Furthermore, in the models, the cognitive differences between
people with PTSD and trauma-exposed people are predicted to be most marked for trauma-
related material. That is, PTSD is assumed to have effects on cognitions thematically-
related to the traumatising event, and therefore a general prediction of the framework is
that, compared to trauma-exposed controls, PTSD patients should have worse performance
on tests of trauma-related cognition but not on tests with neutral stimuli.
3. PTSD and False Memories
The Deese-Roediger-McDermott (DRM) task is a laboratory paradigm that is very effective

in eliciting false memories [13-14]. In it, participants study a list of words that are strong
semantic associates of a word not presented on the list - the critical lure. For example,
participants may study words like bed, rest, awake, tired, and so forth, all of which are
strongly related to the nonpresented critical item, sleep. On a subsequent test, participants
often falsely recall and recognise the critical lure (in this case, sleep).
A number of researchers have argued that susceptibility to false memories may be due
to a deficit in source monitoring, i.e., incorrect judgments about the origin or source of
information [15]. On this view, the presentation of semantically associated words activates
a concept that is common to all words on the list, namely the critical nonpresented lure.
Thus, the DRM paradigm requires participants to differentiate between internally generated
thoughts and genuine memories of the studied words [16].
There is reason to believe that PTSD patients may have particular problems with
source-monitoring, and thus a tendency towards higher production of false memories, due
to the connection between the disorder and dissociation. For instance, Bremner and
colleagues [17] demonstrated a link between war-induced PTSD and dissociation, and
Winograd and co-workers [18] showed that scores on dissociative scales were positively
correlated with susceptibility to false memories on the DRM task. This hypothesis has been
tested in two studies employing the DRM paradigm with people reporting traumatic
experiences, with or without PTSD. On the one hand, Bremner et al. [19] studied women
with memories of childhood sexual abuse who were suffering from PTSD. The authors
found that these women displayed a higher frequency of false recognition than abused
women without PTSD. However, there were no differences in correct recognition between
the groups. Zoellner and colleagues [20], on the other hand, reported that victims of
criminal assaults with or without PTSD did not differ on either falsely recognising critical
lures or on correctly recognising presented words. When comparing the two trauma-
exposed groups on recall of words from DRM lists, Zoellner et al. [20] reported no
differences in the number of correctly recalled words, whereas Bremner et al. [19] found
that PTSD patients recalled fewer words than participants without PTSD. On numbers of
critical lures mistakenly recalled, neither study reported significant differences between the
two groups, and in both cases the trend was actually for non-PTSD participants to recall
more lures.
The study of Brennen and colleagues [21] aimed at investigating the discrepancy
between these results on correct recall of words from DRM lists and to shed more light on
the unexpected finding in both previous studies that trauma-exposed groups have
equivalent susceptibility to recall critical lures, apparently at odds with the models of
cognition in PTSD. In addition, a novelty of this study was that, in addition to neutral word
lists, trauma-related DRM lists were used. If PTSD patients and trauma-exposed non-PTSD
patients are found to show similar patterns on trauma-related cognitive tasks, this would
undermine models of cognition in PTSD, where PTSD patients are predicted to have
impaired trauma-related cognition. For instance, in Ehlers and Clark’s [12] model, several
sets of factors intervene between trauma exposure and the development of persistent PTSD:
besides the characteristics of the trauma and its sequelae, a person’s beliefs and coping
style will play a role, as well as peritraumatic processing, and of most relevance here, an
individual’s cognitive strategies aimed at inhibiting the reminders of the unpleasant event.
In this model PTSD patients have self-reinforcing thought patterns, where their attempts at
pushing thoughts of the trauma out of their mind actually have the opposite effect of
making the unpleasant thoughts rebound into consciousness more often. Trauma-related
cognition would thus be expected to be impaired for PTSD patients compared to trauma-
exposed controls.
To test this question, Brennen et al. [21] tested 50 participants with war-related PTSD
and 50 traumatised controls without PTSD. The inducing events for the PTSD patients had
occurred at least 7 years previously, during the war in Bosnia. Based on cognitive models,
it was expected that war-related source-monitoring should be worse in PTSD, leading to
more false recall of the war-related critical lures. The study revealed that PTSD patients did
not show a higher susceptibility to falsely recalling neutral critical lures. This finding is
consistent with previous results [19-20]. However, PTSD patients exhibited higher rates of
false recall of war-related critical lures, while simultaneously showing a lower rate of
correct recall.
In agreement with models such as Ehlers and Clark’s [12], trauma-related source-
monitoring appears to be impaired in PTSD patients, even compared to a group of trauma-
exposed controls. Taken together, this study provides evidence suggesting that PTSD
patients have a particular susceptibility to trauma-related false memories, but backs up

previous findings of no difference for recall of neutral false memories.
4. Recovered Memories and False Memory Effects
By far the most controversial topic in the field of trauma concerns the accuracy of
recovered memories of childhood sexual abuse. The concept of repressed and recovered
memories has been deeply divisive in psychology and psychiatry and has led to the so-
called ‘memory wars’ [22-23]. Some scholars claim that amnesia for trauma and/or
subsequent recovery of traumatic memories can be demonstrated in clinical populations [5,
24], whereas others have questioned the existence of repressed and recovered memories
because of the lack of solid evidence for such memories [25-26]. Moreover, skeptics have
warned that memories may be susceptible to distortions [27] and hence that therapies
intended to recover memories of childhood sexual abuse may unintentionally foster false
memories of childhood sexual abuse [28].
Despite the furore surrounding recovered memories, almost no research has been
conducted on the cognitive functioning of people at the heart of this debate, namely people
with reported repressed and recovered memories of a trauma. This situation may have
arisen because few clinicians possess expertise in laboratory research and few cognitive
psychologists have access to trauma populations. In fact, Richard McNally, Susan Clancy,
and their colleagues at Harvard University were the first to apply experimental methods to
investigate memory functioning in people reporting repressed and recovered memories of
childhood sexual abuse. More specifically, McNally and his group have been conducting
studies on four groups of participants: adults who report remembering the abuse after years
of not thinking about it (recovered memory group), adults who believe they were sexually
abused as children but who have no explicit autobiographical memories of childhood abuse
(repressed memory group), adults who have always remembered being abused (continuous
memory group), and adults without a history of abuse (control group) [26]. By using
several cognitive tasks, McNally and colleagues showed that the repressed and recovered
memory group did not exhibit a superior ability to forget trauma-related words on directed
forgetting tasks [29-30; see also 31]. Furthermore, they showed that people with recovered
memories of childhood sexual abuse are more prone to exhibit false memory effects on
neutral DRM word lists [32].
However, no study has considered these false memory effects for trauma-related
material in survivors of childhood sexual abuse. Would people with recovered memories of
abuse show the same trauma-related source monitoring deficit that is seen in PTSD
survivors in the study of Brennen and colleagues [21]? Recently, Geraerts and colleagues
[33] addressed these questions by employing neutral and trauma-related DRM lists to
traumatised individuals. They investigated whether participants who reported having
recovered memories of childhood sexual abuse would display higher rates of false recall
and recognition for neutral and trauma-related words relative to other participants.
Following the procedure of Clancy et al. [32], they recruited participants through
advertisements in local newspapers. In these advertisements, they invited women to come
to the lab when they a) had recovered memories of childhood sexual abuse, b) believed
they had been sexually abused as a child, c) had a history of sexual abuse which had never
been forgotten or d) had no history of sexual abuse.
The results replicated the robust false recall and recognition effects typically found
with the DRM paradigm [14]. That is, overall, participants falsely remembered many of the
critical lures. Replicating earlier findings of Clancy et al. [32], the results also lend support
to the idea that women reporting recovered CSA memories are more susceptible than other
participants to this memory illusion. More specifically, women with recovered memories of
CSA exhibited higher rates of false recall and false recognition of critical lures than the
other participants. This study was the first to show that this was true for both neutral and
trauma-related word lists.
As already mentioned, a number of researchers have argued that susceptibility to false
memories may be due to a deficit in source monitoring [15]. The results of Geraerts et al.
[33] suggest that women reporting recovered CSA memories may have a source monitoring
deficit for all types of material, whether the content is neutral or trauma-related. It can be
speculated that especially these women have difficulties with the identification of the origin
of a memory and that they may have a tendency to adopt an internally generated thought as
being a genuine memory. This could have serious real-life implications, both for the
reliability of their autobiographical memory and for the development of their knowledge
and beliefs. Additionally, it might well be the case that source monitoring confusion can
produce pseudomemories. Therefore, it is very important to recognise that the influence of
source monitoring on the origin of recovered memories warrants further study.
5. Malingering and Trauma
The debate about repressed and recovered memories of sexual abuse is however not the
only controversy in the field of trauma. Whereas all the aforementioned studies relate to
benign memory distortion, one should be aware that false claims of PTSD are a reality. For
instance, Frueh and colleagues [34] demonstrated the problem of deliberate exaggeration of
symptoms in veterans seeking to obtain a diagnosis of PTSD. Because in many countries
there are civil and criminal laws that regulate financial compensation for victims of war
trauma, it is obvious that, in some cases, people present themselves as victims in an attempt
to profit from financial or judicial regulation.
Sparr and Pankratz [35] were the first to identify such false claims of PTSD in
individuals reporting disability from combat in Vietnam when in fact it can be shown that
the claimants had never been to that country. Until recently, such false claims remained
largely ignored. Burkett and Whitley [36] pointed out how widespread the problem was by
describing many cases where entire combat histories had been falsified. In a recent study,
Kozariü-Kovaþiü and co-workers [37] explored the change in the diagnosis of PTSD which
was related to the introduction of a new national regulation on compensation-seeking by
Croatian war veterans. The legal regulation of compensation-seeking of these veterans was
first established in 1992 within a law, including all immediate combat and civilian victims
of war trauma. This regulation was extended in 2001, allowing war veterans that had not
been covered by the previous law to apply for compensation due to prolonged or delayed
PTSD [38]. It was found that there were significant differences in the diagnosis of PTSD
made before and after the introduction of the new law in 2001. The diagnoses made by
psychiatrists changed towards the diagnoses with higher compensation rates. On a related
note, it has also been shown that the details of the rules governing compensation appear to
influence the way some veterans report their symptoms when they are being evaluated for
PTSD [39].
Clinical researchers need to increase the attention given to these issues and to realise
that it is essential to differentiate between malingered and genuine PTSD symptoms.
Therefore, psychometric instruments for the evaluation of malingered PTSD are needed.
One promising test is the Morel Emotional Numbing Test (MENT) [40]. This is a forced-
choice task to detect response bias in PTSD assessments. Updated in 2004 [41], it consists
of 60 two-alternative items. Briefly, the test uses 20 coloured slides of 10 facial expressions
posed by a man and a woman. Their expressions reflect happiness, frustration, sadness,
anger, fear, calmness, surprise, shyness, confusion, and sleepiness. The slides are presented
on a computer screen along with verbal labels describing emotions. The participant is
instructed to identify the emotion word that best matches the expression portrayed on the
slide. In a first series of 20 trials, participants see one slide on the computer screen and are
asked to circle one of two words (e.g., “happy”; “surprised”) describing the slide. In a
second run of 20 trials, participants view two slides, but only one word and are asked to
identify the slide that best matches the word. In a final run of 20 trials, participants are
shown two slides and two words which have to be matched to each other. Before the task is
given to participants, they are primed with the instruction that many PTSD patients suffer
from emotional numbness and that this may cause them to have difficulties with the
recognition of facial expressions. The idea is that individuals who tend to overreport PTSD
symptoms will intentionally produce more errors on this deceptively simple test. Findings
from Morel [40] pointed out that war veterans who were suspected for false PTSD claims
made more errors on the MENT than credible claimant groups and patient groups with
alcohol dependency or schizophrenia. At the moment, the MENT is being employed in a
large sample of compensation-seeking Croatian war veterans. The aim of this ongoing
study is to examine the possibility of distinguishing between simulated and genuine
symptom presentation, based on scores on the MENT and several other diagnostic tools
[42].
6. Summary and Clinical Implications
Cognitive research on PTSD has produced substantial evidence that PTSD patients show
deficits in memory for trauma-related material. Studies on autobiographical memory reveal
impairments in the ability of PTSD patients to access specific episodes from their past.
Additionally, the hypothesis that trauma survivors, especially those with a history of
childhood sexual abuse, have developed skills for expelling disturbing material from
awareness has been undermined by directed forgetting methods. These methods even point
in the opposite direction: trauma survivors exhibit an impaired ability to forget disturbing
material. Likewise, studies using a false memory paradigm point out that PTSD patients
show enhanced false memory effects for trauma-related material.
This cognitive research on PTSD is required to elucidate the information-processing
characteristics associated with PTSD and to test the main tenets of psychological theories
of PTSD. Furthermore, several clinical implications are suggested by this line of research.
For example, problems accessing specific episodes from the past should alert clinicians to
difficulties patients may come across in cognitive therapy or in other interventions that
require one to access specific episodes from one’s past. Furthermore, clinicians should take
into account that PTSD patients are more prone to falsely recalling trauma-related material,
at least in the laboratory. Additionally, one should be attentive for the relationship between
source monitoring deficits and recovered memories of childhood sexual abuse. Finally, it is
important to realise that a diagnosis of PTSD should not only rely on self-report inventories
or other assessment procedures which may be vulnerable to symptom overreporting.
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42 Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder
M.J. Roy (Ed.)
IOS Press, 2006
Psychotic features of combat related

chronic posttraumatic stress disorder and
antipsychotic treatment
Dragica KOZARIû-KOVAýIûa 1 , Nela PIVACb
a,
Referral Centre for the Stress Related Disorders of the Ministry of Health of the
Republic of Croatia, Department of Psychiatry, Dubrava University Hospital, Avenija
Gojka Šuška 12, HR-10000 Zagreb, Croatia,
b
Division of Molecular Medicine, Rudjer Boskovic Institute, POBox 180, HR-10002
Zagreb, Croatia,
Abstract. Combat-related posttraumatic stress disorder (PTSD) is a severe

debilitating psychiatric illness associated with different comorbidities. When
complicated with comorbid psychotic features, PTSD is usually refractory to
treatment and requires the use of other pharmacotherapeutic strategies, i.e. typical
or atypical antipsychotics. In 81 male war veterans with chronic combat related
PTSD with psychotic features, treatment response, clinical symptoms and adverse
events were assessed using Watson‘s PTSD questionnaire, Positive and Negative
Syndrome Scale (PANSS), Hamilton Rating Scale for Depression (HAMD),
Clinical Global Impression Severity Scale (CGI-S), CGI-Improvement (CGI-I),
Patient Global Impression Improvement Scale (PGI-I) and Drug Induced Extra-
Pyramidal Symptoms Scale (DIEPSS). War veterans were treated for 6 weeks with
fluphenazine (27 patients), olanzapine (28 patients) in a dose range of 5-10
mg/day, or risperidone (26 patients) at a dose of 2-4 mg/day, as monotherapy.
Treatment with the atypical antipsychotic olanzapine or risperidone for 6 weeks
improved significantly most of the PTSD and psychotic symptoms in war veterans
with combat-related chronic psychotic PTSD. Olanzapine and risperidone showed
similar efficacy and tolerability and induced fewer side effects than fluphenazine,
suggesting that atypical antipsychotics might have beneficial effects in war
veterans with treatment-resistant psychotic PTSD. In an open study the effect of
clozapine was evaluated in war veterans with combat-related PTSD complicated
with severe insomnia and nightmares: 34 patients were treated for 7 days with
clozapine, and 37 patients with sedatives. Clozapine was shown to be effective in
veterans with PTSD as well as in severe sleep disorders and nightmares, due to its
strong sedative and anxiolytic effect.
Keywords. Combat related Posttraumatic Stress Disorder, War veterans,

Psychotic features, Treatment, Atypical Antipsychotics, Olanzapine, Risperidone,
Clozapine
1. PTSD and Co-morbidity
1
Corresponding author: Dragica KOZARIû-KOVAýIû, Referral Centre for the Stress Related Disorders of
the Ministry of Health of the Republic of Croatia, Department of Psychiatry; Dubrava University Hospital,
Avenija Gojka Šuška 6, HR-10000 Zagreb, Croatia, E-mail: dkozaric_kovacic@yahoo.com
D. Kozarić-Kovačić and N. Pivac / Psychotic Features of Combat Related Chronic PTSD 43
Epidemiologic and clinical studies have shown that posttraumatic stress disorder
(PTSD) commonly occurs with other psychiatric disorders [1-5]. The rate of
comorbidity is especially high in combat-related PTSD. A recent epidemiological
survey indicated that approximately 80% of combat veterans with PTSD meet criteria
for at least one psychiatric diagnosis. The most frequent diagnoses are major depressive
disorder, other anxiety disorders, substance abuse, somatization, personality disorders,
and dissociative disorders [6].
Comorbidity patterns in combat-related PTSD have been suggested to be socio-
culturally and geographically specific [7]. There are also atypical clinical pictures of
PTSD, as well as the difference in clinical presentation of symptoms. Recently, it has
been shown that 30-40% of combat related PTSD patients have psychotic symptoms
[3,8,9]. Psychotic features add to the severity of symptoms in combat related PTSD
patients [8].
Some studies show different subtypes of PTSD with depressive, psychotic, and
panic features. Levels of cognitive, emotional, and behavioral disturbances in patients
with comorbid PTSD and psychotic disorders exceed those seen in patients with PTSD
without psychosis, or in patients with only another psychotic disorder. The question is
whether a patient had any psychotic episode before his current diagnosis, i.e. current
and chronic PTSD, or the psychotic episode occurred after the development of PTSD.
There is active debate regarding whether the psychotic symptoms should be recognized
as an unique entity, a malignant form of a disorder, or psychosis comorbid with PTSD
or major depressive disorder. Before the incorporation of PTSD into American
Diagnostic Nomenclature (DSM-III), patients suffering from PTSD were diagnosed
with schizophrenia or other psychotic disorders. Many of these patients presented
hallucinations, paranoid ideation, or disorganized behavior.
Up to 40% of combat veterans with PTSD may have comorbid psychotic
symptoms or meet criteria for a comorbid psychotic disorder diagnosis. PTSD with
psychotic features may be a distinct subtype of the disorder [8, 10-15], and it has been
found that psychotic features may occur in 30-40% of patients with combat PTSD [8].
Positive symptoms of psychosis, e.g. hallucinations that are moderate to severe in
intensity, are now included as an aspect of “flashbacks” in the re-experiencing
phenomena of the diagnostic criterion in PTSD. The avoidance symptoms of PTSD—
avoidance of activities, places, or people reminiscent of the trauma, feeling detached or
estranged from others, restricted range of affect, and diminished interest or
participation in significant activities—resemble the negative symptoms associated with
schizophrenia.
2. Clinical picture of psychotic symptoms in PTSD and psychometric assessment
Combat veterans with PTSD on the Minnesota Multiphasic Personality Inventory

(MMPI / MMPI-2) have their highest mean elevation on clinical scale 8 (the
“schizophrenia” scale), suggesting prominent symptoms of thought disturbances and
psychosis [16]. Patients with psychotic features scored at least 4 (moderate severity) on
the Positive and Negative Syndrome Scale (PANSS) positive items (delusions,
conceptual disorganization, hallucinatory behavior, suspiciousness/persecution) [8].
Hamner et al. [15] described psychotic features in PTSD which include auditory and
visual hallucinations and delusional thinking. The content of hallucinations may refer
44 D. Kozarić-Kovačić and N. Pivac / Psychotic Features of Combat Related Chronic PTSD
to the traumatic experience (“soldiers screaming” or “incoming rockets”), but also may
include not readily identifiable content (the sounds of “garbled voices” or “shadows
seen out of the corner of patient‘s eye”). Delusions are generally paranoid or
persecutory in nature. PTSD patients are generally distressed by the psychotic
symptoms and retain some reality testing and insight. They do not have the
characteristic disturbances(e.g., constricted or inappropriate) of affect or thought
disorder (e.g., loose associations or disorganized responses). Complex, bizarre, or
absurd delusions, which are common in schizophrenia, are rare in PTSD.
3. Croatian combat war veterans and comorbidity
In studies of Croatian war veterans with combat-related PTSD, Kozariü-Kovaþiü and

Borovecki [17] found that 57-62 % of patients met criteria for comorbid diagnoses. The
most prevalent diagnoses were: alcohol abuse, major depressive disorder, anxiety
disorders, panic disorder and phobia, psychosomatic disorder, psychotic disorders,
substance abuse, and dementia. The study included 680 men who experienced combat
stress and had diagnoses of PTSD. The psychotic symptoms in PTSD consisted of two
types: depressive or schizophrenia-like. Psychotic disorders were confirmed in 17%
and major depressive disorder with psychotic features in 15% of patients with PTSD.
Psychotic symptoms were accompanied by auditory or visual hallucinations in 68% of
patients. Delusional paranoid symptoms occurred in 32% of patients.
4. Are there implications of comorbid psychotic features for understanding the

biology of PTSD?
The concentration of plasma dopamine beta-hydroxylase (DBH) is elevated in

psychotic vs. nonpsychotic PTSD and normal control subjects [18], a finding directly
opposed to the findings observed in psychotic depression, i.e. a reduced DBH
concentration. Altered DBH may be a biological marker reflecting the increased risk to
develop psychotic symptoms in the context of trauma. Since DBH catalyzes the
conversion of norepinephrine to dopamine, higher DBH would yield more
norepinephrine relative to dopamine biosynthesis. Higher norepinephrine biosynthesis
may be characterized by more severe PTSD symptoms and consequent psychotic
symptoms.
In extensive studies evaluating the activity of the hypothalamic-pituitary-adrenal
(HPA) axis in PTSD, Yehuda and her group [19,20] demonstrated that some aspects of
the biology of PTSD differ from that of major depression. PTSD is associated with
alterations in the HPA axis, including increased concentrations of cerebrospinal fluid
(CSF) corticotrophin-releasing factor (CRF) and adrenocorticotropic hormone (ACTH),
low baseline urinary cortisol, and alterations in the secretion and metabolism of
norepinephrine and dopamine [20,21]. CRF is released throughout the brain during
stress, and mediates endocrine and behavioral responses to stress. CRF released from
the hypothalamus increases the release of ACTH from the anterior pituitary, which
subsequently stimulates the release of cortisol from the adrenal gland [22]. In PTSD,
CRF is elevated, as demonstrated by high basal CSF concentrations of CRF obtained
via a single lumbar puncture [23], and from serial lumbar puncture sampling [24]. The
finding that PTSD with psychotic symptoms is associated with elevated CRF shows
that PTSD with psychotic features is characterized by extreme perturbations of the
neuroendocrine system, supporting the hypothesis that PTSD with psychotic symptoms
is a distinct subtype of PTSD [25].
Noradrenergic dysregulation has long been implicated in PTSD [26], with
exaggerated norepinephrine responses to pharmacological [27], psychological [28], and
physical [29] stressors. Yehuda et al. [30] reported a positive correlation between
urinary norepinephrine excretion and PTSD symptoms. Severe PTSD symptoms in
patients with psychotic PTSD, reflected by the strong correlation between CAPS and
PANSS ratings, may be mediated by norepinephrine dysregulation, and elevated DBH
concentrations support this hypothesis.
PTSD with secondary psychotic symptoms (PTSD-SP) is associated with increased
somatotropin-release-inhibiting hormone (SRIF), an inhibitory peptide that has wide
cortical and limbic distribution. SRIF is released from the anterior pituitary and serves
to inhibit the secretion of growth hormone-releasing factor, ACTH, and other pituitary
hormones. High levels of SRIF, that covary with CRF [31], have been reported in
PTSD [23].
5. The relationship between PTSD-SP and schizophrenia
It is important to determine whether the psychotic symptoms that occur in PTSD with
psychotic features are similar to schizophrenia, or are unique to PTSD. PTSD-SP is not
associated with a family history of schizophrenia, hence it has been proposed that
PTSD with psychotic features may be a severe subtype of the disorder that is distinct
from the primary psychosis [32]. These findings are supported by other studies,
showing a high prevalence of psychotic symptoms in combat PTSD patients, assessed
with a strict exclusion criteria for schizophrenia [3,8,15,17].
6. Possible etiologies of psychotic symptoms in psychotic PTSD
The increased activation of CRF circuitry could produce psychotic symptoms by

several different mechanisms [25].
One hypothesis is that the increased activation of the neuroendocrine axis in
PTSD-SP causes psychosis by increasing activity of the mesocortical dopaminergic
system. Increased secretion of hypothalamic CRF would produce increased cortisol
secretion from the adrenal gland, which would increase CNS dopamine activity. This
hypothesis is supported by findings from animal studies showing that the peripheral
administration of corticosterone leads to the release of dopamine in the prefrontal
cortex [33], and increases in homovanillic acid (HVA) concentration from the caudate
nucleus [34]. The intraperitoneal administration of dexamethasone increases dopamine
metabolites in the nucleus accumbens and hypothalamus [35]. Clinical studies
supporting this hypothesis have demonstrated that the administration of ACTH and
cortisol leads to delayed increases in plasma HVA in normal control subjects [36].
Other studies have shown that psychotic depression is associated with more prominent
activity of the HPA axis [37], and higher plasma HVA levels [38], than non-psychotic
depression.
A second hypothesis is that the higher levels of CRF found in PTSD-SP patients
produce psychotic symptoms through the mechanism of CRF achieved at the cyclic
adenosine monophosphate (cAMP) level in the frontal cortex [39]. This hypothesis
presumes that high levels of CRF in PTSD-SP augment dopaminergic stimulation of
cyclic AMP in frontal cortex, because both CRF receptor subtypes use G-protein
stimulatory receptors that increase cyclic AMP levels when activated by CRF.
Stimulation of the D1 dopamine receptor, but not the D2 receptor, increases levels of
cAMP. The D1 receptor is most often associated with antipsychotic effects after
pharmacologic blockade, which decreases the intraneuronal levels of cAMP when
activated by dopamine.
The third hypothesis: since CRF brain circuits are located outside the HPA axis,
which mediate emotional responses and arousal, it is possible that increase in frontal
dopamine circuit activity during psychotic symptomatology activates some of these
systems, resulting in increased secretion of CRF in the CSF of patients with PTSD-SP.
Regions outside of the hypothalamus that contain CRF include the locus ceruleus (LC),
cortical areas, bed nucleus of the stria terminalis, amygdala and hippocampus.
Psychological stressors can activate some of these circuits without involving the
hypothalamic CRF neuroendocrine system [40].
7. Pharmacotherapy of psychotic PTSD
Since PTSD is classified as an anxiety disorder, the treatment of PTSD includes the use
of specific psychotherapeutic and pharmacotherapeutic interventions, primarily
antidepressants such as tricyclic antidepressants, monoamine oxidase inhibitors,
selective serotonin reuptake inhibitors (SSRIs), adrenergic and antianxiety agents,
benzodiazepines, and mood stabilizers [41,42].
Due to the occurrence of psychotic symptoms in PTSD, and/or persistence and
refractoriness of the symptoms, thymoleptics or atypical neuroleptics might be used.
The presence of psychotic symptoms in PTSD is often associated with treatment
resistance, and requires additional pharmacological strategies, such as the use of
neuroleptics or atypical antipsychotics. There are few studies assessing the efficacy of
different neuroleptics [43-45], or antipsychotics such as risperidone [46-50], olanzapine
[44,51-55] or quetiapine [56,57] in PTSD. Hamner [58] reported a good response to
clozapine in a veteran with comorbid PTSD and psychosis.
Preliminary open-trial experience suggested that low doses of atypical
antipsychotics may alleviate positive symptoms of psychosis in some PTSD patients.
Initial reports suggest that atypical antipsychotics may be helpful either alone or as
adjunct therapy to antidepressants or other agents, at least when targeting the comorbid
psychosis.
In a preliminary open trial of add-on therapy [57], 20 combat veterans meeting
DSM-IV criteria for PTSD were treated for 6 weeks with quetiapine. The starting dose
was 25 mg at bedtime with subsequent titration based on tolerability and clinical
response. Quetiapine demonstrated significant improvement in the core PTSD
symptoms, positive and negative psychotic symptoms, general psychopathology, and
depressive symptoms in war veterans. The tolerability of quetiapine was high with few
reported side effects. Patients experiencing sedative effects noted increased duration of
sleep and reduction in frequency and intensity of nightmares, other nocturnal anxiety
symptoms, and night time awakenings.
8. Studies with Croatian war veterans
Figure 1: Baseline scores in Positive and Negative Syndrome Scale (PANSS) subscales (mean ± SD) in
Croatian war veterans with psychotic PTSD before 6 weeks treatment with fluphenazine (Flu), olanzapine
(Olan), or risperidone (Risp)
In the studies evaluating the effects of antipsychotics in the trials in Croatian war
veterans with psychotic combat-related PTSD [44,50], 81 male war veterans with
combat-related PTSD participated in the 6 weeks open studies (Figures 1-6, Table 1).
War veterans (27 patients) were treated with fluphenazine, 28 patients received
olanzapine (5-10 mg/day), and 26 patients were treated with risperidone (2-4 mg/day),
as a monotherapy. Fluphenazine exhibits a high affinity of D2 and D1, and moderate
affinity for H1 histaminergic receptors [59]. Olanzapine has a high affinity for the 5-
HT2A, 5-HT2C, 5-HT3, D1adrenergic, dopamine D1, D2 and D4, and muscarinic M1 to
M5 receptors [60]. Risperidone has the affinity for 5-HT2A, 5-HT7, dopamine D2, D1, D2
adrenergic receptors and its high 5-HT2A/D2 ratio is characteristic of the atypical
antipsychotic profile [60].
The presence of psychotic symptoms in PTSD was associated with treatment
resistance. Patients included in this study were those with current and chronic PTS who
had comorbid psychotic symptoms. The diagnosis of current and chronic combat-
related PTSD was confirmed by administration of the structured clinical interview for
DSM-IV disorders. The existence of current PTSD was also assessed with Watson’s
PTSD questionnaire based on DSM-III-R. Patients were excluded from this study if
they had any psychiatric disorder before the war, major depressive disorder, a primary
diagnosis of another psychiatric disorder (currently or in the previous three months), a

serious concomitant medical condition, clinically significant ECG or laboratory
findings, serious risk of suicide, history of seizure, or misuse of alcohol or drugs.
Figure 2: Scores in Positive and Negative Syndrome Scale (PANSS) subscales (mean ± SD) in Croatian war
veterans with psychotic PTSD treated for 6 weeks with fluphenazine (Flu), olanzapine (Olan), or risperidone
(Risp)
Psychotic symptoms were evaluated by the PANSS in 4 categories: positive items

(delusions, conceptual disorganization, hallucinatory behavior, suspiciousness/
persecution); negative items (emotional withdrawal, and passive/apathetic social
withdrawal); the general psychopathology subscale (guilt feelings, depression, motor
retardation, unusual thought content, disorientation, disturbance of volition, poor
impulse control, and active social avoidance); and the supplementary subscale (anger
and affective lability).
The clinical picture of psychotic symptoms could be categorized into a) the

schizophrenia-like characterized mostly by conceptual disorganization, delusions and
suspiciousness/persecution; b) the psychotic depression-like, manifest by hallucinatory
behavior, depressive psychotic accusations, anddepressive delusions; and c) a mixed
clinical picture, with conceptual disturbances and disorganization, persecutive and
depressive delusions, visual and auditory hallucinations.
All patients were evaluated before and after 6 weeks of treatment. Instruments
used to measure outcomes were: Watson‘s PTSD Scale to assess PTSD symptoms;
Positive and Negative Syndrome Scale (PANSS) to assess change in positive psychotic
symptoms, negative symptoms, global psychopathology, and supplementary items;
Clinical Global Impression Severity Scale (CGI-S), Clinical Global Impression
Improvement Scale (CGI-I), and Patient Global Impression Improvement Scale (PGI-
I). For safety and tolerability assessments, vital signs and adverse events were recorded
using the Drug Induced Extra-Pyramidal Symptoms Scale (DIEPSS).
Before treatment, the age of patients, duration of combat experience and scores in
all measurement instruments were similar among veterans with combat-related PTSD
receiving fluphenazine, olanzapine or risperidone treatment.
Figure 3: Baseline scores in Watson’s trauma re-experiencing, avoidance and hyperarousal scores (mean ±
SD) in Croatian war veterans with psychotic PTSD before 6 weeks treatment with fluphenazine (Flu),
olanzapine (Olan),or risperidone (Risp)
After 6 weeks of treatment, all three antipsychotics (fluphenazine, olanzapine and

risperidone) were associated with comparable significant reductions in the symptoms
listed in PANSS positive (Figures 1 and 2), and Watson’s trauma re-experiencing
(Figures 3 and 4) subscales. However, treatment with olanzapine or risperidone induced
greater reductions in PANSS negative, general psychopathology and supplementary
items subscales (Figures 1 and 2) than fluphenazine treatment. In addition, olanzapine
or risperidone reduced more the scores in Watson’s avoidance and increased arousal
(Figures 3 and 4) subscales, and in scores in CGI-S (Figure 5), CGI-I, and PGI-I
(Figure 6), than fluphenazine treatment
When compared to fluphenazine, olanzapine and risperidone reduced cognitive and
depressive symptoms, alleviated aggression, suicidality, and impulsivity, and had
beneficial effects on nightmares and flashbacks, while improving participation in social
activities in psychotic PTSD patients. In addition, olanzapine and risperidone improved
the symptoms of insomnia, nightmares, hypobulia, and anhedonia, and increased the
interest and pleasure in daily activities in PTSD patients. Olanzapine and risperidone
decreased the frequency and intensity of intrusive thoughts and visual images.
Figure 4: Scores in Watson’s trauma re-experiencing, avoidance and hyperarousal scores (mean ± SD) in
Croatian war veterans with psychotic PTSD after 6 weeks treatment with fluphenazine (Flu), olanzapine
(Olan), or risperidone (Risp)
Fluphenazine induced more extrapyramidal symptoms (Figure 6) than olanzapine or

risperidone treatment. Olanzapine and risperidone demonstrated overall greater
improvement than fluphenazine.
Figure 5: Clinical Global Impression Severity Scale (CGI-severity) scores (mean ± SD) in Croatian war
veterans with psychotic PTSD after 6 weeks treatment with fluphenazine, olanzapine, or risperidone
Figure 6: Scores (mean ± SD) in Clinical Global Impression-Improvement (CGI-I), Patient Global
Impression Improvement Scale (PGI-I), and Drug Induced Extra-Pyramidal Symptoms Scale (DIEPSS) in
Croatian war veterans with psychotic PTSD after 6 weeks fluphenazine (Flu), olanzapine (Olan), or
risperidone (Risp) treatment

significantly improved most of the PTSD and psychotic symptoms in war veterans with
combat-related PTSD. Olanzapine and risperidone showed similar efficacy and
tolerability and induced fewer side effects than fluphenazine. Our data suggest that
atypical antipsychotics might have beneficial effects in war veterans with treatment-
resistant psychotic combat-related PTSD.
9. Sleep disturbances in PTSD
The most prominent symptoms of PTSD are sleep disturbances. Treatment of severe
insomnia and nightmares in war veterans with PTSD with clozapine is effective in the
malignant form of PTSD, or PTSD with psychotic features. Clozapine affects large
number of neurotransmitters, and interacts with serotonergic 5-HT2A, 5-HT6, 5-HT7
receptors, D2, D1, D4 receptors, muscarinic and histaminergic receptors [60].
An open-label study was done with 71 war veterans with combat-related PTSD
having severe insomnia and nightmares with a duration of at least 4 weeks prior the
beginning of the study [61]. The diagnoses were determined by ICD-10 criteria,
investigation variant. The patients had a stable leucocyte count and were without
psychotic symptoms. They CGI-S and PGI-S scale scores or at least 4. Patients with
comorbid diagnoses, head trauma, central nervous system disturbances, epilepsy, liver
and kidney diseases or other heavy physical diseases were excluded.
The patients were divided into two groups. Thirty-four patients received 50mg
dose of clozapine each evening for 7 days, and 37 patients (control group) were given a
sedative (flurazepam 30mg or zolpidem 10mg).
The Hamilton depression scale (HAM-D) items for insomnia, D1 item from
Watson‘s scale, CGI-S, and PGI-S were used as outcome measures.
In Croatian war veterans with combat related PTSD and severe insomnia and
nightmares, 7 days of treatment with clozapine significantly decreased all measured
items for the particular sleep disturbances. Clozapine showed better efficacy than the
sedatives.
Table 1. Analysis of variance (ANOVA) for the group of PTSD patients treated with clozapine (Clozapine,
N=34) and PTSD patients treated with classical sedatives (Sedatives, N=37)
significance
1st day 7th day two-tailed
Scales Clozapine Sedatives Clozapine Sedatives Clozapine Sedatives
HAMD items
for insomnia 5.08 ± 0.71 5.11 ± 0.77 1.17 ± 0.79 2.22 ± 0.63 0.001 0.911
W-PTSD D1
item 5.41 ± 0.93 6.05 ± 0.66 1.62 ± 0.49 2.54 ± 0.51 0.001 0.001
CGI-S
5.85 ± 0.56 5.97 ± 0.60 1.79 ± 0.88 3.03 ± 0.69 0.001 0387
PGI-S
5.91 ± 0.75 6.27 ± 0.61 1.97 ± 0.79 3.57 ± 0.55 0.001 0.032
10. Conclusions
We believe that psychotic features in combat related PTSD represent a specific subtype
of chronic PTSD and should be included as a distinct nosological entity in the future
classifications of mental disorders.
significantly improved most of the PTSD and psychotic symptoms in war veterans with
chronic combat-related PTSD.
Olanzapine and risperidone showed similar efficacy and tolerability; each was
more effective and induced fewer side effects than fluphenazine.
Atypical antipsychotics might have beneficial effects in war veterans with
treatment-resistant psychotic combat-related PTSD.
Clozapine was shown to be efficient in veterans having PTSD as well as in severe
sleep disorders and nightmares due to its strong sedative and anxiolytic effect.
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Section II
Diagnosis and Screening
M.J. Roy (Ed.)
IOS Press, 2006
Efforts to Improve the Diagnosis and

Treatment of Posttraumatic Stress Disorder
Michael J. ROY, MD, MPH 1 , and Patricia L. KRAUS.
Division of Military Internal Medicine, Department of Medicine,
Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Abstract. Posttraumatic stress disorder (PTSD) is a frequent and debilitating

consequence of exposure to war and other life-threatening events. PTSD often goes
undiagnosed and even when it is diagnosed; treatment is all too often inadequate or
ineffective. It is imperative to identify more effective diagnostic and therapeutic
approaches. We discuss currently available screening and treatment measures, and
present approaches we are planning to try to improve each of these modalities.
Keywords: Posttraumatic stress disorder, combat stress, depression, pharmacotherapy,

virtual reality, behavioral therapy
Introduction
Posttraumatic stress disorder (PTSD) became part of our lexicon in the aftermath of the
Vietnam War, but the symptoms and associated functional impairment it represents have
been known for centuries. Perhaps Cain was the first to suffer the torment of this disorder,
and Homer certainly depicts its symptoms in his account of Achilles in The Iliad. More
recently, the medical literature has featured hundreds of accounts from the American Civil
War, both World Wars, and other national and international conflicts. Authors identify
myriad physical and psychological symptoms that escape efforts to ascribe them to specific
environmental factors, but are linked to the stress of war. PTSD is also well documented
in many victims of terrorism, genocide and personal assaults such as rape. An estimated
10,000 Croatian Homeland War veterans (15% prevalence) have PTSD, with an alarmingly
high suicide rate. The current conflict in Iraq, involving snipers and suicide bombings, as
1
Corresponding Author: LTC Michael Roy. Department of Medicine, Uniformed Services University of the
Health Sciences, 4301 Jones Bridge Road, A3062, Bethesda, MD, 20814 USA. Telephone: (301) 295-9601; Fax:
(301) 295-3557; Email: mroy@usuhs.mil.
60 M.J. Roy and P.L. Kraus / Efforts to Improve the Diagnosis and Treatment of PTSD
well as concerns about prisoner mistreatment, is a recipe for PTSD. This provides an
opportunity to improve the care of combat veterans while defining optimal diagnostic and
therapeutic approaches.
1. Psychological Effects of Traumatic Experiences
The first large study of American troops returning from duty in Iraq, conducted by Hoge et
al., documented a rate of 12.9% meeting a strict case definition and 18% meeting a more
broad definition of PTSD [1]. Subsequent evaluations of injured soldiers receiving care at
Walter Reed Army Medical Center have indicated that initial screens may miss as many as
70% of those who meet criteria within 6 months, indicating both high rates and the need for
repeated screening. Early experience with veterans of the Iraq conflict also underscores the
high prevalence of other psychiatric disorders after all are common after such experiences,
with nearly 30% of those surveyed by Hoge et al. meeting criteria for some mood or
anxiety disorder. In addition, rates of alcohol and substance abuse have been found to be
higher in individuals diagnosed with PTSD. In patients with PTSD, one national study
identified a lifetime history of at least one other psychiatric disorder in 88% of men and
79% of women with PTSD [2], underscoring the importance of screening for more than just
PTSD. The PRIME-MD is a particularly useful validated instrument that screens for
depression, panic and other anxiety disorders, eating disorders, somatoform disorders, and
alcoholism [3].
PTSD is not solely associated with war, but has also been identified as a common
reaction to traumatic events ranging from personal assaults such as rape or mugging to life-
threatening acute medical conditions. Briefly, PTSD is characterized by symptoms that can
be divided into three categories, which persist for at least one month, following a
threatening event that initially elicited fear, helplessness, or horror. The first category
covers symptoms of re-experiencing the event, including intrusive thoughts, recurrent
dreams, flashbacks, and physiologic changes induced by stimuli reminiscent of the event.
The second category includes manifestations of avoidance of stimuli associated with the
trauma, such as avoiding activities, places, thoughts or feelings related in any way to the
trauma, inability to recall an important aspect of the trauma, anhedonia, detachment from
others, restricted range of affect, and a sense of a foreshortened future. The final category
incorporates symptoms of increased arousal, such as insomnia, irritability, impaired
concentration, hyper-vigilance, and an exaggerated startle response.
In the general population, while a history of some traumatic exposure is more likely than
not, PTSD has an estimated point prevalence of 2-5%, a lifetime prevalence of 8-12% and
higher yet in combat veterans [2, 4-12]. The current environment in Iraq is likely to result
in particularly high rates of PTSD. It often goes undiagnosed for months or years;
consequently effective treatment is not provided. PTSD is associated with high rates of
depression and other psychological conditions, poorer physical health, missing work,
impaired function at work and at home, and significantly higher healthcare costs. Rapid
diagnosis could enhance individual function and military readiness. PTSD is associated
with increased somatic complaints, making it even more likely that someone with PTSD
M.J. Roy and P.L. Kraus / Efforts to Improve the Diagnosis and Treatment of PTSD 61
will seek the help of their primary care physician, so that the prevalence of PTSD in
primary care is undoubtedly significantly higher than in the general population. Recent
studies in primary care found that 9-12% of patients met criteria for PTSD [7-8]. Samson
et al. identified PTSD in 38.6% of patients who were referred by their primary care
providers for mental health services based on suspicion of depression or anxiety [7].
However, like most mental disorders, PTSD often goes undiagnosed in primary care, and
such patients are frequently not referred to mental health. Several studies have examined
the likelihood of developing PTSD after a traumatic event, and estimates that combine all
stressors range from 9.2% to 25% [2, 8-10, 12]. Terrorist events have been shown to result
in markedly elevated rates of PTSD. After terrorists released the nerve agent sarin in a
Tokyo subway, 60% of those who presented for medical care after the incident had
symptoms of PTSD that persisted at least 6 months, even though most did not have
evidence of physical exposure to sarin [13]. In fact, PTSD not uncommonly results in those
not directly exposed to the event, as evidenced by the 7.5% of Manhattan residents
(including 20% of those living near the World Trade Center) meeting criteria for PTSD 5-8
weeks after September 11, 2001[14]. Moreover, 44% of adults outside of New York City
reported substantial symptoms of distress 3-5 days after 9/11/01 [15]. Wartime deployment
is also associated with high rates of PTSD—we identified PTSD in 83 of 651 (12.7%)
veterans of Operation Desert Shield/Desert Storm, upon completion of evaluation at Walter
Reed Army Medical Center 4-6 years after their deployment, consistent with other reports
[16-17]. PTSD is in turn associated with noticeably higher rates of depression and other
psychological conditions, poorer physical health, missing work, impaired function at work
and at home, and significantly higher healthcare costs [18-21]. Subthreshold PTSD,
represented by the multiple symptoms but failure to meet strict criteria for the full disorder,
has been reported to have at least an equal, if not greater, prevalence compared to full
PTSD, and has also been shown to be associated with significant disability [6,11].
2. Screening Instruments
2.1 A model: The PHQ-9 for Depression
The under-diagnosis, comorbidities, somatic complaints, functional impairment, and health

care utilization described for PTSD are also characteristic of depression. The PHQ-9
(Patient Health Questionnaire) is a 9-item screen for depression that has been validated in
3000 primary care and 3000 obstetrics and gynecology patients [22]. The PHQ-9, included
in Appendix B, consists of nine questions taken directly from the DSM-IV criteria for
major depression. A score is given for each of the 9 responses, based upon whether the
symptom bothered the individual not at all (0), for several days (1), more than half the days
(2), or nearly every day (3), in recent weeks. A composite score can then be generated,
with a range from 0 to 27; the scores have been shown to correlate with the severity of
depression, as well as the frequency of physician visits, and measures of functional status.
The PHQ-9 has been shown to identify about twice as many cases as primary care
physicians were able to diagnose on their own. Using a cut-off score of 10 to diagnose
depression, the PHQ-9 has a sensitivity and specificity of 88% each [22]. The scores can be
used not only to make an initial diagnosis of depression, but also, upon re-administration of
the questionnaire, to monitor the response to therapy, to determine whether an individual
patient is satisfactorily responding to treatment or not. In this way, the PHQ-9 provides an
invaluable tool for the primary care physician, who has long had effective monitoring
measures for other chronic diseases that are frequently encountered: hypertension (blood
pressure cuff), diabetes mellitus (hemoglobin A1C), and hyperlipidemia (LDL). Prior to
the PHQ-9, there was not such an instrument for depression, rendering diagnosis more
difficult, with numerous studies indicating that depression was missed about half the time
in a primary care setting.
The PHQ-9 fulfills ideal criteria for a screening instrument. It is quick, inexpensive,
easy to administer, is well validated, with relatively high accuracy, can educate patients in
providers with regard to criteria for the diagnosis, can be used to follow progress over time,
and there is also some evidence that its use is associated with improved prognosis.
2.2 Existing screens for PTSD
Numerous screens for PTSD have been previously developed. However, most are complex
and time-consuming. A previous review of available instruments found that nearly all did
not have well-established validity and reliability. Of those with some evidence of validity,
it has generally not been demonstrated across both combat veteran and civilian populations.
Since the time of that review, two instruments have become popular. The first is the
Clinician-Administered PTSD Scale (CAPS), which is 17 pages long, must be administered
by a professional, and features detailed instructions and complex scoring [23]. The CAPS
has become the gold standard instrument for the diagnosis of PTSD in the research setting,
with a recent review confirming strong validity and documenting its use in more than 200
studies [24]. However, it is not a practical instrument for use in a high-volume, rapid
turnover setting, whether the primary care physician’s office, or with combat veterans
returning from deployment and eager to be reunited with their families. Efforts to use the
CAPS to follow response to treatment have also proven more problematic [25]. The other
widely used instrument is the PTSD Checklist (PCL), a 17-item screen, which can be self-
administered, having the advantages of rapid completion, little expenditure of professional
time in administration, and relatively simple scoring. Although it compared favorably with
the CAPS for initial diagnosis of PTSD in combat veterans, it was less effective in
assessing response to treatment [26]. Unfortunately, it also fared poorly in the only study to
assess its utility in primary care, with a sensitivity of 32% [7], and while using a lower
threshold score would improve the sensitivity, the PCL still may not be very useful to
primary care physicians trying to diagnose this enigmatic condition. Since our experience
with the PHQ-9 at Walter Reed has been overwhelmingly positive, as a site for its initial
validation as well as a site where it is used on a regular basis to screen primary care
patients, we chose to develop a PTSD screen patterned after the PHQ-9. Like the PHQ-9, it
is comprised of questions taken directly from DSM-IV criteria for the disorder being
screened for, and each is then scored on a scale from 0-3 based on the self-reported
frequency of the feature. We seek to compare the efficacy of this instrument, as well as
other available brief screens, in comparison to the more cumbersome, but gold-standard,
CAPS. Since it has twelve questions, we have given our new instrument the appellation of
PTSD-12.
3. Treatment of PTSD
Over the past decade, selective serotonin reuptake inhibitors (SSRIs) such as sertraline,
fluoxetine and paroxetine have been shown to be superior to placebo in the treatment of
PTSD [27-28], as well as in preventing relapse if they are continued after achieving a
clinical response [29]. SSRIs improve the quality of life of those with PTSD in multiple
domains, improve functional status, decrease symptom severity, and reduce vulnerability to
stress. In addition, non-pharmacologic therapies such as cognitive behavioral therapy
(CBT) and exposure therapy have also shown efficacy, and probably have a greater
duration of response in the absence of ongoing treatment [30-32]. CBT corrects irrational
beliefs and thoughts and promotes rational behavioral changes, while exposure therapy
helps individuals to confront stimuli associated with their traumatic experience through
progressively more intense exposure, to identify and neutralize behavioral cues. Exposure
therapy appears to be most useful when employed within the context of CBT. A recent
Cochrane review demonstrated that CBT/exposure therapy had clear superiority over usual
care and other psychological therapies such as supportive therapy and psychodynamic
therapy [33]. While the identification of effective therapies for PTSD is good news, the
downside is that sizeable numbers of those with PTSD have an inadequate response.
Overall, it appears that pharmacotherapy results have a response rate of 40-60%, and non-
pharmacologic approaches are not appreciably better.
We postulate that a combination of pharmacologic and non-pharmacologic therapies
should prove superior to either alone. This hypothesis has not yet been adequately tested,
and it is important to do so, as the possibility that one form of therapy might interfere with
the other can not be rejected out of hand. Functional magnetic resonance imaging (fMRI)
or some other objective measure of the effect on neural pathways might be a particularly
valuable measure to incorporate in such studies, to assess the interaction, if any, between
the two different approaches.
Virtual reality (VR) is a form of exposure therapy with particularly high potential. In
recent years, virtual reality technology has been utilized to help patients overcome phobias
(e.g., claustrophobia [34], fear of flying [35], fear of heights [36], fear of spiders [37-38],
and fear of driving after an automobile accident [39] ), as well as for anxiety disorders [40]
and PTSD. In the latter case, small numbers of Vietnam War veterans [41] and World
Trade Center survivors [42-43] have each been reported to improve through the use of
progressively more realistic and intense virtual reality exposures. Imaginal exposure
therapy has been found to be effective in multiple clinical trials, and expert consensus
treatment guidelines published in 2000 characterized it as the non-pharmacologic treatment
of choice [44], but it is only recently that technology has reached the point where virtual
reality has reached sufficient quality to make it a realistic manner of administering this
form of therapy.
While both exposure therapy and pharmacotherapy are effective treatment for PTSD,
there are still significant numbers of patients who will not respond to one or the other. No
study has previously examined both types of therapy combined, but given the diversity of
the alternatives, it is reasonable to consider that combination therapy may result in a higher
response rate than either therapy alone. On the other hand, the fact that each form of
therapy has demonstrated superiority to placebo makes it unethical to include a pure
placebo arm. Prior studies with both pharmacotherapy and desensitization therapy suggest
that patients with PTSD are more sensitive than those with other psychiatric disorders, so
that medication should be started at a low dose and gradually increased. Starting with too
high a dose, even though such a starting dose might be appropriate for a condition such as
depression, may exacerbate anxiety and lead to discontinuation of the therapy. Similarly,
desensitization is most likely to be successful if started slowly, with most of the successful
studies taking this approach; however, there is less experience with desensitization, and
some believe efficacy may be greater with relatively intense exposure early in the course of
treatment.
We have assembled an experienced team of experts on both sides of the Atlantic to
conduct a randomized controlled trial assessing the efficacy of combined pharmacotherapy
and CBT/VR exposure therapy vs. mono-therapy. The study will be carried out at both
Uniformed Services University in the Washington, DC area, and the University of Zagreb
in Croatia, in order to facilitate treatment of both recent American veterans from the Iraq
and Afghanistan theaters, as well as veterans of the Croatian Homeland war with PTSD of
longer duration. Inclusion of the diverse study populations will facilitate generalizability of
results.
4. Summary
In a relatively short period of time, PTSD has been clearly identified and delineated, and
effective treatment has been established. Simple approaches may improve diagnostic rates,
and new technologies have the potential to significantly enhance the efficacy of treatment
further. In an increasingly complex world, the likelihood of exposure to life-threatening
disasters is greater than ever, and medical science must keep pace.
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M.J. Roy (Ed.)
IOS Press, 2006
Assessment of Available Diagnostic

Instruments for Posttraumatic Stress Disorder
Louis JEHEL, MD, PH.D1 Kathleen DULLEA
Psychotraumatologiy Unit, Tenon, University Hospital,Ap-HP, Paris France
Abstract. The under recognition of the psychological effects of trauma in medicine

requires a modification of clinical evaluation strategies, given the gravity of the
consequences of such conditions if left untreated. The most significant problems are
Acute Stress Disorder (ASD) and Post Traumatic Stress Disorder (PTSD), along with
comorbid disorders. The most significant comorbidities are abusive alcohol
consumption, depressive episodes, symptoms of generalized anxiety, phobia symptoms,
of panic disorders, as well as somatic complaints. We distinguish between the measures
requiring the intervention of an evaluator and self-report measures. To follow a patient
and adapt a treatment it is necessary to know the severity of the peritraumatic reaction.
Two major characteristics of the trauma response have been clearly identified;
dissociation (measured with the Peri-traumatic Dissociative Experience Scale and
distress (measured with the Peri-traumatic Distress Inventory). Some Instruments have
been validated that measure the psychopathological consequences related to a traumatic
event. The recognized gold standard (Clinician Administered PTSD Scale, or CAPS) is
time-consuming and requires an experienced professional to administrate. The most
frequently used self-report measures are the Impact of Event Scale-Revised and the
Posttraumatic Check List. To measure non-specific psychological consequences of a
traumatic event we propose the General Health Questionnaire-28 and The Beck
Depression Inventory. Other potentially useful measures are described to aid with the
evaluation of traumatized patients.
Keywords. Posttraumatic Stress Disorder; depression, selfreport, evaluation,

psychometry, validity
Introduction
In general, PTSD (Post-Traumatic Stress Disorder) is not necessarily difficult to diagnose,

if the clinician investigates the trouble with the appropriate questions. The under
recognition of PTSD in medicine requires a modification of clinical evaluation strategies
given the gravity of the consequences of such a disorder if left untreated. Whether the event
is recent or not, before deciding on a treatment strategy, the clinician must evaluate the
range of symptoms and their severity. Some have expressed concern that thorough,
systematic questioning could have a suggestive effect on reported symptomatology, but
1
Corresponding author : Louis JEHEL Psychotraumatologiy Unit, Tenon, University Hospital,Ap-HP, Paris
France, 4, rue de la Chine75020 Paris France. louis.jehel@tnn.aphp.fr
68 L. Jehel and K. Dullea / Assessment of Available Diagnostic Instruments for PTSD
there is not in fact evidence to support such concern; quantitative evaluation must be
supplemented by congruent global assessment performed by the clinician. Screening tools
should be used when clinically indicated, and the clinician should tailor the evaluation and
the choice of instruments according to the circumstances of the meeting and the clinical
state of the patient. Evaluations should assist both the clinician and the patient.
1. Challenges in Evaluation
The diagnosis of PTSD rests on specific anxiety features following a traumatic event, but
associated comorbid disorders and assorted symptoms may also ensue following the
trauma, and may contribute significantly impairment of function. Acute Stress Disorder
(ASD) and Post Traumatic Stress Disorder (PTSD) represent the most salient consequences
of trauma. In this work we have chosen DSM-IV criteria, which we will detail; we also cite
the principle criteria of the International Classification of Diseases, 10 th Edition (CIM-10),
which provides additional tools. The DSM criteria have been criticized for their reductionist
character, differentiating frequently observed symptoms in pathological states, such as
psychosomatic symptoms. The DSM IV is also criticized for its inability to identify the
severity of the disorder by a dimensional approach, but its greatest value is to permit
standardized assessment, facilitating comparisons with other studies utilizing these criteria
and enabling a scientific approach to clinical psychopathology.
Post-traumatic psychological problems evolve spontaneously over time, most often
resulting in a reduction in the number and severity of symptoms [1]. Many authors,
including Kessler [1], Breslau et al. [2], and McFarlane & Papay [3], also note that the
evolution also witnesses the development of a series of comorbid symptoms and disorders,
especially abusive alcohol consumption, depressive episodes, symptoms of generalized
anxiety, phobias, panic disorders, and somatic complaints.
2. Objectives of Quantitative Evaluation
Quantitative evaluation enables both identification of the disorder, as well as assessment of

the severity. DSM-IV and CIM-10 (International Classification of Diseases) are category-
specific instruments because they assign a diagnostic category to an individual. An
alternative, or perhaps additive, measure is to evaluate where the patient is situated along an
explored dimension to give an indication of intensity or severity. One speaks in this case
about instruments of dimensional measure. The dimensional approach examines
psychological phenomena that may not be directly measurable, but are linked to the
accumulation of indicators that are directly measurable. The instruments discussed in the
ensuing section are intended to evaluate the severity, or intensity, of symptoms associated
with PTSD.
L. Jehel and K. Dullea / Assessment of Available Diagnostic Instruments for PTSD 69
3. The Main Instruments
We distinguish here between measures that require administration by an expert, versus self-
reported or self-administered questionnaires.
3.1. Instruments specifically related to traumatic reaction
Two major Characteristics of the trauma response have been clearly identified.
3.1.1. Peri-traumatic Dissociative Experience Questionnaire

This questionnaire consists of 10 items, scaled from 1 to 5. It measures the intensity of the
dissociative state following a traumatic event. According to the authors, dissociation is one
of the best indicators of acute stress and is an excellent predictor of PTSD [4] The
symptoms of disassociation are characterized by reduced consciousness, and/or a
focalization or blunting of affect with a feeling of being detached from the environment. A
score is obtained by an average of the responses to 10 items. The "clinical threshold” of this
measure is an average of 1.5. The translation and validation in French of this instrument
was coordinated by Alain Brunet [5] with the collaboration of the authors: Marmar, C.R., et
al [6].
3.1.2. Peri-traumatic Distress Inventory (PDI)

This instrument was constructed by Alain Brunet [7] to measure criterion A2 of PTSD in
the DSM-IV classification, and was translated and validated in France by Louis Jehel and
collaborators [8]. It is currently being developed in other languages as well. It consists of 13
items coded 0 to 4. The scores range from 0 to 52. The instructions for each item are to
mark the response according to “what you felt during and immediately after the critical
event”. The average score is obtained by totaling the items and dividing by the number of
items. The quality of the psychometrics and its capacity to predict post-traumatic disorders
[9], warrant recommending the use of this instrument.
3.2. Instruments that Measure the Psychopathological Consequences Related to a

Traumatic Event
First we cite valid measures for an evaluator performed -evaluation done by a trained
clinician, then the measures allowing self-evaluation by patients, providing information on
the severity of symptoms and not on the diagnosis.
*Instruments available for a clinician performed evaluation
The Clinician Administered PTSD Scale (CAPS): The CAPS [10] measures the
frequency and intensity of each symptom using standard questions. The CAPS permits the
evaluation of current PTSD as well as post traumatic disorders occurring in the individual’s
past. The CAPS rigorously follows the diagnostic criteria of PTSD as defined by the DSM-
IV. The CAPS-1, the most frequently used, investigates symptoms that have duration of at
least a month. Another version, the CAPS-2, focuses on symptom prevalence in the
previous week, facilitating more regular response to treatment, such as in the case of
pharmacological studies. In the research setting, the CAPS is the instrument of choice to
establish the PTSD diagnosis according the DSM-IV criteria. This instrument has been
used in more than 200 published studies on psychological trauma; the psychometric
qualities of the original version are excellent [11]. Other instruments relating to global
standardized evaluation of psychiatric disorders with a specific module related to PTSD are
the MINI and the SCID which are presented below.
3.2.1. Available Instruments for self-evaluation

3.2.2. The Impact of Event Scale-Revised (IES-R).
This is a revised version of the original Horowitz scale (IES). The IES-R was validated
using a specific traumatic event evaluated during the specific time frame of the past 7 days.
It consists of 22 items scored from one to five, yielding a severity score of posttraumatic
symptoms with 3 sub-scores which must be averaged: intrusion, avoidance and
hyperarousal. The IES-R does not provide a diagnosis as there are no “cutoff” points.
However, this instrument is not only the most widely used and the oldest (IES) but also
provides an evaluation of the severity of the acute stress of PTSD. It has been recognized
for use in clinical trials, among the validated scales of severity, by a committee of experts
assembled by the ECNP-ECST [12].
This measure is validated in many languages, including Chinese [13], French [9],
German [14] Japanese [15], and Spanish [16], and its psychometric quality has been proven
in each to be comparable to the English language version.
This measure is recommended for use in future research to continue to trace the waxing
and the waning course of symptoms of PTSD [17].
3.2.3. Posttraumatic Check List (PCL)

This scale evaluates the severity of post-traumatic stress, incorporating 17 items that
represent the criteria of DSM-IV. Three versions are developed: “C” for civilian, “M” for
Military and “S” to describe a reaction to a Specific event. The validity of the English
language version has been verified [18], as has the French translation done by Cottraux [19-
20]. For each item the intensity is evaluated for the past month, according to the traumatic
event described, based on a scale of 1 (not at all) to 5 (very often). The total score
represents the sum of each of the 17 items. Three sub-scales can be researched which
correspond to the criteria B, C, and D from DSM-IV, with measures of repetition for
intrusion in items 1-5, avoidance in 6-12, and hyperarousal in 13-17. A notable quality of
this measure is the identification of a threshold at 44 recommended by Blanchard et al [21],
to consider the presence of PTSD by PCL-S. Less information is available concerning the
civilian version. With the military version the preferred cutoff is at 50.
3.2.4. The PTSD-Interview

Though developed for veterans by Watson and colleagues [22], it can also be used for
civilian populations. Seventeen items reflect PTSD symptoms as outlined in the DSM-IIIR.
Any symptoms receiving a score of 4 or higher count towards a PTSD diagnosis.
It was designed to be suitable for use by lay interviewers. The two final questions determine
whether symptoms were present for at least one month, and if they occurred the previous
month or not. The scale appears to have sufficient validity and reliability in veteran
populations, including in French and Spanish translations.
In table 1 we present the main characteristics of specific questionnaires of PTSD.
Table 1. Summary Descriptions of 17 Standardized Self-Report Measures of Posttraumatic Stress (Norris &
Hamblen 2004)
Scale Number Evidence Evidence of Evidence Reporting Anchored to

of items of Stability consistency of validity period identified
event
NWS Module 20+ Kappa = .45 na Strong Lifetime No
PTDS 17 r = .83 .92 Strong Past Yes
month
PCL 17 r = .96 .97 Strong Past Varies
month
Davidson TS 34 r = .86 .97 Strong Past week Yes
Purdue PTSD-R 17 r = .71 .91 Moderate Past Yes
month
PTSD-Interview 20 r = .95 .92 Strong Lifetime Yes
SPTSS 17 na .91 Moderate Past 2 No
weeks
SRIP 22 .60 – .97 .90 – .94 Strong Past 4 No
weeks
PTSS 10–12 na .85 – .90 Moderate Past week No
Perm inventory 26 r = .96 .94 Moderate- Past Week No
strong
TSC.-40 40 na .90 – .92 Moderate 2 months No
TSI 100 na .74 – .90 Moderate- 6 months No
strong
MMPI-PTSD 46 r = .94 .95 Moderate- Not No
strong explicit
CR-PTSD 28 na .93 Moderate Past 2 No
weeks
SCL-Supplemented 43 na na Moderate Past 2 No
PTSD weeks
Revised Civilian 30 r = .84 .86 – .92 Moderate- Varies Partially
Mississippi strong
HTQ 16 + 14 r = .92 .96 Moderate- NA Partially
strong
Note. NA: data not available.

3.3. Instruments That Measure Non-Specific Psychological Consequences of a Traumatic

Event.
The strongest comorbidity is found for mood disorders, followed by anxiety disorders such
as phobias and panic attacks [1, 23-25].
3.3.1. Available Instruments for a clinician administered evaluation:

• The SCID : Structured Clinical Interview for DSM
The SCID [26] is the structured tool most commonly used in the diagnosis of general
psychopathology. It systematically uses all the criteria and symptoms in the clinical tables
as they were defined by DSM-IV, featuring a question that the clinician or researcher must
ask the patient with regard to each disorder. It is not limited to Axis I of the DSM, since a
specific version (the SCID II) evaluates Axis II disorders (personality disorders). A module
is devoted to acute stress disorder and another to the post traumatic stress disorder.
The general evaluation thus allows one to investigate psychiatric comorbidity and
personality disorders. The dichotomous nature of this instrument does not provide an
evaluation in terms of severity. It has been used in many studies on populations of victims
of post traumatic events [27, 24]. The French version has not been validated.
• The MINI
Le M.I.N.I (M.I.N.I. Mini International Neuropsychiatric Interview French Version 5.0.0)
was constructed thanks to a coordinated collaboration by Yves Lecrubier for the French
version and David Sheehan [28] for the English language version. It is currently used
internationally. Its objective is to put at the disposal of health professionals a tool that
facilitates the diagnosis of primary psychiatric disorders according to DSM-IV criteria. It
consists of a structured interview featuring several modules. It includes module A for Major
Depression, module E for Panic Disorder, module F for Agoraphobia and module L for
Post-Traumatic Stress Disorder. This information provides a standardized categorical
evaluation.
3.3.2. Available Instruments for a clinician administered evaluation :

General Health Questionnaire 28 [29].
This instrument has particular relevance for the prospective evaluation of psychological
repercussions of victims [30,31]1998). Darves-Bornoz has demonstrated the validity of this
measure in a population of victims of sexual aggression. It features four components that
constitute a measure of the validity of depression, social dysfunction, the intensity of
somatic disorders and somatisation, and a measure of anxiety symptoms. The GHQ consists
of 28 items—7 for each component: somatic symptoms, anxiety and insomnia, social
dysfunction and major depression. Here again these scores only reflect the dimensional
aspects of symptomatology and do not necessarily correspond to a psychiatric diagnosis.
The sensitivity of the GHQ varies from 44% to 100% in various studies, with a specificity
of 74 to 93% (average 82%). If one wants to detect a specific case, different thresholds have
been proposed. For the GHQ-28, a threshold of 4 or more is commonly recognized [32].
• The Beck Depression Inventory (BDI)
This questionnaire is the most widely used in adult populations to measure the intensity of
depression. The revised version, the BDI-II [33], corresponds better to DSM-IV criteria.
The validity of the French version has been verified and threshold marks have been
identified. This questionnaire consists of 20 items. Each item is coded from 0 to 3 and a
global score is obtained by adding the items. This version is available from Editions du
Centre de Psychologie Appliquée. The original BDI has been used by Mezey and Taylor
[34] in the study of trauma victims.
• The Scale “Hospital Anxiety and Depression” (HAD)
The HAD scale is a self-report questionnaire consisting of 14 structured items, developed
by Zigmond and Snaithin [35] to screen for the most common psychopathological
symptoms. Its goal is to identify the existence of pathologic anxiety and then to evaluate its
severity. It has the distinction of not taking into account somatic symptoms in order to
avoid confusion with somatic pathologies, and for this reason it is commonly used with
outpatients and hospitalized patients, including both surgical and psychiatric patient
populations.
Each symptom is marked from 1 to 3 according to the intensity of symptoms during the
previous week. The anxiety subscale contains 7 items, the same as for depression. The
range of possible scores is from 0 to 21 for each subscale. Some authors [36] recommend a
score of 8 as the optimal threshold for each subscale, though others [37] favor a global
threshold score of 19 to diagnose an episode of major depression. This scale is therefore
dimensional in nature with less attention to symptom features.
• The Social Support Questionnaire (SSQ)
The SSQ (Sarason et al [38]) provides two different measures of social support, one
addressing the number of available people and the second the perceived quality of support,
consisting of 6 items each. A French version has been adapted by Bruchon-Sweitzer et
Paulhan[39, 19]. This measure is easily used and is considered as a reference [40].
4. The Sensitivity of the instruments to change
Sensitivity, as defined by Pichot [40], describes the discrimination provided by an

instrument. It is directly related to the number of items in the scale and the number of
scores for each item. A compromise is necessary because a scale containing a large number
of items is more sensitive but its use will be more difficult. Categorical instruments
focusing on a response of yes / no for a diagnosis are less sensitive to change, excluding the
CAPS, which offers an evaluation of intensity and a diagnosis but its usability remains
difficult outside the research setting. As noted by Weathers et al [11], the CAPS has been
used in more than 200 published studies, has excellent psychometric properties, and is
notable for its sensitivity to change.
Among the dimensional instruments which offer the best compromise to measure the
change of intensity of post-traumatic stress disorder with the best sensitivity, one can
recommend the use of the IES-R and the PCL. For depressive symptomatology, the HAD is
a good compromise given its ease of use.
5. Research Perspectives
A diagnosis whose validity is contested but which corresponds to a number of clinical

situations is « complex PTSD » [42] (Friedman 2003) or DESNOS (Disorder of Extreme
Stress Not Otherwise Specified [43]). This covers symptoms which are not incorporated in
the diagnosis of PTSD, such as behavioral troubles (impulsivity, aggressivity,
hypersexuality, eating disorders, substance or alcohol abuse, and self-destructive behavior),
emotional disorders, (affective instability, anger, depressive mood, panic symptoms),
cognitive difficulties, (fractured thinking, dissociative symptoms, partial amnesias) and
somatic disorders.
This diagnosis of DESNOS can be made in association with PTSD or independently.
DESNOS is more common in individuals with a history of repeated traumas [44] but there
is no currently consensual instrument to identify this disorder. It is an area where further
research is required.
6. Conclusions
The choice of measurement instruments in psychopathology depends on the objective of the

evaluation and the method of implementing the evaluation. In general, self-evaluation is
favored for a first evaluation in particular with a large population [45]. It is important to
assess whether the proposed measures correspond to the questions posed and are adapted to
the size and availability of the population. It is then necessary to assure the validity of the
instrument using rigorous criteria, including for translated versions. Regarding this subject,
one can demand precision from authors or translators. The translation of an instrument into
a foreign language requires a precise process. The use of questionnaires appears often to be
the simplest and most efficacious procedure, but it must always be done within a strict
ethical context because it constitutes for the patient an important step. The patient must be
clearly informed about what is expected from this measure.
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IOS Press, 2006
Psychological Screening Validation with

Soldiers Returning from Combat
Paul D. BLIESE, Kathleen M. WRIGHT, Amy B. ADLER 1 , and Jeffrey L. THOMAS
Walter Reed Army Institute of Research
Note: The views expressed in this abstract are those of the authors and do not reflect the
official policy or position of the US Department of the Army or Department of Defense.
Abstract. Soldiers returning from combat military operations are at risk for developing
a range of psychological problems. One way to facilitate the identification of these at-
risk soldiers is to have them complete a psychological screening survey. Such a survey
can be used to link soldiers reporting psychological problems with appropriate mental
health services. The challenge of developing such a screen is to ensure that it is valid,
short, and easy to administer. The US Army Medical Research Unit-Europe has been at
the forefront of developing a valid psychological screen for use with soldiers at post-
deployment. Research conducted prior to 2004 showed that screening needed to include
five domains: post-traumatic stress disorder, depression, alcohol problems, anger, and
relationship problems. Blind validation studies conducted in 2004 led to the selection of
scale items and cut-offs for each domain resulting in an effective short screen with good
sensitivity and specificity values. Finally, the question of when to conduct
psychological screening at post-deployment has also been addressed through a
comparison of prevalence estimates at immediate reintegration and three months post-
deployment. Future research will examine scale refinement and the use of sleep
problem questions in subsequent screening efforts.
Keywords: Combat stress, posttraumatic stress disorder, mental health screening,

deployment health
1. Psychological Screening Validation with Soldiers Returning from Combat
Psychological screening in the US military provides service members with the opportunity
to identify themselves as needing mental health support. While various mechanisms for
screening exist, the U.S. Army Medical Research Unit-Europe (USARMU-E), an overseas
activity of the Walter Reed Army Institute of Research, is engaged in developing a short,
easily-administered and validated screening procedure for use with military personnel pre-
1
Corresponding Author: LTC Paul Bliese. Commander US Army Medical Research Unit-Europe. Nachrichten
Kaserne, Karlsruher Str. 144, 69126 Heidelberg, Germany. Telephone: ++49-6221-17-2626, email:
paul.bliese@us.army.mil.
P.D. Bliese et al. / Psychological Screening Validation with Soldiers Returning from Combat 79
and post-deployment. The goal of such screening is not selection, nor is it an effort to
identify which individuals are fit to join the military and which should be excluded. Rather,
psychological screening is a pro-active attempt to bring military mental health support to
service members. The procedure is also transparent. The screen is designed to be straight-
forward, and service members know the purpose of the screen and the consequence of
endorsing symptoms (e.g., that they will potentially be referred for further mental health
evaluation).
2. Background
Originally, psychological screening was mandated by the Office of the Secretary of

Defense for Health Affairs in 1996 for U.S. service members deployed for more than 30
days to the Bosnia Area of Operations. The scales selected for inclusion in the original
screening program were primarily scales published in the open literature and validated on
civilian populations. The degree to which these scales and their associated cut-offs were
valid for the military population, however, was not known. After the screening program in
Bosnia was concluded in 1999, psychological screening continued to be requested by
commanders for other operations (for a review of the program, see Wright et al. [1]. Thus,
screening remained an important component of the health support provided to military
personnel across the deployment cycle.
In 2003, a mandated screening program was implemented with service members
returning from combat operations in Iraq and Afghanistan (Department of Defense Form
2796). This newly mandated program underscores the continued importance that
psychological screening has as part of the US military’s health program for deploying
military personnel.
Throughout the implementation and development of the psychological screening
program, USAMRU-E has analyzed screening data and published several reports [2-3, 1-4,
5]. In total, USAMRU-E has processed screening data on over 100,000 Soldiers. Across a
range of screening contexts, 15-28% of Soldiers have scored positive on the primary
screening survey and 2 to 12% were recommended for a follow-up evaluation based on a
brief clinical interview. Less than 1% of those screened were found to need immediate
services because of threat to self or others.
3. Screening Validation Research
In 2002, USAMRU-E research on psychological screening shifted to focus on assessing the

validity of the scales and cut-offs used on the primary screening survey. At that time, a
series of USAMRU-E studies developed the groundwork for systematically validating the
psychological screening program [4].
The first in this series of studies involved the screening of US Soldiers preparing to
deploy on a peacekeeping operation. This study was designed to assess the content validity
of the screen. In all, 885 Soldiers were interviewed and 864 consented to have their data
80 P.D. Bliese et al. / Psychological Screening Validation with Soldiers Returning from Combat
analyzed for research purposes. From this study [4], five content areas were identified as
targets for screening: (1) traumatic stress, (2) depression, (3) relationship problems, (4)
alcohol problems, and (5) anger problems. In addition, the screening survey also included
selected background questions such as demographic information and clinical and personal
history items. These additional questions were included because previous research had
found them to be useful variables in predicting those who required follow-up services [1,
6].
Although the optimal content areas were identified, the scales that were used to screen
for these clinical dimensions were lengthy. In addition, the scoring on some of the scales
tended to be complicated. The scales were also a combination of those selected from the
literature and had not been specifically validated with military personnel. Thus, there was a
need to develop shorter, validated scales that could be used in a quick screening procedure.
The subsequent USAMRU-E validation studies have focused on reducing the number
of scale items and improving the sensitivity and specificity of the clinical scales. In each of
the three studies conducted so far, a specific validation procedure was used. The procedure
began with the administration of the psychological screening survey. All of those Soldiers
exceeding previously established criteria on the clinical scales were interviewed as were a
random selection of 20-30% those not exceeding established criteria. Those clinicians
conducting the interview were blind to the individual’s status on the screening survey. A
determination was then made based on the structured clinical interview as to whether
follow-up clinical evaluation and/or services were needed. A flowchart describing the
process is presented in Figure 1.
No Follow-up Needed
Primary Moderate Symptoms

100% of Yes (subclinical)
Screen Exceed Structured
completed cut off? interview
and scored 20% of No Standard Evaluation
by Mental Health
Immediate Evaluation
by Mental Health
Figure 1. Flowchart for psychological screening research procedures.
This screening procedure was used twice in 2004. First, 732 US Soldiers stationed in
Germany preparing to deploy to Iraq for a year were screened. In all, 356 were
interviewed. Results from the pre-deployment screening study found that 75 (10.2%)
Soldiers were referred for follow-up evaluation based on a brief clinical interview. Second,
1,568 US Soldiers recently returned from a year in Iraq were screened, and 592 were
interviewed. Results from the post-deployment screening study found that 106 (6.8%) were
referred for follow-up based on a brief clinical interview.
Note that although these two studies included a pre-deployment and post-deployment
sample, these were two very different units located in two different countries. A third
study, conducted in 2005, involved post-deployment screening of those Soldiers who had
participated in the 2004 pre-deployment data collection. Data presented here are taken
from the 2004 studies only. Complete reports on these data are available [7-8].
4. Screening Results
Sensitivity and specificity analysis compared the scores on the primary screening surveys
with results from the structured clinical interviews (in part adapted from the Mini-
International Neuropsychiatric Interview [M.I.N.I., 9]. Bliese, Wright, Adler, Thomas [7]
provided a detailed review of the sensitivity and specificity associated with each of the five
clinical domains compared to the structured clinical interview results. For the purposes of
the present brief report, we primarily review the results from the analysis assessing post-
traumatic stress disorder. Post-traumatic stress disorder and trauma-related symptoms were
the most common reason for referral to follow-up mental health services in the post-
deployment sample. Thus, this clinical domain seems particularly relevant to Soldiers’
post-deployment psychological health.
In predicting traumatic stress referrals we evaluated two measures: (1) the 17-item
Post-Traumatic Stress Checklist [10], and (2) the 4-item Primary Care – Post-Traumatic
Stress Disorder screen (PC-PTSD) which is also used in the DD Form 2796, the mandated
Department of Defense screening form. The stem question on the PC-PTSD was “Have
you ever had any experience that was so frightening, horrible, or upsetting that, in the past
month, you…” (1) Have had any nightmares about it or thought about it when you did not
want to? (2) Tried hard not to think about it or went out of your way to avoid situations that
remind you of it? (3) Were constantly on guard, watchful, or easily startled? (4) Felt numb
or detached from others, activities, or your surroundings? Response options were no and
yes.
Table 1 shows how various cut-off values on the PC-PTSD correspond to clinical
providers' ratings as a result of the brief clinical interview based on the PTSD Module from
the M.I.N.I. When the cut-off value was set at one, the primary screen identified 32 of the
37 Soldiers who were identified as positive by the clinical providers. This resulted in a
sensitivity value of 0.86. At the same time, however, the criterion of requiring only one of
the four items to be endorsed produced 148 false positives for a specificity value of 0.73.
Table 1: PC-PTSD survey scores compared with provider referrals for post-traumatic stress symptoms
Primary Screen with 1 or More
Clinical Provider Negative Positive
Negative 405 148
Positive 5 32
Negative 488 65
Positive 10 27
Negative 538 15
Positive 20 17
Negative 552 1
Positive 29 8
A large reduction in false positives was garnered by requiring Soldiers to endorse at

least 2 items. In this case, the sensitivity and specificity were 0.73 and 0.88, respectively.
When the cut-off value required Soldiers to endorse 3 or more items, the test sensitivity
dropped fairly dramatically (0.46) and more referred Soldiers were missed by the primary
screen than were identified. At the same time, though, the specificity increased to 0.97 and
very few false positives were identified.
A summary of the sensitivity and specificity values is provided in Table 2 (see also [8]
for complete details). The table also includes phi-coefficients. These are measures of
association bounded by 1 and -1. Values above 0.30 suggest moderately strong to strong
relationships.
Table 2: Sensitivity and Specificity for post-traumatic stress disorder screening cut-offs
Index used for Evaluating Cut-off
Cut-Off on PC-PTSD Phi-Coefficient Sensitivity Specificity
1 or more 0.31 0.86 0.73
2 or more 0.41 0.73 0.88
3 or more 0.46 0.46 0.97
4 or more 0.42 0.22 1.00
When we compared the PC-PTSD to the PCL, we found that the three cut-offs
recommended in the literature for the 17-item PCL (i.e. 30, 44 and 50) performed no better
than did the four-item PC-PTSD. As can be seen in Table 3 below, sensitivity and
specificity from the PCL was .94 and .79, respectively for the cut-off of 30; .60 and .96,
respectively for the cut-off of 44, and .29 and .98, respectively for the cut-off of 50.
Table 3: PCL survey scores compared with provider referrals for post-traumatic stress symptoms
Primary Screen with PCL Score of 30 or More
Negative 435 115

Positive 2 33
Negative 530 20
Positive 14 21
Negative 539 11
Positive 25 10
Based on the need to create a short and highly specific test in screening survey, we
recommend the PC-PTSD, using a cut-off value of 3 or more positive responses as the short
screen criteria for identifying Soldiers with symptoms of traumatic stress. Soldiers’
responses to the PC-PTSD questions corresponded well to clinical providers’ evaluations.
However, providers may want to consider a lower cut-off value depending upon interview
resources. These results are comparable to results from a validation of the PC-PTSD
conducted with civilians [11].
Initial validation work was also completed on depression. Two measures of depression
were compared: The PHQ-Depression measure [12] and the Self-Rating Scale for
Depression [13]. In general, PHQ-Depression items were generally more predictive of
referrals than Zung items. The four best items from the PHQ were identified and a cut-off
of one item resulted in good sensitivity and specificity both with the post-deployment
sample (.77 and .88, respectively) and with the pre-deployment sample (.80 and .81,
respectively). The four items selected were: (1) Little interest or pleasure in doing things,
(2) Feeling down, depressed, or hopeless, (3) Poor appetite or overeating, and (4) Trouble
concentrating on things such as reading the newspaper or watching television. Based on the
validation study results from both pre- and post-deployment, we recommend using the four
item PHQ-Depression measure and selecting individuals for follow-up clinical interviews if
they report having one of these symptoms “More than Half the Days” in the last 2 weeks.
The remaining dimensions, relationship problems, anger problems, and alcohol
problems, also had acceptable sensitivity and specificity values and are presented in a
separate technical report [7]. Further development is currently underway to increase their
accuracy and ease of scoring. The two validation studies thus resulted in the selection of
items for inclusion in a short screen, and a focus on those items that need to be improved in
terms of their sensitivity and specificity. Furthermore, results from the screening studies
identified an interesting problem in terms of the optimal timing for conducting
psychological screening at post-deployment.
5. Timing
In terms of timing, post-deployment screening has been conducted anywhere from the
immediate post-deployment reintegration period to several months later. The post-
deployment psychological screening study conducted by USAMRU-E in 2004, however,
showed an increase in psychological symptom levels at 90 to 120 days post-reintegration in
Soldiers returning from combat in Iraq [7]. In a matched sample of 509 Soldiers providing
data both immediately post-reintegration and at 120 days post-reintegration, USAMRU-E
found reports of depression, PTSD, anger, and relationship problems increased (see Table 4
for results from this matched data set). Interestingly, co-morbidity also increased over
time. That is, at reintegration, over 80% of the soldiers who scored positive endorsed only
one dimension; whereas 120 Days later, less than 60% endorsed only one dimension.
Table 4. Comparison of symptom rates at Reintegration and 120 Day Post-Reintegration
Immediate 120 Days Post-

Reintegration Reintegration
Values Percent Values Percent
Traumatic Stress 15 / 488 2.98% 42 / 457 8.42%
Depression (PHQ) 5 / 502 0.99% 26 / 478 5.16%
General Distress (K6) 4 / 503 0.79% 24 / 479 4.77%
Anger Scale 44 / 456 8.64% 97 / 402 19.44%
Any of the above 53 / 448 10.58% 110 / 379 22.49%
While the 120-day rates in the matched sample of 509 are lower than rates reported in
other comparative samples at the same time point [14], the results nonetheless show that
psychological symptoms increase during the time from immediate reintegration to 120 days
post-reintegration. This, in turn, suggests psychological screening may be particularly
useful at 90 to 120 days post-reintegration relative to being conducted immediately at
reintegration. Based on these results, the Commanding General of the US Army, Europe
(USAREUR) tasked the Europe Regional Medical Command (ERMC) to develop a plan to
screen all USAREUR Soldiers at 90 to 120 days after returning from a combat deployment.
6. Program Implementation
The first Army unit to be affected by this plan, the 1st Armored Division (1AD), adopted
the USAMRU-E’s newly developed short screen for their 120 day post-deployment
screening program. The 1AD was able to implement the plan using primarily Division
medical resources. Execution was delegated to Brigade Surgeons and in a little over two
weeks nearly 6,000 Soldiers were screened. Estimates from this screening experience can
be made to predict the impact of screening combat Soldiers at post-deployment on mental

health resources.
Specifically, from this experience, it is estimated that 27.5% of every 1000 combat
Soldiers screened at post-deployment will score above cut-off criteria. Furthermore, we
can estimate that for every 1,000 Soldiers, 28 Soldiers will require immediate referral to
assess for harm to self or others; 8 Soldiers will be referred for alcohol problems; 17
Soldiers will be referred for family/relationship problems; 69 will require a standard mental
health care appointment; and 153 will not require any referral, will refuse care, or will be
lost to follow-up.
Subsequent to the 1AD implementation of the screening program, the US Army,
Europe screening program was noted by the Office of the Secretary of Defense for Health
Affairs and a 26 January 2005 press release announced the wide-scale implementation of
the screening program. On 10 March 2005, an official policy letter was signed, mandating
120-day post-deployment screening across the entire military [15]. The actual screening
tool to conduct this screening is currently under consideration. USAMRU-E meanwhile is
still engaged in further refining measures and optimal cut-off scores.
USAMRU-E is engaged in re-validating the short screen and improving the measurement
of alcohol problems and relationship problems. In addition, USAMRU-E is assessing a
short, valid screen for sleep problems because research with the 1AD showed there were
high prevalence rates of sleep problems particularly among those Soldiers with high combat
exposure. Finally, USAMRU-E has just conducted the first program evaluation of the
screening program. This program evaluation is one part of an additional goal to determine
the impact screening has on the stigma associated with mental health problems and on
perceptions of barriers to care. Through the development of an efficient one-page
screening tool, recommendations for a brief structured clinical interview, and procedures
that may help reduce stigma and other barriers to care, the USAMRU-E psychological
screening program of research is geared to meet the needs of service members across the
deployment cycle.
References
[1] Wright, K.M., Huffman, A. H., Adler, A. B., & Castro, C. A. (2002, October). Psychological screening
program overview. Military Medicine, 167, 853-861.
[2] Adler, A.B., Huffman, A.H., Bliese, P.D., Castro, C.A. (2005). The impact of deployment length and
experience on the well-being of male and female soldiers. Journal of Occupational Health Psychology,
10(2), 121-137.
[3] Adler, A.B., Wright, K.M., Huffman, A.H., Thomas, J.L. & Castro, C.A. (2002). Deployment cycle effects
on the psychological screening of soldiers. U.S. Army Medical Department Journal, 4/5/6, pp. 31-37.
[4] Wright, K.M., Thomas, J.L., Adler, A.B., Ness, J.W., Hoge, C.W., & Castro, C.A. (2005). Psychological
screening procedures for deploying U.S. Forces. Military Medicine 170.
[5] Martinez, J.A., Huffman, A.H., Adler, A.B., & Castro, C.A. (2000). Assessing psychological readiness in
U.S. soldiers following NATO operations. International Review of the Armed Forces Medical Services, 73,
139-142.
[6] American Psychiatric Association. (1994). Diagnostic and Statistical Manual of Mental Disorders (4th ed.).
Washington, DC: Author.
[7] Bliese, P.D., Wright, K.M., Adler, A.B., Thomas, J.L. (2004). Validation of the 90 to 120 day post-
deployment psychological short screen (U.S. Army Medical Research Unit-Europe Research Report 2004-
002). Heidelberg, Germany: USAMRU-E.
[8] Bliese, P.D., Wright, K.M., Adler, A.B., Thomas, J.L., & Hoge, C.W. (2004). Screening for traumatic stress
among re-deploying soldiers (U.S. Army Medical Research Unit-Europe Research Report 2004-001).
Heidelberg, Germany: USAMRU-E.
[9] Sheehan, D.V., Lecrubier, Y., Sheehan, K.H., Amorim, P., Janavs, J., Weiller, E., et al. (1998). The Mini-
International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured
diagnostic psychiatric interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry, 59, 22-33.
[10] Weathers, F.W., Litz, B.T., Herman, D.S., Huska, J.A, Keane, T.M. (1993). The PTSD Checklist (PCL):
Reliability, validity, and diagnostic utility. Paper presented at the annual meeting of the International
Society for Traumatic Stress Studies, San Antonio.
[11] Prins, A., Ouimette, P. Kimerling, R., Cameron, R.P., Hugleshofer, D.S., Shaw-Hegwer, et al. (2004). The
primary care PTSD screen (PC-PTSD): Development and operating characteristics. Primary Care
Psychiatry, 9 (1), 9-14.
[12] Spitzer, R.L., Kroenke, K., & Williams, J.BW., and the Patient Health Questionnaire Primary Care Study
Group. (1999, November). Validation and utility of a self-report version of PRIME-MD: The PHQ primary
care study. Journal of American Medical Association, 282(18), 1737-1744.
[13] Zung, W. W. K. (1965). A Self-Rating Depression Scale. Archives of General Psychiatry, 12, 63-70.
[14] Hoge, C.W., Castro, C.A., Messer, S.C., McGurk, D., Cotting, D.I., & Koffman, R.L. (2004). Combat duty
in Iraq and Afghanistan, mental health problems, and barriers to care. New England Journal of Medicine,
351(1), 13-22.
[15] Assistant Secretary of Defense for Health Affairs Memorandum, Policy for Department of Defense Post-
deployment Health Assessment, March 10, 2005.
Acknowledgments
We thank Ms. Rachel Prayner, Ms. Angela Salvi, Ms. Andrea Bellis, Ms. Kelley Rice, SGT
Deena Carr, and SPC Nicol Sinclair for their technical support and gratefully acknowledge
the support of the Europe Regional Medical Command (ERMC); the Southern European
Task Force (SETAF); COL Richard Trotta, Commander, Vicenza Health Clinic and CPT
Robert Johnson, Division Psychologist, 1st Infantry Division.
M.J. Roy (Ed.)
IOS Press, 2006
Psychophysiological Responses to Trauma-

Related Stimuli in PTSD: Potential for
Scenario Adaptation in VR Exposure Therapy
Tanja JOVANOVIûa,1 , Sinisa POPOVIûb, and Dragica KOZARIû-KOVAýIû c

a,1
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine,
Atlanta, GA, USA
b
University of Zagreb, Faculty of Electrical Engineering and Computing, Zagreb, Croatia
c
Referral Centre for the Stress Related Disorders of the Ministry of Health of the Republic
of Croatia, Department of Psychiatry, Dubrava University Hospital, Zagreb, Croatia
Abstract. The following article reviews the use of psychophysiological tools in

diagnosis and treatment assessment of posttraumatic stress disorder (PTSD). Several
different psychophysiological systems are described and evaluated in terms of their
diagnostic utility. The article further makes recommendations regarding strategies for
the use of psychophysiology in future assessment of the disorder and for
implementation within virtual reality exposure therapy.
Keywords. Combat related Posttraumatic Stress Disorder, War veterans,

Psychophysiological responses, Startle, Heart rate, Skin Conductance, Blood Pressure
Introduction
One of the central symptoms of posttraumatic stress disorder (PTSD) is hyper-arousal in

response to trauma reminders. Such arousal induces physical symptoms, such as racing
heart, sweating, and shortness of breath. These symptoms are controlled by the autonomic
nervous system and can be measured using psychophysiological equipment.
Psychophysiological measurements include recordings of several autonomic nervous
system outputs, such as heart-rate, blood pressure, skin conductance, respiratory rate, and
body temperature. Thus, these measurements provide an objective way to measure the
1
Corresponding Author: Tanja JOVANOVIC, Department of Psychiatry & Behavioral Sciences, Emory
University School of Medicine, 1365 Clifton Road, Atlanta, Georgia 30322, E-mail: tjovano@emory.edu
88 T. Jovanović et al. / Psychophysiological Responses to Trauma-Related Stimuli in PTSD
hyper-arousal symptoms related to trauma reactivity. Technological advances in the last

decade have made such measurements possible with only a few pieces of equipment and
without extensive training in psychophysiology. In other words, hyper-arousal can be
measured in most clinical settings, and can be used in the diagnosis and treatment of PTSD.
1. Overview of psychophysiological measures
Based on the DSM-IV criterion of hyper-arousal in PTSD [1], several investigators have
examined the utility of psychophysiological recording in diagnosing the disorder (see [2]
for recent review). Most of these studies have recorded from multiple psychophysiological
systems, namely, the cardiovascular, electrodermal, electromyographic, and electrocortical
systems. The first two systems are under the control of the autonomic nervous system
(ANS), whereas the second two are under the control of the central nervous system (CNS)
[3]. The cardiovascular measurements include electrocardiograms (ECG), blood pressure
(systolic BP and diastolic BP), and respiratory rate (see Figure 1). Electrodermal responses
measure changes in sweat gland activity and are measured from the skin on the fingers (see
Figure 2). Electromyographic (EMG) measurements include measuring the muscles that
control facial expression and eyeblink [3]. Electrocortical recordings are made from the
scalp and record evoked response potentials from cortical areas—as opposed to the first few
measurements, these require much more sophisticated equipment and are not as readily
interpreted; therefore, we will focus on the first three systems.
1.1. Cardiovascular system
Electrocardiograms can be used to analyze heart-rate in beats per minute (BPM), heart-rate
variability (inter-beat interval, IBI), and respiratory sinus arrhythmia (RSA). Heart-rate is a
direct index of sympathetic nervous system activation and is a very good indicator of
hyper-arousal. Heart-rate variability and RSA are measures of parasympathetic nervous
T. Jovanović et al. / Psychophysiological Responses to Trauma-Related Stimuli in PTSD 89
Figure 1. Placement of electrodes for facial electromyograph (EMG), and electrocardiogram (ECG). The X’s
mark the placement of ECG electrodes (on the skin surface). The chest band measures respiration rate.
system activity which inhibits arousal; therefore, these measures are good indicators of
individual differences in resilience to trauma. These measures can be easily recorded from
electrodes placed on the wrist or on the chest. The chest placement is less sensitive to
motion artefact and is therefore preferred over the wrist placement. Blood pressure and
respiration rate can also be automatically measured using a wrist sensor and chest band,
respectively (see Figure 1). These measures are useful concomitants to ECG, and
respiration rate is necessary in order to assess RSA.
1.2. Electrodermal system
Electrodermal measurements assess changes in sweat gland activity in the skin (Figure 2)
that affect the electrical conductivity of the skin [3]. The electrodermal response measures
skin conductance level (or skin resistance) and is also a direct index of sympathetic nervous
system activation and thus a good measure of arousal. Historically it has been termed the
Galvanic skin response (GSR) and is the most commonly used indicator of physical arousal.
It has been used to measure habituation and learning effects as well as hyper-arousal.
Electrodes can be placed either on the index and middle finger (Figure 2) or on the palm.
Figure 2. Placement of electrodes for measuring skin conductance response
1.3. Electromyographic system
Electromyographic measurements target the muscles in the face that control facial
expression (Figure 3) [3], most commonly the zygomaticus muscles (cheek muscles that
stretch the face during smiling, Figure 3A), the corrugator muscles (eyebrow muscles that
control frowning, Figure 3B), and the frontalis muscles (forehead muscles that arch the
eyebrows, Figure 3C). Electromyographic recordings are also made of the orbicularis
muscles (Figure 3D) that contract during the eyeblink component of the startle reflex. Since
these are under the control of the central nervous system, they are also under some degree
of voluntary control. Thus, facial expressions, such as smiling or frowning can be
purposefully generated or suppressed by the individual. For this reason, these measures are
not as objective as the cardiovascular or electrodermal responses, which are not under
voluntary control. However, electromyographic measurements of facial muscles are
preferred when the stimuli can have either negative or positive interpretations [4]. Studies
that examine positive as well as negative emotions can measure facial expressions using
this system. While these muscle groups would not necessarily be of interest in analyzing
hyper-arousal to trauma reminders, it may be useful in investigations of emotional numbing
symptoms of PTSD.
C
B
D
A
Figure 3. Placement of facial EMG electrodes. A=zygomaticus muscle, B=corrugator muscle, C=frontalis
muscle, and D=orbicularis muscle.
Another muscle group that is measured using electromyographic equipment is the

orbicularis muscle which contracts during the startle reflex (Figure 3D). This measure has
been used frequently to assess exaggerated startle response, which is one of the most
commonly reported symptoms of PTSD. While blinking is to some degree under voluntary
control, the startle reflex has a short latency (30-120 ms) and thus occurs too quickly to be
intentionally generated. However, the startle reflex itself can be modulated by different
emotional states, such as fear. A large body of literature has examined the increase in the
startle response during fearful situations, called fear-potentiated startle [5]. This is also a
good laboratory measure of fear and has the potential to be used in assessment of PTSD.
2. Psychophysiology as a diagnostic tool for PTSD
2.1. Hyper-arousal to audiovisual combat stimuli
As mentioned above, one of the cardinal symptoms of PTSD, according to the DSM-IV, is
physiological hyper-arousal, or exaggerated reactivity, to trauma reminders [1]. Early
studies capitalized on this symptom and used combat-related stimuli to evoke arousal in
Vietnam veterans with PTSD. The first studies to examine hyper-arousal using
physiological measurements used standardized combat stimuli, such as combat sounds like
mortar explosions or gunfire, and standardized pictures of combat. In these studies all
participants would be exposed to the same sets of stimuli while their responses were
measured. In a series of studies, Blanchard and collaborators have successfully
discriminated veterans with or without PTSD on the basis of heart-rate responses to combat
sounds (95% correct for veterans with PTSD and non-veteran controls [6]; 81% correct [7];
86.4% correct for combat veterans with PTSD vs. without PTSD [8]). They measured
heart-rate, systolic and diastolic blood pressure, skin conductance, and frontalis EMG in
response to three conditions: (a) resting, (b) mental arithmetic, and (c) a combination of
music, silence, and combat sounds and found that PTSD veterans had higher heart-rate
responses to all sounds relative to non-PTSD veterans (Figure 4). Furthermore, Blanchard,
Kolb, and Prins [9] found that a discriminant function based on measures of heart-rate alone
correctly identified an initial sample of 84% of combat veterans with PTSD and 75% of all
veterans. Studies using standard audiovisual combat imagery found that heart-rate was the
most sensitive psychophysiological measure in distinguishing traumatized individuals with
and without PTSD. While heart-rate alone showed a high degree of discrimination, there
was still a relatively high rate of both false positive (i.e. non-PTSD patients classified as
PTSD), and false negatives (PTSD patients classified as non-PTSD) according to interview
diagnoses.
PTSD VETERANS
COMBAT VETERANS
84
HEART RATE (bpm)
79
74
69
64
MUSIC SILENCE COMBAT
SOUNDS
Figure 4. Heart-rate in response to different sounds in veterans with and without PTSD. Adapted from
Pallmeyer et al. [8]
While the advantage of using standardized combat stimuli is that all participants have
the same exposure and therefore the differences in response could be attributed to the
disorder, it is possible that the standard stimuli did not encompass all possible combat
experiences, i.e., that some veterans experienced different types of trauma and the
“standard” stimuli might not serve as trauma reminders for a particular individual’s unique
experiences. Therefore, a veteran with PTSD may not show hyper-arousal to stimuli that
are not part of his traumatic experience [2].
2.2. Hyper-arousal to script-driven imagery
In order to address the problems with standardization of trauma imagery, Orr and Pitman
[10] modified a procedure developed by Lang and colleagues to study phobias [11]. In this
method, the participant describes an actual traumatic event from their combat experience
(see Box 1). This event is then edited into a 30-second script which is read and recorded by
the experimenter [10]. The script is then played back to the participant who is then
instructed to imagine the scene while psychophysiological data are recorded and compared
to physiological recordings made during a resting period. This method has been used with
many different PTSD populations: World War II veterans [12], Korean War veterans [12],
Vietnam War veterans [13], Israeli War veterans [14], Vietnam War combat nurses [15], as
well as sexual assault victims [16]. In all these populations, PTSD patients exhibit a
stronger HR and SC response to scripts than non-PTSD trauma survivors (Figure 5) [11, 12,
13, 15, 16]. In studies using script-driven imagery, skin conductance was found to be the
most sensitive measure of hyper-arousal in PTSD. Pitman and colleagues [11] have
suggested that the skin response may be more sensitive to specific autobiographical combat
trauma rather than standard combat images, and thus may have more discriminative power
than heart-rate. While script-driven imagery is more flexible in evaluating different types of
trauma, it is relatively time consuming, introduces variability, and may decrease hyper-
arousal by pre-exposing the individual during script construction.
You’re at a field hospital in Vietnam. It’s been another long day in the oppressive
heat and you’re very tired. Suddenly you hear the sound of incoming helicopters.
You take a deep breath and your heart starts to pound. You pause for a minute to
listen more closely. The sounds are stronger and louder than usual. This can only
mean another mass casualty situation. Your muscles tensing, you spring into action
to get ready for the wounded. As you look down at the first young victim, you feel a
trickle of sweat roll down your neck. You try not to recoil at the sight of his
devastating wounds. Despite the nausea you feel inside, you force yourself to smile
reassuringly. [17]
Box 1. Example of a trauma script from a Vietnam War nurse.
HR CHANGE SC RESPONSE (microohm) SC CHANGE

HEART RATE (bpm)
0.6
8
0.5
6 0.4
4 0.3
0.2
2
0.1
0 0
PTSD CONTROL PTSD CONTROL
Figure 5. Heart-rate and skin conductance change in response to trauma imagery compared to resting
baseline. Adapted from Pitman et al. [13]
In 1998 Keane and colleagues [18] published the results of the largest study to date to
look at the utility of psychophysiological measures in diagnosing PTSD. The study was a
multi-site Department of Veterans Affairs Cooperative Study investigating 1,461 Vietnam
veterans using script-driven imagery and standardized combat images with
psychophysiological recordings. While the study did not find a perfect correlation between
interview-based PTSD diagnosis and psychophysiological reactivity, the authors concluded
that psychophysiological data did provide useful and objective assessment of the disorder.
However, there was still concern regarding false positives and false negatives in terms of
classification, indicating the need for further study to explore whether the interview
processes needs re-evaluation or the psychophysiology alone does not provide enough
information for assessment.
2.3. Exaggerated startle response
Although exaggerated startle response was one of the earliest symptoms related to combat
stress, the psychophysiological evaluation of startle in PTSD patients has not yielded
consistent results; in fact, this finding is the most equivocal of all (reviewed in [2]). Studies
of Gulf War veterans with PTSD found both self-reported [19] and physiologically [20]
exaggerated startle compared to non-PTSD veterans. On the other hand, Vietnam veterans
with PTSD did not show increased startle [21], unless they were subjected to a threatening
context [22]. Grillon [23] concluded that increased baseline startle may be related to
recency of combat exposure and may decline after a few years. On the other hand, all
veterans may be more sensitive to anxiety or fear-potentiated startle [23].
2.4. Dissimulation of response
Given the argument that psychophysiological measurements provide an objective

assessment tool free of the risk of malingering and subjectivity of self-report measures, it is
important to address whether psychophysiological reactivity can be “faked”. Several studies
have examined this issue. In the first study Gerardi and colleagues [7] instructed veterans
with PTSD to consciously lower their physiological responses in order to appear to be
without PTSD; while veterans without PTSD were instructed to consciously elevate their
physiological responses to combat stimuli so as to appear to have PTSD. While the PTSD
veterans could not decrease their physiological response, non-PTSD veterans could elevate
their heart-rate and frontalis EMG response. However, when blood pressure and resting
heart-rate were included in the analysis, both the “real” and “fake” PTSD patients were
correctly classified to their respective categories with high accuracy. In another study Orr
and Pitman [24] replicated the findings with non-PTSD veterans. When instructed to
respond to the combat stimuli “as if they had PTSD” and to get “emotionally worked-up”,
the non-PTSD veterans could elevate their heart-rate; however, there were still significant
differences in skin conductance and corrugator EMG between the “real” and the “fake”
PTSD veterans to allow a discriminant function to accurately classify the patients to their
categories. In terms of the exaggerated startle response, the reflexive contraction of the
eyeblink muscle occurs approximately 30 to 120 ms after the auditory stimulus—this time
frame is too short to allow for conscious elevations of startle; thus it may be the most
difficult to influence voluntarily. Taken together, these studies indicate that some
psychophysiological measures may be easier to dissimulate than others; therefore, several
different measures should be collected in order to achieve reliable psychophysiological
assessments.
3. Psychophysiology as assessment of PTSD treatment
As markers of arousal, psychophysiological measurements can provide useful information

during treatment, especially during exposure-based therapy. First, psychophysiological data
can indicate the level to which the patient is engaged in the exposure, or activated by the
memories of the traumatic events. One of the key components of exposure therapy is to
activate the patient during exposure so that he or she is reliving the traumatic experience.
Second, psychophysiological monitoring can indicate within-session habituation to the
exposure treatment; this information can guide the therapist in increasing or decreasing the
level of exposure. Finally, psychophysiological reactivity to traumatic stimulation can be
used as an outcome measure for treatment efficacy. Most therapists use subjective units of
distress (SUDs) or other similar subjective measures to gauge the patient’s level of
engagement and habituation throughout the exposure therapy session. However,
psychophysiological data offer the benefit of objective measurement of these phenomena.
Several early case reports of Vietnam veterans [25, 26] measured psychophysiological
responding during imaginal flooding, a technique similar to exposure therapy, and found
that the patients were highly activated during exposure and decreased responding with
treatment. A study by Boudewyns and Hyer [27] examined psychophysiological responding
during script-driven imagery and found that 3 month follow-up reductions in symptoms
were associated with decreases in heart-rate and especially skin conductance responses to
traumatic imagery immediately after therapy. Finally, Pitman and colleagues [28] examined
heart-rate, skin conductance, and facial EMG during imaginal flooding treatment and found
that the heart-rate habituation to exposure within a session and between sessions was
associated with fewer daily memory intrusions of the traumatic event that was treated. A
recent study used heart-rate and acoustic startle response as a treatment outcome measure
for cognitive-behavior therapy in PTSD [29]. These research studies suggest that measures
of physiological responses to traumatic imagery can be a valuable objective evaluation of
therapeutic interventions. The accessibility of these techniques should increase their use as
evaluation tools in treatment, especially with the increase in new approaches to exposure
therapy, such as virtual reality exposure therapy (VRET).
4. Virtual reality exposure therapy and PTSD
Virtual reality provides a new way to use exposure therapy in treatment of PTSD. It has
been successfully used in treatment of phobias, such as fear of flying [30] and fear of
heights [31]. There have been two studies that have used virtual reality in PTSD treatment.
The first study was with Vietnam veterans (Virtual Vietnam [32, 33]) and the second was
with survivors of the 9/11/2001 terrorist attacks on the World Trade Center in New York
(Virtual WTC [34, 35]). In both of these studies, the exposure treatment resulted in
decreases in SUDs; however, psychophysiological responses were not measured. The
studies with treatment of phobias in virtual reality that have monitored physiological
response found that changes in heart-rate and skin conductance were associated with
immersiveness or presence in the virtual environment. Thus the psychophysiological data,
as an objective index of arousal, can provide useful markers of the patient’s activation in
the virtual reality exposure therapy session. Furthermore, Ressler and colleagues [31] found
that a reduction in the number of fluctuations in skin conductance during exposure to the
virtual elevator in the fear of heights study was associated with across-session habituation
and symptom improvement.
5. Future use of psychophysiology in virtual reality exposure therapy
Future studies as well as clinical treatment trials using VRET should make use of
psychophysiological monitoring in diagnosis and assessment of treatment. New computer
technology allows for cross-integration of psychophysiological output and computer-
generated exposure therapy so that the computer can adjust the virtual exposure and adapt
the scenario for each individual patient. In such a closed loop feedback system the
computer could increase or decrease the level of stimulation according to the arousal level
of the patient. However, it is important to note that the psychophysiological information
should not be used to the exclusion of therapists. As mentioned above, the
psychophysiological data and interview-based diagnoses do not correspond perfectly. Thus
it is very important to use several different measures of psychophysiological systems and to
use these measures in conjunction with standard self-report symptom scales and clinician-
based interviews. Such a multi-modal assessment plan would have a high degree of
sensitivity and specificity for the disorder. Furthermore, the exposure therapy should still be
guided by a clinician who can interpret the psychophysiological data as well as use clinical
judgment with regard to the patient’s activation and habituation during VRET.
6. Design of VRET study in Croatia
6.1. Participants
The participants will be Croatian combat veterans with and without PTSD. The sample will
be recruited from an estimated 1,000,000 people exposed to combat trauma from 1991 to
1995 [36]. PTSD will be diagnosed using a multi-modal assessment plan, including
structured diagnostic interview, psychiatric evaluation, psychometric examination, tests of
malingering, and psychophysiological assessment. The psychophysiological assessment
will evaluate hyper-arousal in response to trauma stimuli and startle to loud sounds.
6.2. Apparatus
Patients will be tested for hyper-arousal before and after treatment using the Biopac system
MP150 (Biopac Systems, San Diego, CA) for psychophysiological data recording. We will
record heart-rate, systolic and diastolic blood pressure, respiration rate, skin conductance,
body temperature and facial EMG. The combat stimuli will be presented in the Virtual
environment. In the Virtual environment the patients will first be habituated to the VE for
10 minutes after which we will collect resting baseline data on all the psychophysiological
measures. We will measure psychophysiological responsiveness to the combat imagery as
both a component of diagnostic assessment and to track activation and progress in the VE.
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Section III
Management of Posttraumatic Stress Disorder
M.J. Roy (Ed.)
IOS Press, 2006
Pharmacotherapy Research in Post-

traumatic Stress Disorder
Neven HENIGSBERG 1
Croatian Institute for Brain Research, Medical School, University of Zagreb, Croatia
Abstract. Given the high prevalence and considerable individual and societal costs
of PTSD, there are relatively few randomized, placebo-controlled trials in PTSD.
Four placebo controlled trials have been performed with MAOIs, three with TCAs.
Only one randomized placebo controlled trial was performed with benzodiazepines
class, showing no effect of alprazolam on core PTSD symptoms. The majority of
trials were done with SSRIs and novel antidepressants, the most of them showing
moderate effect sizes over placebo. In past clinical trials antidepressants appeared
with the best overall efficacy for the treatment of PTSD, although their effect may
not be present in all symptom clusters. Although duration of majority of trials in
psychiatry is conventionally set to 12 weeks, clinical trials in PTSD may require
the acute phase of treatment to go beyond initial 12 weeks of treatment, especially
if the trial includes more severely ill patients. Further clinical research is
warranted, using new compounds, as well as those already marketed for other
indications. It remains essential to investigate if certain treatments are more
effective for particular symptom sets or for some subgroup of PTSD patients. Due
to high placebo response and moderate effects of drugs researched in PTSD it is
difficult to avoid the use of placebo in PTSD trials.
Keywords. Pharmacotherapy, pharmacological treatment, PTSD, medications,

SSRIs, antidepressants, benzodiazepines, placebo, effect size
1. Use of Placebo in PTSD Trials
Khan et al.[1] evaluated the Food and Drug Administration (FDA) Summary Basis of
Approval (SBA) reports to compare the magnitude of placebo response, magnitude of
psychotopic drug response, and drug placebo differences among various diagnostic
groups such as depression, anxiety, and psychotic disorders. In all psychiatric
indications placebo response was considerable. The average percent improvement on
placebo in PTSD trials was around 32% on primary outcome measure. This finding
suggests that placebo use should be continued for newer agents being tested for all of
the psychiatric disorders, including PTSD. This is further corroborated by 38% of
placebo responders in PTSD trials, the percentage which was found in several trials
involving both investigational drugs and placebo.
Due to so high placebo response in PTSD clinical trials, the most clear ground to
establish the superiority of test drug remains the trial involving placebo. The other
1
Corresponding Author: Neven Henigsberg, Head, Department of Psychopharmacology, Croatian Institute
for Brain Research, Medical School, University of Zagreb, Salata 12, HR-10000, Zagreb, Croatia; E-mail:
neven.henigsberg@zg.t-com.hr.
102 N. Henigsberg / Pharmacotherapy Research in Posttraumatic Stress Disorder
approach, based on showing non-inferiority of the test drug over the drug with already
known efficacy was not used so far in published trials, probably because the large
sample sizes would be needed to reach appropriate statistical power.
2. Effect Size Estimation
Clinical trials are usually performed within a framework of hypothesis testing.

Assuming that a new treatment is more effective than a comparative one, researcher
would create the null hypothesis that the new treatment is not effective, and then will
try to reject it. An alternate hypothesis is then accepted, stating that the new treatment
is significantly better than the comparative one. Such an approach fits the purpose of a
particular trial, but observed level of statistical significance could not be usefully
compared between the different trials.
If a researcher would like to compare results from two different trials, both
involving comparable study design, an alternative approach of constructing confidence
intervals around a point estimate for a difference between active drug and placebo
could be used. That approach is appropriate only if the same primary parameters were
used in both studies. However, a number of outcome measures have been employed in
clinical trials in PTSD, making impossible direct comparison of primary endpoints.
The standardized mean difference is the effect size generally recommended in
clinical trials assessing treatment effects on outcomes measured on a different
continuous scales. Unlike significance tests, these indices are independent of sample
size. In general, effect size is measured as the standardized different between two
means, where pooled standard deviation is denominator. By standardizing the effect,
the effect size becomes dimensionless. Cohen[2] defined effect sizes as "small, d = .2,"
"medium, d = .5," and "large, d = .8". Generally, the larger the effect size, the greater is
the impact of an intervention.
In order to enable comparisons between different outcome measures used in PTSD
trials, effect size estimation is used in this paper to compare efficacy of different
medications wherever possible.
3. Medications Studied in PTSD
Review of scientific literature shown only 26 randomized placebo-controlled clinical

trials in PTSD. Active medication studied in these trials, duration of trials and number
of subjects included in them is displayed in Table 1. As could be noted, four drug
classes were investigated more extensively in PTSD: monoamine oxidase inhibitors
(MAOIs), tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors
(SSRIs) and serotonin-potentiating non-SSRIs.
Only two MAOIs were studied in randomized, controlled trials (RCTs): phenelzine
and brofaromine, the later being studied in considerably larger number of subjects. Of
the four placebo-controlled trials with MAOIs, there is one positive and one negative
phenelzine trial, and one partly positive and one largely negative brofaromine report.
Similarly with TCA trials, most MAOIs studies were performed with combat veterans
known to be treatment-refractory.
The SSRIs are the most studied drug class in PTSD, with the largest number of
placebo-controlled, double blind clinical trials, and with largest number of study
N. Henigsberg / Pharmacotherapy Research in Posttraumatic Stress Disorder 103
subjects enrolled in those trials. Sertraline and paroxetine have the largest databases
regarding placebo-controlled, double-blind clinical studies in PTSD, and these two
SSRIs are the only FDA-approved drugs for PTSD.
Table 1. Summary of randomized clinical trials in PTSD

Active Number of Duration of
Trial
Treatment Subjects Trial
Monoamine Oxidase Inhibitors
Shestatzky et al. (1988)[3] phenelzine 13 5 weeks
Kosten et al. (1991)[4] phenelzine 37 8 weeks
Katz et al. (1994)[5] brofaromine 68 14 weeks
Baker et al. (1995)[6] brofaromine 113 12 weeks
Tricyclic Antidepressants
Reist et al. (1989)[7] desipramine 18 4 weeks
Davidson et al. (1990)[8] amitriptyline 46 8 weeks
Kosten et al. (1991)[4] imipramine 41 8 weeks
Selective Serotonin Reuptake Inhibitors
van der Kolk et al. (1994)[9] fluoxetine 64 5 weeks
Connor et al. (1999)[10] fluoxetine 53 12 weeks
Hertzberg et al. (2000)[11] fluoxetine 12 12 weeks
Martenyi et al. (2002)[12] fluoxetine 301 12 weeks
Brady et al. (2000)[13] sertraline 187 12 weeks
Amital et al. (1999)[14] sertraline 51 10 weeks
Davidson et al. (2001)[15] sertraline 208 12 weeks
Zohar et al. (2002)[16] sertraline 42 10 weeks
sertraline,
Tucker et al. (2003)[17] 58 10 weeks
citalopram
Tucker et al. (2001)[18] paroxetine 307 12 weeks
Marshall et al. (2001)[19] paroxetine 551 12 weeks
Serotonin-Potentiating Non-SSRIs
Davis et al. (2004)[20] nefazodone 41 12 weeks
Davidson et al. (2003)[21] mirtazapine 29 8 weeks
Mood Stabilizers
Hertzberg et al. (1999)[22] lamotrigine 15 12 weeks
Antipsychotics
Butterfield et al. (2001)[23] olanzapine 15 10 weeks
Benzodiazepines
Braun et al. (1990)[24] alprazolam 16 5 weeks
Other
Kaplan et al. (1996)[25] inositol 13 4 weeks
Raskind et al. (2003)[26] prazosine 10 20 weeks
Heresco-Levy et al. (2002)[27] D-cycloserine 11
low-dose
Aerni et al. (2004)[28] 3 3 months
cortisol
Serotonin-potentiating non-SSRIs is the group of medications that predominantly

potentiates serotonin though a number of different mechanisms[29]. They may block
the reuptake of serotonin, but they are non-selective. Some block various post-synaptic
serotonergic and noradrenergic receptors, while others may block the reuptake of
norepinephrine to a lesser extent. Of that class, only nefazodone and mirtazapine were
studied, but both studies included low number of patients. Nefazodone primarily blocks
serotonin 5-HT2 post-synaptic receptors but also it moderately inhibits the pre-synaptic
reuptake of serotonin and norepinephrine, causing the diffuse stimulation of 5-HT
receptors, expect 5-HT2. Nefazodone posses potent anxiolytic properties. Mirtazapine
is an antagonist to 5-HT2 and 5-HT3 receptors, and is a potent antagonist of D2 –
autoreceptors, that results in potentiation of both norepinephrine and serotonin.
The use of anticonvulsants in treating PTSD arouse from the fact that some of the
symptoms belonging to the hyperarousal cluster, especially anger outbursts and
irritability, occur also in epilepsy and are effectively treated by anticonvulsants. It’s
potential use in PTSD is also along with a kindling model suggested to elucidate some
PTSD symptoms. Until now, only one RCT was performed with anticonvulsant
medication in a study by Hertzberg et al. The most promising finding of that study was
that 50% of subjects of the lamotrigine group versus 25% of the placebo group were
assessed responders.
A number of retrospective trials indicated a possible role of benzodiazepine
treatments in PTSD, but only one RCT was performed, failing to prove these
assumptions. Braun et al. performed a 5-week crossover design study, but no between-
group differences between alprazolam and placebo were observed in core PTSD
symptoms. As this study enrolled only seven subjects, it may miss the appropriate
power to show the effect. Still, although benzodiazepines may seem a logical choice for
the treatment, use of benzodiazepines in PTSD was not proven by RCTs. Since some
preventive studies performed with benzodiazepines shown aggravating effect of drugs,
instead of improvement, further research of benzodiazepines in RCT is certainly
indicated. The observed lack of benzodiazepines efficacy in PTSD is consistent with
neuroimaging findings of reduced benzodiazepine receptor binding in prefrontal cortex
in PTSD. This is along with the results of animal experiments evidencing that stress
downregulates benzodiazepine receptor binding in the frontal cortex and hippocampus.
Recently, neurobiological studies analyzed the role of dopamine in amygdala and
other limbic structures implicated in PTSD, proposing that dopaminergic transmission
could have a modulatory role in function of limbic system. Only olanzapine was tested
in PTSD in a placebo-controlled clinical trial. Olanzapine was also studied as an
adjunctive therapy in a double-blind controlled study. Stein et al. (2002) found that
olanzapine was associated with significantly reduced PTSD symptoms when used as an
adjunctive therapy for PTSD with comorbid depressive symptoms and sleep
disturbances that had not responded to an SSRI. The large effect size (1.07) was
observed in this study.
Adrenergic agents were also investigated in PTSD and reports are suggesting their
efficacy particularly in treating nightmares and hyperarousal symptoms.
Thus, although some medication classes are commonly used in clinical practice to
treat PTSD symptoms, their efficacy was still not confirmed by controlled clinical
trials. This particularly refers to benzodiazepines, anticonvulsants and antipsychotics.
No placebo-controlled trials were performed in pediatric or geriatric subjects.
4. Response Rates
Response rates in larger clinical trials, usually defined as 30% improvement on the
primary parameter, are displayed in Table 2. The most of drugs studied in larger PTSD
trials displayed proportion of responders ranging from 53% to 60%. Still, placebo
responders were also numerous, in range from 32% to 44%.
Interestingly to note, response rate in meta-analysis of psychotherapy trials was
comparable to the rate observed in medication trials: in trials using psychotherapy it
was 62% for psychotherapy and 38% for placebo.
5. Comparative Efficacy
It should be repeated that in majority of trials sample sizes were very small, which
could in some cases lead to uncertain estimation of the effect size. Still, the observed
effect size may be used as a rough indication of overall efficacy of the treatments.
As assessed by Stein et al. (2005) the overall effect size of psychopharmacological
treatment is 0.46. This estimation includes those studies that have used rating scales
based on DSM diagnostic criteria sufficiently different that a standardized mean
difference was determined. The effect size of such magnitude confirms the efficacy of
medication over placebo, but displays only near a moderate effect for the whole group.
Table 2. Response rates in major clinical trials in PTSD

Active Treatment Placebo
sertraline Davidson, 2001 60% 38%
sertraline Brady, 2000 53% 32%
fluoxetine Martenyi, 2002 59.9% 43.8%
paroxetine Tucker, 2001 60% 38%
paroxetine Marshall, 2001 62% (20 mg/day) 38%
58% (40 mg/day)
mirtazapine Davidson, 2003 65% 22%
nefazodone Hidalgo et al, 1999 46%
(meta-analysis of 6
trials)
lamotrigine Hertzberg, 1999 50% 25%
psychotherapy Sherman, 1998 62% 38%
Table 3. Effect sizes in placebo-controlled clinical trials in PTSD

Reference Active treatment Effect Size (active
treatment over
placebo)
Frank et al. (1988) imipramine[30] 0.25
Katz et al. (1994) brofaromine[31] 0.4
Kosten et al. (1991) phenelzine[32] 0.95
Shestatzky et al. (1988) phenelzine[32] -0.17
Reference Active treatment Effect Size (active

treatment over
placebo)
Davidson et al. (1990) amitryptiline[30] 0.64
Reist et al. (1989) desipramine[30] 0.05
Van der Kolk et al. (1994) fuoxetine[32] 0.77
Conner et al. (1999) fluoxetine[31] 0.91
Brady et al. (2000) sertraline[30] 0.3
Davidson et al. (2001) sertraline[30] 0.4
Marshall et al. (2001) paroxetine[30] 0.5
Davidson et al. (2003) mirtazapine[30] 0.49
Braun et al. (1990) alprazolam[32] 0.25
Despite earlier reports suggested that serotonin more specific agents are more
effective than other classes, the current evidence base of controlled trials is unable to
demonstrate superior efficacy or acceptability for any particular medication class[31],
and even the analysis of drop-out rates does not confirm superior tolerability of SSRIs
over other classes.
6. Duration of the Trial
The majority of performed clinical trials lasted from 8 to 12 weeks. The appropriate
duration of the trial in PTSD is still doubtful. Despite duration of trial of 2-3 months is
a kind of a standard in clinical trials in psychiatry, there is some evidence that longer
duration may be more appropriate in clinical trials in PTSD. In a 24-weeks study by
Londborg et al.[33] which was continuation of initial 12-weeks of sertraline treatment ,
it was found that the huge majority of patients (92%) who had responded during an
initial 12 weeks of treatment continued to respond in additional 6 months. On the other
side, over the half (54%) of the patients who had not responded in initial 12 weeks of
sertraline treatment were responders in the prolonged phase. It is of particular interest
that delayed treatment response was associated with a higher severity of baseline PTSD
symptoms.
Although duration of majority of trials in psychiatry is conventionally set to 12
weeks, clinical trials in PTSD may require the acute phase of treatment to go beyond
initial 12 weeks of treatment, especially if the trial includes more severely ill patients.
7. Efficacy in Relation to Baseline or Symptom Characteristics
It difficult to find any clinical trial in PTSD showing balanced effect on all cluster of
symptoms.
The imipramine study by Kosten et al. displayed decrease of intrusive symptoms
relative to placebo, but no imipramine benefit was observed for avoidance symptoms.
The same was found in a study with phenelzine.
The largest trial with fluoxetine shown a significantly greater response to
fluoxetine versus placebo, significantly greater response on the intrusive cluster, and
the hyperarousal cluster, but only a trend for the avoidance cluster. Finding of interest
is also that having combat-related trauma and being young were associated with
significantly greater improvements. As with SSRIs, in treatment with novel
antidepressants the response was better in patients who experienced civilian trauma.
Sertraline was evaluated by large trial of Brady et al. in 187 patients. Avoidance,
numbing and hyperarousal clusters shown significant improvement in a 12 week-
period, but re-experiencing cluster did not. Post hoc analyses in sertraline trial
displayed a significant difference in women. However, subsequent analyses did not
confirm a gender effect.
Better effect of medication on intrusion than on avoidance symptoms was also
displayed in meta-analysis by Stein et al. (2005): summary statistics of trials show that
weighted mean difference for intrusion on the Impact of Events Scale was -3.81, while
for avoidance cluster it was -3.31.
Therefore, all major clinical trials in PTSD displayed some differences in relation
to baseline characteristics of study population or differences in efficacy by symptom
clusters.
Antidepressants have the largest database in relation to randomized clinical trials
in PTSD. Despite medications belonging to that class are primarily aimed to treat
depressive symptoms, meta analysis of RCTs shown that the effect size in treating
anxiety symptoms present in PTSD patients was considerably higher than the effect
size on treating depressive symptoms. This may suggest that depressive symptoms
within PTSD are more difficult to treat or are driven by different mechanism[34].
Southwick et al. (1994) in their meta-analysis of trials where patients were treated with
antidepressants for comorbid PTSD and major depressive disorder had the same
assumption and have indicated that PTSD symptoms responded independently of the
antidepressant effect.
With respect to a substantial proportion of patients who do not respond to
pharmacological treatment, and considering assumptions that phenomenology of PTSD
is heterogeneous, it remains essential to investigate if certain treatments are more
effective for particular symptom sets or for some subgroup of PTSD patients.
Comorbid symptoms
Studies: sertraline,
amitriptyline, imipramine,
phenelzine
Figure 1. Effect size on global PTSD symptoms, depression and anxiety (data from Stein, 2005)
8. Prevention Studies
Studies aimed to prevent the PTSD have been performed with different drug classes,
including antidepressants and benzodiazepines.
Trial using imipramine and chloral hydrate resulted in greater reduction in acute
stress disorder symptoms in a group receiving imipramine. Promising results were also
observed in trial using morphine in burns and hydrocortisone in septic shock.
Mellman et al. found that benzodiazepines were not effective in preventing PTSD.
Furthermore, use of benzodiazepines could be even detrimental, as they found PTSD
present in 69% of those treated with benzodiazepines, and only 15% in a control group.
In addition, depression later developed in 54% of benzodiazepine treated, whereas in a
control group was not present.
9. Summary
Relatively few placebo-controlled, randomized clinical trials were performed in PTSD.

The majority of them involved very small number of subjects.
Recent decade acknowledged the heterogeneity and complexity of clinical features
observed in PTSD. There is growing evidence that certain medications are effective in
acute treatment of PTSD. Clinical research, using new compounds, as well as those
already marketed is clearly warranted. In past clinical trials antidepressants appeared
with the best overall efficacy for the treatment of PTSD, although their effect may not
be present in all symptom clusters. Benzodiazepines were not proven as effective to
treat core PTSD symptoms, so far. Mood stabilizers show some promise, especially for
the treatment of impulsivity and mood fluctuation. There is still limited data
demonstrating efficacy of the atypical antipsychotics in PTSD.
Further clinical research is warranted, using new compounds, as well as those
already marketed for other indications.
Table 4. Main results of prevention studies

Trial Reference Active treatment Duration Main result
Robert et al imipramine vs chloral 2 weeks greater reduction in ASD
(1999)[35] hydrate in ASD symptoms in imipramine
treatment
Pitman et al propranolol vs 10 days no significant difference in
(2002)[36] placebo PTSD symptoms 1 and 3
months posttrauma
Saxe et al morphine (in burns) significant effect on reduction
(2001)[37] vs other medication on PTSD symptoms at 6
months follow-up
Mellman et al benzodiazepines short term no protection from developing
(2002)[38] full PTSD criteria
Gelpin et al benzodiazepines prolonged higher rates of PTSD
(1996)[39]
Schelling et al hydrocortisone in short term lower incidence of PTSD after
(2001)[40] septic shock 2.5 years
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Canadian Forces Approach to the

Identification and Management of
Operational Stress Injuries
Col Randy Boddam CD, BSc, MD, FRCPC1
Abstract. Military Operations expose personnel to stresses not normally experienced in

garrison or in civilian life. The consequence of such exposure is the development of
Operational Stress Injuries. The Canadian Forces has developed and continues to
improve upon a phased response to assist its members in better being able to respond to
these stresses beginning at recruitment and extending throughout the military career.
This process is summarized. As a final point, early intervention, a subject of
considerable discussion in the literature is addressed through a proposed model aimed at
promoting resiliency and early treatment where needed.
Keywords. posttraumatic stress disorder, stress, early intervention, screening, military

psychiatry
Introduction
Military operations expose Canadian Forces (CF) personnel to stressors and experiences
which may lead to mental illnesses or other forms of suffering. While Posttraumatic Stress
Disorder (PTSD) is the first illness that usually comes to mind when thinking about
psychological suffering related to operations, the range of potential suffering is much
broader. In fact, the Operational Stress Injury Social Support (OSISS) programme has
coined the term “Operational Stress Injury” (OSI) to cover this range of suffering. It has
been defined by OSISS as, “An operational stress injury (OSI) is any persistent
psychological difficulty resulting from operational duties performed by a Canadian Forces
member.”[1]
The CF has taken a staged and sequential approach to the management of OSI’s.
Management of OSI’s begins with recruitment and, with the help of our colleagues at
Veterans Affairs Canada (VAC) extends beyond active duty. This paper will outline the
steps undertaken by the CF at differing stages of the service career to address OSI’s. It will
then focus upon the work of the Operational Trauma and Stress Support Centres (OTSSC’s)
as they work towards the assessment and treatment of OSI’s. Finally, the paper will
1
Corresponding Author: Col R Boddam, Rm 406, Health Care Centre, 1745 Alta Vista Drive, Ottawa, Ontario,
Canada, K1A 0K6. Email to:Boddam.R@forces.gc.ca
112 R. Boddam / Canadian Forces Approach to the Identiﬁcation and Management of OSI
conclude with on overview of a proposed model for early intervention for CF members
exposed to potentially traumatic events (PTE’s).
1. Recruitment
Not all people are created equal in terms of their potential vulnerability to operational
stress. Stating that, however, there are very few absolute contraindications, from a
psychiatric perspective, to enrolment in the military. Selection of candidates for service in
the CF is a difficult task. On the one hand there is the need of the CF for personnel. On the
other hand the Canadian Charter of Rights and Freedoms protects Canadian citizens from
undue discrimination. This challenge is further compounded by a relative lack of empiric
evidence concerning longer term psychological fitness.
Clearly, psychotic disorders and recurrent mood disorders represent one class of illness
for which operations pose a risk. That risk is, of course, bidirectional; operational stress
and exigencies may predispose the individual for a recurrence of their illness and their
illness may recur during deployment placing themselves and other members of their unit at
risk. A person presenting with such a medical history can be easily screened from
enrolment. What about a person with a past history of, say, sexual abuse? Literature and
experience has demonstrated that such a person is at increased risk of suffering PTSD if
exposed to a PTE. [2-4] The reality, however, is that not all people with such a history will
develop PTSD if operationally exposed. Protective or resiliency factors, as yet hard to
measure, may also mitigate the effects of traumatic stress. Further, the disorder can occur
in the absence of such a history. Accordingly, and in the absence of a sensitive and specific
screening tool with significant positive predictive power some people will be recruited who
may carry a relatively increased risk of developing an OSI. The recruitment process can be
seen as only a very course filter from which further work to mitigate PTE’s and minimize
the risk of OSI’s.
Basic training is the next step following recruitment and, similarly, it is the site of the
next focus of intervention. Although basic training is configured, by its very nature, as a
vehicle by which recruits are exposed to stress and learn some basic mechanisms by which
to handle it, other activities can be undertaken. Recently and as part of career long
educational programme developed by OSISS recruits have been exposed to a half day of
training concerning the history, nature and presentation of OSI’s including education about
what to do in the face of suffering or observing a colleague suffering with an OSI. Similar
training is currently being developed under the supervision of the Canadian Defence
Academy and with the oversight of the CF’s OSI Steering Committee (OSI SC) for
inclusion at other developmental phases of a service member’s career. Such training targets
officers and non-commissioned members alike.
R. Boddam / Canadian Forces Approach to the Identiﬁcation and Management of OSI 113
2. Baseline Care
Recently, the CF undertook an epidemiologic survey, conducted by Statistics Canada (the

national statistical organization) and in concert with Statistics Canada’s Canadian
Community Health Survey (CCHS Ver 1.2). This survey, using structured interviews and
the Composite International Diagnostic Interview developed by Kessler et al allowed the
CF to look, for the first time in its history, at the level of psychopathology in its members.
[5,6] Although one of the reasons for doing so was to better understand what the health care
service requirements of its members are, another advantage of this survey was that it
permitted the putting of a “real face” on the nature and extent of mental illness in the CF.
1 year and lifetime prevalence figures for members of the Regular Force are summarized in
Table 1.[7]
Table 1. CIDI-derived 1 yr and Lifetime prevalence figures for six disorders studied by the CCHS Ver 1.2
epidemiologic survey. Prevalence figures are presented as percentages of the population. MDD is Major
Depressive Disorder, GAD is Generalized Anxiety Disorder. Diagnostic Criteria are derived from the Diagnositce
and Statistical Manual for Mental Disorders, Fourth Edition
Disorder 1 yr lifetime
MDD 7.6 16.2
Alcoholism 4.0 8.3
Social Phobia 3.6 8.7
PTSD 2.7 7.2
Panic Disorder 2.2 5.0
GAD 1.8 4.7
It is important to note that when compared to age and sex-matched Canadian civilians
that the prevalence values of MDD and panic disorder are significantly increased relative to
the civilian population.
Two of the listed disorders were not measured in the Canadian civilian population.
When compared to other published, epidemiologic surveys both PTSD and GAD appear to
be as prevalent as found in civilian populations.
Another relevant finding of this study was the correlation between number of deployments
and lifetime burden of suffering with PTSD as shown in Table 2.[7] These data suggest that
deployment, not surprisingly, is a risk factor for the development of PTSD and the more
often that a CF member deploys, the higher the likelihood of having developed this
disorder.
Table 2. Prevalence of PTSD as a percentage of the population expressed as a function of the number of
deployments (Depl) that CF members had engaged in. RegF refers to members of the Regular Force whereas ResF
refers to reservist members. The Reserve results, due to relatively small numbers having deployed more than twice
and to maintain statistical power, have been collapsed into either a having deployed or not having deployed
category. The Survey was conducted in 2002.
last year lifetime
# Depl RegF ResF RegF ResF

none 1.7 0.9 5.9 4.2
1-2 2.7 2.4 6.7 7.2
3+ 4.7 10.3
To address the clinical needs of CF personnel, revitalization and restructuring of health

care have been undertaken. This restructuring, under the supervision of Project Rx 2000,
aims to provide health care to at least that available to the average Canadian, regardless of
where the CF member is employed.[8] Mental health care delivery is similarly being
restructured to improve access to and delivery of mental health clinical services. At the
same time, a new directorate, Force Health Protection, has been established. The healthy
lifestyle cell of this directorate is engaged in disseminating activities and programmes that
promote resiliency. One such programme is “Take Charge!”, a skill building programme
aimed at helping CF members improve their ability to manage stress. Although yet to be
seen, it is anticipated that these combined activities will both lower the point prevalence of
mental illness (thereby reducing vulnerability) while enhancing the resiliency of CF
members when confronted with PTE’s.
3. Deployment
As deployment poses a risk for the development of an OSI, it seems reasonable that this
time should be used to make a more focussed effort to prevent the disorder. There are,
however, distinct phases that a serving member transits during the deployment cycle.
These phases derive from the time frame the CF member is in relative to their deployment
and are called, predeployment phase, deployment phase, and postdeployment phase.
When a unit or units are tasked to undertake a mission one of the first activities is an
administrative review of the personnel selected to go. This review (part of the Departure
Assistance Group or DAG) assesses whether a CF member is “fit” to deploy. A relatively
recent addition to this process is a psychological screen consisting of the Short Form 36, the
PRIME-MD and the PCL followed by an interview with a mental health care provider and
subsequent referral as needed. This activity has demonstrated a relatively low yield,
unfortunately, raising the question of its value as a predeployment activity. Other activities
during the predeployment phase are aimed at enhancing resiliency. Consistent with the
principles of Stress Inoculation Training, realistic mission training forms one means by
which resiliency is developed.[9] Perceived support, or the ability of the service member to
feel that their peers and work environment is there to support them, is another. Undergoing
predeployment training as formed groups is an area that leadership attempts to assure so as
to bring about that important group cohesion. Educational briefs are also provided about
stress, OSI’s and means by which PTE’s can be managed. A further predeployment activity
involves the training of peer debriefers. It is believed that these individuals are given extra
skills which enhance the sense of support that the unit provides to a member who
experiences a PTE.
When a service member is deployed they are, depending upon the size of the
deployment, accompanied by a uniformed mental health care provider. That person is
there, in addition to the routine medical staff, to facilitate early interventions for those who
may develop emotional distress. They also function to facilitate repatriation of individuals
for whom that is the only response to their level of suffering. MH care providers are
encouraged, as much as possible, to integrate and get to know the units that they are
supporting. In this way the threshold of presentation is hoped to be lowered so that care can
be delivered as quickly as possible. In this way the “I” of the PIE acronym (Proximity,
Immediacy and Expectancy) developed for the management of Combat Stress Reaction is
respected. Although the PIE approach was developed for the management of CSR it is
thought to have general relevance to other mental illnesses and OSI’s. More prominent in
the past, Critical Incident Stress Management techniques may still be employed.
Psychological Debriefings may still be provided but are no longer considered to be
mandatory and need to be requested by the unit in which exposure to a PTE/critical incident
has occurred.
Another activity that happens during the deployment is the provision of reintegration
briefings. These briefings are aimed at providing for the service member education about
the stresses and strains they will face as they return to Canada after having been away from
home. Families go on and life goes on but when a family member has not been a part of it
he or she may not be in tune with role changes and history that the family has experienced.
Reinsertion into the family can lead to challenges and difficulties. If the mission
commander suspects that the degree of change is substantial, such as moving from a war-
fighting environment to downtown Canada, then “third location decompression” can be
undertaken. This activity was employed when members of the 3rd Battalion, The Princess
Patricia’s Canadian Light Infantry came home from Kandahar in 2002 and was generally
felt to be a helpful activity. That mission was perceived as a war fighting operation and the
Commanding Officer felt it important that a suitable period of time be given to his unit to
make the cognitive shift from War to Peace. Objective data assessing the preventive value
of these activities does not, regrettable exist although consumer satisfaction is reported as
high.
Given that deployments are associated with a greater risk for the development of PTSD
the next challenge is to try to find cases so that they can be addressed early, and hopefully
at a time in the clinical trajectory that will reduce longer term disability and suffering. In
addition to a basic medical screen when CF members return home from their mission there
is a post-deployment questionnaire and interview (exactly like the predeployment
interview) aimed at case finding. This activity has met with high acceptance and has led to
the referral to appropriate mental health care services of members who hadn’t otherwise
presented for care. Accordingly it is believed to be a clinically valuable tool. In addition to
this active case finding, the usual system of mental health care delivery continues to support
CF members should they feel the need for care.
4. Operational Trauma and Stress Support Centres
In 1995 and in response to Senate committee recommendations the Psychiatry Department

of National Defence Medical Centre created the PTSD programme. Patterned on a Day
Hospital model it offered four weeks of care to members who had been diagnosed as
suffering with PTSD. This programme underwent significant revision in 1997 and by 1998
senior CF leadership wanted PTSD clinics “across the country” to deal with the perceived
need of peacekeepers who were returning from increasingly dangerous peacekeeping
missions. Recognizing that PTSD is one of several OSI’s these clinics were established but
their mandate was broadened to deal with the range of OSI’s. They were to be “Centre’s of
Excellence” maintaining a cutting edge knowledge of various OSI’s, providing three basic
services, in order of priority: Clinical Assessment and Consultation, Clinical Educative
Outreach to health care providers caring for CF members who may have an OSI, and
limited treatment. The doors were opened in 1999 and since that time they have seen many
patients.[10] An early problem was a relative shortcoming in the civilian clinical
community upon which the OTSSC’s were depending for access to individual therapy—
clinicians specializing in trauma work were in short supply. The OTSSC’s responded
individually to attempt to address this need resulting in drifting away from the central
mission. Accordingly, the mental health restructuring team also took on the task of
standardizing clinical care in the OTSSC’s.
The goal of this standardization work was to build upon what made clinical sense, that
is, comprehensive assessment and care with interdisciplinary input and case review. As an
example of this interdisciplinary input a working group was held in June 2001 to
standardize the assessment protocol to be used by all of the OTSSC’s. This working group
included membership from each of the OTSSC’s as well as the VAC Ste Anne’s Hospital
(Ste Anne de Bellevue, near Montreal, Quebec). This latter Hospital was this working
group is demonstrated in figure 1.
Figure 1. The flowchart here represents the assessment model that was developed in June 2001. The model has
changed slightly since development (walk-ins, for example are no longer accepted directly) but the principle
elements (initial diagnostic assessment followed by an interdisciplinary case conference followed be other
assessments followed by a final case conference to develop a treatment plan) remain in place.
Since that time other work has been undertaken with an aim of ensuring that patients can
depend upon the same manner of assessment and care, no matter where their duty takes
them. There is a treatment standardization committee that exists to review the literature and
ensure that best practices are employed in the care of OTSSC patients.
5. Ongoing Improvement
Practices are informed by experience and research. What was considered fashionable and
sound a few decades ago can become inefficient, inappropriate or potentially harmful. The
CF is committed to ongoing review of its healthcare practices. An example of this is found
in the approach to early intervention in the face of a PTE. In the late 1980’s and early
1990’s there was considerable interest in what was then called critical incident stress
debriefing. In fact, in Canada a specific policy was developed to ensure that CF members
who had sustained a critical incident would undergo this process. The hope was that it
would prevent the development of PTSD. For many clinicians the model made sense.
Experience, scientific review and discussion with peers and colleagues started to show,
however, that Critical Incident Stress Management (CISM) did not have the preventive
effects that we hoped it might have. [11] Alternatively, the CISM process did provide the
opportunity to intervene fulfilling a need commanders have to support their personnel in
difficult times. Participants also reported that they found the process to be satisfying. The
challenge is then to determine if there is a technique or intervention (or series of
interventions) that will provide what CISM was hoped to.
Military personnel engage in inherently stressful tasks. Providing mechanisms to
enhance their resiliency in such circumstances becomes a “force multiplier”. Literature
suggests that perceived support is an important predictor of posttraumatic distress. History
indicates that unit cohesion and leadership are also important mitigators of stressful
operational environments. Using these facts a new model has been proposed and is
currently being reviewed for potential implementation in the CF. The model is shown in
Figure 2.
As shown in Figure 2, stress management is seen as a process that starts before
exposure to any PTE. The Directorate of Force Health Protection (FHP) of the CF Health
Services is responsible for the development and deployment of programmes that prevent
adverse health outcomes. One such programme, Healthy Lifestyles, has as one of its
components, stress management. Techniques to manage stressful events are taught and
skills developed by participants. It is anticipated that CF members will use these skills as
they experience PTE’s. It is hoped that through realistic training, a form of stress
inoculation, CF members will have ample opportunity to put these skills into practice.
Mental health care and mental illness both carry a stigma in both civilian and military
cultures in Canada. Regrettable (and the focus of concerted efforts through a number of
avenues) but this reality also has to be taken into consideration in the development of a
response to a PTE. Exposure to a PTE carries with it the risk of the development of a stress
injury such as PTSD. Earlier treatment creates a better prognosis. Accordingly, a
successful early intervention programme needs to tackle the stigmata that present a barrier
to presentation for necessary treatment. One way to accomplish this is to build a
constructive and positive relationship between health care providers and the population that
they serve. Uniformed mental health care providers will build this relationship by
participating in training and other experiences with units with which they will form an
habitual association. They will also be involved in periodic teaching and other such
activities. It is hoped that these activities will make it easier for people who need care to
present.
Educ ation ab out

care availab ility
Unit and warni ng signs
Context/Culture Unit
E motional support
Red uc e 2ar y trauma
Associated MH
B as ic H um an N eeds Care Provider
Ongoi ng follo w-u p /
monitori ng Peer /
F ac ilitate refer ral Leadership /
Disaster
CF Member Chain of
Critical
Command
Incident Fac ilitate
Refer ral
Early
Development
Force of Symptoms F ac ilitate
Referral
Health
Protection
Late Facilitate
Stress Mgmt / Refer ral
Health y Development
Lifestyle
of Symptoms
Problematic lifestyle /
personality changes
Life Goes On
Figure 2. Proposed model and flow for early intervention for members of the Canadian Forces. The model relies
upon the development of a supportive unit, preparation through learning stress management techniques and
supportive leadership. At any stage after exposure to a PTE leadership or peers can facilitate a referral to mental
health care providers. This referral process has been facilitated by the development of a positive and constructive
relationship with uniformed mental health care providers established prior to PTE exposure.
It is expected that two factors will be important stress mitigators at the time of
exposure to a PTE. Unit cohesion and stress management techniques should reduce the
experience of posttraumatic distress. At the same time leadership can intervene possibly by
attending to basic needs, reducing secondary trauma, reinforcing support and stress
management and remaining vigilant for persons experiencing excessive distress or
dysfunction. At any time thereafter this latter observation can promote earlier presentation
for professional assessment or definitive treatment as is appropriate.
6. Summary
Military operations carry the risk of psychological injury for those members who deploy. A
number of points in a CF member’s career, from enrolment to retirement, have been
targeted to enhance the resiliency or remove potential barriers for those who may need
mental health care. This process is not static; as data and experience demonstrate the need
for improvement interventions can evolve to best ensure that the fewest CF members
possible will be left with the scar of an Operational Stress Injury.
References
[1] www.osiss.ca
[2] Peleikis, D.E. et al. The relative influence of childhood sexual abuse and other family background risk
factors on adult adversities for female outpatients treated for anxiety disorders and depression. Child Abuse
Negl. 2004. 28(1): 61-76.
[3] Thompson, K.M. et al. Psychopathology and sexual trauma in childhood and adulthood. J Trauma Stress.
2003. 16(1): 35-8.
[4] Johnson, DM et al. Factors predicting PTSD, depression and dissociative severity in female treatment-
seeking childhood sexual abuse survivors. Child Abuse Negl. 2001. 25(1):179-98.
[5] Kessler, RC et al. Clinical calibration of DSM-IV diagnoses in the world mental health version of the World
Health Organization (WHO) Composite International Diagnostic Interview (WMHCIDI). Int J Methods
Psychiatr Res2004. 13(2): 122-139.
[6] Kessler, RC and TB Ustun. The World Mental Health Survey Initiative version of the World Health
Organization (WHO) Composite International Diagnostic Interview. Int J Methods Psychiatr Res2004. 13(2):
93-121.
[7] www.forces.gc.ca/health/information/op_health/stats_can/engraph/StatsCan_home_e.asp
[8] www.forces.gc.ca/health/news_pubs/engraph/hcreform_home_e.asp?Lev1=4&Lev2=6
[9] Saunders, T et al. The effect of stress inoculation on anxiety and performance. J Occup Health Psychol 1996.
1(2):170-186.
[10] www.forces.gc.ca/health/services/engraph/otssc_home_e.asp?Lev1=1&Lev2=2
[11] Rose S et al. Psychological debriefing from preventing post traumatic stress disorder (PTSD) The Cochrane
Database of Systematic Reviews 2002, Issue 2. Art. No.: CD000560. DOI: 10.1002/14651858.CD000560.
M.J. Roy (Ed.)
IOS Press, 2006
“Stress and Psychological Support in

Modern Military Operations”
NATO Human Factors and Medicine
HFM081 Research Task Group RTG020
History, Status, Objectives and

Achievements to date
Jamie G H HACKER HUGHES, PsychDa1, Amy ADLER, PhDb, Vlastimil TICHY,
MD, Lt Colc, & Yves CUVELIER, Lt Kold
a
ACDMH, King’s College London, UK
b
US Army Medical Research Unit – Europe
cCentral Military Hospital, Prague
d
Chair, RTG-020
Abstract. The NATO Human Factors and Medicine Panel (HFM081) Research
Task Group (RTG) 020 provides military mental health professionals from 19
nations with an opportunity to work together to develop and exchange information
related to guidelines for military leaders on stress and psychological support in
order to enhance effectiveness in modern military operations. The RTG, initially
organized in 2002, was approved for full status in 2003. Bi-annual meetings
facilitate the work of the RTG members and have resulted in the completion of
reports on best practices, unit climate assessments, clinical tools, education and
training requirements for military mental health professionals and education and
training for military members on mental health issues. The RTG has also produced
a draft series of guidelines for mental health support before, during and after
military operations, which is currently under review by operational commanders
and military mental health professionals in each participating nation. By 2006, the
RTG’s goal is to complete a Military Leaders’ Survey on perceived mental health
training and support needs across the deployment cycle and to conduct a NATO
HFM (Human Factors and Medicine) symposium. Information from feedback on
the draft report, the survey and symposium will be integrated into a final series of
guidelines, also to be promoted as a lecture series, which can be adapted for use as
a NATO standard for mental health support on modern military operations.
Keywords. Stress, psychological support, military operations
1
Corresponding Author: Jamie Hacker Huges. ACDMH, King’s College London, Weston Education Centre,
10 Cutcombe Road, London, Telephone: ++44 (0) 207 848 5144 Fax: ++44 (0) 207 848 5408 ; Email:
j.hacker-hughes@iop.kcl.ac.uk
122 J.G.H. Hacker Hughes et al. / Stress and Psychological Support in Modern Military Operations
Introduction
NATO RTG 020 is an international group of military mental health professionals from
NATO or PfP (Partnership for Peace) nations whose objective is to develop information
and practical guidelines for military leaders on stress and psychological support in
order to enhance effectiveness in modern military operations. This RTG is a time-
limited working group with specific objectives. The development of the RTG, the
work that has been produced to-date, and the timeline for completing the group’s
objectives are reviewed here.
1. Formation of RTG 020
In 2002, an Exploratory Team, ET016, was established by NATO’s Research and

Technology Organization (RTO) and the Human Factors and Medicine Panel (HFM) to
consider the topics of stress and psychological support in modern military operations
within the context of NATO and PfP. (Information on RTO and HFM can be found at:
RTO: http://www.nato.int/docu/handbook/2001/hb141201.htm and RTA:http://www.
rta.nato.int).
ET016 first met in Brussels, Belgium, from 24-26 April 2002. Fourteen delegates
attended from nine nations (Austria, Belgium, Canada, France, Germany, Luxemburg,
Sweden, the Netherlands and United Kingdom). At the second ET meeting in Gosport,
UK, from 11-13 October 2002, fourteen delegates from ten countries attended, with the
nine original countries having now been joined by Croatia.
Following this second meeting, the RTB (Research and Technology Board)
approved HFM-081 RTG-020 - Stress and Psychological Support in Modern Military
Operations (S&PSiMMO) as an official RTO activity with any participant to this Task
Group (TG), from NATO, PfP or any other nation sponsored by a member-nation,
requiring to be officially nominated by their National Coordinator with a security
clearance being sent to RTO. An HFM-081/RTG-020 initialized forum was instituted
for all communication via www.rta.nato.int allowing the group to have all files in one
central place and allowing the Group to upload and review documents and inform all
members by e-mail.
2. RTG 020 Meetings
After RTG 020 was approved by HFM, bi-annual meetings were conducted in order to
facilitate the exchange of information, clarification of group objectives, and the
delivery of a series of products. These meetings provide an explicit framework for
communication that occurs throughout the year among representatives in the RTG.
Sub-groups addressing the group’s goals communicate between meetings via a list-
server, established especially for the purpose, and results are then presented for the
review of the entire membership. These meetings are rotated across member nations.
Thus far, there have been five meetings held with three more meetings planned before
the end of the RTG’s period of activity:
J.G.H. Hacker Hughes et al. / Stress and Psychological Support in Modern Military Operations 123
• The first meeting of HFM 081 RTG 020 “Stress and Psychological Support in
Modern Military Operations” took place in Paris (France) from 28 to 30 April
2003. A considerable enlargement of the group was achieved with 25
delegates attending from 17 nations including, for the first time, Czech
Republic, Denmark, Lithuania, Slovakia, Romania, Spain and Sweden.
• The second meeting of RTG-020 was held in the German Air Force Institute
of Aviation Medicine (Division VI – Aviation Psychology) in
Furstenfeldbruck (Germany) from 17-19 September 2003. 22 members from
14 nations attended this meeting.
• The third meeting of the RTG was held in Split (Croatia) between 21-23 April
2004. 28 team members from 17 different countries participated in the
meeting.
• The fourth meeting of the Group was held in Bratislava (Slovakia) between 05
and 08 October 2004. 25 team members from 16 different countries
participated.
• The fifth meeting of the working group was held in Quebec City (Canada)
from 12 to 15 April 2005. 25 members from 15 countries were present.
• Future meetings are planned for the fall of 2005 (in Kaunas, Lithuania), the
spring of 2006 (in Brussels, Belgium), and the fall of 2006 (in Bucharest,
Romania).
3. Participating Nations and Membership
At the time of writing the Group consists of over 30 members from 20 nations: 17
NATO countries - Belgium*, Bulgaria, Canada, Czech Republic, Denmark, France,
Germany, Hungary, Lithuania, Luxemburg, The Netherlands, Romania, Slovakia,
Spain, UK and USA and 3 PfP countries – Austria, Croatia and Sweden. The goal is to
establish a point of contact for all remaining NATO nations. The Chair is Lt Col Yves
Cuvelier (Belgium). The members are all military or civilian clinical and industrial /
organizational or occupational psychologists, psychiatrists, sociologists and social
workers.
4. Achievements
So far the Group has produced reports based on an exchange of information among
member countries. These include reports on best practices, unit climate assessments,
clinical tools (for assessment and intervention with individuals or groups before, during
and after operations) and education and training for service personnel on mental health
issues.
4.1 Draft Guidelines
The Group has also produced a report which describes fundamental areas of agreement
for psychological support on modern military operations (the “Interim Report”). The
report is organized by deployment phase: before deployment, during deployment, and
after deployment. The appendices to this report include the results of the information
exchange.
The fundamental areas of agreement which are addressed in the report include:
• Assessing the risks for psychological stress across operations
• Psychological preparation before deployment
• Psychological assessment before deployment
• Psychological support during deployment
• Psychological support after deployment
• Psychological support for families
• Practical organization of psychological support
The fundamental premise underlying the interim report is that the success and
effectiveness of psychological support requires two things. Firstly, it is the individual
responsibility of service members to monitor their own mental health and to seek
assistance when needed. Just as military personnel are accountable for their physical
fitness; military personnel are accountable for their individual psychological fitness.
Military personnel should prioritize their psychological health, as it is a critical
component of the overall mission fitness of their organization. Secondly, it is the
military’s responsibility to provide psychological support and create and facilitate
access to mental health services.
Individual mental health is critical for the readiness and performance of military
units and has the potential to enhance (or detract from) the mission fitness of the
organization as a whole. Thus, the recommendations provided in the Interim Report
involve guidelines for supporting the mental health of service members across the
deployment cycle. By their very nature, these recommendations are global statements
based on areas of agreement - despite national differences in approaches and
assumptions. A review of research conducted by the Group showed a paucity of
relevant research in many areas and therefore some of the recommendations are based
on consensus agreement by Team Members on what constitutes best practice. The
Interim Report describes what some countries are already doing to support mental
health of service members and provides a framework for countries just beginning to
address these issues.
Several different issues are addressed in the guidelines provided by the Interim
Report. For example, in terms of pre-deployment issues, the Group agreed that the
purpose of psychological support, and details of how it may be accessed, should be
addressed during pre-deployment training and informational briefings. Such training
should address such questions as: (1) What can an individual or unit expect on a
deployment? (2) What healthy coping tools are at the unit or individual’s disposal? And
(3) How can individuals or units access outside help?
Guidelines for mental health support during deployment are also addressed in the
Interim Report. For example, the Group agreed that the military should conduct
continuous monitoring of personnel to detect adverse reactions early, by formal or
informal assessment by peers, leadership, and/or recognized psychological support
professionals. It was also recommended that the military should consider unit-level
monitoring to detect adverse reactions to deployment-related stress and that Military
Leaders should have access to the necessary tools in order to perform psychological
monitoring of their troops.
The final section of the Interim Report addresses guidelines for mental health
support after deployment. For example, it was agreed upon by the Group’s member
nations that a structured homecoming and reintegration program should be provided for
service personnel and their families. The program should be designed to ease the
process of transition to family, work, and social life following a deployment. Military
Leaders should consider providing long term support in terms of telephone support
services and medical services. The Group’s Interim Report also contains an
acknowledgement that there continues to be a need to research long term effects of
deployment.
4.2 Feedback on Interim Report
The Interim Report and the areas of agreement identified in the draft document are now
being reviewed by member nations. Feedback from operational leaders, policy makers,
and mental health professionals is now being sought in each country. This feedback
will be used to revise the guidelines for mental health support on modern military
operations provided in the report.
4.3 Military Leaders’ Survey
In addition, a Military Leaders’ Survey has been designed and is currently being
administered by members of the RTG. The goal of the survey is to conduct a needs
assessment from the perspective of military operational leaders on psychological
support before, during and after military operations. Sample areas addressed in the
survey include (1) Is the training they receive on mental health support of subordinates
adequate to their needs? (2) What kind of training do operational leaders want in
handling subordinates’ psychological stress? These questions are to be administered
either as a survey or a semi-structured interview. Although not intended to provide a
scientific sampling of operational leaders across RTG nations, the Military Leaders’
Survey is designed to provide feedback from military leaders across a range of ranks,
operational experience, and national backgrounds. The common themes identified by
the survey will serve as a basis which can inform that final draft of the Group’s
guidelines for mental health support on military operations.
4.4 HFM Symposium
Another source of information that will be used to develop the final report and series of
guidelines is a NATO symposium entitled, “Human dimensions in military operations:
Military leaders’ strategies for addressing stress and psychological support”. This
symposium, sponsored by RTG 020 as a joint initiative with the NATO Committee on
Medical Services Military Psychiatry Working Group (the COMEDS MP WG , will be
held in Brussels (Belgium) from 24 to 26 April 2006. The goal behind the symposium
is to provide a venue for exchange between military mental health professionals and
military leaders. Various tracks will be offered, including one for Junior Leaders.
The six primary areas or tracks basically parallel the objectives of the Interim
Report topics:
• Assessing, building and maintaining unit morale
• Assessing individual mission fitness
• Psychological preparation for military operations
• Families and military operations

• Incident handling, psychological first aid and early interventions.
• The psychological contract (and significance in terms of retention issues)
4.5 Final Report
Feedback on the Interim Report, results obtained from the Military Leaders’ Survey,
and information from the workshops held as part of the HFM Symposium will be
integrated into the development of the final report from RTG 020. This final report will
be adapted so that it may be suitable for use as a NATO standard for mental health
support on modern military operations. The report will be made available on the
internet and also as a CD-ROM, thus making all the material in the report and
appendices available for both military mental health professionals and operational
leaders across the range of interested nations.
4.6 Lecture Series
Finally, it is the intention of the Group to organize an RTO Lecture Series to promote
the messages contained in the Intermediate and Final Reports and Appendices informed
by the results of the Military Leaders’ survey and the Symposium.
5. Conclusion
Participation in military operations is potentially harmful to the mental health of service

members. Historically, the negative effects of exposure to potentially traumatic events
on military operations has been recognised and documented using different terminology
(shell shock, combat fatigue, combat stress, PTSD, etc.). Regardless of the
terminology, it is also recognized that effective military leadership can moderate the
effect of deployment stressors on service members and can sustain operational
readiness and morale. The role of the military leader in managing the effects of stress
on service members is critically important to unit effectiveness and well-being. The
RTG is focused on supporting these military leaders on modern military operations.
Modern military operations encompass the range of military missions from peace
enforcement, peace support and humanitarian operations as well as combat operations.
Each of these different kinds of operations has the potential to expose service members
to significant stressors, including forced neutrality and non-intervention, witnessing
atrocities, culture shock and separation from one’s family as well as existential
questions induced by the situation. Every one of these stressors can disrupt the normal
psychological functioning of the individual soldier, sailor or aviator who might deploy
on such operations.
Psychological stress is not just limited to high intensity conflicts in which killing
and life threatening situations occur frequently. That this is so not only affects the
operational effectiveness and mental well being of the individual during the operation,
it also affects family, social and work reintegration together with attitudes towards the
organisation following the operation. Adverse stress reactions may have long term
detrimental effects on an individual’s functioning and well being and on the well being
of the service man or woman’s family unit.
By providing guidelines to military leaders on assessment for psychological risk,
psychological preparation of individuals and units, psychological education and
training, psychological support before, during and after operations, psychosocial
support of partners and families and on the organization of psychological support
services. It is the goal of the RTG that these may be adopted as standardized NATO
and PfP practice as part of a range of measures to support our Armed Forces on
military operations which they may be asked to carry out on behalf of all of us -
whatever or whenever that may be.
6. Persons to contact
If you wish to comment, find out more about the task group’s work or to assist in our
objectives, please contact your RTG-020 national representative or the Chairman*.
National representatives
AUSTRIA
LtCol Mag. Christian LANGER
Psychology Service of the Austrian Armed Forces
Am Fasangarten 2
A 1130 VIENNA (WIEN)
AUSTRIA
Tel.: + 43 1 5200 55400
Mobile: +43 676 7036752
email: hpa.hpd@bmlv.gv.at or magchristianlanger@hotmail.com
BELGIUM
LtCol Psy Yves CUVELIER*
DOO-SAO
Kwartier Koningin Astrid
Bruynstraat 200
1120 NEDER-OVER-HEEMBEEK (BRUSSELS)
BELGIUM
Tf: +32 – (0)2 – 264 5300
Fax: +32 – (0)2 – 264 5461
email: yves.cuvelier@mil.be
CANADA
Mr Jason DUNN
DQOL 9-2 Research
Directorate of Quality of Life
NDHQ – National Defence Headquarters
101 Col By Drive
OTTAWA, ON
CANADA KIA OK2
Tf: +1 – (613) – 995 – 0706

Fax: +1 – (613) – 995 – 9175
email: Dunn.JR@forces.gc.ca
CROATIA
Major Mladen TRLEK
Ministry of Defense of the Republic of Croatia
Zvonimirova 12
10000 ZAGREB
CROATIA
Tf: +385 1 3786489
Fax: +385 1 3786763
email: mladen.trlek@morh.hr
CZECH REPUBLIC
LtCol Jiri KLOSE
Clinical Psychology Dept.
Central Military Hospital
PRAGUE
CZECH REPUBLIC
Tf: +42 (0) 973 203470
Fax: +42 (0) 973 203465
email: jiri.klose@uvn.cz
DENMARK
Ms Birgitte HOMMELGAARD
Psychologist, MA
Institute for Military Psychology
Royal Danish Defense College
Ryvangs Alle 1
DK – 2100 Copenhagen OE
Tf: +45 39 15 19 44
Fax +45 30 15 19 01
email: imp-21@fak.dk
FRANCE
Médecin en Chef Patrick CLERVOY
Professeur agrégé du Val-de-Grâce
Service de psychiatrie
Hôpital d’instruction des armées Sainte-Anne
BP 600
83 998 TOULON NAVAL – France
Tel : +33 (0)4 94 09 91 85
Fax : +33 (0)4 94 09 98 35
email : patrick.clervoy@wanadoo.fr
GERMANY
Mr Bernd WILLKOMM
FlMedInstLw/Div VI
P.O. Box 1264 KFL

D-82242 FUERSTENFELDBRUCK
Tf : +49 – (0)8141 – 5360 – 2212
Fax : + 49 – (0)8141 – 5360 – 2909
email : BerndWillkomm@BUNDESWEHR.org
LITHUANIA
Lt Danute LAPENAITE
Military Clinical Psychologist
KAUNAS Military Medical Center
LITHUANIA
Tf: +370 37 320702
Fax: +370 37 204602
email: danute1@yahoo.com
LUXEMBURG
LtCol Psy Alain WAGNER
Psychologue de l’Armée
Caserne Grand-Duc Jean
BP 166
L-9202 DIEKIRCH
LUXEMBURG
Tf : + 352 – 26809 302 or 352 – 021 – 184441
Fax : + 352 – 809474
email : alain.wagner@cnfpc.lu + svmed@cm.etat.lu
ROMANIA
Col. (Ret’d) Dr. Gheorghe PERTEA
Head of Laboratory for Military Psychology
Military Intelligence General Directorate
GENERAL VASILE MILEA street, number 3-5
District 5
7000 BUCHAREST
ROMANIA
Phone:+40214102590
Fax: +40214113502
E-mail: pertea@easynet.ro or geopertea@yahoo.com
SLOVAKIA
Major Dr. Pavol SMYKALA
Armed Forces Head Psychologist
J1 General Staff
Slovak Ministry of Defence
Kutuzovova 8
832 28 BRATISLAVA
SLOVAKIA
Tf: + 421- 960 313127 or + 421-960 312359
Mobile : + 42-1907 735 777
email: SmykalaP@mod.gov.sk or smyky2002@zoznam.sk
SPAIN
Captain Psy José María PUENTE
Inspección General de Sanidad/Unidad de Psicología (Inspection)
General of Medical Service/Unit of Psychology)
C/Reina Mercedes, 21
28020 MADRID
SPAIN
Tf: +34 91 456 1969
Fax: +34 91 456 1976
email: jmpuenteo@oc.mde.es and jpuenteont@correo.cop.es
SWEDEN
Dr. Kristina POLLACK
Director Military Psychology
HQ GRO/UTB
S-107 85 STOCKHOLM
SWEDEN
Tf: +46 – (8) 788 75 45
Fax: +46 -
email: k.pollack@swipnet.se
THE NETHERLANDS
LtKol Coen van den BERG MSc
Royal Netherlands Military Academy
Faculty of Military Management Sciences
Social and Behavioral Sciences and Philosophy
P.O Box 90.002
4800 PA BREDA
The NETHERLANDS
Tf: + 31 (0)76-5273279
Fax: + 31 (0)76-5273255
email: ce.vd.berg@mindef.nl
LtKol drs Peter H.M. van KUIJCK

Military Psychologist – Certified Mental Health Psychologist
Personnel and Organization Service
Behavioural Sciences Division
Frederikstraat 467-469
2514 LN DEN HAAG
The NETHERLANDS
Tf: +31 – (0)70 – 316 5458 or 5450
Fax: +31 – (0)70 – 316 5452
email: cdpogw@army.dnet.mindef.nl
UNITED KINGDOM
Mr Paul CAWKILL
Human Sciences
Room G003, Building A3
Dstl
Ively Road
Farnborough
Hants
GU14 0LX
UNITED KINGDOM
Tf: +44 - (0)1252-455779
Fax: +44 - (0)1252-455062
email: pecawkill@dstl.gov.uk
UNITED STATES
LTC Paul BLIESE
US Army Medical Research Unit –
Europe/Walter Reed Army Institute of Research
Nachrichten Kaserne
Karlsruher Strasse 144
69126 HEIDELBERG
GERMANY
Tf: + 49-6221-17-2626
Fax:
email: paul.bliese@us.army.mil
HFM EXECUTIVE
Cdr Marten Meijer, PhD
HFM Executive
Tel: +33 15561 2260
Fax: +33 15561 9645
E-mail: meijerm@rta.nato.int
Section IV
Virtual Reality Therapy in the Treatment of
Posttraumatic Stress Disorder and Related
Psychiatric Conditions
M.J. Roy (Ed.)
IOS Press, 2006
Scenario Self-Adaptation in Virtual Reality

Exposure Therapy for Posttraumatic Stress
Disorder
Sinisa POPOVIC 1 , Miroslav SLAMIC, Kresimir COSIC
University of Zagreb, Faculty of Electrical Engineering and Computing, Croatia
Abstract. Several studies using VR exposure therapy for PTSD have been
conducted to date, with promising results. The need for better accuracy of the
patient’s arousal assessment requires aggregation of various measures of arousal,
including physiological ones, which may increase the mental burden on the
therapist. Assessment of the patient’s arousal, automated by the computer, may
therefore be useful. As the therapist also needs to manipulate user interface to
introduce appropriate trigger stimuli in the virtual environment, automated
adaptation of VR scenarios in response to the patient’s level of arousal may
alleviate this task. This paper describes the architecture of the software that
performs appropriate automation according to the rules of graded exposure
therapy, and discusses issues for successful implementation of such software.
Keywords. VR exposure therapy, PTSD, automated adaptation, adaptive control,

physiology, SUDs, arousal, anxiety, self-adaptation.
Introduction
Several studies using VR exposure therapy (VRET) for PTSD have been conducted to
date, with promising results. PTSD patients involved in these studies include Vietnam
War veterans [1-2] and survivors of the September 11 attack on World Trade Center
(WTC) [3]. In an uncontrolled study of 10 Vietnam War veterans with PTSD, average
reduction in PTSD symptoms between 15 and 67 percent was noted [2,4]. A case
report of a PTSD-suffering survivor of WTC attack documented a decrease in
depression and PTSD symptoms of 83 and 90 percent, respectively. Also, the
prototype virtual environment (VE) and clinical interface have been built, and further
development efforts are currently ongoing, for the VRET of military personnel coming
home from Iraq; initial clinical trials are expected in 2005 [5,6].
To improve the benefits of using VR in exposure therapy, it is also necessary to
evaluate and minimize downsides and inconveniences of the technology for the users.
Consequently, human factors are an important research topic [7-8]. A dissertation
addressing usability issues in VRET provides a variety of suggestions regarding
usability improvements in the therapist’s user interface [9]. Therapist-oriented
usability improvements are also addressed in this paper.
1
Corresponding Author: Sinisa Popovic, University of Zagreb, Faculty of Electrical Engineering and
Computing, Unska 3, 10000 Zagreb, Croatia; E-mail: sinisa.popovic@esa.fer.hr.
136 S. Popovic et al. / Scenario Self-Adaptation in Virtual Reality Exposure Therapy for PTSD
We present the architecture of the software for performing automated adaptation of

scenarios in VRET for PTSD according to various measures of the patient’s arousal,
and discuss issues for successful implementation of such software. The concept of
automated adaptation of VR scenarios has been previously discussed in another context
[10], and VR systems driven by the patient’s physiology have been described
elsewhere [11]. Automated adaptation could improve the usability of PTSD VRET
systems, with regard to the speed of acquaintance and ease of use by the therapist,
because it would decrease the therapist’s efforts related to the assessment of the
patient’s arousal and changes in the patient’s exposure. The quality of the therapy
could also be improved as a result, since the therapist could concentrate better on the
communication with the patient during exposure sessions. In particular, high-accuracy
assessment of the patient's arousal might become a mentally-intensive process for the
therapist, when various arousal-related measures are used and need to be aggregated,
including subjective units of discomfort (SUDs), physiological measures (e.g. skin
conductance, heart rate, etc.), changes in the patient’s behavior (e.g. anxious
movements), and so on.
1. Therapist’s General Reasoning in Graded Exposure Therapy
The topmost goal of the therapist during exposure therapy is to cure the patient [9].
Regardless of the medium used in the exposure therapy, this goal may be broken down
into three sub-goals [9], two of which have direct impact on the therapy: to determine
patient’s fear (alternatively, arousal), and to change patient’s exposure.
Changing the patient’s exposure is based on the therapist's assessment of the
patient's arousal, where the therapist tries to produce an optimal therapeutic effect on
the patient. In particular, with PTSD, during the patient's imaginal recollection and
description of the trauma, the therapist communicates with the patient and tries to avoid
two extreme conditions—that patient becomes totally overwhelmed by the trauma, or
that the patient is unable to engage emotionally [12]. For non-extreme situations, the
therapist conducting graded exposure therapy for PTSD exposes the patient to a
hierarchy of increasingly evocative scenarios which address the patient's traumatic
memories [1,3], and the patient should progress through these scenarios at his/her own
pace [12]. Such reasoning of the therapist may be described by these few general rules:
x If the patient is emotionally detached, then try to engage the patient in the
memory via conversation, by asking specific questions [12]
x If the patient has habituated (arousal is low), then increase the intensity of
exposure (e.g. move the patient to the next scenario in the hierarchy)
x If the patient has not habituated (arousal is significant), then maintain the
intensity of exposure (e.g. repeat the same scenario until the patient has
habituated)
x If the patient is overwhelmed by the trauma (arousal is too high), then
decrease the intensity of exposure. The therapist may accomplish this by
reinforcing the patient’s feeling of safety [12]. In VRET, the therapist may
also need to close the VE, show a relaxing scenario, or re-introduce a prior
scenario, for the most therapeutic effect in particular circumstances.
In order to apply these rules successfully by the computer during graded VRET for
PTSD, the means to assess the patient’s arousal and to change the intensity of the
S. Popovic et al. / Scenario Self-Adaptation in Virtual Reality Exposure Therapy for PTSD 137
patient’s exposure are necessary. The software support for the use of these rules in
graded VRET for PTSD is described in more detail later, and the next section addresses
the literature relevant for automation of the assessment of the patient’s arousal.
2. Patient’s Arousal Assessment
There are several different measures of arousal; one source describes the following
four, in an increasing order of objectivity: SUDs, self-report scales, overt behavioral
observation, and physiology [13]. All measures except self-report scales may be used
to determine the patients' arousal during the actual exposure sessions.
2.1. PTSD Studies with VR
The studies of VRET for Vietnam veterans and WTC attack survivor contextually
present the closest literature to the issue of software assessment of the patient's
arousal—both deal with PTSD, and both include VR as a source of trauma-related
stimuli. With respect to the arousal evaluation measures applied during exposure
sessions, these studies have used SUDs and, likely, overt behavioral observation. In
the case of VRET administered to WTC attack survivors, the authors have used a well-
defined SUDs-based rule to determine the appropriate moment to suggest the next
sequence of events to the patient. That is, this rule together with behavioral
observation of the patient has been used to determine when the patient has reached
adequate habituation.
The use of SUDs in these studies belies the importance and convenience of SUDs
for assessment of the patient’s arousal in VRET for PTSD, which is not surprising,
since SUDs have been used frequently in a variety of research studies. As these two
VR-PTSD studies do not address physiological measures of arousal, additional possible
sources of relevant literature seem to be PTSD studies employing physiological
measures with methods of stimuli presentations different from VR.
2.2. PTSD Studies without VR
In two recent reviews of the psychophysiology of PTSD, a vast amount of related

literature has been addressed [14-15]. Some mentioned differences between the
individuals with and without PTSD are that PTSD individuals exhibit heightened
physiological responsiveness to trauma reminders, exaggerated startle, and elevated
tonic or baseline physiological activity [14]. Of these, heightened physiological
responsiveness to trauma-related stimuli is found to be highly replicable across the
examined studies, and able to discriminate PTSD from non-PTSD individuals with a
sensitivity between 60 and 90 percent and specificity of 80 to 100 percent.
In the other review article [15], the authors advocate a greater role for direct
psychophysiological evidence in the diagnosis of PTSD, referring to substantial
consistent findings in the literature regarding physiological reactivity to trauma cues.
The authors mention that psychophysiological information needs to be viewed in the
context of other assessment methods like self-report or interviews. Different measures
viewed together may provide ambiguous evidence, in which case aggregation from
multiple sources of evidence is necessary. Despite this, the divergence of evidence can
be highly informative regarding the patient's state.
Further emphasis is given to the fact that the majority of psychophysiological
research, focused on differences between PTSD and non-PTSD groups, has limited
value for the clinician and an individual patient [15]. For example, even though there
are many studies demonstrating heightened physiological responsiveness in a group of
individuals with PTSD, they help little in determining whether a physiological response
of a given individual is "heightened." The authors point out the need for research
leading to future diagnostic criteria that will offer standards for determining whether a
particular response represents a clinically meaningful elevation or diminution. Such
research would be of direct relevance for the automation of the patient’s arousal
assessment.
2.3. Studies of Other Psychological Disorders with VR
Studies merging VR and other anxiety disorders, which incorporate physiological

measures of the patients' arousal, can also provide some useful insight. Physiology has
been applied in VR exposure therapy for fear of flying VEs, acrophobia VEs, fear of
public speaking VEs, and perhaps others, addressing the topics like: evocation of
presence in VEs [16-19], discrimination of phobics from nonphobics in VR exposures
[17-18,20], monitoring of treatment progress in VRET [20-21], and the impact of
physiological feedback to patients on sustainability of effects [21]. The physiological
channels that have shown some significant discriminating powers in various contexts
addressed by these studies include skin resistance/conductance [16,18,20-21], heart rate
[16-17], and skin temperature [16]. There is also evidence that brain wave activity
offers the potential to discriminate in several frequency bands between the subjects
who self-report high subjective arousal and those who self-report low subjective
arousal [13]. Interestingly, one fear of flying study had a group of subjects who
progressed through the scenarios solely by their skin resistance level, and not by
typically used SUDs [21]. This change appeared to have no adverse impact on the
effectiveness of the treatment (100% of these patients later flew a plane without
medications or alcohol). Therefore, various physiological measures may be desirable
complements to SUDs and overt behavioral observation in determining the patient's
arousal, in order to guide the patient’s exposure in VRET sessions.
The literature related to VRET also recognizes that subjective and physiological
arousal do not have to occur simultaneously [13]. When both of these arousals occur,
they are overall positively correlated [22], but the subjective and physiological arousals
do not necessarily fluctuate in the same manner during an entire therapy session.
Related to this is Hodgson and Rachman's concept of synchrony, which describes the
effect when physiological and subjective measures move together over treatment [13].
The breaks in synchrony present ambiguous evidence regarding the patient’s arousal,
which is problematic for software decision making, unless the ambiguity has been
studied, explained, and the resolving strategy has been incorporated into software.
3. Architecture of PTSD VRET System with Automated Scenario Adaptation
Scenario self-adaptation includes the identification of the patient’s arousal level, as

well as control over the patient’s exposure, to achieve the best therapeutic results. In
the process of experimental identification, based on input and output measurements, a

mathematical model of a system can be derived, including identification of its
parameters [23]. However, from a control system theory aspect, the patient’s PTSD
structural dynamics are unknown, complex, nonlinear, time variant, multi-input multi-
output, with state vector of unknown dimension, i.e. definitely black-box. In control of
such systems, some form of intelligent control must be applied, such as fuzzy logic
rules and/or artificial neural networks [24].
Figure 1. Architecture of PTSD VRET system with automated scenario adaptation
Figure 1 illustrates the constituent components of the VRET system that includes
automated adaptation of VR scenarios, together with the users of the system. By means
of visual, audio, and perhaps other types of input stimulations, the patient’s subjective,
physiological, and kinematical reactions are elicited. These reactions are captured by
the Data Acquisition Subsystem and sent to the Adaptive Control Software (ACS),
which computes appropriate control signals for therapeutic changes in the VE. The
therapist engages in observation and conversation with the patient, and interacts with
the ACS and the VE by means of user interface. Automated adaptation of VR scenarios
may be viewed as minimization of the therapist’s input to these two parts of the system;
dashed pointing lines on Figure 1indicate this.
The therapist’s general reasoning during graded exposure therapy, outlined in
section 1, may be captured by decomposition of the ACS into three computational
components on Figure 1:
x Arousal Level Computation (represents the antecedents of general rules from
section 1). This component determines the patient’s arousal by using various
inputs: subjective (SUDs), physiological (skin conductance (SC), heart rate
(HR), EEG, blood pressure (BP), skin temperature (ST), respiration rate (RR),
EMG…), kinematical (pitch, yaw and roll angles from the head tracker, which
may be potential arousal indicators as they describe the patient’s head

movements)
x Adaptation Goal Selection (represents the actual general rules from section 1).
Decision making in this component determines the general goal for the
scenario adaptation on the basis of the patient's level of arousal from Arousal
Level Computation
x VE Modification Selection (represents the consequences of general rules from
section 1). This component selects the specific changes in the VE, based on
the goal of adaptation received from Adaptation Goal Selection component
Further design and development of lower-level decision making within the ACS may
also benefit significantly from the therapists’ insight. ACS may become an expert
system if it ends up relying heavily on the therapist’s line of thinking on both high and
low levels. However, ACS is not currently anticipated to use all the channels that the
therapists naturally have at disposal for gathering information about the patient’s
emotional state. For example, conversation and overt behavioral observation still may
be too complex for handling by the software, given current state of the art in the fields
of real-time natural language processing [25], video analysis and interpretation [26],
and affective computing [27].
Although the remainder of the paper focuses on ACS computational components,
ACS also contains supporting storage facilities—Log, Baseline Knowledge Database
and PTSD Patient Knowledge Database (Figure 1). Log is used to store in sufficient
detail the data flowing within ACS, so as to allow subsequent scenario replay and
provide the developers with a low-level insight into ACS execution. Baseline
Knowledge Database keeps the baseline physiological data of healthy subjects and
patients, against which the baseline measurements of a given patient may be compared
in a variety of ways. PTSD Patient Knowledge Database contains aggregated patient’s
data, which ACS computational components can use in decision making and the
therapist can find useful for session review.
Each ACS computational component has a somewhat different mechanism used in
its decision-making logic. We expect Arousal Level Computation to use if-then rules
with fuzzy antecedents and fuzzy consequents, as it is likely that the relationship
between the patient’s manifestations of arousal and the actual level of arousal is a fuzzy
one. Adaptation Goal Selection may then use the patient’s fuzzy arousal level to
determine the crisp general goal of adaptation—"next scenario", "habituation",
"previous scenario", "relaxation scenario", or "shutdown"—according to the if-then
rules from section 1. Based on this goal, VE Modification Selection can determine the
appropriate changes to the VE, according to state machines that define its decision-
making logic.
3.1. Arousal Level Computation
Input variables for Arousal Level Computation, namely SUDs, SC, HR, EEG, BP, ST,
RR, EMG, pitch, yaw, roll and the output variable arousal may be represented as
linguistic variables typically consisting of from three to seven fuzzy sets with
characteristic names, like {"small", "medium", "big"}, {"zero", "small", "medium",
"big"},…, {"negative big", "negative medium", "negative small", "zero", "positive
small", "positive medium", "positive big"}. It should be noted that the names of input
variables here do not only relate to the raw measures, but actually refer to a set of
relevant derived measures that are used to assess patient's arousal. For example, SUDs
may include raw SUDs and change in SUDs [9], SC may include raw SC and relative
change in SC with regard to baseline [19] etc. Likewise, the output variable arousal
represents several forms of arousal needed for successful automated scenario
adaptation, like current arousal at a given moment and average arousal during the
execution of a given scenario. The former is important for assessing whether the
patient becomes overwhelmed with the exposure, plus for calculating the latter, and the
Figure 2. Possible membership functions defining input and output linguistic variables
latter may be needed for determining whether the patient shows habituation on repeated
exposures to the same scenario.
Besides deciding on the number of fuzzy sets for each linguistic variable, further
degrees of freedom relate to the type and actual shape of membership functions
defining the fuzzy sets. Figure 2 illustrates a few types of membership functions
(triangular, trapezoid, Gaussian …), with partitions into fuzzy sets, for the output
variable arousal and two measures belonging to the SC input variable. The universe of
discourse for arousal is a [0, 1] segment, which is arbitrary; the actual membership
functions are the part that is important in decision making. Input linguistic variables
each have their own physical units, so sets comfortably containing the typical ranges
for human beings may be taken as universes of discourse. For example, raw SC is in
the range of 2–20 ȝS (microsiemens) for humans [28], yielding a segment [0 ȝS, 30
ȝS] as a sufficiently wide universe of discourse. The universe of discourse for
relativeSC on Figure 2 is provisionally [–1, 1] and may be adjusted if needed.
Decision making in Arousal Level Computation is accomplished by if-then rules of
the form:
if (SUDs =<value> and SC = <value> and HR = <value> and EEG = <value> …)

then (arousal = <value>),
where <value> is a placeholder for the name of any fuzzy set included in a particular
linguistic variable. Only input variables that have been shown in the literature to be
sensitive enough, and those that prove sensitive in the actual experiments, will be used
in these rules. For example, an actual rule may be:
if (rawSUDs =“small” and relativeSC = “zero” and relativeHR = “zero”)

then (arousal = “small”),
where relativeSC is defined as in Figure 2, and relativeHR is defined analogously.

Aside from a challenge to define suitable membership functions and rules
experimentally, a particular issue in determining the patient’s arousal properly is
related to the ambiguity resulting from various measures during exposure. Addressing
several topics may be helpful here:
x The identification of frequently occurring types of ambiguity during VR
exposure therapy (e.g. SUDs vs. SC, SUDs vs. HR, SC vs. HR …). This is
helpful for identifying which antecedents in fuzzy rules indicate ambiguity
x The rationale for why particular types of ambiguity occur. Determining the
patient’s arousal when faced with explainable ambiguity is easier than if
ambiguity cannot be explained
x A detailed understanding of the methods used by therapists to assess the
patient’s arousal in the presence of significant and unexplained ambiguity. It
may be helpful to assess the importance of the methods of overt behavioral
observation and conversation with the patient in such situations, since these
methods are very difficult to implement in the software as mentioned before.
A "prerequisite experiment" for determining the precise decision-making logic of
Arousal Level Computation could use VRET with currently available manual scenario
modifications conducted by the therapist via user interface. The software would be
enhanced with meticulous logging in time of the patient's SUDs, various physiology
channels, and the moments of therapist's modifications to the VE. As the systems for
physiological measurements, visualization and analysis are already available, one
would need to add custom software tools for recording of SUDs (which have been
shown useful for the therapists [9]), and software support for manual or automatic
registration of the changes in the VE introduced by the therapist. Similar software may
already exist, like the Phloem tool set developed at University of Southern California
Institute for Creative Technologies [29]. The analysis within the experiment needs to
address the issues we have previously noted, such as confirming the most appropriate
channels for arousal assessment, finding the best-derived measures, and observing
ambiguity and synchrony between channels. Instances of ambiguity should be
documented with regard to factors such as their intensity, the channels and situations in
VE where they typically show up, and the therapist’s assessment of the patient’s
arousal when faced with ambiguity. If the cases of unexplained ambiguity occur
during the therapy session anyway, the software may also be programmed to behave
cautiously and to address those measures that imply greater arousal in order to avoid
stressing the patient outside the therapeutic limits.
3.2. Adaptation Goal Selection
As goals within Adaptation Goal Selection are selected on the basis of the patient’s
arousal, the rule base of this component has fuzzy antecedents corresponding to the
arousal linguistic variable. Crisp rule consequents corresponding to adaptation goals
are used instead of fuzzy ones, since a particular goal can either be selected or not
selected. A simple weighting scheme may be used for resolving the selection of the
goal if multiple rules are activated. For example, if the numerical value of the arousal
variable that comes out of Arousal Level Computation has membership in fuzzy sets
“small” and “medium”, both following rules will become eligible for activation:
if (arousal = “small”) then (goal = “next scenario”),

if (arousal = “medium”) then (goal = “habituation”),
but the higher value of membership will determine the actual goal to be selected.
Some current approaches to changing the patient’s exposure in VRET can be
mapped to similar rules. Approaches we encountered in the literature include:
x The therapist suggests to the patient that more evocative content be introduced
in the VE when the patient’s SUDs during the scenario decrease by at least
50% of their initial value [3]
x Changes in the VE are introduced based exclusively on physiological
measures, like skin resistance (SR) [21]
x The therapist introduces changes in the VE during verbal communication with
the patient while attempting to match the patient’s trauma description [1]
Since the computers are unable, with the current state of technology, to conduct
conversation with people like humans can, the implementation of the last approach is
not considered here. The first approach may be represented by the following rule:
if (SUDs < 0.5*initialSUDs) then (goal = “next scenario”).
Regarding the second approach, we have been unable to find the exact logic of using
SR to progress through VR scenarios. If this logic uses a comparison with some
threshold, it may be represented by a rule similar to the previous one:
if (SR > threshold) then (goal = “next scenario”),
where SR may stand for some measure derived from the raw SR, like the relative
change from the average baseline value, perhaps also averaged across the duration of a
given scenario. Since both SUDs and physiology are used within Arousal Level
Computation to compute arousal, the outlined current approaches to changing the
patient’s exposure are taken into account in the design of the software architecture.
3.3. VE Modification Selection
After Adaptation Goal Selection decides on the general adaptation goal, VE

Modification Selection turns this goal into exact control signals that produce the
desired changes in the VE. These changes need to be well structured to aid automated
handling by the software, while still providing enough flexibility to accommodate the
modifications that can currently be accomplished by therapists.
We assemble the structure according to a description of exposure changes in
Virtual Vietnam [1, 30], as these have been described in some detail and appear as
sufficiently diverse representatives of exposure changes in VRET-PTSD literature.
The application has two major scenarios, a Huey helicopter and an open field
environment. The Virtual Huey scenario includes the patient taking off on a Huey,
riding and landing, during which the therapist can add a variety of visual and audio
effects according to his/her own judgment (e.g. explosions, B52 rumble etc.). This
indicates that exposure changes may be conducted on several hierarchical levels:

scenario selection, main scenario logic, and additional scenario logic.
The top level of the control logic in VE Modification Selection deals with
changing entire scenarios in response to the goals output by Adaptation Goal Selection.
This logic is a simple state machine, with scenarios as states and adaptation goals as
conditions that trigger transitions between states (Figure 3).
Figure 3. Scenario selection logic
Figure 4. Structure of a generic scenario, with mapping of example scenario
The scenarios have all the information about both static (e.g. 3D models of objects)
and dynamic (e.g. behavior) characteristics of the VE. Thus, when a scenario is
selected, it defines the static content of the VE, but also activates its two-level control
logic, where both levels may be defined via state machines. The main scenario logic
may be viewed as describing the plot of the scenario, while the additional logic may
expose the patient within this plot to some typical combat-related events that may
improve realism, increase the exposure, or perhaps prevent scenario staleness if the
scenario is executed several times in a row.
Figure 4 illustrates the structure of the generic scenario according to the reasoning
just presented, and shows how the logic of the Virtual Huey scenario maps on the
generic scenario. The main logic of the Virtual Huey scenario is sequential, but in any
state of the main logic, there may potentially be more simultaneously active states in
the additional logic. Appropriate software already exists that provides flexibility to
incorporate into the scenario logic such as more complex behavior, like autonomous
goal-driven entities and their coordination; one example is a hierarchical concurrent
state machine (HCSM) framework [31]. The figure also does not show the conditions
associated with transitions in either state machine of the Virtual Huey scenario. It
appears these transitions are under the control of the therapist in the Virtual Vietnam
application [30], but we are unaware which specific conditions instruct the therapist to
introduce corresponding changes. If the therapist performs some changes in the VE
arbitrarily, these may be modeled in the software via random selection of available
events. In all other situations the therapist relies on some preconditions, and these
preconditions need to be implemented before the state machine can use them to execute
its transitions.
4. Conclusions and Future Work
This article has presented our approach for assisting the therapist during VRET in the
aggregation of multiple measures when assessing the patient’s arousal, and for
relieving him/her of user interface manipulation when changing the content of the VE
to keep patient’s exposure optimal. Delegating these tasks to the software may
improve the quality of the therapy, since the therapist will be able to focus more on the
therapeutic conversation with the patient. Therefore, architecture of the software
intended to perform these tasks automatically has been presented, together with issues
that need to be addressed in future research so that automation can be done properly.
Important issues are related to proper inferring of the patient’s arousal from multiple
arousal-related subjective, physiological and kinematical measures.
In order to avoid the possibility that the software makes any inappropriate
decisions in actual therapy, there is a paramount need for its thorough validation,
starting in early development. One safe approach is that the software only makes
recommendations to the therapist with regard to the patient’s arousal and the need to
change the exposure, but the therapist has the freedom to accept or entirely disregard
these recommendations based on their appropriateness. Thus, VRET may be
conducted as it currently, with the therapist assessing the patient’s arousal, deciding
when to introduce the changes in exposure and, sometimes, which changes to
introduce, and finally performing these changes via user interface. The only
enhancements are the recommendations from the software that the therapist may freely
accept or reject. By keeping track of the therapist’s evaluations, and communicating
with the therapists, the development team can get insight into strengths and weaknesses
of the software for subsequent improvements. Even after the software starts making
proper recommendations frequently, for safety’s sake the therapist may need to retain
ultimate control over changes in the patient’s exposure.
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M.J. Roy (Ed.)
IOS Press, 2006
Advanced Technologies in Military Medicine
Brenda K. Wiederhold, Ph.D., MBA a,b 1, Alex H. Bullinger, M.D., MBAc,

and Mark D. Wiederhold, M.D., Ph.D., FACPb
a
Interactive Media Institute, San Diego, CA b Virtual Reality Medical Center, San Diego,
CA
c
Center of Applied Technologies in Neuroscience (COAT-Basel), Switzerland
Abstract. Controlled studies by groups throughout the world have proven the efficacy
of virtual reality (VR) exposure for “mental rehabilitation,” including treatment of
Specific Phobias (SP), Social Phobia (SoP), and Panic Disorder with Agoraphobia
(PDA). In addition, many are now showing the power of adding VR to protocols to
treat individuals with Posttraumatic Stress Disorder (PTSD) as well as to prevent PTSD
by “inoculating” individuals against stressful situations they may encounter (Stress
Inoculation Training). Others have shown how VR can be added to protocols for those
needing “physical rehabilitation” to improve patient compliance and outcomes. In
addition, studies have shown the addition of physiological monitoring and feedback to
the VR protocol can have added benefit, both in terms of short term effectiveness and in
terms of lowering recidivism in the long term. VR allows stimuli to be presented in a
systematic, controlled fashion, and physiology provides objective evidence of when the
stimuli are eliciting appropriate responses in the patient or trainee. This enables
treatment and training to be individualized, focusing in on those specific parts of the
experience which cause the individual the most difficulty. By combining such measures
as subjective ratings, physiological data, personality type, and self-report questionnaire
scores, with expert clinical observations; it is possible to further refine and improve
clinical and research-based protocols. Decades after the first simulators were used to
train fighter pilots, advanced technologies and simulations are now impacting military
medicine. This paper highlights illustrative studies to introduce the reader to this area.
Keywords. Physiology, anxiety, phobias, posttraumatic stress disorder, stress

inoculation training, panic disorder, virtual reality, rehabilitation.
Introduction
The first studies indicating the possibility of VR as a useful tool in behavioral healthcare
were published over a decade ago. Since then, controlled studies from around the world
1
Corresponding Author: Brenda K. Wiederhold, Interactive Media Institute, 6160 Cornerstone Court East, Suite
161, San Diego, CA 92121; E-mail: bwiederhold@vrphobia.com.
B.K. Wiederhold et al. / Advanced Technologies in Military Medicine 149
have continued to show the value of adding VR as an adjunct to traditional cognitive-

behavioral therapy protocols. Prior to VR, most anxiety disorder treatment protocols
included exposure as 1 of the components. This was either done in the unpredictable real-
world environment (in vivo exposure), or relied on the imaginal skills (visualization) of the
patient. VR is an appropriate middle ground and allows the patient and therapist to control
the pace of exposure more precisely and focus in on those specific areas significant to the
individual patient. It is less overwhelming as a starting point than in vivo and more realistic
for most individuals than visualization. The addition of physiological monitoring helps in
determining objectively what parts of the simulation are triggering anxiety in the patient,
and the physiological feedback helps the patient learn to recognize both arousal and
relaxation and develop physiological control which may be useful in real-life situations.
While it is clear that self-report measures do not produce the desired level of accuracy
for measurement of treatment effectiveness, and may be influenced by numerous patient
and event-specific confounds, studies have shown that heart rate variability, skin
conductance, and EEG are useful analogs of absorption and presence. A high level of
presence and immersion seems to be correlated with faster movement through therapy, a
higher level of therapeutic success, and less recidivism [1].
At present, 2 systems are necessary to both present visual VR stimuli and to measure
physiology. We hope to create future systems that will combine both tasks into an easy-to-
use product that makes this form of therapy easier to deliver. An integrated system
incorporating a virtual world and physiological monitoring may allow real-time data
analysis to occur. The ultimate goal may be to have virtual reality systems that are driven
by the patient's own physiology. This will likely include intelligent software that would
automatically control the level of difficulty the patient experiences in achieving desired
parameters in training. Newer and less invasive methods to measure patient physiology also
need to be developed as the current methods are intrusive to some patients and may affect
their levels of immersion in the virtual environment.
This paper will focus on advanced technologies and how they are being applied in
military medicine. It is clear that these same procedures can be translated to the civilian
population.
1. Medical Training
In 1995, we were given the unique opportunity to become involved in several military
medical training exercises in Southern California. These exercises are very important to
provide personnel with hands-on training of a mock-up of a war-time triage scenario.
Those involved do, however, realize that there are some deficits. One of the things often
used is “moulage,” which allows for “fake wounds” to be applied to soldiers so that the
medical personnel can practice procedures on various wounds. Realizing the importance of
increasing the realism, however, and using the power of advanced technologies, we are now
funded by the Telemedicine and Advanced Technology Research Center (TATRC) to
utilize “Hollywood” make-up techniques to create realistic wounds, applied to actors and
actresses who are coached by medical and psychological personnel to react appropriately
150 B.K. Wiederhold et al. / Advanced Technologies in Military Medicine
based on the “wounds” they have received. These “wounded soldiers” can then be
imbedded in realistically created computer simulations, allowing personnel to practice and
“overlearn” skills. After the appropriate level of skills are attained, personnel can then be
tested to see if those simulation training skills then transfer to the near real-world setting in
a Hollywood style studio with all the special effects, including exploding bombs, gunfire,
smoke and all the confusion one would normally associate with battlefield scenarios.
Controlled studies are being conducted to determine if this more realistic training,
combining both VR/computer simulation training and real-world training will contribute to
attainment of skills. In addition, by creating these simulations on laptop computers,
anytime/anywhere refresher training will be able to be performed so that skill decrements
may be lessened.
VRMC is also developing a number of adjunctive training programs for combat
casualty care. To fill a gap in simulation training that exists for Echelon 1 and Echelon 2,
we are working with special effects artists, and make-up professionals who prepare lifelike
wounds that allow role players or selected troops to appear as casualties during tactical
training exercises. Training exercises combine: casualty care, evacuations, and tactical
decision making combine with appropriate battlefield stressors and confusion to provide a
realistic experience. VRMC is working to produce simulation tools that will allow medical
personnel to perform actual procedures on live actors or troops safely but with a high
degree of realism and clinical accuracy.
2. Student State Training
For optimal learning to occur, it is imperative to keep the student in the proper mental state
while training is under way. We were funded by the Defense Advanced Research Projects
Agency (DARPA) to test military personnel while they were learning skills on a computer
simulation. Physiology was monitored in real time to provide an objective measure of
arousal state. Using an off-the-shelf game, 2 training groups were assessed. One group
was trained while having a stressor applied (having to return enemy fire while treating
wounded patients). Another group was trained while having no real stressor (only treating
the patients but not having to return enemy fire). Both groups were then tested in a new,
novel simulation environment. As one would expect, those trained with stress were able to
perform better in the new test environment than those who were trained without high stress.
In addition, subjectively, individuals were unaware when they were becoming too
physiologically aroused and perhaps not in the optimum training state. We also were able
to see changes in HR, brain wave activity, and skin conductance that correlated with peak
performance. We are now performing a follow-on study in which VR worlds are being
developed to train and test skills more effectively.
The military has at its disposal many new technologies for the purpose of training
personnel in new and updated procedures. These technologies are complex and varied, and
they require a process by which to compare and assess the diverse capabilities of one
technology vs. another. We have prepared a testing protocol that makes use of not only
standard examination processes to determine learning, but brain wave measurements to
ensure that the student using the simulation is sufficiently immersed to maintain focus.
This process may then be applied to objectively compare differing simulator technologies
and confidently invest military funding into products with tested results.
2.1. Anticipated Benefits/Potential Commercial Applications
Because this testing process can easily and efficiently compare very different types of
instructional technology, it can be adapted to comparisons of many teaching materials and
devices. Training programs throughout the military, beyond medicine, may all benefit from
this protocol.
3. Stress Inoculation Training
Rates of PTSD in those returning from the Vietnam War have been reported at 15.2% for
males and 8.5% for females. Percentages for those returning from Iraq have been estimated
at 15.6% for both males and females, with the equal numbers being attributed to an
increasing number of females in combat zones. These rates are higher than those reported
for Somalia (8% for males and females) and the Gulf War (8% for males and 16% for
females). We realize from past studies in other areas such as phobias, anger management,
and peak performance training for athletes; that by providing “stress hardening” or stress
inoculation training prior to sending individuals into potentially stressful situations, we may
be able to provide some protection from the development of posttraumatic stress disorder
(PTSD) [2-5].
To encapsulate, on the military medicine side of the house, our mission is to develop,
test, validate and deliver a highly effective training experience using innovative technology
integrated with medical science, which can successfully train, prepare, and produce stress
hardened troops.
We have extensive experience in the creation of three-dimensional environments. Our
graphics and software groups are skilled in the creation of tactical training facilities both
real and idealized. We have developed a number of training protocols in which tactical
decision making in virtual environments can be tested at real Military Operations on Urban
Terrain (MOUT) facilities. This unique combination of real and virtual spaces allows for
the objective evaluation and quantification of simulation training transfer efficiency. The
simulated worlds are also useful as mission planning tools, or as an after action/debriefing
adjunct.
VRMC has developed stress inoculation training protocols for both tactical military
training and training for casualty care. Traning in both simulated and real environments
can be conducted while personnel wear non-invasive, wireless physiological monitors. The
real time assessment of heart rate, electrocardiogram, respiration rate, peripheral skin
temperature, and other vital signs allows trainers to assess levels of stress and anxiety
during training exercises. The ability to train under stress and achieve mastery of important
skills has been associated with successful stress hardening and potential reduction in the
incidence of PTSD. Simulations can be viewed on desktops, laptops, through a head-
mounted display (HMD), or as a 3-wall cave projection system depending on the needs of
the specific population to be trained. High fidelity virtual environments, combined with 3-
D sound, smell, and tactile feedback enhance the training experience. These graphical
environments become “The Future of Reality.”
Current training scenarios are unable to meet existing and future demands for
homeland security. Many investigators have shown that training skills acquired in a static
classroom environment do not prepare the individual for the stressful and often
unpredictable situations encountered in real-life missions or during wartime.
Because of these findings, training must be implemented under stressful conditions and
under those conditions that allow the individual to benefit from exposure to maximal
variation in outcomes. In general, many training systems today are static and to a certain
extent can be “gamed” by the user so that training sessions often become laborious and
result in a disinterested and less qualified first responder or warfighter.
Today, many younger members who are entering the armed forces and law
enforcement are not only computer literate, but quite proficient at Internet and videogame
usage. In addition, many younger people are bored with educational programs presented on
the blackboard, since they are accustomed to wide-screen televisions, full color graphic
videogames, and Internet access. We would like to be able to offer the trainee an
experience that is engaging and enjoyable, but more importantly the training should
challenge the student and truly build skills that can be fully implemented in real-life
wartime situations. To a certain extent, Special Forces and the Army have been using
videogames for combat training with some success. These pilot studies provide an initial
example of how inexpensive and easy-to-use systems can be of benefit during training.
Ideally, these kinds of training scenarios should be available to the first responder and
warfighter whenever, wherever, and under the circumstances necessary to provide them
what they need at the time.
One of the major challenges to training is to provide developers and directors a system
of objective measurements and metrics that not only track performance during the training
session, but provide a realistic predictor of real-life performance. In addition, because
knowledge and skill decrement continue to be a problem with current methods of training,
the next generation of training systems should be designed in such a way that the user is
drawn into the learning process and provided with a compelling environment that immerses
them in their tasks.
We are interested in providing an assessment structure that relies on both subjective
and objective measurement tools. We have extensive experience over the past 9 years
using analysis protocols while patients learn skills in virtual environments for the treatment
of certain clinical disorders. We have conducted an in-depth study of the methods that we
have used in our clinic and compared them to lessons learned from the stress inoculation
training protocols of the Tactical Decision Making under Stress (TADMUS) program, as
shown in the table below [6]. (The TADMUS project is sponsored by the Office of Naval
Research and was spawned by the 1998 USS Vincennes incident in which an Aegis cruiser
engaged in a peace-keeping mission shot down an Iranian Airbus. The resulting
investigation suggested that stress may have effects on decision making. TADMUS was
designed to address this concern.)
TADMUS VRMC
Stress Exposure Training Cognitive Behavioral Therapy
(CBT)
Education Information provision Patient education
Skill Building Skill acquisition and practice Physiological feedback and
training
Cognitive Schema Confidence building – Cognitive coping techniques,
application and practice desensitization in virtual reality
then in vivo (real life)
Degree of Over-learn Over-learn
Exposure
Training Training generalizes to real- Therapy generalizes to real-life
Generalization life missions situations
Content Skills generalize to novel Other phobias not specifically
Generalization tasks and novel stressors trained show improvement
Method of Gradual increase in stressors Gradual exposure is important
Exposure results in skill building
VR Advantages Virtual reality simulations Virtual reality simulations allow
crucial in allowing for a for over-learning and gradual
gradual increase in stressors exposure to more and more
intense situations
Internal Belief A sense of control and Self-efficacy and a sense of
mastery occurs mastery occurs
Ongoing Support Refresher sessions provide Booster sessions provide
maintenance of skills maintenance of skills
Pace of Exposure Initial exposure to high- Flooding does not result in
demand/high-stress development of skills
conditions does not result in
skill development and
generalization
TADMUS VRMC
Order of Exposure Develop basic physiological Teach physiological control first
control strategies first to
control stress/reduce
attention allocated to
emotions
Quality of Absolute fidelity is not Virtual reality simulations better
Exposure necessary or desirable than real video
Lessons Learned Take-home message: Take-home message: CBT
(pg 213): “an effective reduces anxiety, results in higher
method for reducing anxiety levels of functioning, and
and enhancing performance increases quality of life.
in stressful environments.
The results of this analysis
should clearly encourage
further application and
research."
TADMUS vs. VRMC: a 1-to-1 correlation
TADMUS highlights several very important facts about training and the lack of
appropriate training, which can have very serious consequences. In general, training tasks
must be performed under an equal or higher level of stress in order for effective training to
take place. Second, the training environment does not necessarily need to replicate the real-
life scenario in true fidelity. Third, before training skills can be learned, basic coping
mechanisms must be mastered in order to build confidence and self-efficacy in trainees.
This preparation allows the trainee to completely focus attention on the tasks at hand and
avoids a major problem of training, which is distraction.
Although not generally used in training, the measurement of real-time physiology
during the training program can provide invaluable information as to the level of
engagement, anxiety, or boredom during training. We have found that by measuring self-
reported anxiety in combination with EEG brainwaves, skin conductance, and heart rate
variability from the EKG, we can not only assess performance during training (or therapy),
but also predict who will perform well and who may need additional training or
remediation.
As the photos below illustrate, our teaming strategy is to combine the flexibility
afforded by simulation and virtual training with the realism enabled by the Strategic
Operations Tactical Training Laboratory.
Uses of virtual environments and simulations for training, although pioneered by the
military, are finding increased applications in clinical psychology and executive training in
the private sector. Studies have shown that training of skills in a non-stress condition does
not transfer to improved task performance when those same skills are then performed in a
stressful situation. Therefore, it would be advantageous to employ more real-world stress
simulations to allow for more generalizability of skill sets. In 1988, a National Research
Council study on enhancing military performance found that when a person is given
knowledge of future events, stress surrounding those events is then reduced [7]. In general,
this occurs because stress is viewed as a new, novel task. Stress training therefore renders
the task less novel and improves the trainee’s self-efficacy, which in turn improves
performance.
At the Virtual Reality Medical Center (VRMC), we have used a combination of
cognitive-behavioral therapy and physiological monitoring for the treatment of a variety of
psychological disorders. We have evaluated over 5,000 sessions in virtual environments
and have noted that successful treatment of stress and anxiety-related disorders requires
gradual exposure to more and more stressful situations, which allows the patient to over-
learn coping skills and renders the task less novel, which allows for a sense of mastery and
an increase in self-efficacy.
4. Post Traumatic Stress Disorder
The DSM-IV classifies Posttraumatic Stress Disorder as a heterogeneous disorder that

develops following exposure to traumatic events such as a serious injury or threat of injury
or death to the self or others. Symptoms of PTSD, which must persist for at least 1 month,
include increased anxiety or arousal, dissociation, avoidance of stimuli associated with the
trauma and numbing of general responsiveness, as well as flashbacks to the traumatic
experience [8]. Both anxiety-reducing medication as well as CBT can help in recovery. In
recent years, VR has been shown to improve treatment efficacy for PTSD in survivors of
motor vehicle accidents (MVA), war veterans, and those involved in the 9/11 World Trade
Center attacks, as well as in other areas [9-15].
4.1. VR Training/Therapy for Pre-Deployment/Post-Deployment in U.S. Military Personnel
The Virtual Reality Medical Center has been funded by the Office of Naval Research
(ONR) to develop virtual reality worlds and test them, using our established clinical
protocols in combination with physiological monitoring and feedback, to treat non-
combatants (including SeaBees and medical personnel) returning from Iraq who are
diagnosed with PTSD. The systems will be tested at Balboa Naval Hospital and Camp
Pendleton. In addition, we are investigating treatment protocols at both facilities with
combatants returning from Iraq utilizing software developed by USC’s Institute for
Creative Technologies. Initial results indicate that the worlds do elicit arousal,
physiologically and subjectively, in those reporting PTSD symptoms. After treatment,
individuals tested thus far no longer meet criteria for PTSD.
In a second study funded by ONR, Stress Inoculation Training (SIT) protocols are
being tested to determine if providing stress hardening skills prior to deployment can
decrease incidence of PTSD.
And a third project, funded by the Telemedicine and Technology Research Center, is
allowing us the opportunity to ship a VR system to Iraq in August 2005. This will allow us
to receive crucial feedback from troops in theater on how the software might need to be
adjusted to better meet their needs. Having the end user in the development loop has been
an important attribute we have encouraged over the past decade and provides for quicker
iterations in the development cycle and a more useful end product.
Hyperarousal to presentation of combat-related stimuli has been shown in several

physiological measurements, including heart rate [16] and electrodermal activity [17-18].
Veterans with PTSD clearly show an increased physiological response as compared to
veterans without PTSD. To build on this research, a 1996 article measured visual event-
related potentials (ERPs) in both a control group and PTSD patients [19]. Event-related
potentials reflect neural activity associated with information processing. The P3 component
of the ERP reflects stimulus relevance, and its amplitude and latency are thought to be
determined by the subjective value of a stimulus [20]. The N1 component of the ERP
reflects early-stage selection and its amplitude is dependent on the physical attributes of a
stimulus [21]. PTSD patients showed increased P3 and N1 amplitudes in response to
combat-related pictures, and also earlier P3 and N1 components for combat-related
pictures. They did not show these increases when presented with neutral pictures. The
control group of combat veterans who did not have PTSD did not show these patterns. It is
important to further explore these measures as virtual reality graded exposure therapy
(VRGET) begins to be used to treat this population. It has been hypothesized that the ERP
paradigm could possibly be used as a diagnostic tool for PTSD. The 3-dimensional nature
of the VR stimuli could allow for more accurate representation of stimuli and would allow
for systematic presentation of the relevant stimuli [19]. Dr. Alex Bullinger from the
University of Basel has been engaged to provide consulting on these measures. He has
been an industry leader in this area of research over the past decade, having published
results of several studies indicating the usefulness of 3-dimensional stimuli and its direct
effect on physiology.
4.2. Discussion
VR has proven an effective method of exposure for those suffering from PTSD, whether it
is due to a MVA, natural disaster, terrorism, or war-related trauma. Often in PTSD
treatment it is not practical or advisable to re-expose the patient to the trauma in a real-
world setting. VR, however, can effectively place the patient back into that scenario so that
the necessary processing of memories can occur, allowing the individual to move through
the trauma and on to recovery.
In order to provide a more time-sensitive solution to those who have been exposed to
recent combat situations, several groups are now developing VR worlds and have begun
initial testing to treat those returning from Iraq who are suffering from PTSD and Acute
Stress Disorder. It is hoped that by providing treatment earlier, many of the co-morbid
conditions which often occur, such as substance abuse, can be avoided. Treatment response
is also hoped to be greater since the PTSD is not as long-standing.
5. Physical Rehabilitation
VRMC is developing advanced computer-assisted rehabilitation systems specifically

designed to improve the treatment of the physical and cognitive injuries resulting from
battle-related trauma. By employing recent advances in simulation and measurement
technology, as well as improved rehabilitation paradigms that leverage the brain’s ability to
relearn after an injury (neuro-plasticity), it is possible to bring next-generation rehabilitation
technology to bear upon the immediate needs of injured military personal .
A funded project by DARPA to test inexpensive off-the-shelf videogame
environments, such as the EyeToy, as an adjunct to traditional physical therapy protocols
will begin pilot testing in September 2005 at the Walter Reed Hospital in Bethesda,
Maryland. It is hypothesized that the adjunctive treatment will increase compliance, while
decreasing depression and anxiety rates. It is also anticipated that many of the amputees
may be experiencing PTSD symptoms due to their physical trauma. These amputees will
also be potential participants for an additional arm of our PTSD study.
The long-term benefit of this project will be the development and deployment of
advanced rehabilitation technologies and strategies. While these technologies will have
immediate benefit for injured military personal, their development will also serve to
catalyze improvement and change within clinical rehabilitation at large.
6. Conclusion
After more than a decade of using VR to treat anxiety disorders, a database of thousands of
sessions with patients in virtual worlds has been accumulated. What began with the
controlled studies and protocols for the treatment of specific phobias (flying, driving, public
speaking, claustrophobia, heights, and spiders) has now expanded to include, amongst
others, PDA, PTSD, and SoP. Perhaps the lesson that has been learned above anything else
is that there is no “one-size-fits-all” treatment. Responses to virtual worlds vary not only
between phobic and non-phobic groups, but also from individual to individual. There is a
great deal of variance in the pace at which each patient progresses, as well as their personal
feeling of presence in the world. As study results indicate that such variables as personality
characteristics and previous VR experience can affect one’s level of immersion (measured
through subjective, emotional, and physiological responses), researchers and clinicians,
working together in multidisciplinary teams, must continue to create more complex virtual
worlds, providing richer and more realistic experiences that can be customized to suit the
needs of individual users. Further, as we have learned that this sense of immersion may
need to vary among the different phobias being treated, we must continuously refine our
protocols. While a person with a specific fear may need to become deeply immersed in the
world and ignore his/her surroundings, a patient with PTSD or SoP may feel the need to
verbalize feelings during exposure. Finally, we are learning there is a wide range of new
technology available, which can be utilized for our common goal of improving the
behavioral healthcare field.
All studies presented in this paper, whether they were conducted in a million-dollar
immersive chamber, HMD, the Internet, or a modified videogame, have shown positive
results that point to a promising future for the healthcare application of VR.
In developing new virtual reality tools, it is important to keep several concepts in
mind. Existing therapeutic concepts should form the basis for the construction of virtual
worlds. Virtual reality technology must be understood in light of existing science and
established paradigms. The application of virtual reality in relation to existing therapeutic

approaches and a consideration of the costs of using this technology need to be central in
assessing the clinical applications of virtual reality. Multi-disciplinary teams of experts can
be very helpful in the development and delivery of virtual reality systems.
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M.J. Roy (Ed.)
IOS Press, 2006
Indications provided by the Eating Disorder

Module of the VEPSY Updated Project:
towards a new generation of virtual
environments for clinical applications
Gianluca CASTELNUOVO, Ph.D.1abc, Gianluca CESA, M.S. ac,
Andrea GAGGIOLI, Ph.D. ad, Fabrizia MANTOVANI, Ph.D. ae,
Mauro MANZONI, M.S. ac, Enrico MOLINARI, Ph.D. bc,
Giuseppe RIVA, Ph.D. abc
a
Applied Technology for Neuro-Psychology
Istituto Auxologico Italiano, Milan, Italy
b
Clinical Psychology Lab, Catholic University, Milan, Italy
c
Clinical Psychology Lab,
Istituto Auxologico Italiano, Verbania, Italy
d
Laboratory of Psychology, Department of Preclinical Sciences LITA Vialba,
University of Milan, Milan, Italy
e
Centre for Studies in Communication Sciences (CESCOM),
University of Milan Bicocca, Milan, Italy
Abstract. This chapter stresses in particular some clinical observations obtained in the
eating disorder module of the VEPSY Updated Project and it also proposes some
clinical considerations to take into account during the development of new virtual
environments for mental health care purposes. For further information, please contact
Gianluca Castelnuovo: gianluca.castelnuovo@auxologico.it
Keywords. e-health, cybertherapy, eating disorders, obesity, clinical psychology,

psychotherapy, virtual reality
Introduction
In recent years, clinical applications of virtual reality (VR) and telemedicine have been
rapidly developing both in medicine and in clinical and rehabilitation psychology [1]. Many
1
Corresponding author: Gianluca Castelnuovo. San Giuseppe Hospital, Istituto Auxologico Italiano, Casello
Postale 1-2892, Intra (Verbania) Italy Telephone: +39 0323514339-4278 Fax: +39-0323514338 Email:
gianluca.castelnuova@auxologica.it
162 G. Castelnuovo et al. / Indications Provided by the Eating Disorder Module
terms have been coined to denote this newly developed match between technology and
care: cybertherapy and e-health, the integration of telehealth technologies with the Internet
and shared virtual reality, are only two examples. This chapter stresses in particular some
clinical observations of the eating disorder module of the European funded project VEPSY
Updated Project also proposing some clinical considerations to take into account in the
development of new virtual environments for mental health care purposes.
1. The VEPSY Updated Project and the Eating Disorder Module
The main goal of the "Telemedicine and Portable Virtual Environment in Clinical
Psychology"--VEPSY UPDATED--a European Community-funded research project (IST-
2000-25323, www.cybertherapy.info) was to study the technical and clinical viability of
using portable and shared Virtual Reality systems (shared care) in clinical psychology. The
selected disorders were anxiety, male sexual disorders and obesity and eating disorders
[2, 3]. Particularly its specific goal was the development of different PC-based virtual
reality modules to be used in clinical assessment and treatment of social phobia, panic
disorders, male sexual disorders, obesity, and eating disorders.
About the Eating Disorder Module in the VEPSY Project, the ATN-P Lab – Istituto
Auxologico Italiano, the leading partner in this module, has developed the Experiential
Cognitive Therapy (ECT), an integrated inpatient/outpatient (4 weeks) and telemedicine
approach (24 weeks) that tries to enhance the classical cognitive-behavioral method used in
the treatment of eating disorders, through VR sessions and telemedicine support in the
follow-up stage. Particularly, using VR and telemedicine, ECT is able to address body
experience disturbances, interpersonal relationships, self efficacy and motivation to change,
key issues for the development and maintenance of eating disorders that are somehow
neglected by actual clinical guidelines [4-9].
Distorted body image, negative emotions, difficulty in maintaining positive outcomes
in the long term and lack of faith in the therapy are typical features of obesity and eating
disorders treatment. To target these issues different groups are trying to enhance traditional
cognitive-behavioral therapy (CBT) with the use of a virtual environment [1, 10-12]. ECT
shares with the Cognitive Behavioral Therapy (CBT) the use of a combination of cognitive
and behavioral procedures to help the patient identify and change the maintaining
mechanisms. However it is different for:
• Its use of Virtual Reality (VR): 10 VR sessions.

• Its focus on the negative emotions related to the body, a major reason patients want to
lose weight.
• Its focus on supporting the empowerment process. VR has the right features to support
the empowerment process, since it is a special, sheltered setting where patients can
start to explore and act without feeling threatened.
The VR session can approximate natural settings, providing an alternative for exposure
and desensitization exercises as well as a more general enhancement to therapy.
G. Castelnuovo et al. / Indications Provided by the Eating Disorder Module 163
Specifically, VR is believed to increase motivation by allowing individuals to virtually

witness changes in their behavior and shape and reach their own conclusions based on
actual experience. During typical VR sessions, patients are asked to wear a head mounted
VR display system. An approach similar to guided imagery is used to lead the subject
through various zones over the course of ten sessions. Stimuli that contribute to abnormal
eating behaviors are identified, and associated anxiety and body experiences are targeted
for modification. Subjects are also asked to identify figures that most closely resemble their
current and ideal body sizes. They are also confronted with a photograph of their actual
body.
This approach was validated through different case studies [13] and trials. In the first
one, uncontrolled, three groups of patients were used [14]: patients with Binge Eating
Disorders (BED), patients with Eating Disorders Not Otherwise Specified (EDNOS), and
obese patients with a body mass index higher than 35. All patients participated in five
biweekly therapy sessions. All the groups showed improvements in overall body
satisfaction, disordered eating, and related social behaviors, although these changes were
less noticeable in the EDNOS group.
This approach was recently tested in further controlled studies. The first one involved
twenty women with BED who were seeking residential treatment [15]. The sample was
assigned randomly to ECT or to CBT based nutritional therapy. Both groups were
prescribed a 1,200-calorie per day diet and minimal physical activity. Analyses revealed
that although both groups were binge free at 1-month follow-up, ECT was significantly
better at increasing body satisfaction. In addition, ECT participants were more likely to
report increased self-efficacy and motivation to change.
In a second one, the same randomized approach was used with a sample of 36 women
with BED [16]. The results showed that 77% of the ECT group quit binging after 6 months
versus 56% for the CBT sample and 22% for the nutritional group sample. Moreover, the
ECT sample reported better scores in most psychometric tests including EDI-2 and body
image scores. In the final one ECT was compared with nutritional and cognitive-behavioral
treatments, using a randomized controlled trial, in a sample of 211 female obese patients.
Both ECT and CBT produced a better weight loss than NT after a 6-month follow-up.
However, ECT, as compared with CBT and NT, was able to significantly improve both
body image satisfaction and self-efficacy. This in turn resulted in a reduction in the number
of avoidance behaviors as well as an improvement in adaptive behaviors.
In the VEPSY Updated Project the Spanish research group, led by Cristina Botella,
worked also as second centre of investigation in the eating disorder module. This group has
compared the effectiveness of VR to traditional CBT for body image improvement (based
on Cash [17] in a controlled study with a clinical population [18]. In particular, they
developed six different virtual environments including a 3D figure whose body parts (arms,
thighs, legs, breasts, stomach, buttocks, etc.) could be enlarged or diminished. The
proposed approach addressed several of the body image dimensions: the body can be
evaluated wholly or in parts; the body can be placed in different contexts (for instance, in
the kitchen, before eating, after eating, facing attractive persons, etc.); behavioural tests can
be performed in these contexts, and several discrepancy indices related to weight and figure
can be combined (actual weight, subjective weight, desired weight, healthy weight, how the
person thinks others see her/him, etc.).
In the published trial eighteen outpatients, who had been diagnosed as suffering from
eating disorders (anorexia nervosa or bulimia nervosa) according to the DSM-IV criteria,
were randomly assigned to one of the two treatment conditions: the VR condition
(cognitive-behavioural treatment plus VR) and the standard body image treatment condition
(cognitive-behavioural treatment plus relaxation). Thirteen of the initial 18 participants
completed the treatment. Results showed that following treatment, all patients had
improved significantly. However, those who had been treated with the VR component
showed a significantly greater improvement in general psychopathology, eating disorders
psychopathology, and specific body image variables. Since then, the group has also
developed a VR simulator of food and eating [19] actually under evaluation with patients.
In summary, the data from both Italian and Spanish trials suggest that VR can help in
addressing two key features of eating disorders and obesity not always adequately
addressed by existing approaches: body experience disturbances and self-efficacy.
2. Why to use VR in clinical psychology: added value and limits
2.1 Advantages
The advantages that VR has over traditional approaches have been repeatedly underlined
by different studies, overall all in comparison with standard exposure therapies [20-25].
This is understandable given that the majority of the studies about VR-based psychological
treatments have used this tool as a new procedure of applying the exposure technique. From
this perspective, the following advantages have been pointed out:
2.1.1. VR exposure allows an almost total control of everything occurring in the situation
experienced by the person in the virtual world
If a patient fears being trapped in a lift, or the turbulences and bad weather during a flight,
we can assure him/her that these threats are not going to occur until he/she feels prepared to
cope with them and, in fact, he/she accepts them to happen in the virtual world. The same
can be said for numerous elements that are present in the situation and can make it more or
less threatening. For instance, number of feared persons, animals or objects, size and degree
of closing/opening of virtual spaces, the height of the spaces, if there is or not protecting
elements, the time a determined situation last, etc. This makes it possible a personalized
construction of the exposure hierarchy enabling the user to cope with the feared situation or
context at his/her own pace. A VR system can generate as many audiences and social
situations as the person requires and such situations can be at his/her disposal when is
needed and as many times as the person desires. The only mission of the avatars and the
whole virtual world is to be there in order to help. Therefore, VR provides valuable
opportunities regarding training and self-training. A person with fear of driving following a
motor vehicle accident can practice as many times as needed different feared elements
(overtaking a track, driving with rain, entering a tunnel, or passing over a bridge) in the
virtual world. This possibility of continuous practice in many diverse contexts may help to
generalize the therapy achievements to the real world.
2.1.2. VR helps the person to feel present and judge the situation as real
In fact, a central element of VR is that it provides the person a place where he/she can be
placed and live the experience. Furthermore, the therapist is able to know what is always
happening in the situation, what elements are being faced by the patient and what is
disturbing to him/her. Obviously, this also contributes to the control of the situation and the
protection of the patient.
2.1.3. VR allows going beyond reality

We have seen many times in therapy (and also in the real world) the importance of certain
situations considered extreme in order to definitely overcome a problem. There would be
different thresholds of difficulty/threat; once a very high threshold is overcome, to cope
with the remaining ones is much easier. Virtual worlds allow the creation of situations or
elements so “difficult or threatening” that they are not expected to happen in the real world.
For instance, in our claustrophobia application one of the walls can be displaced (producing
a loud noise) reducing the room to a very small space. The first patient who was treated
with this application indicated precisely this: “If I am able to cope with that wall I can
confront everything” [26]. The same can be made in other virtual worlds; a person with
spider phobia unexpectedly has to cope with thousands of spiders, or spiders whose size
increases so much that they turn into monsters.
2.1.4.VR is an important source of personal efficacy [21, 26, 27]

According to Bandura [28], from all possible sources of personal efficacy, performance
achievements are especially useful. We think that VR is an excellent source of information
concerning personal efficacy. VR allows the construction of “virtual adventures” in which
the person experiences him/herself as competent and efficacious. VR is flexible enough to
permit the design of different scenarios in which the patient can develop personal efficacy
expectations of highest magnitude (including from easy performances to very difficult
ones) generalization (referred to very different domains) and, strength (difficult to
extinguish, to achieve the patient perseveres regardless of difficulties). The goal is that the
person finds out that the obstacles and feared situations can be overcome through the
confrontation and effort.
2.1.5. VR offers privacy and confidentiality

The possibility offered by VR of confronting many fears inside the consulting room,
without the necessity of in-vivo exposure, represents a significant advantage.
2.2. Limitations
Besides these advantages that VR has over the traditional exposure technique, from a more
braoder treatment perspective, VR also has limitations that should be mentioned.
The first barrier is the lack of standardization in VR devices and software. The PC-based
systems, while inexpensive and easy-to-use, still suffer from a lack of flexibility and
capabilities necessary to individualize environments for each patient [29]. To date, very few
of the various VR systems available are interoperable. This makes difficult their use in
contexts other than those in which they were developed.
The second one is the lack of standardized protocols that can be shared by the
community of researchers. In reviewing two clinical databases – Medline and PsycInfo - we
found only five published clinical protocols: for the treatment of eating disorders [30], fear
of flying [31, 32], fear of public speaking [33] and panic disorders [34].
A third limitation is the expense required for to set up trials. As we have just seen, the lack
of interoperable systems added to the lack of clinical protocols force most researchers to
spend a lot of time and money in designing and developing their own VR application: many
of them can be considered "one-off" creations tied to proprietary hardware and software,
which have been tuned by a process of trial and error. According to the VEPSY Updated
studies [35] the cost required for designing a clinical VR application from scratch and
testing it on clinical patients using controlled trials may range between 150000 and
200000 €.
Finally, the introduction of patients and clinicians to VEs raises particular safety and
ethical issues [36]. In fact, despite developments in VR technology, some users still
experience health and safety problems associated with VR use. It is however true that for a
large proportion of VR users these effects are mild and subside quickly [37].
3. Conclusion
To close this chapter it is important to point out some questions that each VR developer has
to take into consideration in designing virtual environments for clinical applications (see
Table 1).
Table 1. Issues to consider in designing virtual environments in clinical applications.
Key questions → Possible answers → Applications and indications

for VR designers
1) Are VEs useful, effective Evaluation of possible Development of VEs that have
and efficient in clinical advantages and limits. to ensure only the factors of
applications? Cost/benefit analysis. presence requested by each
application.
2) Do VEs reproduce the Attention on graphics and Development of VEs that have
physical and perceptual technical characteristics. to ensure realism and a level
characteristics of real Focus on realism and of presence as non-mediation
environments? graphical issues. and immersion.
3) Do VEs allow users to Attention on cultural and Development of VEs that have
function in an ecologically social aspects. Focus on to ensure ecological situations
valid way? interaction, interactivity. of interaction, interactivity.
Importance of relationships
and context.
4) Do VEs allow users to Evaluation of qualitative Development of VEs in order
experience optimal aspects in virtual experiences. to allow optimal experiences,
experiences (flow) during Attention on users’ good compliance and high
virtual sessions? psychological state. motivation
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M.J. Roy (Ed.)
IOS Press, 2006
Treatment of Mental disorders with Virtual

Reality
Azucena GARCIA-PALACIOSa1 , Cristina BOTELLAa, Hunter HOFFMANb, Rosa M
BAÑOSc, Jorge OSMAa, Verónica GUILLÉNa & Conxa PERPINAc
a
Jaume I University, Castellon, Spain
b
HITLab, University of Washington, Seattle, WA, USA
c
Universidad de Valencia, Spain
Abstract. Virtual reality is a new technology that has been applied to the treatment
of several mental disorders. The first case study using this new tool was published
in 1995. After ten years, several studies have been conducted in the field of
Clinical Psychology, mainly in the application of VR for the treatment of anxiety
disorders. The present work is a review of the use of Virtual Reality in the
treatment of mental disorders. The advantages and limitations of virtual reality are
discussed and the findings to date are reviewed.
Keywords. Virtual reality, Clinical Psychology, Psychological treatments, Anxiety

disorders, PTSD, phobias, eating disorders.
Introduction
Immersive Virtual Reality (VR) utilizes technology that enables the creation of 3D
computer-generated environments. To have a VR experience we need a computer,
software to create the environment, a Head Mounted Display (HMD) or other mean for
the user to visualize the VR environment, and a device to move around the
environment, such as a mouse or a joystick. The essence of VR is that it allows the
simulation of reality in which the user has the illusion of “being” in the computer-
generated environment and interacting with the VR objects. This is what we call sense
of “presence”. This is a unique feature of VR that is very relevant for use in clinical
psychology. Some researchers in this field of psychology initiated studies intended to
design and test VR applications for the treatment of mental disorders. The main goal
was to explore whether the use of this new tool could help to enhance the efficacy of
psychological treatments or to overcome some or their limitations. The first work
describing the application of a VR program in the treatment of a mental disorder was
published ten years ago by Rothbaum, Hodges, Kooper, Opdyke, Williford, & North
(1995). Since then the VR research community has been growing all over the world,
facilitating additional efficacy studies exploring the utility of this new tool for various
psychological treatments. The aim of this paper is to review the studies exploring the
efficacy of VR in the treatment of mental disorders. We will limit our review to
Immersive Virtual Reality, and will not include other new technology approaches like
1
Corresponding Author: Azucena Garcia-Palacios. Jaume I University, Dept. Psicologia Basica,
Clinica y Psicobiologia, Avola Vincent Sos, Baynat s/n, 12071Castellon, Spain, email: azucena@psb.uji.es.
A. Garcia-Palacios et al. / Treatment of Mental Disorders with Virtual Reality 171
telepsychology or non-VR computer-assisted treatment programs. First we will review

the use of VR as a tool to apply exposure therapy. This has been the main application
of VR in clinical psychology, and we can say that the history of VR exposure is the
history of the more general field of VR and clinical psychology. Then we will review
the application of VR to other mental disorders like eating disorders or addictions, and
we will mention other applications of VR like Health Psychology. The final section
will be devoted to drawing some conclusions.
1. Virtual reality and anxiety disorders
Anxiety disorders are among the most prevalent of all mental disorders (Kessler et al.,
1994). Exposure is one of the most effective therapeutic techniques to treat these
problems. One of the essential features of anxiety disorders is avoidance. For example,
people suffering social phobia avoid social situations because they fear a negative
evaluation from others; panic disorder and agoraphobia sufferers avoid public
transportation, crowded spaces, etc., because they think if they have a panic attack in
those situations it will be difficult to escape or to get help. The essence of exposure is
to confront the feared situation in a repeated, gradual, and systematic way. One of the
processes involved in the efficacy of exposure is emotional processing (Rachman,
1980). Foa & Kozak (1986) used this concept to explain fear reduction during
exposure. This approach assumes Lang’s bio-information theory of emotion in which
fear is a cognitive structure that includes representations of stimuli, responses, and their
meaning (Lang, 1979). Foa & Kozak suggested that exposure to feared stimuli allows
the activation of the fear structure and the presentation of corrective information
incompatible with the pathological elements of the fear structure. This process is
especially relevant in the case of PTSD. Foa and collegues (e.g. Foa & Riggs, 1993)
developed an emotional processing theory to explain PTSD.
In order to develop new patterns of acting, thinking, and feeling toward the feared
stimuli, exposure therapy requires the practice of new beliefs and actions in the
presence of stimuli that elicit the anxiety. Exposure may occur through imagining the
anxiety-provoking stimuli, or in vivo, where there is exposure to the real life situation
that arouses the anxiety. The therapeutic strategies involve identification of the cues
that activate anxiety associated with the feared situation. The individual is then
exposed to those cues through imaginal or in vivo exposure. The individual can also
receive training in other therapeutic skills including relaxation and cognitive
restructuring in order to use these strategies during exposure. With the help of a
therapist, the individual learns how to self-manage the anxiety response in the presence
of the feared cues. When some clinicians learned about virtual reality they saw a new
way of applying exposure. Virtual reality allows simulating reality in a controlled way,
but it goes beyond other technological means like video or pictures. Virtual reality
gives the user the illusion of “being” in a 3D environment. From a clinical point of
view this means having a tool that can make exposure easier to apply. I can expose a
patient to fly without leaving the consultation room, and repeat the exact same task
once and again in the same session: that is, the patient can take off many times in the
same session. Or, I can expose an agoraphobic patient to different situations without
leaving the office. I can have a virtual bus, a virtual mall, and a virtual tunnel in the
consultation room and I don’t have to wait until it is Saturday afternoon to have the
mall crowded, I can just press a key on the computer keyboard and my virtual mall will
172 A. Garcia-Palacios et al. / Treatment of Mental Disorders with Virtual Reality
be crowded. I can control every single element to make exposure more gradual if
needed. I can expose a patient to fly without turbulences until he overcomes that
situation and then progress to fly with turbulence; I do not have that possibility in real
flights. VR also allows going beyond reality. For example, in a VR environment for the
treatment of claustrophobia we have a room where, pushing a key on the computer, we
can make one of the walls move toward the patient with a sound effect to create a sense
of closure. Overcoming this kind of exposure enhances the sense of self-efficacy in the
patients. On the other hand, as a therapist I can play with the fact that VR situations are
“not real”. Because of avoidance, some patients are very afraid of confronting the
feared situations, even in a therapeutic setting. In fact, although exposure is very
effective, around 25% of phobics refuse enrolment or drop out during the course of
treatment. In a study with people with high fear of spiders we found that when making
them choose between being involved in a VR exposure program vs. an in vivo exposure
program, most of the sample chose VR exposure (Garcia-Palacios et al. 2001). We
replicated this finding with a sample of clinical phobics (Fabregat, 2004).
In summary, some clinicians and researchers had the idea that VR exposure could help
to overcome some of the limitations of in vivo exposure: a) It could be more accepted
by some patients; b) It allows graduating the exposure tasks with high accuracy; c) It
allows repetitions of the same exposure tasks, promoting overlearning; d) It provides an
opportunity to go beyond reality, enhancing self-efficacy; e) .We can expose the patient
to different situations without leaving the office, saving time in trips to the feared
situations; f) Finally, the fact that we can conduct exposure at the consultation room
assures confidentiality.
These potential advantages made a group of researchers start to explore the
efficacy of VR exposure in the field of anxiety disorders. The first approaches were
aimed to treat specific phobias and in the most recent years VR has taken a step
forward to study its efficacy in more complex anxiety disorders like panic disorder and
agoraphobia, social phobia, and Posttraumatic stress disorder (PTSD). In the next
paragraphs we will review the findings up to date in the field of phobias and we will
pay special attention to the application of VR to the treatment of PTSD.
1.1. Specific phobias, social phobia, and panic disorder and agoraphobia
The application of VR to the treatment of phobias is the most developed field of

research in the study of VR and Clinical Psychology. Phobias have provided a wide
number of efficacy results in this area of research. The pioneer work testing the utility
of VR for the treatment of a phobia was carried out by Rothbaum and collegues
(Rothbaum, Hodges, Kooper, Opdyke, Williford, & North, 1995) in a case of
acrophobia. Apart from this first experience, six case studies and four controlled studies
have been reported to date in acrophobia. All case studies and one non-controlled study
(Bouchard, St-Jacques, Robillard, Coté & Renaurd, 2003; Choi, Jang, Ku, Shin & Kim,
2001; Jang et al., 2002; North, North & Coble, 1996a,b,c; Rothbaum et al., 1995)
showed positive efficacy results. One case study, however, (Kamphuis, Emmelkamp &
Krijn, 2002) reported no efficacy of VR exposure.
The controlled studies have shown VR to be more effective than no treatment
(Rothbaum, Hodges, Kooper, Opdyke, Williford & North 1995), as effective as in vivo
exposure at post-test and six-month follow-up (Emmelkamp, Krijn, Hulsbosch, de
Vries, Schuemie & van der Mast, 2002), and as effective at six-month follow-up if
using either a head-mounted display (HMD), that is, low presence or a computer
automatic virtual environment (CAVE), that is, high presence (Krijn et al., 2004). In
conclusion, the four controlled studies and most of the case studies show that VR
exposure is effective in treating fear of heights.
Flying phobia is the specific phobia where most studies have been carried out.
Several case studies have reported results of the efficacy of VR therapy (Baños,
Botella, Perpiñá & Quero, 2001; Klein, 2000; North, North & Coble, 1997; Rothbaum,
Hodges, Watson, Kessler & Opdyke, 1996; Wiederhold, Gervitz & Wiederhold, 1998).
Seven more studies, which differ in the degree of methodological control, support the
effectiveness of VR for the treatment of flying phobia. Wiederhold (1999) found that
VR exposure with physiological feedback was more effective than imaginal exposure at
three-month follow-up. Mühlberger, Herrmann, Wiedemann, Ellgring & Pauli (2001)
showed that VR was more effective than relaxation. These authors also found that
motion simulation did not enhance VR treatment effectiveness (Mühlberger,
Wiedemann & Pauli, 2003). Rothbaum, Hodges, Smith, Lee & Price (2000)
demonstrated in a well-designed controlled study that VR was more effective than a
waiting list condition and as effective as in vivo exposure. These authors reported that
these results were maintained at 12-months follow-up (Rothbaum, Hodges, Anderson,
Price & Smith, 2002). Maltby, Kirsch, Mayers & Allen (2002) found VR to be more
effective than an attention-placebo condition at post-test and at six month follow-up.
Finally, Botella, Osma, García-Palacios, Quero & Baños (2004) reported effectiveness
at 12-month follow-up using a multiple baseline design.
Similar results have been found in spider phobia, although there are no studies
comparing VR exposure with in vivo exposure or offering long-term effectiveness.
Hoffman’s research group has reported three studies examining the effectiveness of VR
exposure for the treatment of spider phobia: a case report (Carlin, Hoffman &
Weghorst, 1997) showed the efficacy of immersive virtual reality and mixed reality
(consisting of touching real objects which patients also saw in VR) in a 37-year old
female with severe and incapacitating fear of spiders. Later, this promising result was
supported by two controlled studies. In the first one García-Palacios, Hoffman, Carlin,
Furness & Botella (2002) compared VR exposure therapy with a waiting list condition.
Results showed that 83% of patients in the VR treatment group improved using strict
criteria of clinically significant improvement compared with 0% in the waiting list. The
second work (Hoffman, García-Palacios, Carlin & Botella, 2003) found that VR
treatment effectiveness was increased by providing the patient the illusion of physically
touching the virtual spider, using a real tactile cue (toy spider).
There are some preliminary results from a case study, a case series study and an
open trial (Wald & Taylor, 2000, 2003; Walshe, Lewis, Kim, O’Sullivan &
Wiederhold, 2003) addressing the effectiveness of VR exposure in the treatment of
driving phobia.
There are also studies using VR in the treatment of social phobia. The first
preliminary studies were designed for the treatment of specific social phobia, that is,
public speaking fear (North, North & Coble, 1998; Anderson, Rothbaum & Hodges,
2003). Harris, Kemmerling and North (2002) conducted a study with subclinical
population comparing VR exposure therapy and waiting list control group. Participants
in the VR condition showed an improvement on several questionnaires after
treatment.There has been also a preliminary between-subject study testing the efficacy
of VR exposure in social anxiety disorder (Klinger et al., 2005). A VR exposure
therapy group was compared with a CBT group. The results showed that both groups
improved significantly.
Positive results about for the effectiveness of VR exposure in the treatment of

claustrophobic fear have been reported in the three studies carried out by Botella’s
research group: A case report (Botella, Baños, Perpiñá, Villa, Alcañiz & Rey, 1998a), a
single case study (Botella, Villa, Baños, Perpiñá & García-Palacios, 1999) and a
multiple baseline design study (Botella, Baños, Villa, Perpiñá & García-Palacios,
2000). In these studies, VR was effective in the reduction of claustrophobic fear, and
results were maintained at three-month follow-up. However, the most important result
from these studies was that a generalization of improvement to other agoraphobic
situations not specifically treated was observed. This result led the researchers to design
a VR environment for the treatment of a more complex disorder, panic disorder with
agoraphobia.
VR has been used to conduct exposure as one of several components in a
Cognitive Behavioral Therapy (CBT) approach to panic disorder with agoraphobia.
In the first study, published in 1996, North et al. reported good efficacy data of VR
exposure in a sample of subclinical panic compared with no treatment. Data from Jang,
Ku, Shin, Choi & Kim (2000) failed to support the efficacy of VR therapy since most
of the seven participants were not able to feel present in the virtual environment (tunnel
with traffic jam). More recently, Vincelli, Anolli, Bouchard, Wiederhold, Zurloni &
Riva (2003) compared two CBT programs, one of which included VR exposure. The
results showed that both conditions were equally effective. Another study was
conducted by Botella, Villa, García-Palacios, Baños, Quero, Alcañiz and Riva
(submitted). Randomization to one of three experimental conditions was employed: VR
exposure that permits exposure to external stimuli and interoceptive stimuli; in vivo
exposure; and waiting list). Thirty-six participants were randomly assigned to one of
the three experimental conditions. The results showed that VR exposure and in vivo
exposure were equally effective, with both treatment arms superior to waiting list
status.
In short, results obtained so far in the field of VR exposure and phobias suggest
that VR is efficacious in the treatment of specific phobias. First, several controlled
studies support that VR exposure therapy seems to be more effective than control
conditions, and as effective as in vivo exposure. One important aspect to highlight is the
fact that the skills learned in VR environments generalize to real situations. One of the
concerns about the use of VR exposure was that patients would overcome their fears in
the virtual environments but that achievement would not transfer to the real situation.
The results from empirical studies support the fact that patients are able to confront real
situations after going through a VR exposure program. We know this because most
studies included a Behavioral Avoidance Test (that involves confronting the real
situations) as an outcome measure. Second, we have some evidence from follow-ups
confirming the maintenance of treatment gains at long-term. Third, we also have some
evidence of the preference of VR exposure vs. in vivo exposure before starting
treatment in subclinical and clinical samples of phobics (Fabregat, 2004, García-
Palacios et al., 2001). With regard to other more complex phobias like panic disorder
with agoraphobia, and social phobia, preliminary results are promising but still scarce.
More controlled studies, with larger sample sizes, are needed in order to test long-term
efficacy.
1.2. Post-traumatic stress disorder
CBT has been demonstrated to be an effective approach for the treatment of Post-
traumatic Stress Disorder (PTSD) (Foa, Keane & Friedman, 2000). A central feature of
these interventions is the exposure-based technique providing participants with
opportunities to confront the thoughts, situations and emotions related with the
traumatic experience, and to learn to control their own emotional responses, correcting
the misinterpretations regarding the traumatic event and its consequences. The
treatment program for PTSD with the most empirical support is Prolonged Exposure
(PE), developed by Foa & Rothbaum (1998), which involves imaginal exposure to the
traumatic experience.
VR offers a promising alternative to imaginal exposure. VR can help to overcome some
of the limitations of imaginal exposure. This type of exposure relies upon the
individual’s imagination and memory to recall the traumatic experience. Some patients
have difficulties in their ability to imagine. Others may resist or refuse to recall the
traumatic event, particularly since one of the PTSD features is avoidance of thoughts
and memories related to the trauma. Finally some individuals are able to think about the
trauma, but at the same time they are emotionally detached from it. Lack of emotional
engagement has been associated with poor treatment outcomes (Jaycox et al., 1998).
Reliance upon imagination makes it easier for the patient to use avoidant strategies that
interfere with the success of treatment. As previously noted, VR has the capacity to
draw the individual into the virtual world, creating “presence”(Hoffman et al., 1998).
The virtual environment can recreate the situation where the trauma occurred. The
patient is exposed to the trauma not only through imagining what happened, but seeing
and “being” in the situation. On the other hand, the possibilities of the computer-
generated environment allow graduated exposure to the traumatic situation in a careful
way (for example, in a victim of the September 11th attack in New York we can start by
exposing the patient of being at the World Trade Center before the attack, just being
around the Twin Towers, then we can progress to more stressful parts of the traumatic
event). As a result, VR therapy experiences may increase a patient’s feelings of self-
efficacy and of being an active agent of their own progress.
Rothbaum et al. (1999) published the first case study in the use of VR exposure in
the treatment of PTSD for a Vietnam veteran using exposure to virtual environments
recreating combat scenarios in the Vietnam War. Lately, in 2001 these researchers
conducted an open trial with ten Vietnam veterans (Rothbaum, Hodges, Ready, Graap
& Alarcon, 2001). Results showed an important reduction in some PTSD symptoms. In
a recent book, Rothbaum, Ruef, Litz, Han & Hodges (2004) published a case study
describing the use of VR exposure and psycho-physiological monitoring in PTSD with
a Vietnam veteran. One important feature of the work of these researchers is that they
are working with severe PTSD patients who suffered the trauma many years ago. This
makes the results achieved more promising.
Another team has published a case report of the use of VR exposure for the
treatment of PTSD in a survivor of the September 11th attack in New York (Difede &
Hoffman, 2002). In this case, they showed that VR could be an alternative for those
patients who present problems with imaginal exposure. They successfully treated a
patient who did not respond to the traditional CBT program that includes imaginal
exposure. This is the first study in which VR is an effective alternative to the standard
of care for an anxiety disorder—in this case, PTSD. We believe this is an extremely
important finding in which VR helps to overcome the limitations of other types of
exposure. At the present time, these researchers are conducting an open trial with more
individuals who did not respond to imaginal exposure.
Finally, another approach is the one designed by Dr. Botella in Spain. In earlier
studies, VR has been used to simulate traumatic events with high realism in order to
expose participants to feared aspects of the trauma. In Dr. Botella’s approach, the aim
is to design clinically significant environments for each participant, attending to the
meaning of the trauma without the simulation of the physical characteristics of the
traumatic event. The aim is not realism, but using customized symbols and aspects that
help to process the trauma in a safe and protective environment.
We believe that VR technology may provide a useful means to treat PTSD, mainly
in those cases where imaginal exposure is not efficacious. The results until now are
preliminary but encouraging. On the other hand, there is still a long way to go. We need
to conduct controlled studies comparing the efficacy of VR exposure vs. imaginal
exposure. We also need studies demonstrating the long-term efficacy of VR exposure
and studies exploring the acceptance and satisfaction of patients and therapist regarding
the use of this technology.
2. VR and Eating disorders
Another field of application of VR is the treatment of distorted body image in eating

disorders. One of the essential features of eating disorders is a distorted body image.
The treatment of this psychopathology involves confronting the patient with her body
image and correcting misconceptions about her own figure, weight, etc. In recent years,
researchers in the field of eating disorders are paying increasing attention to body
image (e.g., Cash, 1996). However, body image is an abstract concept that is difficult to
define and to apply. This is where VR can help—it can be used to confront the patient
with a mental image, such as in the case of body image. VR can help to “give reality"
to that mental image, creating a representation of it and therefore facilitating the
communication between patient and therapist. Also, VR could be helpful in placing the
patient into virtual situations that s/he would refuse to recognize as being "real", such
as eating "forbidden" food. Finally, facing the patient with his/her fears by means of
VR could help to make the individual less reluctant, increasing his/her motivation.
There are two groups in Europe that have conducted studies testing the efficacy of VR
environments in the treatment of body image.
In Spain, the research group led by Cristina Botella designed a VR environment
including a 3D figure representing the patient body image whose body parts (arms,
breasts, stomach, thighs, legs, etc.) could be enlarged or diminished. The body can be
placed in different contexts (for instance, in a kitchen, before eating, after eating, facing
people with different complexions, etc.); behavioural tests can be performed in these
contexts, and several discrepancy indices related to weight and figure can be combined
(actual weight, subjective weight, desired weight, healthy weight, etc.). Dr. Botella’s
team has compared the effectiveness of VR to traditional CBT for body image
improvement (based on Cash, 1996) in a controlled study with a clinical population
offering long-term efficacy at one-year follow-up in patients suffering bulimia and
anorexia nervosa (Perpiñà et al., 1999, 2004). The results showed improvement in body
image measures as well as in eating and general psychopathology.
In Italy, Dr. Riva and his team designed and tested a unique approach that includes
VR: Integrated Experiential Therapy. They conducted several uncontrolled and
controlled studies with good efficacy results in measures related with body image and
other eating psychopathology (Riva et al., 1999, Riva et al., 2002, Riva et al., 2003).
These studies included mainly patients with Binge Eating Disorder and the results
support the efficacy of this approach in body image compared with CBT-based
nutritional therapy.
In summary, the data from both Italian and Spanish teams suggest that VR can
help in addressing an essential feature of eating disorders, body image disturbances.
VR have an enormous potential in the field of other disorders related to eating
disorders, like obesity. VR can be used to train the patients in healthy eating habits or
other skills in the treatment of this condition
3. VR in the treatment of other mental disorders
As we have already mentioned the main applications of VR to Clinical Psychology

have been done in anxiety disorders. In this section we will summarized the use of VR
for the treatment of other psychiatric conditions.
Dr. Botella’s team in Spain has developed a virtual environment called EMMA for
the treatment of adjustment disorders, concretely pathological bereavement. At this
moment the efficacy of that environment is being tested. This virtual environment uses
virtual tools to work with symbols that represent the loss.
VR has also been applied to childhood disorders like autism (Strickland, 1997). A
useful tool is a virtual classroom developed by Dr. Rizzo for the assessment and
rehabilitation of attention deficits in Attention Deficit and Hyperactivity Disorder
(Rizzo et al., 2000).
An emerging field is the use of VR for the treatment of addictions, mainly for the
delivery of cue exposure. Several research teams are developing virtual worlds for the
assessment and treatment of toxic addictions like nicotine or heroine, and non-toxic
addictions like pathological gambling (i.e. Botella, 2004; Kuntze et al., 2001, Lee et
al., 2003; Nemire, Beil & Swan, 1999).
Another field of application is health psychology. The aim of this paper is to
review the use of VR in the treatment of mental disorders, so we will not detail the
potential for the use of VR in the treatment of medical conditions. However, we believe
it is worthwhile to mention the main lines of research in VR and health psychology.
One of them is rehabilitation. Riva and colleagues edited two books with the aim of
establishing theoretical and practical issues in the use of VR for the assessment and
treatment in neuro-psycho-physiology (Riva, 1997; Riva, Wiederhold & Molinari,
1998). The field has been growing until now with good and promising results. Another
line of research is the use of VR as a distraction technique in the treatment of acute pain
associated with medical procedures. Researchers from the University of Washington
pioneered the use of VR analgesia in acute pain caused by procedures like wound care
and physical therapy in burn patients (Hoffman, Doctor, Patterson, Carrougher &
Furness III, 2000; Hoffman, Patterson & Carrougher, 2000; Hoffman et al., 2001). The
results of VR analgesia are also encouraging in the field of procedural pain related to
medical procedures such as the treatment of cancer with chemotherapy (i.e. Gershon,
Zimand, Lemos, Rothbaum & Hodges, 2003; Gershon, Zimand, Pickering, Rothbaum
& Hodges, 2004; Schneider & Workman, 1999). These results suggest that VR is a
promising technique for adjunctive pain reduction during medical procedures. Its
unique characteristics, such as the possibility of full immersion and interaction, make
VR a powerful distractor. The future of VR analgesia is open to the application of this

technique to treat acute pain in many other medical procedures.
4. Conclusions and future directions
The field of VR and Clinical Psychology has provided evidence of the utility of VR in
the treatment of psychological disorders. In some disorders the results are very
preliminary, as in the case of addictions. The findings are very promising in eating
disorders where VR has proven to be a very useful tool in the treatment of body image
disturbances. However, more efficacy studies are needed. The field of anxiety disorders
is the most developed. We can state now that VR exposure is as efficacious as in vivo
exposure in the treatment of specific phobias, including long-term efficacy. However,
we still cannot say that in the treatment of other anxiety disorders like social phobia or
panic disorder. Studies are still scarce, and controlled studies are needed. As for PTSD
we only have results from case studies and open trials. However, the findings are
promising. It is in the treatment of PTSD where we have preliminary evidence that VR
can be an alternative for those patients who do not respond to imaginal exposure
(Difede & Hoffman, 2002). We believe we need more studies in that line. If VR can
help to increase the number of patients who could benefit from CBT treatment, the
effort of the VR community will have been worthwhile.
This leads us to an important aspect. The APA Task force on Psychological
Intervention Guidelines (1995) set two axes to establish the criteria to consider a
treatment to be empirically validated. Axis one refers to efficacy and axis two to the
therapeutic effectiveness, or clinical utility. The studies in VR until now have provided
results regarding axis one, for example comparing VR exposure to control conditions
and to in vivo exposure. However, we believe that VR is better understood if we
consider axis two. VR is a tool to apply well-established CBT programs and we have to
demonstrate that this tool contribute to the improvement of those well-established
techniques. If VR is proven to enhance the acceptance of exposure, for example by
demonstrating a preference of VR vs. in vivo exposure, that means contributing to the
clinical utility of exposure (axis two). If VR is efficacious in those PTSD patients who
do not benefit from imaginal exposure, that means contributing to the clinical utility of
exposure because with this tool we reach a higher number of patients. The fact that the
VR research community is international (there are research groups in America, Europe,
and Asia), and that the findings are similar across different countries and cultures, is a
result that support axis two. We believe that VR can contribute to the enhancement of
the effectiveness and clinical utility of CBT techniques, and we recommend that
researchers in this field work along this line.
Finally, we would like to make some comments about the limitations that VR
presents. One concern ten years ago was cybersickness. Researchers were concerned
about patients not being able to complete VR sessions because of cybersickness.
However, after ten years of experience treating patients with VR, this has not been a
problem in the efficacy studies published. Another limitation that is being overcome is
the cost of VR equipments. Ten years ago they were very expensive but now the prices
have dropped dramatically. The cost of VR equipment now is around 5,000 Euros
(7,000 US$). A problem still remaining is the lack of standardization of VR software
and hardware, as well as a lack of standardization of the VR treatment protocols.
Technical and clinical researchers should make an effort to standardize hardware,
software and clinical protocols in order to disseminate VR programs and facilitate its
use in daily clinical practice.
The application of VR to Clinical Psychology has a short but fruitful history. We
believe that VR is a valuable tool to enhance the clinical utility of well-established
CBT techniques. The aim is to provide the help needed to all who suffer from mental
disorders. There are many challenges and important studies to conduct to contribute to
that goal.
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M.J. Roy (Ed.)
IOS Press, 2006
Clinical Issues in the Application of Virtual

Reality to Treatment of PTSD
Cristina BOTELLA, PhD.a1 , Soledad QUERO, PhD.a, Nuria LASSO DE LA VEGAa,
Rosa BAÑOS, PhD.b, Verónica GUILLÉNb, Azucena GARCÍA-PALACIOS, PhD.a
and Diana CASTILLAa
a
Universitat Jaume I, Castellon (Spain)
b
Universitat de Valencia (Spain)
Abstract. In this chapter the potential for using new technologies (virtual reality)
with the aim of treating Posttraumatic Stress Disorder (PTSD) is examined. We
have developed a VR application (“EMMA’s room” and “EMMA’s world”) where
the therapist and the patient can represent the experience suffered by the patient
according to the specific therapeutic needs. The goal of the Emma’s virtual
environments is to work with emotions related to the participants’ psychological
problem. The specific emotions depend on the specific ways in which the problem
is symbolized in each of the scenarios. EMMA tools are used to maximize the
effect of these new strategies. EMMA is designed to help the person experience
the emotions and experiences which he/she is going through, to touch them and
feel them; in short, to accept them and to live with them from another perspective.
In this work we present the EMMA environment and the clinical treatment
protocol for PTSD in a case study.
Keywords. Posttraumatic Stress Disorder, Virtual Reality, Emotional Disorders,

Psychological Treatments, Clinical Psychology.
Introduction
Since the introduction of Posttraumatic Stress Disorder (PTSD) in 1980 [1], there has
been an increased emphasis on the identification and treatment of this disorder because
of the significant personal distress, negative consequences, interpersonal and work
impairment (marital problems, loss of job, etc.), and the co morbidity with other mental
disorders that it entails.
Unfortunately, PTSD is related to a very common human condition: reaction to
adversity [2]. Human beings have always tried to confront adversity by using multiple
strategies. At this moment good approaches for the treatment of this condition are
available: Cognitive Behaviour Therapy (CBT) and Proximity, Immediacy, and
Expectancy strategies (PIE).
1
Corresponding Author: Cristina Botella. Jaume I University, Dept. Psicologia Basica, Clinica y
Psicobiologia, Avola Vincent Sos, Baynat s/n, 12071Castellon, Spain, email: botella@psb.uji.es
184 C. Botella et al. / Clinical Issues in the Application of Virtual Reality to Treatment of PTSD
CBT is considered an effective approach for the treatment of PTSD [3]. One of the
central features of these interventions is exposure-based techniques that provide
participants with opportunities to learn to control their own responses when confronted
with stimuli related to the traumatic experience. The use of CBT programs that include
exposure-based techniques currently represents the treatment of choice for PTSD. The
treatment program for PTSD with the most empirical support is Prolonged Exposure
(PE), developed by Foa and Rothbaum [4], which involves imaginal exposure to the
traumatic experience. The aim of this intervention is to evoke the stressful event and to
work on processing it in an adaptive way. The therapeutic strategy involves
identification of the stimulus cues or triggers that activate fears associated with the
traumatic events. The individual is then exposed to those cues. Exposure may also
involve real life situations, objects or individuals that arouse the anxiety. The individual
can also receive training in self-regulation skills including relaxation, cognitive
awareness (self-monitoring), and reframing interpretations of events (cognitive
restructuring or attributional retraining) in order to use these strategies during exposure.
Several meta-analytic reviews pointed out that there is strong empirical support for
the efficacy of CBT interventions for improving PTSD symptomatology [5, 6]. Despite
these encouraging findings, exposure appears to be under-utilized in clinical practice.
Becker, Zayfert and Anderson [7] found that only a small minority of a sample of 852
psychologists used exposure to treat PTSD. Avoidance of the feared stimuli is a central
diagnostic feature of PTSD and the need to confront the trauma in therapy can present a
significant challenge for these patients. They may resist or refuse to recall the traumatic
event as well as situations, objects, or people that remind them of it. Some patients are
able to think about their trauma, but are emotionally detached from the experience. The
lack of emotional engagement can hinder anxiety reduction, resulting in poor treatment
outcomes [8]. Potential negative effects on treatment response can also occur as a result
of the patient’s inability to imagine. Finally, Orsillo and Batten [9] reported limitations
regarding the disseminability and acceptability of exposure in the treatment of PTSD.
Some individuals may be unwilling to emotionally engage with their traumatic
memories because they find this task too aversive.
Regarding PIE strategies, Herbert and Sageman [2] remind us in their work
entitled “First do not harm”: emerging guidelines for the treatment of posttraumatic
reactions” of the classic aphorism: “Primum non nocere”. The thesis Herbert and
Sageman defend is the central influence of the healer-patient dynamic in raising or
lowering expectancy of recovering. These authors point out that Babinski, one of
Charcot’s disciples, stated that hysteria was the result of iatrogenic suggestions which
were inadvertently made to the patient. From this perspective, Babinski [10] proposed
“persuasion” as a cure and called the attention of his colleagues to the great importance
of not eliciting or suggesting possible pathological symptoms.
During World War I the French were the first to adopt Babinski’s ideas on how to
confront and treat emotional casualties. The recommendation was not to suggest
morbid ideas to the victims. On the contrary, the focus was that they were treated as
though they were experiencing a normal reaction to extreme events. Additionally, the
recommendation was that the treatment should take place close to the front, with the
aim of not giving great importance to the situation. This same approach was adopted by
Salmon [11] regarding American casualties in World War I. The victims had to be
immediately treated somewhere close to the front, and they had to be given the
expectation of a quick improvement and recovery. The same approach was also
C. Botella et al. / Clinical Issues in the Application of Virtual Reality to Treatment of PTSD 185
adopted in War World II and “combat stress” (under whatever label) was not a
significant problem at that moment [12].
Later, the acronym PIE was coined with the purpose of emphasizing the following
three prongs: Proximity, Immediacy, and Expectancy. Herbert and Sageman [2]
underline that the experience from the two World Wars was very extensive. This
experience led to an emphasis on expectancies, (the “E” in Salomon’s PIE strategy), an
emphasis consistent with findings on expectancy effects in psychotherapy. However, in
modern approaches to treating posttraumatic reactions the deserved importance to these
strategies has unfortunately not been given.
Although these two perspectives are interested in treating the same problem, they
are focused on different aspects: CBT is mainly focused on the trauma (processing the
traumatic experience), whereas PIE strategies are mainly focused on expectancies, on
the possibility of recovering, (that is, on future life). Virtual Reality (VR) can improve
both approaches.
Regarding CBT, VR can help overcome some limitations of this therapy. VR can
simulate the stressful event with a high degree of realism and, therefore, help the
patients regardless of their ability to imagine. It also permits to have precise control in
presenting the feared stimuli or situations to the patient. This may prevent cognitive
avoidance and therefore enhance emotional engagement, an essential issue in the
efficacy of exposure. VR can also improve PIE strategies by providing a timeless space
where the person can rest and recover resilience in order to confront the future.
Rothbaum’s team [13] published the first case study where VR exposure was used
in the treatment of PTSD. Later this group also reported data from an open trial in
which VR with ten Vietnam veterans was used [14], revealing a trend towards
reduction in some PTSD symptoms. Recently, Rothbaum, Ruef, Litz, Han & Hodges
[15] described a case study highlighting the use of VR exposure in PTSD. In addition,
Difede and Hoffman [16] presented a case study on the use of VR exposure for the
treatment of PTSD in a victim of the September 11th attack with positive results. It must
be underlined that these authors were treating patients who did not respond to the
traditional imaginal exposure. Therefore, they show that VR could be an alternative for
those patients who have problems with imaginal exposure. Also, an application for the
treatment of Iraq war victims has been designed, derived from the X-Box game entitled
Full Spectrum Warrior, although data regarding its efficacy have not been offered yet
[17]. In summary, VR technology may provide a useful means to treat PTSD.
These results are preliminary, but encouraging. However, these studies usually
have been addressed to very specific populations that have gone through the same
traumatic event. The virtual scenario was very similar for all patients. Furthermore, in
these studies the approach was to simulate the traumatic events with high realism.
Although this can be an important aim, a possible limitation of this approach is that it
could be difficult to reach all patients suffering different traumatic experiences.
Nevertheless, if we want to treat different trauma populations (for example, rape
victims, assault victims, terrorism victims, pathological grief, etc.) we need more
flexible virtual scenarios that can evoke the different stressful events. One possible
means of doing so is the use of symbols that represent the trauma. This approach is
addressed by Botella’s team in Spain. The aim is to design clinically significant
environments for each participant, while attending to the meaning of the trauma for the
individual and not merely the simulation of the physical characteristics of the traumatic
event with high realism. The focus is not on realism, but on using customized symbols
and aspects that provoke and evoke an emotional reaction in the participant that helps
achieve the emotional processing of the trauma. At the same time, the process creates a
safe and protective environment that helps him/her to recover and go on with his/her
life.
This study has been conducted within the EMMA project, a research project
funded by the European Union. In the EMMA project we have developed a VR
application (EMMA’s room and EMMA’s world) where the therapist and the patient
can represent the experience suffered by the patient according to the specific
therapeutic needs.
The goal of the EMMA’s virtual environments is to work with negative emotions
related to the participants’ psychological problem (anger, anxiety, sadness). In
EMMA’s room it is also possible to work with positive emotions (joy, relaxation). The
specific emotions depend on the therapy moment and patients needs. EMMA is
designed to help the patient experience the emotions and the experiences which he/she
is going through, to touch them and to feel them. In short, EMMA is designed to help
patients accept their emotions and to live with them from another perspective.
1. Method
1.1. Participant
The patient was a 33-year-old single woman who came to the Emotional Disorders
Clinic at Jaume I University of Castellón. She presented a Posttraumatic Stress
Disorder (PTSD), according to DSM-IV criteria [18, 19], developed from a very
conflictive couple relationship. A month after starting to date her boyfriend, they
decided to live together. In May 2004 the first slight physical aggression took place
after an argument. He apologized, and the patient decided to continue the relationship.
In August 2004 she got pregnant and he asked her to abort, but she decided to wait until
he changed his opinion. Shortly later, a second aggression episode occurred after a
domestic argument. He threw her to the ground and tried to suffocate her by gripping
her neck. She escaped, but her aggressor enclosed her in the house. Finally, the patient
managed to be heard by a neighbour, who called the police. After this episode, she
denounced her aggressor and soon after decided to abort.
When she came to seek help, the patient presented low mood, anxiety,
hypervigilance (she practically did not go out of her house, she made safety behaviours
when she was out at the street, had excessively fearful responses to noises …),
nightmares (about abortion and situations of the relationship with her aggressor),
distressing recurrent and intrusive memories of the trauma, restricted range of affect
(she was not capable of feeling love or expressing affection, emotional detachment
regarding friends and relatives), and avoidance of multiple situations (having social
relations with men, meeting new people, seeing children…). The clinical history
revealed personal antecedents of a major depressive episode two years prior, after the
break up of a 9-year relationship. She received psychiatric treatment for this problem
with good results. She defined this relationship as satisfactory, although with
“excessive dependence towards him”. Another important antecedent was a previous
abortion she had when she was 16, which was dictated by her parents.
Relevant problems in the social or labour areas were not observed. The patient
showed a good level of general functioning and demonstrated a high motivation to
initiate the psychological treatment.
1.2. Measures
1.2.1. Diagnostic Instrument:

Clinician-Administered PTSD Scale (CAPS) [20, 21]. This is a clinician-rated scale
which assesses the presence of traumatizing events in the life of the individual and the
symptoms associated to those events. This instrument also determines the diagnosis of
posttraumatic stress disorder following the DSM-IV [18, 19] criteria. It includes a
checklist of possible traumatizing events. The three most traumatizing events are
chosen and the individual is asked for a description of the event and his/her emotional
response. This instrument also assesses associated features of PTSD like feelings of
guilt and dissociative symptoms.
Several studies have reported good reliability (internal consistency and interrater
reliability) [e.g., 20, 22] and convergent validity [20, 22, 23] for this measure.
Treatment sensitivity has also been reported [e.g., 24]. The mean score of the CAPS for
a clinical sample was 45.9 (SD = 29.1) [25].
1.2.2. Self-report measures:

x Measures directly related to the problem:
- Fear/emotional distress and avoidance scales [Adapted from 26]. The patient and
the therapist established three target behaviours or situations that the patient avoided
because of the traumatic experience and that he/she would like to overcome at the end
of the treatment. The patient rated the level of avoidance in a 0-10 scale where 0 is “I
never avoid it” and 10 is “I always avoid it”; and the level of fear/emotional distress in
another 0-10 scale, where 0 is “No fear” and 10 is “Extreme fear/emotional distress”.
The patient and the therapist also established three target memories, thoughts and
emotions related with the traumatic experience that he/she avoided and rated the degree
of fear/emotional distress and avoidance using the same 0-10 scales.
- Catastrophic thoughts. The main catastrophic thoughts related to the traumatic
experience in the target behaviours or situations were specified. The degree of belief in
these thoughts was assessed in a scale ranged from 0% to 100%: where 0% means that
the patient did not believe the content of the thought at all, and 100% meant that the
patient believed that the thought was totally true.
x Measures related to anxiety, depression:
- Positive and Negative Affect Scales (PANAS) [27]. This is a 20-item
questionnaire to assess two dimensions of affect: positive and negative. Positive affect
ranges from enthusiasm and activation to sluggishness and lethargy; negative affect
ranges from subjective distress and aversive arousal to calmness and serenity. The
items are rated in 5-point scales related to what extent they have felt a list of adjectives
describing mood states over a specified time frame. This scale is administered in 5
minutes and it offers separate scores for the two subscales. Good internal consistency
and test-retest reliability has been reported for the PANAS [27]. The factor structure is
supported by several studies [e.g., 27-29]. The mean for the Positive affect subscale in
a normal sample was 29.7 (SD = 7.9) and for the Negative affect subscale 14.8 (SD =
5.4).
- Beck Depression Inventory (BDI) [30]. This is one of the most widely used
instruments to assess depression symptoms. It includes 21 items. Each item offers four
possible answers. The participant has to choose the statement that best describes his/her
mood state. This instrument assesses mainly cognitive aspects of depression, as well as
behavioural and physiological symptoms.
x Measures related with impairment and improvement:
- Maladjustment Scale (MS) [Adapted from 31]. This instrument assesses the level
of impairment that the problem causes in different life areas (work, social life, leisure,
partner, family, and global impairment) using 0-8 scales where 0 is “Not impaired” and
8 is “severely impaired”. This scale offers good psychometric properties and is
sensitive to the effects of the treatment. In this study only data concerning the global
scale are provided.
- Impairment/Severity rated by the therapist [Adapted from 32]: The therapist
assessed the global severity and impairment of the patient weekly in a scale from 0 to 8
where 0 is “free of symptoms” and 8 is “extremely severe and disabling, all aspects of
normal life affected by the problem”.
x Measures regarding expectations and satisfaction about the treatment:
- Participant’s expectations and satisfaction. An instrument was designed in order
to obtain information about the respondents’ expectations with regard to the treatment
before starting it and about the respondents’ satisfaction at the end of it. Following
Borkovec & Nau [Adapted from 33], several questions to measure expectations for the
treatment were included. The questions were about how logical the treatment seemed,
to what extend it could satisfy the respondent, if the respondent would recommend this
treatment to other people suffering from the same problem, if it could be useful to treat
other problems, its usefulness for the respondent’s problem, and to what extent it could
be aversive. The respondents fill out the same questions at the end of the treatment in
order to assess the satisfaction with the treatment.
1.3. Procedure
A complete assessment was carried out at pre-treatment to evaluate the problem that the
participant suffered. The same assessment was carried out at post-treatment to evaluate
the effect of the treatment. Both assessments included the measures described
previously. The pre-treatment assessment was conducted in two sessions. The first
session lasted about 90 minutes and was dedicated to the assessment of the
psychological crisis that the individual was suffering. The participant went through the
CAPS and filled out the Davidson Trauma Scale (DTS). This first session was
videotaped so an independent clinician could make a clinical judgment about the
diagnosis of the individual. In the second session, which lasted about 60 minutes, the
therapist and the participant established and rated avoidance and fear regarding the
target behaviours and catastrophic thoughts. The patient rated impairment caused by
his/her problem using the Maladjustment Scale. The patient also filled out the Positive
and Negative Affect Scales and the Beck Depression Inventory.
In the second assessment session the patient chose 3D objects and images available
on the list in EMMA’s room that, according to her, reflected her emotions with regard
to the traumatic events (aggression and abortion). Before finishing this session, an
initial VR training session was carried out in which the patient had a first contact with
the EMMA environment and learned how to manage the VR system. She could also
choose a piece of music related to the emotions she experienced with regard to the
traumatic events.
After being informed about the treatment program for PTSD using VR, the patient
signed an Informed Consent form to take part in the study.
1.4. Treatment protocol
For the treatment of PTSD, an adaptation of Foa and Rothbaum’s [4] treatment
program for this disorder was made. The treatment program consisted of 10-12
sessions, each of which lasted approximately 90 minutes. The components used were:
In vivo exposure, Breathing training, and Exposure to the trauma. The virtual
environments and EMMA’s tools were used to provide exposure and processing of the
negative emotions associated with the trauma. The goal of the strategies included in the
treatment programs was to help the patient build a new way of experiencing negative
and positive emotions in order to overcome her psychological problems and improve
her mental health. Following is a brief description of EMMA environment.
1.4.1. Description of EMMA virtual environment
The main elements in the virtual environment are EMMA’s room and EMMA’s world.
EMMA’s room is an architectonic structure, a protecting space that contains very
important elements. There is a database screen, a listing of icons showing all the
elements that a user can manipulate, including three-dimensional objects, music,
sounds, images, colored lights, movies and texts. The “book of life” has an index and
several chapters defined by the user, and in each chapter he/she can describe any idea
or story. It is represented by a virtual book. Different elements can be copied to the
living book from the database screen. A virtual keyboard allows the user to label
elements or chapters in the book of life. Titles can be added to the different chapters.
The purpose is to help the user relive the past as it happened with family photographs
and home videos.
The second main element is EMMA’s world. The VR environment also has
different scenarios or ‘landscapes’ available (a “beach”, a “field”, a “desert”, a “forest”,
a “solitary and snow-covered place”). In EMMA’s world it is possible to modify the
scenario and to graduate the intensity of these modifications in order to reflect and
enhance the emotion that the user is experiencing or to induce certain emotions. The
patient can choose to be placed in a landscape that symbolizes his/her feelings and
emotions. EMMA allows real-time modifications of the virtual environments; the use
of different realistic natural effects (fog, rain, change from night to day, earthquake,
rainbow, etc.); the use of specific objects and significant symbols (from 3D objects to
real photographs of something/someone significant to the person) to anchor the virtual
experience to the personal history. The appearance of EMMA’s world can be
dynamically controlled by the therapist, depending on the emotions that the user is
feeling at each moment.
The aim is to reflect and enhance the emotion that the user is experiencing or to
induce certain emotions. It is possible to include modifications in the scenario and to
graduate the intensity of these modifications in order to reflect the changes in the
participants’ mood states. For example, in the “field” landscape, EMMA’s room is
surrounded by green hills and trees. It is a beautiful sunny day. We can change the
environment, covering the sky with clouds or making it become gradually sunny. Also,
we can make the landscape more colourful (with flowers) and livelier (butterflies and
birds). The “forest” landscape is a deep wood with bushes, blackthorns and big grey
threatening and twisted trees. It is a dark night full of shadows. We can graduate the
environment making the wood invade the space of EMMA’s room, or we can include
strange or unrecognizable sounds that are usually associated with threats (e.g., animals,
or a baby crying). The “desert” landscape is surrounded by rocks. We can graduate the
environment making the sky become red and cloudy as if volcanoes were exploding on
the horizon. Also, there could be a big storm in that red landscape, with clouds, heavy
rain, lightning, and noisy thunder. The ground shakes. The “beach” landscape is a calm
blue sea. It is a beautiful sunny day. EMMA’s room is located in a beach with white
sand. We can graduate the environment making the sky become more blue and bright
or the day can become a beautiful sunset. Finally, the “solitary and snow-covered”
landscape is a winter landscape with a pale light and a grey sky. We can graduate the
environment with heavy rain, fog or a darker sky.
Besides the specific variations for each emotional scenario it is possible to modify
the environment according to time, that is, we can establish day or night in each
scenario. In summary, the different three-dimensional objects, the sounds, the colours,
the lights, the images, the symbols... all of them are designed to reflect or enhance the
participant’s mood state in order to help the person to confront, accept and manage the
emotions and experiences that he/she has gone through previously in his/her life and is
going to experience in the therapy environment. Several images of the EMMA
environment are available at http://www.emma.upv.es
1.4.2. Treatment procedure

In this particular case, treatment was carried out in 12 weekly sessions of
approximately an hour and a half. The first two sessions were devoted to the following
components: logic of the treatment program, guidelines for training in slow breathing,
education about the common reactions to a traumatic event, and in vivo exposure to
traumatic memories about the aggression episode. In the third session, the cognitive
restructuring component was introduced. Sessions using EMMA´s tools began at the
fourth treatment session. In the first session with EMMA, the patient chose the beach
environment (at night) which reflected her feelings with regard to the aggression
(loneliness, sadness…). Later, exposure to this traumatic event was carried out using
some of the objects selected by the patient and following the general guidelines used
for imaginal exposure to traumatic events. The patient was asked to remember the
aggression episode as vividly as possible and to narrate the event in present time in 30-
60 minutes, watching the selected object/s and environment chosen. At the end of the
exposure session the patient could choose to make changes in the EMMA environment
to reflect her emotions at that time. During all VR sessions the same procedure was
followed, using the objects described below:
x Sessions 4 and 5: pictures of “plates” and a piece of sad music. According
to the patient, this picture was reflecting the place where the aggression
episode occurred (kitchen) and also the sensation of “chaos” associated
with this day.
x Sessions 6, 7 and 8: picture of “man-woman aggression”, the object

“bulb” and a piece of sad music. The bulb was representing the diffuse
image that the patient had of her ex-boyfriend during the aggression, since
she could not remember his face (“I see it blurry”).
x Sessions 9, 10 and 11: picture of her ex-boyfriend with her, the object
“bulb” and a piece of sad music.
In addition, the beach environment on a sunny day was used to practice slow
breathing before finishing some especially anxiety-provoking sessions (e.g., session 7),
but after the exposure task was over. Session 12 was devoted to working with the
traumatic event of abortion, following the same procedure as was used in previous
sessions. In this case a photo of “mother with baby” jointly with another piece of sad
music was used. After this last exposure session, the main measures of the assessment
protocol were again administered.
1.5. Hardware
A detailed description of the EMMA technical characteristics is not presented here

since a full description can be found in other chapter of the present book [34]. Different
devices were used: two PCs, a big screen where the environment was projected, two
projectors, a wireless pad and a system of speakers. Brainstorm eStudio software was
used for developing the application. Brainstorm eStudio is an European software that is
sold worldwide. Until now, it has been used mostly for virtual sets in television. In the
EMMA project, we have been the first to use it for virtual reality applications. These
devices were placed in a room with dimensions of 5x9 m. PC1 had the graphical
outputs from its graphic card connected to two projectors, which were used to project
the environment on a metacrilate screen that was placed in the mid part of the room. A
wireless pad was placed on a table on the other side of the room, and the patient was
seated next to it to interact and navigate in the environment. The therapist was seated
next to PC2, and from there she could control the application and the features of the
virtual environment that were shown to the patient. The sound system was composed of
several speakers distributed in the room to conform to a 5.1 configuration.
2. Results
2.1. Diagnostic Instrument
As can be observed in Table 1, at pre-treatment the patient obtained higher scores in the
Davidson scales measuring the DSM-IV criteria for PTSD (Criterion B, C and D) than
the clinical population. However, at post-treatment a notable reduction of the scores
was produced and they were closer to the normal population mean than the clinical one,
compared to pre-treatment assessment. Davidson Scale frequency and severity scores
are also included.
Table 1. Davidson scores compared with normal and clinical populations.

Participant Normal Clinical
population mean population mean
PRE POST
Criterion B 28 12 4.17 (3.16) 22.89 (9.35)

Criterion C 43 16 3.65 (9.53) 29 (11.46)
Criterion D 31 12 4 (8.01) 24.31 (9.44)
Total 102 40 11.83 (22.24) 76.48 (27.01)
Frequency Scale 55 22
Severity Scale 47 18
2.2. Self-report measures
In table 2 scores obtained by the measures directly related to the problem, measures
related to anxiety and depression, and measures related to impairment and
improvement, are presented. As can be seen, the participant showed a reduction in all
measures after treatment: the degree of fear and avoidance of the target-behaviours
(situations or activities), the thoughts, images and emotions related to her trauma, the
degree of belief in the catastrophic thoughts regarding the trauma, the level of anxiety
(PANAS) and depression (BDI), the level of impairment that the problem causes in the
participant’s life according to her (Maladjustment Scale), and the interference and
severity of the problem assessed by the therapist.
Table 2. Scores obtained in the measures related to the problem, with anxiety and depression and with
impairment and improvement.
PRE POST
Situations or activities Fear Avoidance Fear Avoidance
Having sexual relations with men 9 10 2 0
Relating to men in general (friends, known 8 8 0 0
people…)
Seeing children 8 7 2 0
Going out of house 6 6 0 0
Thoughts or images Fear Avoidance Fear Avoidance
Abortion 10 10 3 4
Image of her ex-boyfriend’s face 8 10 2 0
Emotions Fear Avoidance Fear Avoidance
Affect towards other persons (friends and 9 9 2 0
especially men)
Degree of belief in the negative thoughts PRE POST
“You never know who is going to hurt you” 10 4
“Nothing good happens to me” 10 2
Other measures related to anxiety and PRE POST
depression
Panas negative scale 45 21
Panas positive scale 21 22
BDI 23 10
Measures related to impairment and PRE POST
improvement
Maladjustment Scale 42 15
Interference assessed by the therapist 5 2
Severity assessed by the therapist 5 2
Lastly, in Table 3 results regarding expectations and satisfaction about the

treatment are shown. The patient had positive expectations about the treatment before
receiving it and after treatment she had a good opinion of it (she thought the treatment
was logical, she was satisfied with it, she would recommend it to another person
suffering from the same problem, she thought it could be useful for other problems, she
thought it was useful to her and, significantly, she evaluated it as less aversive at post-
treatment).
Table 3. Treatment expectations and satisfaction scores.

PRE POST
To what extent does it seem logical to you? 7 8
To what extent are you are satisfied with it? 8 8
To what extent would you recommend it to other 8 8
people with the same problem?
To what extent do you think it could be useful to 8 8
treat other problems?
To what extent do you think it is useful in your 9 8
case?
To what extent you think it is aversive? 7 5
3. Discussion
Considering the obtained data the treatment seems to offer efficacious and effective
tools for the treatment of this patient. Furthermore, the patient’s opinion regarding
EMMA was very positive. Regarding specific questions about the utility of EMMA’s
tools, the patient noted that she found the possibility of introducing her ex-boyfriend’s
photograph into the VR system especially useful since this enabled her to recognize
angry feelings towards the aggressor. She explained that it helped her to locate her ex-
boyfriend as the subject of the aggression (before that, she avoided seeing him when
she was reminded the aggression episode). She thought the system was immersive and
that it helped her to deepen her emotions. She valued the use of the different
environments to reflect her emotions very positively (“some times it is easier to express
what I am feeling like this than with words”). These are only very preliminary results.
This is just a case study. Now, we are applying this treatment in a between-subjects
controlled study comparing this procedure with the traditional protocol for the
treatment of PTSD by Foa and Rothbaum.
As has been said before, there exist different approaches for the treatment of PTSD
using VR. One possibility is to develop different virtual environments for each
traumatic situation, some of which are very difficult to develop (for instance, regarding
sexual abuse in children). Our design follows a different approach. The goal is not to
“recreate” the reality, but to achieve virtual environments relevant and significant to the
person. The important point is to develop therapeutic contexts and devices which help
people to confront their problems, and to open their future and the possibility of living
their lives in a more satisfactory way.
EMMA’s virtual environment is an “open VR system”. It provides a “timeless
space” where the traumatic events are activated and people can live these experiences
again but in a safe way. In this timeless space the person is supported by the therapist
and the global space reflects her/his emotions and the possibilities of the future.
Basically, what we have tried with this work is to structure “creative engineering”
of exposure such as is recommended by Becker et al. [7], with the aim of improving
these treatment programs for PTSD. Preliminary results of the application of this
system to persons with PTSD or pathological grief are very promising [35, 36]. Perhaps
these new “open” VR systems which consider the relevance and meaning of virtual
environments to be very important permit future additional advances in the field of
psychological treatments.
The aim is to potentate positive expectancies about the future, that is, the “E” from
PIE. This is one of the main objectives of EMMA treatment and it is consistent with the
evidence that support the idea of “creative engineering” exposure to reach a broader
number of individuals suffering stress related disorders [7]. In any case, we must not
forget that, as Summerfield [37] reminds us, human nature is basically sturdy and
resourceful and is able to respond to the different trials of life.
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Acknowledgements
This research was funded through the EMMA project (IST-2001-39192), funded by the
European Community: V Framework Programme (IST Programme, 8th call, “Future
and Emerging Technologies”).
M.J. Roy (Ed.)
IOS Press, 2006
Virtual Reality in the Treatment of

Survivors of Terrorism in Israel
Naomi Josmana1 , Azucena Garcia-Palaciosb, Ayelet Reisberga Eli Somerc, Patrice L.
(Tamar) Weissa and Hunter Hoffmand
a
Department of Occupational therapy, University of Haifa, Haifa Israel
b
Jaume I University, Castellon, Spain
c
School of Social work University of Haifa, Haifa, Israel
d
HITLab, University of Washington, Seattle, WA, USA
Abstract. Due to the numerous terrorist attacks that have occurred in Israel during
the last five years there are many people suffering from PTSD who are seeking
therapeutic help. Previous studies support the role of virtual reality (VR) as an
effective tool for the treatment of PTSD. This chapter describes the development
of a VR environment for the treatment of PTSD for people who were traumatized
by suicide bus bombings in Israel. We present an overview of the simulation
software and the study design including the clinical protocol and outcome
measures. Included in these measures is the client’s occupational performance
which, to date, has received less attention by those investigating PTSD.
Keywords. PTSD, terror, Virtual reality
Introduction
Over 1,000 Israelis have been killed in a series of attacks over the last five years,
including: shooting incidents, car bombings and suicide bomb attacks which have
frequently targeted public transport. Many more people have been physically wounded,
and an uncountable number of people have become psychological casualties; these
"silent" victims do not assume a special status or become heroes, are frequently
ashamed of their disability, and moreover are destined to suffer for prolonged periods,
possibly for the rest of their lives
Since the beginning of the Palestinian "Intifada", or uprising, in September 2000,
6979 Israeli civilians have been treated for trauma in the aftermath of deadly terrorist
attacks. On the Palestinian side, between September 29, 2000 and July 8, 2003, 2,572
Palestinians have been killed, and more than 41,000 injured.
An initial telephone survey conducted in Israel examined the impact of terrorism
on a nation-wide representative sample [1]. Using a stratified sampling method, 512
participants responded to the survey aimed at assessing the psychological impact of
1
Corresponding author: Naomi Josman. Department of Occupational therapy, Faculty of Social Welfare &
Health Studies University of Haifa, Mount Carmel Haifa, 31905 Israel, Phone # 972-4-8240610 Fax # 972-4-
8249753 Email: naomij@research.haifa.ac.il
N. Josman et al. / Virtual Reality in the Treatment of Survivors of Terrorism in Israel 197
ongoing terrorism in Israel. Survey results revealed that 45% of the sample had been
impacted by terror. Six percent of the sample experienced personal exposure or had
relatives or friends who were wounded or killed. An additional 3.3% had personal
exposure or relatives or friends who were exposed but not wounded, and 7% had been
personally exposed but did not have relatives or friends who were exposed. Sixteen
percent had no personal exposure but had relatives or friends wounded and/or killed,
while 12% had no personal exposure but had relatives or friends who were exposed but
not wounded.
Nothing in life can prepare a citizen for the horror of an act of terrorism. Even in
Israel, despite the statistics presented above, few expect such a thing to happen to them.
Reactions to the abnormal events of terrorism include a wide range of powerful
feelings that may feel abnormal to the person having them or seem strange to those
who have not gone through such a disaster. Terrorism evokes a fundamental fear that is
a manifestation of helplessness. The violent actions are random, intentional,
unprovoked by the individuals attacked, and often targeted at defenseless citizens.
This chapter describes the development of a VR environment for the treatment of
PTSD as an alternative to conventional imaginal exposure therapy. We present an
overview of the simulation software, developed especially to represent bus-bombings
in Israel, and the study design including the clinical protocol and outcome measures.
Included in these measures is the client’s occupational performance which, to date, has
received less attention by others investigating PTSD.
1. The effects of terrorism
Victims of terror, including those who have not been physically injured, frequently
manifest a severe emotional reaction. People who have experienced the trauma often
fall into the following categories:
x Survivors of past traumatic events (e.g. veterans, survivors of wars, terrorism,
or torture, and survivors of domestic violence, child abuse or street crime);
these individuals may have a heightened sense of vulnerability.
x People who personally witnessed or were victims of the terrorist attack.
x People who experience traumatization from learning of relatives, friends and
acquaintances that were subject to the violence, or from exposure to repeated
media accounts of the trauma.
x People who provide aid and assistance to terror victims [2-3].
Timely secondary prevention may reduce the risk for ASD or PTSD. Posttraumatic
distress may include one or all of the following symptoms:
x shock and numbness
x intense emotion
x fear
x guilt
x anger and resentment
x depression and loneliness
x isolation
x physical symptoms of distress
x panic
x inability to resume normal activity.
198 N. Josman et al. / Virtual Reality in the Treatment of Survivors of Terrorism in Israel
The DSM-IV-TR [4] groups PTSD symptoms in three categories: re-experience of

the trauma, avoidance, and increased arousal. A delayed reaction may occur in some
individuals. They may indeed be energized by the initial stressful situation and not
react until weeks or months later. Mental health professionals need to educate the
public and community physicians about this risk [2, 5].
A number of therapeutic approaches have been developed for the treatment of
PTSD. These include Exposure Therapy, Pharmacotherapy, Eye Movement
Desensitization and Reprocessing (EMDR), Group treatment, and Brief
Psychodynamic Psychotherapy. Exposure therapy, often regarded as the gold standard
for successful treatment of PTSD, focuses primarily on evoking self-generated images
to facilitate the recreation of the client’s traumatic memories. This approach, however,
poses a major difficulty since the clients' natural inclination is to avoid thinking about
or imagining the traumatic event thereby preventing or hampering subsequent
treatment improvement.
2. Virtual Reality as an intervention tool for PTSD
VR-based therapy has been shown to be highly effective for the treatment of phobias
[6-7] and for the reduction of pain during burn care [8] and venipuncture [9].
More recently, VR has been successfully used to treat PTSD in case studies and a
non-controlled trial. Until the recent introduction of VR based therapies, imaginal
exposure therapies relied primarily on the imaginative and memory capacity of
patients. Virtual reality affords opportunities not only to capitalize on the patient’s
imagery ability, but also to supplement them with visual and auditory computer-
simulated experiences. For patients who are hesitant or unable to recall the traumatic
events, the sensory-rich virtual environment engenders an evocative therapeutic
experience which may nurture the patient’s emotional engagement. Since the patient
encounters the virtual environment at a self-determined pace, it is easier to distinguish
between the act of remembering (and staying in control) and the act of reliving
(becoming overwhelmed by the re-experience) [10]. Additionally, VR technology
allows for graded exposure to increasingly feared virtual environments/objects/events
that can be carefully monitored and tailored to the individual patient. As a result, VR
therapy experiences may increase a patient’s feelings of self-efficacy and of being an
active agent of his or her own therapeutic experience.
VR based therapy for PTSD was introduced by Rothbaum and colleagues. Based
theories of Foa and colleagues, Rothbaum and colleagues proposed that the illusion of
going into the computer-generated virtual environmemt facilitates emotional
processing of memories associated with the traumatic event. They developed and
evaluated the therapeutic effectiveness of VR exposure (Virtual Vietnam), for the
treatment of combat-related PTSD experienced by soldiers who had been in Vietnam,
as one component of a comprehensive treatment program [11]. In a case study,
Vietnam veterans exposed to a helicopter environment and an open field environment
had strong emotional responses. Results suggested that being immersed in Virtual
Vietnam can effectively assist PTSD sufferers in imagining, visualizing and describing
their traumatic experiences. This participant had a 34% decrease in symptoms on
clinician-rated PTSD and a 45% decrease on self-rated PTSD. Treatment gains were
maintained at the 6-month follow-up examination [11]. In an uncontrolled study, 10
males with PTSD were treated with Virtual Vietnam for eight to 16 sessions. Results
indicated that in the clinician-rated PTSD scale at 6-month follow-up, there was a
statistically significant reduction (p=.0021) in symptoms associated with specific
reported traumatic experiences. Although chronic PTSD in Vietnam Veterans is
notoriously difficult to treat successfully, all eight participants reported reductions in
PTSD symptoms ranging from 15% to 67%, with significant decreases in all three
symptoms clusters (p<.02). Participants’ self-reported intrusion symptoms as measured
by the Impact of Event Scale [33] were significantly lower (p<.05) at 3 months than at
baseline but not at 6 months, although there was a clear trend toward fewer intrusive
thoughts and somewhat less avoidance. The researchers concluded that VR exposure
therapy holds promise for treating PTSD in Vietnam veterans [12].
Difede & Hoffman [10] developed the first virtual environment to treat civilian
PTSD following the terrorist attack on the World Trade Center Twin Towers in 2001.
Using a course of only six one-hour VR exposure therapy sessions involved cognitive
behavioral therapy with VR exposure, a PTSD patient who had previously failed to
respond to traditional PTSD therapy with imaginal exposure was gradually and
systematically exposed to increasingly realistic VR simulations of September 11th. In
her first VR session, the patient put on a VR helmet and looked at the towers with no
attack. Then, virtual planes flew over the World Trade Center without crashing. As the
patient habituated, she was able to tolerate more eventful simulations until in the final
sessions, planes crashed into the buildings with animated explosions and sound effects,
virtual people jumped to their deaths from the burning buildings, the towers collapsed
into dust clouds accompanied by sound effects (screaming, sirens, etc). Depression and
PTSD symptoms as measured by the Beck Depression Inventory [13] and Clinician
Administered PTSD Scale indicated a large (83%) reduction in depression, and large
(90%) reduction in PTSD symptoms
In summary, the results of these preliminary studies indicate that VR exposure is a
promising tool in the field of PTSD. Controlled trials are needed to establish the
efficacy of VR exposure in comparison with imaginal exposure and control conditions.
3. The essence of a client’s occupation
Despite the search for effective interventions for PTSD, no study has as yet examined
the impact that this condition has on the sufferer’s inability to continue participation in
daily occupations and their subsequent rehabilitation to pre-trauma occupational life.
Occupations are what we do for a living. They provide the basis for feelings about
ourselves. Our jobs help engage us in the world around us, and in so doing, enable us to
survive and maintain ourselves. They develop our abilities and skills, allow us to
pursue our interests, relate with other people, and express our values [14].
One of the major goals of occupational therapy is to enable the client to achieve a
satisfying and productive life by the development or rehabilitation of occupation-
related skills, which facilitate functioning at a satisfactory personal and interpersonal
level. The desired outcome of intervention is for the client to be able to meet his own
needs, as far as possible, and to have the motivation to continue working towards
achieving his full potential. Sub-goals which lead to this major goal are to:
x assess client needs in terms of the occupations which are important to him;
x identify the skills needed to support those occupations;
x remove or minimize barriers to successful occupational performance;

x assist the client to develop, relearn or maintain skills to a level of competence
that will allow him to perform occupations to his own satisfaction; and
x help the client to achieve a satisfactory balance of activities in his daily life.
Most interventions that have reported for PTSD clients focus on decreasing the
number and severity of symptoms, and the occupational component is not mentioned in
the literature. We propose adding this component both in our evaluation and
intervention of the PTSD clients.
4. BusWorld: Bus Bomb Survivor PTSD Therapy
A typical immersive virtual reality system consists of a virtual reality helmet that
positions miniature computer displays near the participants eyes, and blocks their view
of the real world. An electromagnetic xyz coordinate position tracking system attached
to the helmet sends information to the computer. When users look around in the virtual
world by moving their head orientation, the computer correspondingly changes what
they see in VR. Clients put on a VR helmet and experience a virtual world designed to
give them the illusion of being on a sidewalk in Israel, across the street from a bus stop
(see Figures 1-4 below).
There are a number of different levels in this graded exposure, which the therapist
controls by pressing a button on the keyboard. For the first level, no bus ever appears
at the bus stop (see Figure 1 below). For the second level, a bus comes around the
corner and stops at the bus stop but there is no attack (see Figure 2). For the third level,
a bus pulls up, and breaks in half as if exploding, but there are no sound effects and no
explosion or fire. Additional levels add explosion sound effects, visual special effects
of an explosion and the bus on fire (see Figure 4), sounds of people screaming and
crying in Hebrew, police sirens and flashing lights that represent the arrival of rescue
vehicles.
BusWorld was designed by several members of our team, based on interviews with
Israeli PTSD victims, therapists. BusWorld was programmed by Worldbuilder Ari
Hollander (www.imprintit.com) using sound effects made available by DaneTracks,
audio clips created by sound engineer Commnander. Russ Shilling, and texture maps
from digitized photos taken in Israel. Photos of actual terrorist bus bomb scenes were
used to guide the special effects used in BusWorld (e.g., the geometry of the bus and
exploded bus frameworks). A video clip showing the full simulation experienced by
the patient on their final therapy session is appended on CD.
Figure 1 Figure 2
Figure 3 Figure 4
All images copyrighted by Ari Hollander, www.imprintit.com, used with permission.
5. Clinical Protocol
The treatment program is virtual reality exposure therapy [12] which is an adaptation of
an empirically validated CBT program, Prolonged Exposure (PE) developed by Foa &
Rothbaum [15] and upgraded by Foa, Hembree & Dancu, [16]. The main component of
the traditional PE program, exposure to the trauma memories, is usually conducted
using imagination. In this study we use a new tool, virtual reality exposure. Exposure
to the trauma is conducted by gradually exposing the clients to the different sequences
of a VR program simulating a bus bombing attack (described in the previous section).
The therapists who apply the PE program with the VR treatment have been previously
trained in the application of the traditional PE program and in the use of VR exposure.
VR therapy is a powerful tool, so it is especially important that therapists are well
trained and experienced in treating PTSD before using it.
The length of the treatment is 10 weekly sessions that last 90-120 minutes each.
The components of the treatment program are the following:
x Education about the common reactions to trauma (Sessions 1 and 2).
x Breathing retraining (sessions 1 and 2).
x In vivo exposure to situations related to the traumatic event (Session 2 through
9).
x VR exposure to the traumatic event (Sessions 3 through 9). Homework for VR

exposure: The Clients will use a DVD of the VR session conducted with the
therapist in the consultation room to conduct exposure at home.
To test the efficacy and effectiveness of this VR program an assessment protocol
including PTSD measures, as well as general psychopathology measures, and
compliance and satisfaction measures is administered at pre-treatment, post-treatment
and follow-ups.
6. Outcome measures
Six different assessment tools are used in this study; all questionnaires are standardized
with Hebrew translations:
1. Clinician Administered PTSD Scale (CAPS): a standardized diagnostic
interview to determine DSM-IV criteria for the PTSD questionnaire [17].
2. Post Traumatic Diagnostic Scale (PDS): a standardized self-report
questionnaire to measure PTSD symptoms [18].
3. Beck Depression Inventory (BDI): a standardized questionnaire measuring
symptoms of depression [13].
4. Brief Symptom Inventory (BSI): a standardized questionnaire measuring
general psychopathology symptoms [19].
5. Presence Questionnaire (PQ): a standardized questionnaire to investigate
perceptions and feelings of presence in the VR environment [20].
6. Activity Card Sort (ACS): a standardized measure of activity participation
[21]. The ACS employs pictures of people involved in real-life activities and
thus can elicit vivid responses from participants. This instrument was adapted
to Israeli culture through several in-depth studies [22-23].
7. Progress to date
The software was first tested with more than 30 non-symptomatic users who
viewed and interacted with it while wearing an HMD at various demonstration
events. Overall these users found the environment to be realistic and evocative of
a suicide bombing. It was clear that key features such as the trademark green bus,
palm trees and distant sight of the Mediterranean were in accordance with a true
Haifa city view. There were no reports of cybersickness-like side effects although
some users requested to stop the simulation due to feelings of distress. Feedback
from these non-PTSD sufferers provided strong support for the ecological validity
of BusWorld.
8. Conclusions
This chapter describes the development of BusWorld, a VR environment for the

treatment of PTSD as an alternative to conventional imaginal exposure therapy. We
presented an overview of the simulation software, developed especially to represent
bus-bombings in Israel. Feedback from non-PTSD sufferers provided initial support for
the ecological validity of BusWorld. We are currently recruiting five subjects with
PTSD due to suicide bus bombings to test the feasibility and effectiveness of VR-based
exposure therapy.
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M.J. Roy (Ed.)
IOS Press, 2006
Virtual Vietnam: Virtual Reality Exposure

Therapy
Barbara Olasov Rothbaum, Ph.D. 1

Department of Psychiatry, Emory University School of Medicine, Atlanta, Georgia
Abstract. Virtual reality (VR) offers a new human-computer interaction paradigm in

which users are no longer simply external observers of images on a computer screen but
are active participants within a computer-generated three-dimensional virtual world.
Posttraumatic stress disorder (PTSD) is a severe and often chronic and disabling anxiety
disorder, which can develop following exposure to a traumatic event that involves actual
or threatened injury to self or others. The term exposure therapy refers to several
behavioral and cognitive behavioral treatment programs that involve confronting feared
but safe thoughts, images, objects, situations, or activities in order to reduce pathological
(unrealistic) fear, anxiety, and anxiety disorder symptoms. In the treatment of PTSD,
exposure therapy usually involves prolonged, imaginal exposure to the patient’s memory
of the trauma and in vivo exposure to various reminders of the trauma. There is
substantial evidence that exposure programs are highly effective in the treatment of
PTSD. A Virtual Vietnam environment was created to explore the efficacy of VR
Exposure therapy with Vietnam combat veterans with PTSD. Two virtual environments,
a virtual Huey helicopter and a virtual clearing surrounded by jungle were created.
Patients were exposed to their most traumatic Vietnam memories while immersed within
the virtual environments following a standard treatment manual. Data are presented, and
other applications of VR exposure therapy in the treatment of PTSD are discussed.
Keywords. Virtual reality, exposure therapy, PTSD, posttraumatic stress disorder,

virtual reality exposure therapy, Vietnam veterans
Introduction
Virtual reality (VR) offers a new human-computer interaction paradigm in which users are
no longer simply external observers of images on a computer screen but are active
participants within a computer-generated three-dimensional virtual world. Virtual
environments differ from traditional displays in that computer graphics, various display and
input technologies are integrated to give the user a sense of presence or immersion in the
virtual environment. Virtually BetterTM (www.virtuallybetter.com) is intended to be a
1
Corresponding Author: Barbara Rothbaum, Department of Psychiatry, Emory Univerrsity School of Medicine,
1365 Clifton Road, Atlanta, Georgia 30322. Tel.: 404-778-3875; fax 404-778-3875. Email: brothba@emory.edu.
206 B.O. Rothbaum / Virtual Vietnam: Virtual Reality Exposure Therapy
component of a comprehensive treatment package. It is recommended at the point in therapy

when exposure therapy would be introduced. Virtual reality exposure (VRE) has the
advantages of conducting time-consuming exposure therapy without leaving the therapist's
office, with more control over exposure stimuli and less exposure of the patient to possible
harm or embarrassment.
1. Literature review: VRE
A thorough review of the literature on the efficacy of virtual reality exposure therapy
(VRET) is beyond the scope of this chapter; the reader is referred to Rothbaum [20]. In
general, VRET has been shown to be effective in the treatment of specific phobias such as
arachnophobia, [7] claustrophobia [3], acrophobia [25], social phobia including the fear of
public speaking [1], and fear of flying [12]; [23]; [20], among others. The latter study
represents the largest controlled study of VRE to date with 87 patients enrolled.
2. Introduction to exposure therapy for PTSD: Theoretical Perspectives
Posttraumatic stress disorder (PTSD) is a severe and often chronic and disabling anxiety
disorder, which can develop following exposure to a traumatic event that involves actual or
threatened injury to self or others. Symptoms include re-experiencing the traumatic event
through intrusive unwanted memories of the event, flashbacks of the event, nightmares, and
intense emotional and physiologic reactions to trauma-related cues, persistent avoidance of
the trauma related cues and emotional numbing, and increased physiological arousal
manifested by sleep problems, hyper vigilance, increased anger or irritability, and
exaggerated startle. Prospective studies indicate that most traumatized individuals
experience symptoms of PTSD immediately after the trauma. In a prospective study of rape
victims, 94% met symptom criteria for PTSD in the first week following the assault [21].
Therefore, the symptoms of PTSD are part of the normal reaction to trauma. The majority
of trauma victims naturally recover from the trauma as indicated by a gradual decrease in
PTSD symptom severity over time. However, many continue to exhibit severe PTSD
symptoms. Therefore, PTSD can be viewed as a failure of natural recovery which reflects in
part a failure of fear extinction following trauma.
Consequently, several theorists have proposed that conditioning processes are involved
in the etiology and maintenance of PTSD. These theorists invoke Mowrer’s [16] two-factor
theory, which posits that both Pavlovian and instrumental conditioning are involved in the
acquisition of fear and avoidance behavior. Through a generalization process many stimuli
come to elicit fear and avoidance. Consistent with this hypothesis, emotional and
physiological reactivity to stimuli resembling the original traumatic event even years after
the event’s occurrence is a prominent characteristic of PTSD and has been reliably
replicated in the laboratory [2, 18]. Cognitive and behavioral avoidance strategies are further
hypothesized to develop in an attempt to avoid or escape these distressing conditioned
B.O. Rothbaum / Virtual Vietnam: Virtual Reality Exposure Therapy 207
emotional reactions. The presence of extensive avoidance responses can interfere with
extinction by limiting the amount of exposure to the CS in the absence of the UCS.
Conceptualizing PTSD within the framework of emotional processing theory, Foa,
Steketee and Rothbaum [11] suggested that the traumatic memory could be conceived as a
mental fear structure comprising a network of information about the feared stimuli;
information about verbal, physiological, and overt behavioral responses; and interpretative
information about the meaning of the various stimuli and responses contained in the
network. Foa and Kozak [8] suggested that two conditions are required for the reduction of
fear. First, the fear memory must be activated. That is, as suggested by Lang [15], if the fear
structure remains unaccessed in storage, it will not be available for modification. Second,
they proposed that information must be provided which includes elements "incompatible
with some of those that exist in the fear structure, so that a new memory can be formed. This
new information, which is at once cognitive and affective, has to be integrated into the
evoked information structure for an emotional change to occur" (p.22). Therapy is aimed at
reducing fear presumably by changing this fear structure. Exposure therapy is notoriously
good at accessing the fear structure. Then, information incompatible with associations
between stimuli and anxiety responses must be provided during therapy.
The term exposure therapy refers to several behavioral and cognitive behavioral
treatment programs that involve confronting feared but safe thoughts, images, objects,
situations, or activities in order to reduce pathological (unrealistic) fear, anxiety, and anxiety
disorder symptoms. In the treatment of PTSD, exposure therapy usually involves prolonged,
imaginal exposure to the patient’s memory of the trauma and in vivo exposure to various
reminders of the trauma. Prolonged exposure (PE) is a specific exposure therapy program
that typically consists of four components administered in 9-12 sessions lasting 90-120
minutes each: (1) psychoeducation about the symptoms of PTSD and factors that maintain
PTSD along with a thorough rationale for exposure therapy, (2) training in controlled
breathing that patients may use as a stress management skill, although patients are
discouraged from using it during exposure exercises, (3) prolonged imaginal exposure to the
trauma memory conducted in therapy sessions and repeated as homework, and (4) prolonged
in vivo exposure implemented as homework. There is substantial evidence that exposure
programs are highly effective in the treatment of PTSD, no compelling evidence that any
CBT program is more effective than exposure therapy, and no evidence for the usefulness of
adding other components to exposure therapy [10].
3. Applying Exposure Therapy to PTSD in Vietnam Veterans
PTSD is one of the most disabling psychopathological conditions affecting the veteran
population. Approximately 15.2% of the men and 8.5% of the women who fought in
Vietnam were found to be suffering from PTSD 15 or more years after their service. An
estimated 830,000 veterans currently have symptoms of chronic combat-related PTSD [31].
Evidence suggests that behavioral therapies with an imaginal exposure component have
been more effective than most other types of treatment for combat-related PTSD [28, 30],
although the effects are not robust in veterans.
Both exposure in imagination and exposure in vivo to trauma related events appear to be
therapeutic. The exposure treatment that has been developed by Foa and her colleagues
typically incorporated imaginal exposure that has the patient recall the traumatic memories
in the therapist's office. The patient is asked to relive the trauma in his or her imagination.
The patient is asked to close his or her eyes and to describe it out loud in the present tense,
as if it were happening now. Very often, this narrative is tape recorded (audiotaped) and that
tape is sent home with the patient so that s/he may practice imaginal exposure at home,
usually daily, between therapy sessions. Although this reliving is often painful for the
patient initially, it quickly becomes less painful as exposure is repeated. The idea behind this
type of treatment is that the trauma needs to be emotionally processed, or digested, so that it
can become less painful. The process is similar to the grief process: when a loved one dies,
it is extremely painful, but by expressing that pain, it gradually becomes less painful. Also,
many patients with PTSD mistakenly view the process of remembering their trauma as
dangerous and therefore devote much effort to avoiding thinking or processing the trauma.
Imaginal reliving serves to disconfirm this mistaken belief and thus helps reduce the PTSD
symptoms associated with this belief. For the sake of brevity, only the literature on exposure
therapy for PTSD in Vietnam veterans is briefly reviewed below.
Imaginal exposure was successfully applied to PTSD in a case study by Keane and
Kaloupek [14]. Only three controlled studies have examined the utility of prolonged
imaginal exposure (PE) for reducing PTSD and related pathology in male Vietnam veterans.
Treatment was conducted over 6 to 16 sessions. In one study, all clients received the
"standard" PTSD treatment (weekly individual and group therapies) in addition to exposure
[6]. In the second study by Keane et al., [13], PE was compared to a waiting-list control
group. During each session, patients were initially instructed to relax. The patients then
received 45 minutes of imaginal flooding, followed by relaxation. In the third study, all
patients received a group treatment milieu program; one-half received additional PE and the
remaining patients received weekly individual traditional psychotherapy [4-5].
All three studies found some benefit from the PE compared to the control groups, but
the effects were small. In the Cooper and Clum [6] study, PE reduced the PTSD symptoms,
but had little effect on depression or trait anxiety. A mixed picture emerged from the Keane
et al. [13] study: therapists rated exposure clients as more improved on PTSD symptoms
than control clients, but on self-report measures of these symptoms no differences were
detected. However, exposure patients did rate themselves as more improved on general
psychopathology measures than those in the waitlist control. Boudewyns and Hyer [5] found
no group differences on psychophysiological measures, but at the three-month follow-up,
the exposure group improved more on the Veterans Adjustment Scale (VAS). In further
analysis of the data with additional patients, a higher percentage of the exposure-treated
clients were classified as successes when compared with those receiving traditional therapy
[4]. An uncontrolled report found that flooding benefited Vietnam veterans with PTSD only
on avoidance symptoms as measured by the IES and self-recorded number of daily
intrusions [17].
4. Virtual Reality Exposure Therapy for Vietnam Veterans with PTSD
Obviously, in vivo exposure to combat situations is not a viable option. Thus, a Virtual
Vietnam environment was created to explore the efficacy of VRE with Vietnam combat
veterans with PTSD. Two virtual environments, a virtual Huey helicopter (see Figures 1-4)
and a virtual clearing surrounded by jungle were created. In the virtual jungle clearing, the
audio effects include recordings of jungle sounds i.e., crickets, gunfire, helicopters, mine
explosions, and men yelling “Move out! Move out!” which can be increased in intensity.
Visual effects include muzzle flashes from the jungle, helicopters flying overhead, landing
and taking off, and fog. In the virtual helicopter, audio effects include the sound of the
rotors, gunfire, bombs, B52s, engine sounds, radio chatter, and men yelling “Move out!
Move out!” Visual effects include the interior of a Huey helicopter in which the backs of
the pilot’s and copilot’s heads with patches are visible, instruments, controls, as well as the
view out of the helicopter side door.
Figure 1. The landing zone (clearing) of the Virtual Vietnam.2
2
Figures reprinted with permission from Virtually Better, Inc (www.virtuallybetter.com).
Figure 2. The view out of the virtual helicopter in the Virtual Vietnam. 3
This view includes aerial shots of other helicopters flying past, clouds, and the terrain below
which included rice paddies, jungle, and a river. Patients were exposed to their most
traumatic Vietnam memories while immersed within the virtual environments following a
standard treatment manual. The therapist attempts to match what the patient is describing for
imaginal exposure (e.g., “The chopper is landing now and I hear explosions all around me.”)
with what the patient sees and hears and feels in the virtual reality (e.g., landing the
helicopter amid explosions and gunfire). A difference between standard Prolonged Exposure
for PTSD [9] and virtual reality exposure for PTSD is that in VR, patients’ eyes are open to
see the stimuli.
3
Figure 3. The landing zone (clearing) of the helicopter Virtual Vietnam 4
Figure 4. The view inside of the virtual in the Virtual Vietnam. 5
During virtual reality exposure sessions patients wear the head-mounted display with
stereo earphones that provide visual and audio cues consistent with looking out over
Vietnam terrain from a Huey helicopter and walking around a swampy clearing. To increase
the effectiveness of the illusion of actually being in a helicopter, patients are seated in a
"Thunder seat" similar in structure to an airplane seat with a woofer below the seat that adds
vibrations. Metal may interfere with the position sensors, so wood or plastic chairs should be
4-5
used. In all the environments the patient experiences only computer-generated audio and
visual stimuli while "real-world" stimuli are shut out. The therapist communicates with the
patient with a microphone connected through the computer to the headphones. The therapist
is able to control the apparent closeness of the stimuli with the audio effects and volume
control.
The patient should be encouraged to expose him or herself to traumatic memories
triggered by the virtual environments, following guidelines for standard exposure therapy.
As most Vietnam veterans have several traumatic memories, it is important to address each
in a separate session per incident unless they are naturally tied together by the patient. The
therapist asks the patient to give a SUDs (Subjective Units of Discomfort, 0= no anxiety and
100=maximum anxiety) rating approximately every five minutes during all exposures as an
indication of level of anxiety. The therapist makes appropriate comments and encourages
continued exposure until anxiety has habituated. The patient is allowed to progress at his/her
own pace (see below for the Summary Treatment Outline). The therapist simultaneously
views on a video monitor all of the virtual environments in which patients are interacting
and therefore is able to comment appropriately. Therapist's comments are identical to what
would be expected for conventional exposure. Treatment is terminated when the patient
indicates no anxiety associated with the exposures or after the predetermined last session,
whichever is first.
Session 1 is devoted to information gathering by the therapist, explaining the rationale
for treatment, building rapport, and acquainting the patient with virtual reality using a
neutral virtual environment (VE). Information can be gathered on the patient's Vietnam
service and combat experience. Information is collected on the 3 most traumatic experiences
in Vietnam. The rationale for treatment centers on emotional processing theoretical account
of the helpfulness of exposure therapy and briefly reviewing the efficacy of VRE therapy.
The patient is given a handout explaining the rationale for treatment. At the end of the
session, the patient is familiarized with VR using a neutral VE. Any questions are answered
and discussed.
Exposure treatment begins in Session 2. Treatment proceeds in an additive manner. The
first sessions expose the patient to the virtual environments of Vietnam only without
incorporating any imaginal exposure to his own traumatic memories. This VE only exposure
continues until the patient has demonstrated habituation as evidenced by a decrease in SUDs
and clinical judgment. Once habituated to VE only exposure, the next step is exposure to
triggered memories. The patient is asked what memories are triggered by the VE. The
therapist focuses on one memory at a time and asks the patient to repeat it until he has
habituated. The patient describes the memory in the present tense with eyes open to view the
VE. When the patient has habituated to the first memory, he is asked what other memories
the VE triggers and continues in the same manner through that memory and others that arise.
Once the patient has habituated to these triggered memories, he is asked to recount his most
traumatic memories that had been discussed in Session 1. He is asked to recount that
experience in the present tense, making sure to include stimuli, responses, and meaning,
repeatedly until anxiety has habituated to that memory. Then the next traumatic memory
will be recounted for exposure, and so on, until anxiety has habituated to the 3 to 5 most
traumatic memories. These sessions should be tape recorded (audio) and the tapes given to
the patient to practice imaginal exposure as homework. It is very important to audiotape all
imaginal exposure to the traumatic memories and assign imaginal exposure (obviously
without virtual reality) with the audiotape at home daily. Simply turn on the tape recorder
during the session as the imaginal exposure is begun. The therapist should inquire at the
beginning of each session about how the imaginal exposure at home is going.
The therapist should attempt to match the virtual stimuli to the patient’s description of
his traumatic experience, for example by landing the helicopter at the appropriate time in the
memory, or by having gunfire, bombs, fog, or night time to match the memory. This is only
attempted during the phase of treatment in which the patient is exposed to his most
traumatic memories while in the VR. The therapist should make appropriate comments and
encourage continued exposure until anxiety has habituated. Some sample comments include:
"You are doing great! You see, by staying with it your anxiety is coming down."
"Make sure your eyes are open."

"It's okay to feel anxiety. That's what we're here for."
"If you didn't feel any anxiety, this wouldn't be working."
"We'll stay at this level as long as you like. We're not in any hurry."
"Let me know when you feel ready for the next step."
"What scares you now? Tell me what you fear."
The patient is allowed to progress at his own pace in the preset order of the hierarchy of
exposures. It may be helpful to inform the patient’s significant other (e.g., wife or girlfriend)
of the need for the patient to listen to the tape daily and that this may be upsetting for him
and the need for understanding and support. It is important to warn the patient and his
significant others that it will seem as if he is getting worse before he gets better, and that this
is actually a good sign that he is emotionally processing his traumatic experiences. The
entire course of treatment should last 8 to 12 sessions and may proceed as follows twice
weekly:
The first use of VRE for a Vietnam veteran with PTSD was reported in a case study
[22]. The veteran was a 50-year-old, Caucasian male meeting DSM-IV criteria for PTSD,
major depressive disorder and past alcohol abuse. He served as a helicopter pilot in Vietnam
approximately 26 years prior to the study. Treatment consisted of fourteen, 90-minute indi-
vidual sessions conducted over a 7-week period. Results indicated post-treatment improve-
ment on all measures of PTSD and maintenance of these gains at a 6-month follow-up.
An interesting case report describes the treatment by exposure therapy of a Vietnam

veteran for PTSD related to his war experiences using the Virtual Vietnam. There are
several unique features of this particular treatment and case report. One, the nature of
several of these traumatic memories included guilt over acts that the patient committed in
Vietnam, a sort of history which frequently indicates a poor candidate for exposure therapy.
Two, psychophysiological monitoring occurred throughout the treatment as well as at pre-
and post-treatment. His response to treatment, in terms of guilt, anger, and anxiety,
measured at pre- and post-treatment and follow-ups of 3- and 6-months, and psychophysio-
logical responding, indicated a successful treatment [29].
This case study was followed by an open clinical trial of VRE for Vietnam veterans
[26]. In this study, 16 male patients who met DSM-IV criteria for PTSD were entered and 10
completed VRE. An average of 10, 90-minute exposure therapy sessions delivered over five
to seven weeks resulted in a significant reduction in PTSD and related symptoms. The
average age of the group was 51 years (SD 3.16). Fourteen of 16 were taking one or more
psychotropic medications for PTSD symptoms. Persons who were actively addicted, had
serious heart conditions, psychosis, bipolar disorder, unstable medication regimes, planned
departures from the Atlanta area, uncontrolled suicidal intention and/or lack of approval
from their treating physicians were excluded. All had served in combat operations in
Vietnam and the group averaged heavy combat exposure. The majority was being
compensated through the VA system for disabilities. Follow up in this population proved
difficult, as many of the participants live in remote areas. Ten completed the required
treatment sessions, however one did not attend any post-treatment assessments. Table 1
contains the means and standard deviations on the primary measures at pre-treatment, post-
treatment, and 3- and 6-month follow-ups.
Table 1. Pre- and Post-Treatment, and 3- and 6-month Follow-up (FU) Means (SD)
Measure Baseline (N=9) Post-Tx (N=9) 3 Mo FU (N=5) 6-Mo FU (N=8)

CAPS 68.00 (15.26) 57.78 (20.61) 54.6 (17.47) 47.12 (17.04)
Total Score p=.0727 p=.0256* p=.0021*
% Decrease –15% –27% –31%

Range +41% to –38% –13% to –48% –15% to –67%
CAPS Cluster B 16.33 (6.06) 13.89 (6.33) 9.40 (6.99) 11.12 (4.45)
Reexperiencing p=.2812 p=.0231* p=.0103
CAPS Cluster C 28.22 (8.18) 24.78 (10.74) 23.20 (7.33) 17.25 (9.35)
Avoidance p=.2814 p=.0507 p=.0116*
CAPS Cluster D 23.44 (4.47) 19.11 (8.91) 22.00 (4.69) 18.75 (5.31)
Arousal p=.1163 p=.0777 p=.0021*
IES 42.89 (10.20) 36.11 (21.64) 19.4 (14.71) 29.88 (19.39)
Total Score p=.3988 p=.0327* p=.0912
IES 20.33 (6.10) 16.11 (8.56) 8.00 (9.07) 13.88 (10.48)
Intrusion p=.2126 p=.0135* p=.0949
IES 22.55 (7.88) 20.00 (15.43) 11.40 (5.86) 16.00 (10.61)

Avoidance p=.6259 p=.1585 p=.1412
Beck Depression 26.11 (11.36) 21.77 (10.12) 25.6 (12.28) 17.85 (11.01)
Inventory p=.09 p=.38 p=.01*
After treatment, the majority of patients’ ratings of their global improvement indicated
improvement. At 6 months, 6 of 8 reported improvement. Clinician’s ratings of patients’
global improvement as measured by the CGI indicated that 5 of 6 showed improvement
immediately after the study while one appeared unchanged. At 6 months, 7 of 8 were rated
as demonstrating some improvement. Clinician-rated PTSD symptoms as measured by the
CAPS, the primary outcome measure, at 6 month follow-up indicated an overall statistically
significant reduction from baseline in symptoms associated with specific reported traumatic
experiences. Eight of 8 participants at the six-month follow up reported reductions in PTSD
symptoms ranging from 15 to 67%. Significant decreases were seen in all three symptom
clusters. Patient self-reported intrusion and avoidance symptoms as measured by the IES
were significantly lower at 3 months than at baseline but not at 6 months, although there was
a clear trend toward fewer intrusive thoughts and somewhat less avoidance.
Clinicia n Adminis te re d P TS D
S ca le
70
60
50
40
30
20
10
0
PRE POST 3 mo FU 6 mo FU
Figure 5. Clinician Administered PTSD Scale
Impa ct of Eve nts S ca le

45
40
35
30
25
20
15
10
5
0
PRE POST 3 mo FU 6 mo.FU
Figure 6. Impact of Events Scale.

In conclusion, VRET led to significant reductions in PTSD and related symptoms and
was well tolerated. None of our worst fears were realized. No person de-compensated due to
exposure to the VREs. No participant was hospitalized during the study for complications
related to the treatment. Most of those who dropped out of the study were provided
opportunities for other treatment within the PTSD Clinical Team clinic at the Atlanta VA
Medical Center and did not appear to suffer any long-term problems attributable to their
participation. This preliminary evidence suggests that VRE may be a promising component
of a comprehensive treatment approach for veterans with combat-related PTSD.
4.1 VRE Combined with Medication
Some very recent data suggest that medication may facilitate VRET [19]. D-Cycloserine, a
partial agonist at the N-methyl-D-aspartate receptor, has previously been shown to improve
extinction of fear in rodents. This study utilized a precisely controlled VR exposure
paradigm to examine the ability of D-Cycloserine to facilitate the emotional learning that
occurs in behavioral exposure therapy. Participants with a fear of heights underwent two
therapy sessions, which is considered a suboptimal amount of exposure therapy for
acrophobia. Single doses of placebo or D-Cycloserine were taken prior to each of the two
sessions of VRE. Patients returned at one week and 3 months for post-treatment measures
to determine the presence and severity of acrophobia symptoms. The group receiving D-
Cycloserine during VRE demonstrated significantly greater improvements on general
measures of real-world acrophobia symptoms that was evident early in treatment and was
maintained at 3 months and on measures of anxiety, attitudes towards heights, clinical
global improvement, and number of self-exposures to real-world heights for the DCS group
that was related to improvement. There was also evidence of decreased physiological
responding within the virtual environment. This may have implications for PTSD and the
exposure therapy for other anxiety disorders.
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Acknowledgements
This research was supported by NIMH grant #5 R21 MH55555-02 awarded to

Dr. Rothbaum.
Disclosure Statement: Dr. Rothbaum receives research funding and is entitled to sales
royalty from and owns equity in Virtually Better, Inc, which is developing products related
to the research described in this paper. The terms of this arrangement have been reviewed
and approved by Emory University in accordance with its conflict of interest policies.
M.J. Roy (Ed.)
IOS Press, 2006
Developing A Virtual Reality Treatment

Protocol for Posttraumatic Stress Disorder
following the World Trade Center Attack
JoAnn DIFEDE1ab, Judith CUKOR ab, Nimali JAYASINGHEab and
Hunter HOFFMANcd
a
Weill Medical College of Cornell University, New York, New York
b
The New York Presbyterian Hospital, New York, New York
c
Human Interface Technology Laboratory, University of Washington,
Seattle, Washington
d
Department of Psychology, University of Washington, Seattle, Washington
Keywords. PTSD, Virtual reality exposure therapy, terrorism
Introduction
Posttraumatic stress disorder (PTSD) represents a significant burden for individuals and
their communities in the U.S. General population surveys suggest that anywhere
between 39% and 90% of adult civilians are exposed to at least one traumatic event
during their lifetime and that between 15% and 24% of affected individuals will go on
to develop PTSD [1-3]. Based on such findings, researchers estimate that 8-9% of
individuals in the population to be at risk for at least one episode of PTSD at some
point in their lives [1-3].
People who suffer from this condition are at high risk for developing other
psychological conditions – especially mood disorders, anxiety disorders, and substance
abuse disorders [4]. In addition, PTSD is associated with adverse outcomes such as
marital discord and unemployment [4] and results in a productivity loss of about US$
three billion per year for the nation’s economy [4]. Without treatment, PTSD
symptoms, once established, are often persistent [5]: the National Comorbidity Survey
indicates that more than one-third of PTSD cases never fully remit after many years,
independent of receiving treatment [5].
The terrorist attacks of September 11, 2001 on the WTC claimed the lives of an
estimated 2,948 people in New York City [6]. Tens of thousands of others who were in
the WTC that day escaped. Those who survived exposure to the attacks, however, face
the possibility that PTSD will affect their lives in other ways. Those persons at high
risk include individuals who were working in the towers that morning but escaped,
1
Corresponding Author: JoAnn Difede. Associate Professor of Psychology in Psychiatry Director, Program
for Anxiety and Traumatic Stress Studies Weill Medical College of Cornell University, New York
Presbyterian Hospital525 East 68th Street, Box 200 New York, New York 10021 212-746-3079
220 J.A. Difede et al. / Developing a Virtual Reality Treatment Protocol for PTSD
either injured or physically unharmed; eyewitnesses in the area surrounding the towers
that morning who watched large numbers of people jumping hundreds of stories to their
deaths on the sidewalks as the towers were hit, burned, and finally fell; disaster workers
who rushed to the scene or were involved in recovery efforts; and residents of the
downtown area, many of whom were displaced from their homes.
A telephone survey of selected residents throughout Manhattan conducted between
five and eight weeks after September 11 indicated that some 7.5% of respondents
complained of symptoms consistent with a diagnosis of PTSD and researchers
estimated on this basis that some 67,000 persons in Manhattan alone were suffering
from PTSD at the time [7]. Meanwhile, a door-to-door screening of selected residents
in the area immediately surrounding the WTC conducted at the end of October 2001
indicated that almost 40% of respondents endorsed symptoms consistent with a
diagnosis of PTSD [8]. With regard to disaster workers, another study indicated that
nearly 20% of civilian medical volunteers reported acute PTSD symptoms [9]. These
figures provide a glimpse of the challenge that mental health services professionals face
in addressing the needs of survivors in New York.
Expert treatment guidelines for PTSD were published for the first time in 1999,
recommending that cognitive-behavioral treatment with exposure therapy should be the
first-line therapy for PTSD [10]. For the exposure component of the therapy, most
treatments employ imaginal exposure, in which the patient either listens to the therapist
recounting a vivid description of the traumatic event or the patient self-
generates/recounts their own trauma memories themselves repeatedly with gradually
increasing detail. [11]. In a recent and extensive review of extant research, Rothbaum,
Meadows, Resick, and Foy write that some 12 controlled studies show positive
outcomes for exposure treatment for PTSD[11]. They note, for instance, that studies
have demonstrated the effectiveness of exposure in treating Vietnam combat veterans
[12-17], female victims of sexual assault [18-20], and mixed trauma populations who
have experienced both military and civilian traumas [21-24]. In addition, at least two
preliminary studies have revealed positive results for interventions including exposure
in treating survivors of terrorism [25-26].
Emotional engagement or fear activation plays a critical role in exposure therapy.
Foa and Kozak [27] propose that in order for fear reduction to occur, fear relevant
information associated with the patient’s memory for the traumatic event (i.e., the fear
structure) must be accessed and activated through emotional engagement. In addition,
after the fear structure is aroused through emotional engagement, new or corrective
information is incorporated into the patient’s memory structure. The authors argue that
repeated safe contact with a feared stimulus is necessary for fear structures to change,
thereby allowing long-term habituation to take place.
Though the efficacy of exposure therapy has been established in multiple studies
with diverse trauma populations [11], imaginal exposure presents an impossible
dilemma for some patients: effective imaginal exposure, according to standard
protocols used in PTSD treatment outcome research [25], requires that the patient tell
his/her trauma in the present tense to their therapist, over and over again; yet avoidance
of reminders (e.g., thoughts, emotions, places) of the trauma, is inherent in PTSD.
Hence, most people with PTSD never seek treatment, some patients who seek treatment
refuse to engage in the treatment, and others, though they express willingness are
unable to engage their emotions or senses, retelling a flat emotionless tale, reflecting
their numbness. Such patients typically fail to improve.
J.A. Difede et al. / Developing a Virtual Reality Treatment Protocol for PTSD 221
This is consistent with the few studies that have addressed the question of
treatment failures, and which conclude that failure to engage emotionally predicts a
poor treatment outcome. One of the first and only studies to examine treatment
variables that mediate outcome in the treatment of PTSD investigated the impact of the
variables emotional engagement and habituation on successful outcome of exposure
therapy for chronic PTSD in female assault victims [28]. Results showed that although
all participants made treatment gains, those with high emotional engagement in the
treatment and habituation to emotion-eliciting stimuli were eight times more likely to
meet stringent criteria for good end-state functioning, (e.g., a 50% reduction in PTSD
symptom scores and normal scores on measures of depression and anxiety).
Thus, while imaginal exposure therapy offers considerable promise as an effective
tool in reducing the suffering associated with PTSD, barriers to effective treatment
remain to be addressed. Studies of treatment failure highlight the importance of finding
means to motivate patients and facilitate their emotional engagement in therapy.
Recent developments in Virtual Reality (VR) technologies open new vistas for the
treatment of anxiety disorders, including PTSD. The essence of immersive virtual
reality is the illusion it gives users that they are inside the 3-D computer-generated
virtual world, as if it is a place they are visiting, an illusion known as “presence” in the
virtual world. Virtual Reality affords opportunities not only to capitalize on the
patient’s imaginative and memories capacities, but also to augment them with visual,
auditory, and even haptic computer-generated experiences [29-31]. For patients who
are reluctant to engage in recollections of feared memories, VR provides a sensory-rich
and evocative therapeutic environment, which may allow patients to experience a
“sense of presence” in the Virtual Environment [29]. In addition, VR technology
allows for graded exposure to increasingly feared virtual simulations of traumatic
events that can be carefully monitored and tailored to the individual patient’s needs
[29]. VR environments can be manipulated above and beyond the constraints of the
everyday world, thus creating new possibilities for therapeutic action [29-30,32]. As a
result, VR therapy experiences can increase patients’ feelings of self-efficacy and their
sense of being active agents of their own therapeutic progress. In addition, patients
have been found to be more willing to consider VR therapy than other forms of
exposure therapy [29-32]. For example, in one survey, people with fear of spiders were
asked to choose between in vivo exposure vs. VR exposure therapy, 81% chose VR,
suggesting that VR exposure therapy may eventually prove valuable for increasing the
number of patients who seek treatment for anxiety disorders. The VR world often does
not include the same risks as returning to the feared real world environment or event.
Because therapists view on a computer monitor what the patient is seeing in the helmet,
patients can feel supported in knowing that the therapist is sharing in the patient’s
experiences in the virtual world [29-32].
Hence, in the treatment of PTSD, VR technologies can offer patients who are
fearful or unable to recount their experiences an external setting a computer-generated
environment in which to encounter and master their trauma. The multiplicity of
sensory cues that VR affords also provides a greater possibility of generating patient
involvement and a sense of presence that can facilitate processing of the traumatic
experience. And, because the Virtual Environment can be encountered at the patient’s
own pace, a firm distinction can be created between remembering and reliving.
Several case reports and controlled research studies attest to the utility of VR
exposure in the treatment of anxiety disorders including acrophobia, fear of flying,
spider phobia, claustrophobia, and PTSD [31, 34-42]. In two published reports, VR
graded exposure has been successfully employed in treatment of combat-related PTSD.

Rothbaum and colleagues conducted a 14-session VR treatment of a man who had
served in Vietnam 26 years earlier and suffered from chronic PTSD and Major
Depression at the time of treatment [41]. The patient’s clinician-rated level of PTSD
dropped by 34% (from the severe to moderate range) and his self-reported levels of
PTSD decreased by 45%. Furthermore, these notable clinical gains were maintained at
six-month follow-up. The success of VR treatment for PTSD was further bolstered by
a study of 10 Vietnam veterans [42]. In this study, patients participated in twice-
weekly sessions, with treatment ranging from 8 to 16 sessions. Patients in this study
demonstrated a 15% to 67% decrease in PTSD at six-month follow up. In summary,
VR exposure has been proven to be an effective treatment for a variety of phobias and
although randomized controlled studies have not yet been published using VR for
PTSD, preliminary results have shown that VR can be helpful for treating PTSD.
We recently published the first case report on the use of VR therapy to treat PTSD
following the World Trade Center attacks of September 11, 2001 [50]. The civilian
patient, who witnessed the attack from outside the buildings and had to escape as the
Towers collapsed, was diagnosed with PTSD and a co-morbid depression. She had
been previously unable to engage in imaginal exposure therapy. According to the
standardized treatment outcome measures (Beck Depression Inventory and the
Clinician Administered PTSD Scale), the patient showed a large reduction in both
PTSD (90% reduction) symptoms and depression (83% reduction) after six VR
sessions. Although conclusions cannot be based on the outcome of one patient, the fact
that the patient responded so well to VR therapy after failing to respond to imaginal
exposure therapy provided enough encouraging preliminary evidence to suggest that
more controlled studies were warranted.
The goal of our study is to evaluate the efficacy of the use of virtual reality
exposure therapy in the treatment of PTSD resulting from terrorism in individuals who
directly witnessed the World Trade Center attacks on September 11, 2001. As the data
from the clinical trial are currently being prepared for publication, the following
sections outline the methods and offer commentary on the rationale for our choices.
We also present some discussion of problems in implementation that we thought would
be useful information for others who are thinking about implementing virtual reality
research protocols.
1. Materials and Methods
1.1. Participants and Measures
Enrolled subjects met diagnostic criteria for PTSD and directly witnessed at least part
of the attacks of September 11. Subjects in the treatment group received treatment
based upon a 14–week protocol that integrates virtual reality exposure with other
cognitive-behavioral techniques. Symptoms of PTSD and other significant indicators of
psychopathology were assessed using structured clinical interviews and self-report
measures with well-established psychometric properties at three time points: pre-
treatment, immediately post-treatment, and at six-month follow-up. All clinical
assessments were conducted by an independent assessor. In addition, VR participants
completed self-report measures prior to every treatment session. All VR sessions were
videotaped and reviewed weekly in supervisions with the senior psychologist

associated with the project.
Exclusion criteria were: (1) presence of current organic mental disorder (2) schizo-
phrenia (3) bipolar disorder (4) depression with psychotic features (5) current substance
dependence (6) delusional disorder (7) active suicidal ideation, intent, or plan (8) active
homicidal ideation, intent, or plan (9) history of chronic childhood sexual abuse and
(10) use of pacemaker.
Participants who met the broad inclusion criteria of the study were assessed by a
doctoral-level clinician with the Clinician Administered PTSD Scale (CAPS) [43],
Trauma History Questionnaire [44], and the full SCID (non-patient version) [45]. The
self-report questionnaires include the Posttraumatic Symptom Checklist (PCL) [46],
Beck Depression Inventory, [47], State-Trait Anger Inventory [48], and Brief Symptom
Inventory [49].
1.2. Training
All psychologists conducting treatment had been trained to conduct imaginal exposure
in a diverse trauma sample including civilian and disaster worker survivors of the WTC
attack. All VR exposure sessions were videotaped and reviewed with the senior
psychologist (J.D.) who has fifteen years experience assessing and treating PTSD in
diverse trauma populations. New therapists participated in group supervision with the
clinicians who were already treating patients to learn the structure of the protocol and to
become familiar with issues in implementing cognitive behavioral therapy with
imaginal and VR exposure therapy.
1.3. Equipment
A Dell (www.dell.com) 530 workstation with dual 2-gig CPUs, 2 gigs of RAM, a
Wildcat 5110 video card, Windows 2000 operating system, and MultiGen-Paradigm
Inc Vega VR software (www.multigen.com) was coupled with a 1,024 2 X 768
resolution Kaiser XL-50 VR helmet, with 40 degrees horizontal field of view
(www.keo.com/proviewxl3550.htm). A PolhemusTM Fastrak position tracking system
was used to measure the position of the user’s head (www.polhemus.com).
During VR exposure therapy, the patient wore a head-mounted virtual reality
helmet that positioned two goggle-sized miniature LCD computer screens close to the
patient’s eyes. Position tracking devices kept the computer informed of changes in the
patient’s head location. An electro-magnetic head orientation device fed the x,y,z
coordinates of the patients head to the computer, which could quickly change what the
patient saw in virtual reality accordingly (e.g. the patient saw the streets and buildings
if they looked straight ahead, they saw the WTC towers and sky if they looked up, etc).
The scenery in VR changed as the patient moved her head orientation (e.g., virtual
objects in front of the patient in VR got closer as the patient, wearing the VR helmet,
leaned forward in the real world). The essence of immersive virtual reality is the
illusion it gives patients that they are have gone inside the 3-D computer generated
environment/virtual world.—as if they are “there” in the virtual world. In the present
study, the place the patients visited was lower Manhattan, and the event re-experienced
was a computer simulation of the September 11th attack on the WTC.
After the therapist helped the patient put on their VR helmet, the patient saw the
twin WTC towers from a distance, with no sound effects, with a sunny blue sky, as it
appeared the morning of September 11, 2001. Over the course of the exposure sessions,
the patient progressed through a series of sequences that increased in intensity and
detail. The virtual world was programmed such that the therapist was able to control
what the patient experienced in VR by touching pre-programmed keys on the keyboard.
During the exposure segments, the therapist simultaneously viewed the virtual
environments on a video monitor and provided comments and encouragement to ensure
that the patient is able to continue with exposure until anxiety is sufficiently reduced. .
The therapist monitored the patient’s self-reported Subjective Units of Distress (SUDS)
on a scale of 0 to 100 every five minutes.
The following is a list of the sequences viewed by the patient:
a) A jet flies over the WTC towers, but doesn’t crash, normal New York city street
sounds.
b) Then a jet flies over, hits building, but no explosion
c) Then a jet flies over, crashes with explosion, but no sound effects
d) Then a jet flies over, crashes with explosion, and explosion sound effects
e) Burning and smoking building (with hole where jet crashed), no screaming
f) Burning and smoking building (with hole where jet crashed) and screaming
g) Burning and smoking building (with hole where jet crashed), screaming, and
people
jumping (see Figure 1)
h) Second jet crashes into second tower with explosion and sound effects
i) Second tower collapses with dust cloud
j) First tower collapses with dust cloud
k) The full sequence
Figure 1. A computer-generated avatar (virtual human) falling from the WTC. Patients were exposed to such
images only during the final stages of therapy, when they could tolerate the VR experience without excessive
distress (image created and copyrighted by Hunter Hoffman, U.W.).
1.4. Procedure
The WTC virtual environment was constructed to allow for a graded hierarchical
exposure to the stimuli in the world. The program was carefully constructed in this
fashion to prevent overwhelming or flooding the patient. The treatment followed the
principles of imaginal exposure. The pace was individualized and patient-driven. For
the sequences in the WTC world that were relevant to the patient’s experience, each
sequence in the VR menu was repeated until the Subjective Units of Distress level
decreased by at least 50% . Each sequence was repeated a number of times before
habituation occurred. The next sequence was not approached without the patient’s
verbal assent. This procedure was designed to evoke a level of response that created
discomfort, but was tolerable. Gradually, as the patient habituated to their experience,
they were able to approach sequences that more nearly approximated the traumatic
event.
In addition to the virtual reality exposure therapy, the treatment included common
components of other exposure therapies including: (1) psychoeducation, in which the
patient learned about common reactions to trauma and related these to their experience;
(2) relaxation training, in which the patient learned relaxation and breathing techniques
valuable in the management of anxiety and stress; (3) cognitive restructuring, in which
the patient challenges his thoughts and beliefs about himself, the world and his trauma
experience. Components of each of the sessions are outlined in Table 1.
Table 1. Outline of VR Exposure Therapy Treatment Sessions
Session Components of VR Exposure Treatment

1 • Psychoeducation – patient learns about common reactions to trauma and rationale of
treatment and recounts their trauma experience to therapist to begin to build foundation
for exposure therapy in future sessions
• Stress management – patient learns and practices controlled-breathing and relaxation
techniques
2 • Relaxation – patient is instructed in controlled breathing and commonly-used relaxation
techniques
• Imaginal Exposure – patient participates in imaginal exposure: target 30 minutes in
exposure
3 • Relaxation - techniques and uses are reviewed
• In vivo exposure – patient and therapist discuss avoidance symptoms. The technique of in
vivo exposure is introduced and graded hierarchies are drawn up and assigned to be
completed outside of the session
• VR Exposure – patient is familiarized with VR equipment with a target of 30 minutes in
VR
• In vivo exposure – assignment is reviewed and the next step in the hierarchy is assigned
for homework
• Planning for Pleasure – patient is instructed in importance of scheduling pleasurable
activities and plans pleasurable activities for week
•VR Exposure target 45-60 minutes

• In vivo exposure – assignment is reviewed and the next step in the hierarchy is assigned
for homework
• Planning for Pleasure – assignment is reviewed and patient plans for activities for
upcoming week
• Cognitive restructuring – patient learns rationale for CR and examines changes in beliefs
about self/world
•VR Exposure target 45-60 minutes
6-9 • Relaxation, In vivo exposure, Planning for Pleasure – uses reviewed and upcoming
assignments planned
• Cognitive restructuring – patient examines changes in beliefs about self/world
• VR Exposure to triggered memories target 45-60
10-13 • Relaxation, In vivo exposure, Planning for Pleasure – uses reviewed and upcoming
assignments planned
• Cognitive restructuring – patient examines changes in beliefs about self/world as well as
existential issues such as meaning of life/death
• VR Exposure- while in the VR world, exposure to most traumatic memories VR target
45-60 minutes
14 • Wrap-up - Patient review skills learned and change in symptom picture
• Discussion of schedule for post-treatment assessment and follow-up
2. Clinical Profiles of Our PTSD Treatment Population
To date, nine patients have successfully completed our virtual reality treatment
protocol. Three were utility workers, three New York City firefighters, and three
civilians. Seven of the nine patients entered the VR exposure therapy study only after
failing to respond to traditional PTSD treatment! That makes these results especially
important since there are currently few treatment options available for patients who do
not respond to imaginal exposure therapy. It is possible that VR could become an
effective option for some “non-responders” who fail to respond to imaginal exposure
therapy. The following clinical vignettes are provided so that the reader may have a
more vivid picture of the types of clinical presentations we deemed appropriate for our
virtual reality treatment.
Individuals with PTSD from direct exposure to the WTC usually presented with
anxiety, irritability, and sleep problems, (i.e., sleep latency and continuity), as their
most common complaints [52]. Those in this group usually had direct and prolonged
exposure to the attack beginning on September 11, 2001, as illustrated by Mr. G, a
utility manager. He responded within minutes of the attack, with sufficient time to
observe the Towers fall. His usual responsibilities included responding to emergencies
and assessing safety factors. Thus, he had the burden of knowing his decisions would
affect the safety of his employees and the community. Mr. G. grew up in the same
neighborhood where he currently resided and was a well-respected community leader.
The community was home to scores of firefighters, police, and utility workers. As a
consequence of his stable community ties, he knew countless men who died at the
WTC on September 11, 2001, many of them since their childhood. He continued to
work at the WTC site supervising operations until the site closed in May, 2002 thus he
had ongoing exposure to the carnage of human remains and the pervasive destruction.
Upon presentation, he was anxious and tearful and could no longer control his
irritability. He accepted treatment because he believed that he would be more effective
in his quest to help others, if he was able to accept treatment for himself, and in so
doing serve as a role model to others who could benefit from treatment.
In contrast, the experience and profile of one of our civilian patients’, whose case
has been previously published [50] was quite different. The patient, a 26-year-old
single African American female, was diagnosed with post-traumatic stress disorder
approximately four months after the attack on the WTC. Prior to Sept 11th, she served
as an executive for a large financial institution located near the WTC, she had
functioned well in a very competitive industry. She described herself as optimistic and
ambitious prior to the WTC attacks.
Arriving to work near the World Trade Center on Sept 11th, she was across the
street from the North tower when the first plane hit. During her initial evaluation she
described what happened to her on Sept 11th with little emotion and denied feeling
terror. Her re-experiencing symptoms included frequent unbidden intrusive imagery of
the plane striking the tower, and the building collapsing, being distressed when
confronted with reminders, and occasional flashbacks. The patient’s avoidant
symptoms were extensive, and included avoiding thoughts of the attack, avoiding
reminders of the attack (e.g., refusal to watch TV news or read newspapers) and
avoiding situations where she perceived herself to be especially vulnerable (e.g., she
would not stay in her boyfriend’s apartment because it was on a high floor of a tall
tower). Although she was raised in a close extended family, she described feeling
distant, and cut-off from her family and friends after September 11th. Her symptoms of
hyperarousal included difficulty falling asleep and staying asleep, difficulty
concentrating, an exaggerated startle response and intense anger. Her hypervigilance
extended to sleeping with the lights on and keeping a pair of eyeglasses near the door.
She reported being very irritable and angry with those closest to her. She repeatedly
lost her temper and yelled at her mother and others in her family. She had “no patience”
for them. She noted that this was unlike her. Indeed it was her mother who initially
called the first author to ask for help, noting that she was very worried about her
daughter who “was not herself, and was unusually irritable.”
Using DSM-IV criteria, the patient was diagnosed with PTSD and a co-morbid
major depression. The patient reported moderate to severe symptoms in each of the
three DSM-IV cluster areas for PTSD, but did not have any other Axis I or II disorder.
She had no trauma history.
These two patients illustrate the diverse profiles of patients who have presented to
our clinical research program as eligible for the virtual reality treatment. While the first
patient had multiple previous traumas and pervasive exposure to the WTC attack and
its aftermath, the second patient had no trauma history and experienced the WTC attack
as more of a discrete event without subsequent exposure to the rescue and recovery site.
These cases illustrate that the world was sufficiently flexible and rich in sensory detail
to provide adequate sensory cues to emotionally engage those with widely disparate
experiences of the WTC attack.
3. Issues in the Development of the Study Design
In the following paragraphs we will discuss some issues in the design of the study
regarding patient eligibility criteria as well as discussion of some issues in treatment
implementation that we anticipated would occur in future VR treatment studies. While

this is by no means a complete list of all the issues faced in the design of the study and
in treatment implementation, it addresses questions that have often arisen when we
present our work at professional meetings.
3.1. Patient Eligibility Criteria:
Epidemiological studies estimate that between forty and ninety percent of the United
States population has had a trauma that would place them at risk for PTSD [1-3]. Thus
the simple case of PTSD is more likely a myth than a clinical reality. In light of the
rates of trauma in the United States, we chose not to exclude those with a significant
adult trauma history from the virtual reality exposure protocol. However, those with a
childhood history of chronic sexual abuse were excluded. It was not uncommon across
our research protocols and clinical program [52] to have patients report that memories
from their prior traumas had become activated following the WTC (i.e., a Vietnam
Veteran reporting that he was having a resurgence of intrusive imagery of his Vietnam
experience that had been dormant for decades, as well as his WTC experience).
This was consistent with our experience of another terrorist incident, the 1993
attack on the WTC, as previously reported [53]. Such a clinical picture can be
daunting, especially in the early stages of treatment when there is so much uncertainty
regarding the patient’s clinical presentation. While prior trauma is often perceived as an
obstacle to treating PTSD related to the current trauma, and indeed sometimes is so, it
need not always be the case. In our clinical program, we have observed a temptation on
the part of our trainees to construct their treatment plans to address the traumas in
historical order on the premise that the existence of the prior trauma shaped the
patient’s experience of subsequent trauma and therefore must be dealt with first to
effectively address the subsequent experience. However, in our research protocol we
instructed patients to simply inform us when they had memories or symptoms related to
their prior trauma both in and outside of the VR WTC simulation, but the treatment
remained focused on their WTC experience. The clinician would record the memories
and imagery and tell the patient that they would return to it later. While we were
initially worried as to how the processing of the WTC trauma would impact the
patient’s experience of their prior trauma, we found that our strategy was effective. For
the most part, as our patient’s processed their WTC experience their memories and
symptoms related to their prior traumas remitted. So for example, a Vietnam Veteran
who arrived at the WTC in time to witness the towers collapse presented with
flashbacks and intrusive imagery about the WTC as well as a recurrent intrusive image
of what he described as his worst experience in Vietnam. The Vietnam memory had not
intruded on a regular basis for many years but was now occurring several times a week.
By the end of treatment, the Vietnam memory had receded with minimal processing in
session. Why might this be so? Studies suggest that memory is mood congruent [54-55]
i.e., that we are more likely to recall memories consistent with our current mood state.
These studies have shown for example that when people are sad they are more likely to
remember sad memories than happy ones. Similarly, a person who develops PTSD
usually feels terror, anxiety, sadness and guilt. Thus recalling memories that are
consistent with these mood states seems more likely. By processing these mood states
regarding the current trauma in the context of the exposure therapy, the affective link to
the prior traumas may be broken allowing for the formation of a discreet memory
regarding the present trauma. The current trauma no longer provides the emotional
“fuel” to sustain the activity of the prior trauma memory.
3.2. Substance Abuse and Dependence as Exclusion Criteria
In the context of the VR research protocol, we chose to exclude substance dependence

but not substance abuse. Studies show that the co-morbidity of substance abuse with
PTSD may be as high as fifty percent [5, 56]. Substance use, especially alcohol use, is
common among disaster workers who comprise the bulk of the patients seen in our
larger clinical program from which the VR sample was drawn. Though the prevailing
clinical wisdom is to engage the patient in a plan to quit their substance use, premature
adoption of this strategy may lead to treatment failures [57]. It was our impression that
as undesirable as the excessive alcohol consumption was, we would have lost many
patients to further treatment if we had been insistent on an immediate sobriety plan
because we did not have an adequate substitute to offer that would ease their suffering.
Many refused to consider psychotropic medication as a palliative measure, despite our
urging. There is some debate in the clinical literature as to how to approach the dual
problem of PTSD and substance use. Recent evidence suggests that the PTSD should
be treated concurrently. Otherwise if the substance problem is ignored, any gains made
in the treatment hour might be mitigated by substance abuse. If the substance abuse is
treated first, the patient is likely to relapse because their PTSD symptoms, such as
intrusive imagery, are cues for drinking [58]. A challenge for future virtual reality
studies will be to integrate PTSD and co-morbid substance abuse/dependence
treatment.
4. Treatment Implementation
The development and implementation of virtual reality into our treatment protocol was
not without its challenges. Based upon the principles of exposure therapy and the
theory behind the use of virtual reality, we were able to create a clear set of guidelines
for use of the VR. However, as with any other therapeutic tool, the success of the VR
was based upon applying the general principles to fit the needs of the individual patient.
In the case of VR this challenge was manifested in a number of ways.
As with imaginal exposure therapy, the clinicians had to determine when it was
best to allow the patient to speak without interruption and when it was appropriate to
offer encouraging remarks or prompt the patient with questions. This was an especially
important determination in the virtual reality protocol since VR aims to engage the
patient through the involvement of all of his senses. The clinician had to be sensitive to
the role of his comments and questions and determine whether the interaction would
draw the patient out of the environment, or whether it would help in engaging the
patient within the environment. This may be illustrated by the following example. One
patient was engaged in the exposure exercise as evidenced by his elevated SUDS score
and visible signs of distress. In his recounting of his experience, a significant time gap
in the patient’s story was noted. The therapist thought it would be beneficial to make
the patient aware of this gap, and elicit the missing information. It was especially
noteworthy to find out if the patient was able to remember what had happened or if
avoidance of something too distressing had caused him to omit it. However, the
therapist had to consider that asking the patient a direct question might distract the
patient from the environment and thereby disengage him from the exposure exercise.
Weighing the most beneficial course of action in this situation depended on clinical
skill and experience.
There were two ways to use the VR sequences in this protocol. The clinician could
play a sequence and ask the patient what came to mind and to recount their experience.
Alternately, the patient could begin to describe his experience while the clinician would
match the virtual environment to what the patient described. It was left to the
clinician’s judgment to use each technique when it was best. This knowledge,
however, only came with practice and an understanding of the benefits of each
technique. This was difficult to relay in training and depended mostly on clinical
expertise.
Finally, distinguishing between numbing and habituation was at times a challenge.
Most of the patients seen in the VR protocol were individuals who had been
unsuccessfully engaged in prior treatment. Numbing was common. Virtual reality was
utilized to further engage the patient in the exposure exercise in an effort to access his
emotions. It proved to be a challenge, especially for less experienced clinicians, to
distinguish between scores that were low as a result of numbing and those that were
low due to habituation. Clinical judgment was vital in determining if a patient’s low
SUDS scores indicated that they had habituated to a particular part of their exposure or
were numb. Clinical supervision played a crucial role in the decision-making process
with regard to this issue.
5. Clinical Indicators of Treatment Success
As noted above we used standardized clinical and self-report measures to assess our
patients’ progress. However, it is useful to have early indicators of treatment success
that might predate improvements on objective assessments. The single best early
indicator of prognosis in our clinical experience was the spontaneous recollection of
aspects of the patient’s experience that had been forgotten. To illustrate the point, one
patient, a fifty-five year old New York City Fire Chief and former Navy pilot, who had
a central role in establishing and running the command center at the WTC before it
collapsed. He escaped from the North Tower as it was collapsing. Many around him
died while they were trying to escape with him. He recalled ducking behind a car for
safety and then running through the debris. However, he still did not believe that he
was going to die. After a few VR sessions, while in the VR world, he spontaneously
recalled running past a building near the WTC site where he heard a man, who was
wearing a jacket that said FBI (Federal Bureau of Investigation), say into a walkie-
talkie “There is a third plane coming in”. The patient, a former Navy pilot, concluded
that if there was a third plane coming in that the country must be at war. He thought to
himself for the first time “we are all going to die,” and then had a panic attack. This
memory came as a complete surprise to the patient. (Indeed, he sounded and looked
surprised as he recounted the memory). He had had no recollection of it until that point,
so it was also not possible for the clinician treating him to have been aware of a gap in
his memory. The memory appeared to be triggered by the sight of a building in the
WTC world (i.e. a specific sensory cue) that reminded the patient of the building he
was running past when he saw the FBI agent. This spontaneous recollection served as
pivotal point in the patient’s treatment.
Though much research remains to be done on the efficacy of VR exposure to treat

PTSD, preliminary data from our research group and Rothbaum and colleagues leads us
to consider empirical questions that build upon these results. First, can the efficacy of
VR exposure be enhanced with a pharmacologic agent? To that end we are currently
examining the efficacy of VR exposure in combination with d-cycloserine (DCS,
seromycin) in a randomized placebo controlled clinical trial. D-Cycloserine (DCS;
Seromycin) is a broad-spectrum antibiotic that has been used in clinical trials over the
last decade as a cognitive enhancer. It is a partial agonist at the N-methyl-D-aspartate
receptor, which is known to play an essential role in learning and memory. Both fear
learning and extinction are blocked by antagonists at the glutamatergic NMDA
receptor. D-cycloserine has been shown to facilitate extinction learning in animal
models of conditioned fear and in some human trials of other types of learning.
Preliminary data from Rothbaum and colleagues has demonstrated that DCS when
combined with VR exposure treatment accelerated the learning processes thereby
significantly reducing the number of therapy sessions needed to complete treatment of
fear of heights from six sessions to two [59].
A second question has implications for more efficient world building and is also
germane to an exploration of the efficacy of exposure therapy itself. What is the role of
each sensory modality in the efficacy of VR exposure? How do sensory cues from each
sensory modality differentially affect a patient’s sense of presence and immersion? To
date, much attention has been focused on creating accurate visual worlds to enhance
presence and immersion. Additionally, in VR exposure treatment, attention has been
focused on the verbal processing of the trauma. Little or no attention has been given to
the role of each sensory modality as variables in the creation of presence and
immersion or in the efficacy of VR exposure therapy. Yet the experience of trauma
begins as a multi-sensory experience. Several studies regarding the phenomenology of
trauma memories have suggested that these memories are usually more fragmented and
characterized by sensory-perceptual qualities than non-trauma memories [60-61]. VR
may prove to be a uniquely effective environment in which to process these memories
because of the multi-sensory capacity of the VR simulations. The sensory cues in the
VR world may serve as triggers for the patient’s memory fragments thereby facilitating
both the patient’s emotional engagement and the sensory and emotional processing of
the memory fragment. Though many have postulated that the multi-sensory nature of
VR worlds enhances the patient’s emotional engagement thereby facilitating treatment,
studies have yet to investigate the role of each sensory modality in emotional
engagement or immersion and presence. Though anecdotal, we were impressed that
most of our patient’s identified the sounds from the WTC VR world as the most
powerful sensory cue and credited it with enhancing their engagement in the treatment.
Basic research is needed to examine the role of each sensory modality in the efficacy of
VR trauma worlds.
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Acknowledgements
This research was funded by a NIDA supplement to to J.D. Pfizer Pharmaceuticals

provided a grant (J.D.) to purchase the high quality VR helmet, and head position
tracking system. Dell Computers donated the high-performance PC computer. WTC
world software was created with funding to Dave Patterson, Ph.D. from the Paul Allen
Family Foundation. Creation of WTC world involved MultiGenparadigm VEGA
programming by Howard Abrams, custom 3-D models, and animations by cyberartist
Duff Hendrickson, and use of a 3-D model of Manhattan donated by www.
3dcafe.com, and Digimation. The authors would like to thank Dave Thomas, Ph.D. for
his advice and encouragement.
M.J. Roy (Ed.)
IOS Press, 2006
A Virtual Reality Exposure Therapy

Application for Iraq War Military Personnel
with Post Traumatic Stress Disorder: From
Training to Toy to Treatment
Albert RIZZO a1, Jarrell PAIR a, Ken GRAAP, Brian MANSON a, Peter J. MCNERNEY a,
Brenda WIEDERHOLD c, Mark WIEDERHOLD c, & James SPIRA d
a
University of Southern California Institute for Creative Technologies,
Marina del Rey, California
b
Virtually Better Inc. Decatur, Georgia
c
Virtual Reality Medical Center, San Diego, California
d
Naval Medical Center San Diego, San Diego, California
Abstract. Post Traumatic Stress Disorder is reported to be caused by traumatic events

that are outside the range of usual human experiences including (but not limited to)
military combat, violent personal assault, being kidnapped or taken hostage and terrorist
attacks. Initial data suggests that 1 out of 6 Iraq War veterans are exhibiting symptoms of
depression, anxiety and PTSD. Virtual Reality (VR) exposure treatment has been used in
previous treatments of PTSD patients with reports of positive outcomes. The aim of the
current paper is to specify the rationale, design and development of a Virtual Iraq PTSD
VR application that has been created from the virtual assets that were initially developed
for a combat tactical training simulation, which then served as the inspiration for the X-
Box game entitled Full Spectrum Warrior.
Keywords: Virtual Reality, PTSD, Exposure Therapy, Full Spectrum Warrior
Introduction
In 1997, researchers at Georgia Tech released the first version of the Virtual Vietnam VR
scenario for use as a graduated exposure therapy treatment for Post Traumatic Stress
Disorder (PTSD) with Vietnam veterans. This occurred over 20 years following the end of
the Vietnam War. During that interval, in spite of valiant efforts to develop and apply
1
University of Southern California Institute for Creative Technologies 13274 Fiji Way, Marina del Rey, California
90292; Email: arizzo@usc.edu
236 A. Rizzo et al. / A VR Exposure Therapy Application for Iraq War Military Personnel with PTSD
traditional psychotherapeutic approaches to PTSD, the progression of the disorder in some

veterans severely impaired their functional abilities and quality of life, as well as that of
their family members and friends. The tragic nature of this disorder also had significant
ramifications for the U.S. Veteran’s Administration healthcare delivery system often leading
to designations of lifelong service connected disability status. In mid-2004, the first
systematic study of mental health problems due to the Iraq conflict revealed that “…The
percentage of study subjects whose responses met the screening criteria for major
depression, generalized anxiety, or PTSD was significantly higher after duty in Iraq (15.6 to
17.1 percent) than after duty in Afghanistan (11.2 percent) or before deployment to Iraq
(9.3 percent)” [3]. With this history in mind, the USC Institute for Creative Technologies
(ICT) has initiated a project that is creating an immersive virtual environment system for the
treatment of Iraq War veterans diagnosed with combat-related PTSD. This project has now
been funded as part of a larger multi-year effort by the U.S. Office of Naval Research that
brings together the technical, clinical and creative forces of ICT, Virtually Better, Inc. and
the Virtual Reality Medical Center. The VR treatment environment is based on a cost
effective approach to recycling virtual graphic assets that were initially built for a combat
tactical simulation scenario entitled Full Spectrum Command, which later inspired the
creation of the commercially successful X-Box game, Full Spectrum Warrior. This paper
will present the vision, rationale, technical specifications, clinical interface design, and
development status of the Full Spectrum PTSD treatment system that is currently in progress
at the ICT.
1. Post Traumatic Stress Disorder
According to the DSM-IV [1], Post Traumatic Stress Disorder is caused by traumatic events
that are outside the range of usual human experiences such as military combat, violent
personal assault, being kidnapped or taken hostage, terrorist attack, torture, incarceration as
a prisoner of war, natural or man-made disasters, automobile accidents, or being diagnosed
with a life-threatening illness. The disorder also appears to be more severe and longer
lasting when the event is caused by human means and design (bombings, shootings, combat,
etc.). Such incidents would be distressing to almost anyone, and is usually experienced with
intense fear, terror, and helplessness. Typically, the initiating event involves actual or
threatened death or serious injury, or other threat to one's physical integrity; or witnessing an
event that involves death, injury, or a threat to the physical integrity of another person.
Symptoms of PTSD are often intensified when the person is exposed to situations or
stimulus cues that resemble or symbolize the original trauma in a non-therapeutic setting.
Such uncontrolled cue exposure may lead the person to react with a survival mentality and
mode of response that could put the patient and others at considerable risk. The essential
feature of PTSD is the development of characteristic symptoms that may include:
● Intrusive thoughts and flashbacks ● Anger ● Isolation ● Emotional numbing and

A. Rizzo et al. / A VR Exposure Therapy Application for Iraq War Military Personnel with PTSD 237
constriction ● Anxiety ● Depression ● Substance abuse ● Survivor guilt ● Hyper-alertness

● Suicidal feelings and thoughts ● Alienation ● Negative self-image ● Memory impairment
● Problems with intimate relationships ● Emotional distance from family and others
● Denial of social problems
2. Rationale for Virtual Reality Therapy Applications for PTSD
Prior to the availability of VR therapy applications, the existing standard of care for PTSD
was imaginal exposure therapy. Such treatment typically involves the graded and repeated
imaginal reliving of the traumatic event within the therapeutic setting. This approach is
believed to provide a low-threat context where the patient can begin to therapeutically
process the emotions that are relevant to the traumatic event as well as de-condition the
learning cycle of the disorder via a habituation/extinction process. While the efficacy of
imaginal exposure has been established in multiple studies with diverse trauma populations
[10, 12], many patients are unwilling or unable to effectively visualize the traumatic event.
In fact, avoidance of reminders of the trauma is inherent in PTSD, and is one of the defining
symptoms of the disorder. It is often reported that, “…some patients refuse to engage in the
treatment, and others, though they express willingness, are unable to engage their emotions
or senses.” [1]. Research on this aspect of PTSD treatment suggests that the inability to
emotionally engage (in imagination) is a predictor for negative treatment outcomes [4].
The use and value of Virtual Reality for the treatment of cognitive, emotional,
psychological and physical disorders has been well specified [2, 8]. The first use of VR for a
Vietnam veteran with PTSD was reported in a case study of a 50-year-old, Caucasian male
veteran meeting DSM-IV criteria for PTSD [9]. Results indicated post-treatment
improvement on all measures of PTSD and maintenance of these gains at a 6-month follow-
up. This case study was followed by an open clinical trial of VR for Vietnam veterans [11].
In this study, 16 male PTSD patients were exposed to two HMD-delivered virtual
environments, a virtual clearing surrounded by jungle scenery and a virtual Huey helicopter,
in which the therapist controlled various visual and auditory effects (e.g. rockets,
explosions, day/night, yelling). After an average of 13 exposure therapy sessions over 5-7
weeks, there was a significant reduction in PTSD and related symptoms. Similar positive
results have also recently been reported for VR applied to PTSD resulting from the attack on
the World Trade Center [1]. In this report, a case study was presented using VR to provide
re-exposure to the trauma with a patient who had failed to improve with traditional exposure
therapy. The authors reported significant reduction of PTSD symptoms by exposing the
patient to explosions, sound effects, virtual people jumping from the burning buildings,
towers collapsing, and dust clouds and attributed this success partly due to the increased
realism of the VR images as compared to the mental images the patient could generate in
imagination. Positive treatment outcomes from a wait-list controlled VR study with patients
who were not successful in previous imaginal therapy are currently in press by this group
(Joanne Difede, personal communication, March 17, 2005). Such early results suggest that
VR may be a valuable technology to apply for the treatment of PTSD and that it may be a
promising component of a comprehensive treatment approach for persons with combat-

related PTSD.
3. The Full Spectrum Virtual Iraq PTSD Therapy Application
3.1. Background and Development History
The primary aim of the current project is to use the already existing ICT Full Spectrum
Warrior graphic assets (go to: ftp://imsc.usc.edu/pub/uploads/Skips%20Stuff/PTSD%20
Stuff/ for video demos of the content) as the basis for creating a clinical VR application for
the treatment of PTSD in returning Iraq War military service personnel. The ICT games
project has created two training tools for the U.S. Army to teach leadership and decision
making skills. Full Spectrum Command (FSC) is a PC application that simulates the
experience of commanding a light infantry company. FSC teaches resource management,
adaptive thinking, and tactical decision-making. Developed for the Xbox game console,
Full Spectrum Warrior puts the trainee in command of a nine person squad. Trainees learn
small unit tactics as they direct fire teams through a variety of immersive urban combat
scenarios. These tools were developed through collaboration between ICT, entertainment
software companies, the U.S. Army Training and Doctrine Command (TRADOC), and the
Research, Development, and Engineering Command, Simulation Technology Center
(RDECOM STC). Additionally, Subject Matter Experts from the Army’s Infantry School
contributed to the design of these training tools.
3.2. Technical Specifications
The current VR PTSD application is designed to run on two Pentium 4 notebook computers
each with 1 GB RAM, and a 128 MB DirectX 9 compatible graphics cards. The two
computers are linked using a null Ethernet cable. One notebook runs the therapist’s control
application while the second notebook drives the user’s head mounted display (HMD) and
orientation tracker. We are exploring the usability of three different Head Mounted
Displays (HMDs) for use in this application aiming to find the best instrument available to
conduct deliver this treatment at the lowest cost. This design goal is important in order to
promote maximum accessibility to this system in the future. The three HMDs that are being
tested for this purpose are: 1. The 5DT HMD 800 capable of 800x600 (SVGA) resolution
(see for specs: http://www.5dt.com/products/phmd.html); 2. The Icuiti v920 HMD capable
of 640x480 (VGA) resolution (see for specs: http://www.icuiti.com/); and 3. The eMagin
OLED z800 HMD capable of 800x600 (SVGA) resolution (see for specs: http://www.
emagin.com/). The Intersense InertiaCube2 tracker is being used for 3DOF head orientation
tracking and the user navigates through the scenario using a USB gamepad device. It should
also be noted that while we believe that the HMD display approach will provide the optimal
level of immersion and interaction characteristics for this application, the system is be fully
configurable to be delivered on a standard PC monitor or within a large screen projection
display format. The application is built on ICT’s FlatWorld Simulation Control Architecture
(FSCA). The FSCA enables a network-centric system of client displays driven by a single
controller application. The controller application broadcasts user triggered or scripted event
data to the display client. The client’s real-time 3D scenes are presented using Numerical
Design Limited’s (NDL) Gamebryo graphics engine. The content originally used in Full
Spectrum Warrior was edited and exported to the engine using Alias’ Maya software.
We are also adding olfactory and tactile stimuli to the experience of the environment.
Scent is delivered into the VR scenario through the use of a Scent Palette (Envirodine
Studios, Canton, GA). This machine interfaces with the VR program through the computer’s
USB port and is activated by triggers programmed into the environment via the FlatWorld
Simulation Control Architecture. This allows for the simultaneous delivery of these stimuli
with visual and audio events to create a more realistic multi-modal experience for the user in
order to enhance the sense of presence in the environment. The amount of scent to be
released is specified in seconds. For example, one could have a one second burst of
concentrated scent delivered which would provide a subtle hint of the scent as when passing
by a flower garden while moving between scenes. Conversely, the machine could be
programmed to deliver a longer bust of scent such as might be experienced when
approaching someone wearing cologne. The scents are concentrated and gelled much like
an air freshener cartridge and enclosed within the Scent Palette in an airtight chamber that
fills with compressed air. When activated, the scent is released into an air stream provided
by 4 electric fans inside the Scent Palette so that it moves past the user and then dissipates
into the volume of the room. The scents that have been selected for this application thus far
include burning rubber, cordite, garbage, body odor, smoke, diesel fuel, Iraqi spices and gun
powder. The addition of tactile input in the form of vibration is designed to add another
sensory modality to the virtual environment, again to enhance presence. Vibration is
obtained through the use of sound transducers (Aura Bass Shakers, Aura Sound, Inc. Santa
Fe Springs, CA) driven by an audio amplifier. The sound files embedded in the software are
customized to provide vibration consistent with relevant visual and audio stimuli in the
scenario. For example, explosions and gunfire can be accompanied by this additive
sensation and the vibration can also be varied as when a virtual vehicle moves across
seemingly uneven ground.
3.3. Scenario Settings, User Perspective Options & Clinical Interface Design and
Development
In parallel with our efforts to seek the funding required to create a comprehensive VR
application to address a wide range of possible combat-related PTSD experiences, we
created a prototype virtual environment designed to resemble a middle-eastern city (see
Figures 1-5). This VE was designed as a proof of concept demonstrator and as a tool for
initial user testing to gather feedback from both Iraq War military personnel and clinical
professionals in order to refine the city scenario and to seek guidance for options needed for
the future expansion of the system to include other relevant scenario settings. Current ONR
funding has now allowed us to evolve this existing prototype into a full-featured version 1.2
application that is currently undergoing user-centered design feedback trials with non-PTSD
soldiers at the Naval Medical Center - San Diego (NMCSD) who have returned from an Iraq
tour of duty. The vision for the project includes not only the design of a series of diverse
scenario settings (i.e. city, outlying village and desert scenes), but as well, the creation of
options for providing the user with different first person user perspective options. These
choice options when combined with real time clinician input via the “Wizard of Oz” clinical
interface is envisioned to allow for the creation of a user experience that is specifically
customized to the needs of the patient participating in treatment. This is an essential
component for giving therapist the capacity to modulate patient anxiety as is required for an
exposure therapy approach. Experience customization and flexibility are key elements for
these types of VR exposure applications.
3.4. Scenario Settings
The software is being designed such that clinical users can be teleported to specific scenario
settings based on a determination as to which environment most closely matches the
patient’s needs, relevant to their individual combat related experiences. All scenario settings
are adjustable for time of day or night, weather conditions and lighting illumination. The
following are the scenario settings that are being created for the application:
1. City Scenes – In this setting, we envision two variations. The first city setting
(currently developed in our prototype version 1.2) has the appearance of a
desolate set of low populated streets comprising of old buildings, ramshackle
apartments, warehouses, a mosque, factories and junkyards (see Figures 1-5).
The second city setting will have similar street characteristics and buildings, but
will be more highly populated and have more traffic activity, marketplace scenes
and monuments.
2. Checkpoint – This area of the City Scenario will be constructed to resemble a
traffic checkpoint with a variety of moving vehicles arriving, stopping and then
moving onward into the city.
3. City Building Interiors – Some of the City Scenario buildings will have
interiors modeled that will allow the user to navigate through them. These
interiors will have the option of being vacant (see Figure 5) or have various
levels of populated virtual characters inhabiting them.
4. Small Rural Village – This setting will consist of a more spread out rural area
containing ramshackle structures, a village center and much decay in the form of
garbage, junk and wrecked or battle-damaged vehicles. It will also contain more
vegetation and have a view of a desert landscape in the distance that is visible as
the user passes by gaps between structures near the periphery of the village.
5. Desert Base – This scenario will be designed to appear as a desert military base
of operations consisting of tents, soldiers and an array of military hardware.
6. Desert Road – This scenario has been constructed and consists of a paved
roadway which will eventually connect the City, Desert Base and Village
scenarios. The view from the road currently consists of desert scenery and sand
dunes (see Figure 6) with occasional areas of vegetation, ramshackle structures,
battle wreckage, debris and an occasional virtual human figure standing by the
side of the road.
3.5. User Perspective Options
The system is designed such that once the scenario setting is selected, it will be possible to
select from a variety of user perspective and navigation options. These are being designed in
order to again provide flexibility in how the interaction in the scenario settings can be
customized to suit the clinical user’s needs.
Figure 1. City View Figure 2. City View
Figure 3. “Flocking” Patrol
Figure 4. “Flocking” Patrol Figure 5. Interior View

Figure 6. Desert Road View
Figure 7. HUMVEE View Figure 8. Helicopter View
Figure 9. Clinical Interface
User perspective options will include:

1. User walking alone on patrol from a first person perspective (see Figures 1-2).
2. User walking with one soldier companion on patrol. The accompanying soldier
will be animated with a “flocking” algorithm that will place them always within
a 5-meter radius of the user and will adjust position based on collision detection
with objects and structures to support a perception of realistic movement.
3. User walking with a patrol consisting of a number of companion soldiers using a

similar “flocking” approach as in #2 above (see Figures 3-4).
4. User view from the perspective of being either inside of the cab of a HUMVEE
or other moving vehicle or from a more exposed position in a gun turret above
the roof of the vehicle. Options are provide for automated travel as a passenger
through the various setting scenarios (see Figure 7) or at the driving column that
allow for user control of the vehicle via the gamepad controls. The interior view
will also have options for other occupant passengers that will have ambient
movement. This view is also adjustable to support the perception of travel within
a convoy or as a lone vehicle.
5. User view from the perspective of being in a helicopter hovering above or
moving over any of the scenario settings (see Figure 8).
In each of these user perspective options, we are considering the wisdom of having the user
possess a weapon. This will necessitate decisions as to whether the weapon will be usable to
return fire when it is determined by the clinician that this would be a relevant component for
the therapeutic process. Those decisions will be made based on the initial user and clinician
feedback from the version 1.2 application.
3.6. Clinical Interface
We have created a “wizard of oz” type clinical interface (see Figure 9) to control all of the
above features in the system. This interface is a key element in the application, as it needs to
provide a clinician with a usable tool for placing the user in VE locations that resemble the
setting and context in which the traumatic events initially occurred. As important, the
clinical interface must also allow the clinician to further customize the therapy experience to
the patient’s individual needs via the systematic real-time delivery and control of “trigger”
stimuli in the environment. This is essential for fostering the anxiety modulation needed for
therapeutic habituation.
In our initial configuration, the clinician can use a separate computer monitor or tablet
laptop to display and actuate the clinical interface controls. While the results from our initial
user feedback trials is currently guiding the interface design modifications, our initial
candidate setup provides four quadrants in which the clinician can monitor ongoing user
status information, while simultaneously directing trigger stimulus delivery. The upper left
quadrant will contain basic interface menu buttons used for placement of the patient (and
immediate removal if needed) in the appropriate scenario setting and user perspective. This
quadrant also contains menu keys for the control of time of day or night, atmospheric
illumination, weather conditions and initial ambient sound characteristics. The lower left
quadrant will provide space for real-time display of the patients’ heart rate and GSR
readings for monitoring of physiological status when that feature is integrated. The upper
right quadrant contains a window that displays the imagery that is present in the user’s field
of view in real-time. And the lower right quadrant contains the control panel for the real-
time delivery of specific trigger stimuli that are actuated by the clinician in an effort to
modulate appropriate levels of anxiety as required by the theory and methodology of
exposure-based therapy.
The specification, creation and addition of such trigger stimuli will likely be an
evolving process throughout the life of the application based on relevant patient feedback.
We began this part of the design process by including options that have been reported to be
relevant by returning soldiers and military subject matter experts. For example, Hoge et al.,
[3], in their study of self-reported anxiety, depression and PTSD-related symptomatology in
returning Iraq War veterans, present a useful listing of combat related events that were
commonly experienced in their sample. These events provided a useful starting point for
conceptualizing how relevant trigger stimuli could be presented in a VR environment. Such
commonly reported events included: “Being attacked or ambushed, Receiving incoming
artillery, rocket, or mortar fire, Being shot at or receiving small-arms fire, Shooting or
directing fire at the enemy, Being responsible for the death of an enemy combatant, Being
responsible for the death of a noncombatant, Seeing dead bodies or human remains,
Handling or uncovering human remains, Seeing dead or seriously injured Americans,
Knowing someone seriously injured or killed, Participating in de-mining operations, Seeing
ill or injured women or children whom you were unable to help, Being wounded or injured,
Had a close call, was shot or hit, but protective gear saved you, Had a buddy shot or hit
who was near you, Clearing or searching homes or buildings, Engaging in hand-to-hand
combat, Saved the life of a soldier or civilian.” (p. 18). From this and other sources, we
have begun with our initial effort to conceptualize what is both functionally relevant and
pragmatically possible to include as trigger stimuli in our current clinical interface. There
appear to be at least four general classes of trigger stimuli that are relevant for this
application: 1. Auditory (i.e., weapons fire, explosions, vehicle noise, wind, human
voices), 2. Static Visual (i.e., human remains, wounded civilians and combatants, wrecked
vehicles), 3. Dynamic Visual (i.e., distant views of human and vehicle movement), 4.
Dynamic Audiovisual (i.e., nearby human and vehicle movement, battlefield engagement
with enemy combatants).
Thus far in the Version 1.2 prototype, we have created a variety of auditory trigger
stimuli (i.e., incoming mortars, weapons fire, voices, wind, etc.) that can be actuated by
mouse clicks. We can also similarly trigger dynamic audiovisual events such as helicopter
flyovers above the user’s position and verbal orders from a commanding officer who is
gesturing in an excited manner. The creation of more complex events that can be intuitively
delivered from the clinicians interface while providing a user with options to interact or
respond in a meaningful manner is one of the ongoing focuses in this project. Perhaps it may
be of value to actually immerse the user in varying degrees of combat in which they may see
members of their patrol (or themselves) get wounded or in fact have the capability to fire a
weapon back at enemy combatants. However, such trigger options will require not only
interface design expertise, but also clinical wisdom as to how much and what type of
exposure is needed to produce a positive clinical effect. These issues will be keenly attended
to in our initial clinical trials.
4. Conclusions
War is perhaps one of the most challenging situations that a human being can
experience.The physical, emotional, cognitive and psychological demands of a combat
environment place enormous stress on even the best-prepared military personnel. In this
regard, one of the more foreboding findings in the recent Hoge et al., [3] report, was the
observation that among Iraq War veterans, “…those whose responses were positive for a
mental disorder, only 23 to 40 percent sought mental health care. Those whose responses
were positive for a mental disorder were twice as likely as those whose responses were
negative to report concern about possible stigmatization and other barriers to seeking
mental health care.” (p. 13). While military training methodology has better prepared
soldiers for combat in recent years, such hesitancy to seek treatment for difficulties that
emerge upon return from combat, especially by those who may need it most, suggests an
area of military mental healthcare that is in need of attention. To address this concern,
perhaps a VR system for PTSD treatment could serve as a component within a
reconceptualized approach to how treatment is accessed by veterans returning from combat.
One option would be to integrate VR-delivered combat exposure as part of a
comprehensive “assessment” program administered upon return from a tour of duty. Since
past research is suggestive of differential patterns of physiological reactivity in soldiers with
PTSD when exposed to combat-related stimuli [6, 5] an initial procedure that integrates our
VR PTSD application with psychophysiological monitoring could be of value. If indicators
of such physiological reactivity are present during an initial VR exposure, a referral for
continued care could be negotiated and/or prescribed. This could be provided in a format
whereby the perceived stigma of independently seeking treatment could be lessened as the
soldier would be simply involved in “non-combat reintegration training” in similar fashion
to other designated duties to which they would participate. As well, current generation
military personnel, having grown up with digital gaming technology, may actually be more
attracted to and comfortable with participation in a VR application approach as an
alternative to what is viewed as traditional “talk therapy” (even though such talk therapy
would obviously occur in the course of a recommended multi-component approach for this
disorder). This potential for a reduction in the perceived stigma surrounding treatment has
been anecdotally reported by practitioners who treat civilians with aerophobia (fear of
flying) using VR [13]. These observations indicate that some patients have reported that
prior to treatment, they had “just lived with problem” and never considered seeking
professional treatment. Upon hearing of VR therapy for fear of flying, often via popular
media reports, they then sought out VR exposure treatment, typically with resulting positive
outcomes.
In addition to the ethical factors that make an unequivocal case for the importance of
exploring new options for assessment and treatment of combat-related PTSD, economic
drivers for the Department of Veterans Affairs healthcare system and the military also
provide incentives for investigating novel approaches in this area. Currently there are 13,524
Gulf War Veterans who are receiving compensation for PTSD from the Department of
Veterans Affairs as of September 2004 (VA Fact Sheet, 12/2004). In addition to the direct
costs for benefit compensation, medical care usage by persons with PTSD is estimated to be
60% higher than average [7] and lost income-based tax revenues raise the “hidden” costs
even higher. These data make the initial development and continuing infrastructure costs for
running PC-based VR systems pale by comparison. The military could also benefit
economically by way of reduced “turnover” of soldiers with mild PTSD. These personnel
might be more likely to reenlist if their mental health needs were addressed soon after
combat in a progressive manner via early VR assessment and treatment. As well, such a VR
tool initially developed for exposure therapy purposes, offers the potential to be “recycled”
for use both in the areas of combat readiness assessment and for stress inoculation. Both of
these approaches could provide measures of who might be better prepared for the emotional
stress of combat. For example, novice soldiers could be pre-exposed to challenging VR
combat stress scenarios delivered via hybrid VR/Real World stress inoculation training
protocols as has been reported by [14] with combat medics.
Finally, one of the guiding principles in our development work concerns how VR can
extend the skills of a well-trained clinician. This VR approach is not intended to be an
automated treatment protocol that could be administered in a “self-help” format. The
presentation of such emotionally evocative VR combat-related scenarios, while providing
treatment options not possible until recently, will most likely produce therapeutic benefits
when administered within the context of appropriate care via a thoughtful professional
appreciation of the complexity and impact of this disorder.
References
[1] Hoge, C.W., Castro, C.A., Messer, S.C., McGurk, D., Cotting, D.I. and Koffman, R.L. (2004). Combat Duty
in Iraq and Afghanistan, Mental Health Problems, and Barriers to Care. New England Journal of Medicine,
351 (1):13-22.
[2] Difede, J. & Hoffman, H. (2002). Virtual reality exposure therapy for World Trade Center Post Traumatic
Stress Disorder. Cyberpsychology and Behavior, 5:6, 529-535. DSM-IV. (1994). American Psychiatric
Association, Washington, D.C.
[3] Rothbaum, B.O., Meadows, E.A., Resick, P., et al. (2000). Cognitive-behavioral therapy. In: Foa, E.B.,
Keane, T.M., Friedman, M.J. (eds.), Effective treatments for PTSD. New York: Guilford, pp. 60–83.
[4] Rothbaum, B.O., & Schwartz, A.C. (2002). Exposure therapy for posttraumatic stress disorder. American
Journal of Psychotherapy 56:59–75.
[5] Jaycox, L.H., Foa, E.B., & Morral, A.R. (1998). Influence of emotional engagement and habituation on
exposure therapy for PTSD. Journal of Consulting and Clinical Psychology 66, 186–192.
[6] Glantz, K., Rizzo, A.A. & Graap, K. (2003). Virtual Reality for Psychotherapy: Current Reality and Future
Possibilities. Psychotherapy: Theory, Research, Practice, Training, 40, 1/2, 55–67.
[7] Rizzo, A.A., Schultheis, M.T., Kerns, K. & Mateer, C. (2004). Analysis of Assets for Virtual Reality
Applications in Neuropsychology. Neuropsychological Rehabilitation. 14(1) 207-239.
[8] Rothbaum B., Hodges, L., Alarcon, R., Ready, D., Shahar, F., Graap, K., Pair, J., Hebert, P., Gotz, D., Wills,
B., & Baltzell, D. (1999). Virtual reality exposure therapy for PTSD Vietnam veterans: A case study. Journal
of Traumatic Stress 12, 263-271.
[9] Rothbaum, B., Hodges, L., Ready, D., Graap, K. & Alarcon, R. (2001) Virtual reality exposure therapy for
Vietnam veterans with posttraumatic stress disorder. Journal of Clinical Psychiatry 62, 617-622.
[10] Laor, N., Wolmer, L., Wiener, Z., Reiss, A., Muller, U., Weizman, R. & Ron, S. (1998). The function of
image control in the psychophysiology of posttraumatic stress disorder. Journal of Traumatic Stress, 11, 679-
696.
[11] Keane, T. M., Kaloupek, D. G., Blanchard, E. B., Hsieh, F. Y., Kolb, L. C., Orr, S. P., Thomas, R. G. &
Lavori, P. W. (1998). Utility of psychophysiological measurement in the diagnosis of posttraumatic stress
disorder: Results from a Department of veterans affairs cooperative study. Journal of Consulting and Clinical
Psychology, 66, 914-923.
[12] Wiederhold, B.K., & Wiederhold, M.D. (2004). Virtual-Reality Therapy for Anxiety Disorders: Advances in
Education and Treatment. American Psychological Association Press: New York.
[13] Marshall R.P., Jorm, A.F., Grayson D.A. & O’Toole B.I. (2000). Medical-care costs associated with
posttraumatic stress disorder in Vietnam veterans. Australian and New Zealand Journal of Psychiatry,
December 2000, vol. 34, no. 6, pp. 954-962.
[14] Wiederhold, M.D & Wiederhold, B.K. (2005). Military mental health applications. The 13th Annual Medicine
Meets Virtual Reality Conference. January 29, 2005, Long Beach, CA.
Section V
Other Aspects of Military Healthcare
M.J. Roy (Ed.)
IOS Press, 2006
Advanced 3D Computer-Assisted
Technologies in Improving Patient
Telecare
Ivica KLAPANa,b,c1 , Ljubimko ŠIMIýIûc, Sven LONýARIûd-e
a
University Department of ENT, Head & Neck Surgery, Division of
Plastic and Reconstructive Head & Neck Surgery and
Rhinosinusology, Zagreb University School of Medicine,
b
Zagreb University Hospital Center, Zagreb, Croatia,
c
Reference Center for Computer Aided Surgery and Telesurgery,
Ministry of Health, Republic of Croatia, Zagreb, Croatia,
d
Professor of Electrical Engineering and Computing, Faculty of
Electrical Engineering and Computing, University of Zagreb, Croatia,
e
Department of Electrical and Computer Engineering, New Jersey
Institute of Technology, Newark, USA
This work was in part supported by an unrestricted grant by the Ministry of Science and Technology,
Republic of Croatia, No. 5-01-543
Abstract. Fast development of computer and information technology enables

realization and application of new methods and systems that were not feasible in
the past century. One example of such development is the area of virtual reality
(VR), virtual surgery (VS), virtual endoscopy (VE), computer assisted surgery
(CAS), 3D-CAS, robotic/telerobotic surgery, and Tele-3D-CAS.
The real visual, auditory, and tactile cues are replaced by computer-generated
sensory cues, therefore giving the user a sense of presence in a virtual world. CAS
and VR have found many applications in the field of medicine. Advances in high
performance computing, graphics, and networking, together with new human-
machine interfaces form a technological basis for VR/3D-CAS/Tele-3D-CAS
applications.
Related fields and terminology such as augmented reality, full and partial
immersion, wearable computers, telepresence, and telemedicine will be introduced
in the paper. The aims of the paper are to present VR, 3D-CAS, and Tele-3D-CAS
technology, to provide an overview of some mentioned research activities,
information and research resources. An overview of the current research activities
in the field of medicine of the 21st century includes: education, surgical planning
and simulation, visualization, telemedicine/telesurgery, computer-aided surgery,
human-machine interfaces, and rehabilitation and therapy.
Keywords. Computer assisted surgery, Telesurgery, Three-dimensional

visualization, Endoscopy, Telemedicine, Virtual reality, Virtual endoscopy.
1
Corresponding Author: Ivica Klapan. University Hospital Center Gojka Šuška 12, HR-10000 Zagreb,
Croatia.
252 I. Klapan et al. / Advanced 3D Computer-Assisted Technologies in Improving Patient Telecare
Introduction
Research in the area of 3-D image analysis, visualization, tissue modelling, and human-
machine interfaces provides scientific expertise necessary for developing successful
3D-CAS, Tele-3D-CAS, and VR applications. These technologies represent a basis for
realistic simulations that are useful in many areas of human activity, including
medicine, and can create an impression of immersion of a physician in a non-existing,
virtual environment. Such an impression of immersion can be realized in any medical
institution using advanced computers and computer networks that are required for
interaction between a person and a remote environment, with the goal of realizing tele-
presence.
In human medicine, extremely valuable information on anatomic relationships in
particular regions, while planning and performing endoscopic surgery, is provided by
high quality CT or MRI diagnosis[1] (Fig. 1), thus contributing greatly to the safety of
this kind of surgery[2].
Figure 1. CT of the Nose and Paranasal Sinuses
To understand the concept of virtual reality (VR), it is necessary to recognize that

the perception of the surrounding world created in our brain is based on information
perceived by each of the human senses, along with the help of knowledge that is stored
in our brain. The usual definition says that the impression of being present in a virtual
I. Klapan et al. / Advanced 3D Computer-Assisted Technologies in Improving Patient Telecare 253
environment (VE), such as virtual endoscopy of the patient’s head, which does not exist
in reality, is called VR. The user/physician, has an impression of presence in the virtual
world and can navigate through it to manipulate virtual objects. A VR system may be
designed in such a way that the user/physician is completely immersed in the VE.
The basic requirement in human medicine, resulting from the above mentioned
needs, refers to the use of a computer system for visualization of anatomic 3D-
structures and an integral operative field upon to operate. The mode of computer
visualization of anatomic structures[3] of the human body that has been used prior to
the present day could only provide diagnostic information, and possibly to assist in the
preoperative preparation. Intraoperative use of the computer generated operative field
3D-model has not been widely adopted to date. The intraoperative use of the computer
in real time requires development of appropriate hardware and software to connect
medical instruments with the computer, and to operate the computer via these
instruments and sophisticated multimedia interfaces
1. High Quality Diagnosis (DICOM Standard)
High quality diagnostic imaging is the main prerequisite for appropriate utilization of
computer systems during the preparation, performance and analysis of an operative
procedure.
Development of a system for data exchange between multiple medical diagnostic
devices as well as between diagnostic devices and computer networks has led to the
establishment of DICOM (Digital Imaging and Communication in Medicine) standards
describing the forms and modes of data exchange.
Before the introduction of DICOM standards, image recordings were stored on
films, where the information obtained from the diagnostic device was in part lost.
Under ideal conditions, sixteen different image levels could be distinguished on films at
best. When film images were to be stored in computer systems, films had to be
scanned, thus inevitably losing significant data and often introducing some undesirable
artifacts. The setting level and window width to be observed on the images could not be
subsequently changed. Visualization of the image on the diagnostic device monitor was
of a considerably higher quality, thus it was quite naturally used for record receipt and
storage in computer media. Video imaging allows for the receipt of 256 different levels
at best. It is not possible to subsequently modify the setting level and window width to
be observed on the images that have already been stored in the computer system.
When stored in computer systems by use of DICOM protocol, images are stored in
the form generated by the diagnostic device detector. These image recordings can then
be properly explored through the use of powerful computer systems. This is of special
relevance when data in the form of images are to be used for complex examinations and
testing, or in preoperative preparation where rapid and precise demarcation between the
disease involved and intact tissue is required. It is also very important for the images to
be visualized in various forms and from different perspectives and then – which is most
demanding indeed – to develop spatial models to aid the surgeon in preparing and
performing the procedure, as well as in postoperative analysis of the course of the
procedure.
The entire operative procedure can be simulated, and critical areas avoided during
the real procedure, by employing real patient images in the operation preparatory phase
using complex spatial models and simulated operative field entry (Virtual Endoscopy,
or Virtual Surgery)[4,5]
2. Preoperative Preparation
The real-time requirement means that the simulation must be able to follow the actions
of the user that may be moving in the virtual environment. The computer system must
also store in its memory a 3-D model of the virtual environment (3D-CAS models). In
that case a real-time VR system will update the 3-D graphical visualization as the user
moves, so that up-to-date visualization is always shown on the computer screen. For
realistic simulations it is necessary for the computer to generate at least 30 such images
per second, which imposes stringent requirements regarding computer processing
power.
Use of the latest programs enables development of 3D spatial models, exploration in
various projections, simultaneous presentation of multiple model sections and, most
importantly, model development according to open computer standards ( e.g., Open
Inventor). Such a preoperative preparation can be applied in a variety of program
systems that can be transmitted to distant collaborating radiologic and surgical work
sites for preoperative consultation as well as during the operative procedure in real
time[6] (telesurgery) (Fig. 2).
Such a model in medical applications will enable simulation of changes that the
tissue undergoes when compressed, stretched, cut, or palpated. The computer must then
generate, in real-time, an appropriate visualization of the tissue as it is deformed by the
user. Biological tissue modeling represents an important research area with applications
in many medical areas. In this context, physics-based deformable models represent a
powerful simulation tool. In the context of VR applications, real-time 3-D visualization
techniques are particularly important. The goal here is to develop methods for rapid and
realistic visualization of 3-D objects that are in the VE.
Figure 2. Our 3D models of the human head in different projections. VR systems may be used for medical
visualization in several medical areas: 3-D stereo visualization of anatomical structures, 3-D data fusion of
multiple imaging modalities, VE, visualization of individual patient anatomy for surgical planning and
rehearsal, visualization for image-guided surgery procedures, and visualization of anatomy in radiation
therapy planning
Three-dimensional spatial models developed via advanced technologies facilitate

simulation of endoscopic surgery, making it possible to plan the course of future
procedures (Virtual Endoscopy) or telesurgery (Tele-Virtual Endoscopy). By entering
the models and navigating through the operable regions, the surgeon becomes aware of
the problems he will encounter during the real operation. In this way, preparation for
an operation can be conducted, including identification of the shortest and safest
method for carrying out the real operation[6,7] (Fig. 3).
Figure 3. An example of 3D computer-assisted microsurgery of the nose and paranasal sinuses (3D-C-FESS)
with simulation and planning of the course of subsequent endoscopic operation (VE). Virtual endoscopy
overcomes some difficulties of conventional endoscopy. In classical endoscopy an endoscope is inserted into
the patient to examine the internal organs or spaces. The physician uses an optical system to view interior
spaces of the body.
The two main approaches to visualization are surface rendering and volume
rendering. Surface rendering is a classical visualization method where object surfaces
are approximated using a set of polygonal shapes such as triangles. Most general-
purposed computers use this approach and their wide availability represents an
important advantage of surface rendering. A disadvantage is that surface rendering
cannot represent volume interior. Volume rendering can create appealing
representations of volume interiors, but a disadvantage is that special hardware is
required for acceleration because of computational complexity.
During the course of our Three-Dimensional Computer Assisted Functional
Endoscopic Sinus Surgery (3D-C-FESS) method development, a variety of program
systems were employed to design an operative field model through spatial volume
rendering techniques (www.mef.hr/3D-CFESS). Initially, the modeling was conducted
with the VolVis, Volpack/Vprender, GL Ware programs on a DEC Station 3100
computer. With the advent of 3D Viewnix V1.0 software, we employed this program,
followed by the 3D Viewnix V1.1 system, AnalyzeAVW system, T-Vox system and
OmniPro 2 system on Silicon Graphics O2, Origin200 and Origin2000 computers (Fig.
4).
Figure 4. 3D Viewnix V1.0 and AnalyzeAVW (OmniPro 2 is shown in Fig. 3)
3. Computer Assisted Diagnosis and Surgery
VR, 3D-CAS and Tele-3D-CAS systems can be used for education, assessment of work
skills, training, simulation, 3-D visualization, computer-aided design, teleoperation, and
telemanipulation. If we look at various application areas, we see that one of the more
popular VR applicaton areas is medicine. A potentially useful application is for
minimally invasive surgery (MIS). The learning of MIS techniques is more difficult
than learning open surgery techniques because there is no tactile information, only an
indirect field of view is available, and there are difficulties with hand-eye coordination.
Training is therefore usually conducted either on animals or in the OR with live
patients. More modern computer-based systems for surgical training may prove
superior.
The use of computers during surgery or telesurgery requires highly reliable, stable
and fast computer systems. Computer work stations with UNIX compatible operative
systems are most commonly used. During the procedure, the surgeon is engaged in
performing the surgery, so he cannot operate the computer. Therefore, the presence of a
computer system expert within the operative theater is essential to the conduct of
computer-aided operative procedures.
VR systems may be used to aid the delivery of surgical procedures. In fact, the most
useful systems are augmented reality systems, which combine a patient image with
images obtained using various medical imaging modalities such as CT, MR, and
ultrasound. Such systems for surgical delivery are used for neurosurgery, knee surgery,
endoscopic ENT surgery, and breast biopsy. During such procedures, the surgeon can
voice-operate the computer system (Voice Navigation). Model movements, various
projections and sections can all be brought up on the monitor with simple and short
voice instructions during the surgery.
The system fuses computer-generated images with endoscopic images in real time.
The surgical instruments have 3-D tracking sensors and the instrument position is
superimposed on the video image and CT image of the patient head. The system
provides guidance according to the surgically planned trajectory. The advantages of the
system include reduced time for procedures, reduced training time, greater accuracy,
and reduced trauma for patients.
On initial computer-aided operative procedures, spatial orientation within the
operative field of a 3D computer model, as well as transfer of the particular point to the
real operative field of the patient, were performed by arbitrary approximation of the
known reference points of the operative field anatomy[8]. In this way, the given entities
were recognized on the model and in the real operative field[9].
The use of 3D spatial modeling of the operative field during surgery has highlighted
the need to delineate the instrument (endoscope, forceps, etc.) position tip within the
computer model. The major problem is transmission of the real patient operative field
co-ordinate system to the co-ordinate system of the computer 3D spatial model of the
patient, which has been previously designed from a series of CT images during
preoperative preparation[10] (Fig. 5).
Figure 5. An example of our 3D computer assisted surgery. Advantages of virtual endoscopy and/or tele-
virtual endoscopy are that there are no restrictions on the movement of the virtual endoscope (it can be
moved anywhere through the body), it avoids insertion of an instrument into a natural body opening or
minimally invasive opening, and requires no hospitalization. However, virtual endoscopy also has some
disadvantages such as the fact that current virtual endoscopy techniques do not reveal the look of the tissue
surface (3D imaging techniques do not reveal surface properties).
The modes of instrument localization within the operative field include

electromagnetic, optic and mechanical methods. The electromagnetic method is very
sensitive to environmental electromagnetic fields (electrical devices, lighting) and large
amounts of metal (cabinets, table, instruments), and the basic, ideal precision of
localization within the field is inadequate for surgery performance. Optic locators have
proven suitable but are relatively expensive and less precise than mechanical locators.
Mechanical locators are virtually 3D digitalizers sending their shifts within six degrees
of freedom to the computer, which then converts them to shifts within the co-ordinate
system of the operative field 3D model.
The main problem and shortcoming of current mechanical locators is the inability to
reach deep regions within the operative field. This could be solved by replacing current
tips with thinner and longer endings, or even better by the original surgical instrument
(e.g., forceps or endoscope) (www.mef.hr/MODERNRHINOLOGY). The endoscope is
mounted at the end of the 3D digitalizer instead of the existing ending or outside the
existing ending axis. The depth of the reachable entity is identical to the depth
attainable by the standard endoscope or pump (Fig. 6).
Figure 6. The primary problem encountered in 3D-CA-surgery is how to transmit the real patient operative
field co-ordinate system to the co-ordinate system of the computer 3D spatial model of the same patient,
previously developed from a series of CT images during preoperative preparation
Using a special digitalizer (endoscope simulation) model and computer model, the
preoperative preparation and simulation of the entire procedure can be done on the
computer model of the real patient. Employing a 3D digitalizer during the real
procedure, the tip of the instrument (simulated endoscope) can be precisely identified in
the real operative field and visualized on the computer model[5,11]The freedom of
endoscope manipulation during the procedure is not reduced because the connection is
realized at the instrument handle and endocamera link sites.
4. Computer Assisted Telesurgery
The purpose of a tele-presence system is to create a sense of physical presence at a

remote location. Tele-presence is achieved by generating sensory stimuli so that the
operator has an illusion of being present at a location distant from the location of their
actual physical presence. A tele-presence system extends the operator’s sensory-motor
facilities and problem solving abilities to a remote environment. A tele-operation
system enables operation at a distant remote site by providing the local operator with
necessary sensory information to simulate the operator’s presence at the remote
location. Tele-operation is a special case of tele-presence where, in addition to the
illusion of presence at a remote location, the operator also has the ability to perform
certain actions or manipulations at the remote site. In this way it is possible to perform
various actions at distant locations, where it is not possible to go due to a danger,
prohibitive price, or a large distance. Realization of VR systems requires software
(design of the VE) for running VR applications in real-time. Simulations in real-time
require powerful computers that can perform real-time computations required for
generation of visual displays.
Telemedicine attempts to break down the distance barrier between the provider and
the patient in health-care delivery. VR is able to simulate remote environments and can
therefore be applied to telemedicine. Physicians can have a VR-produced copy of a
remote environment, including the patient, at their physical location. One of the
simplest telemedical applications is medical teleconsultation, where physicians
exchange medical information over computer networks with other physicians, in the
form of image, video, audio, and text. Teleconsultations can be used in radiology,
pathology, surgery, and other medical specialties. One of the most interesting
telemedical applications is tele-surgery. Telesurgery is a telepresence application in
medicine where the surgeon and the patient are at different locations, but such systems
are still in an early phase of research. Patients, who are too ill or injured to be
transported to a hospital may be operated on remotely. Such cases typically represent
the need for a surgical specialist who is located at some distance.
Computer technologies allow for computer-assisted surgery to be performed at
distance. The most basic form of telesurgery can be realized by using audio and video
consultations during the procedure.
Sophisticated endoscopic cameras show the operative field on a monitor mounted
within the operating theater; however, the same image can also be transmitted to a
remote location through video transmission. The latest computer technology enables
receipt of CT images from a remote location, examination of these images,
development of 3D spatial models, and transfer of these models back to the remote
location12. This can be accomplished nearly within real time. These procedures imply
preoperative consultation. During the surgery, those in the operating theater and remote
consultants follow on the patient computer model the procedure images, the 'live' video
image generated by the endoscopic camera, and instrument movements made by the
remote surgeon[6]. Simultaneous movement of the 3D spatial model on the computers
connected to the system providing consultation is enabled[6,12]. It should be noted that

in most cases, intraoperative consultation can be realized from two or more locations,
though the utmost care is required to establish a proper network among them.
The extreme usage of computer networks and telesurgery implies the use of robotic
technologies operated by remote control. In such a way, complicated operative
procedures could be carried out from distant locations. The main idea behind
considering the use of computer networks in medicine is: IT IS PREFERABLE TO
MOVE THE DATA RATHER THAN THE PATIENT (Fig. 7). In the future, we can
expect more applications of VR in medicine. Advances in computer science will make
possible more realistic simulations. VR, 3D-CAS, and Tele-3D-CAS systems of the
future will find many applications in both medical diagnostics and computer-aided
intervention.
Figure 7. An example of our Tele-3D-computer assisted surgery of the nose and paranasal sinuses. The
virtual endoscopic procedure has several steps, such as: 3-D imaging of the organ of interest (e.g using CT, or
MRI), 3-D preprocessing of the acquired image data (interpolation, registration), 3-D image analysis to create
the model of the desired anatomical structures (segmentation), computation of the 3-D camera-target path for
automatic fly-through or manual path selection, and rendering of multiple views along the computed path to
create the animation (either surface or volume rendering).
5. Postoperative Analysis
The surgical workstation should include 3-D vision, dexterous precision surgical
instrument manipulation, and input of force feedback sensory information. The surgeon
operates in a virtual world. The use of computer technology during preoperative

preparation and the actual conduct of surgery enables the storage of all relevant patient
data throughout the process. CT images, results of other tests and examinations,
computer images, 3D spatial models, and both computer and video records of the
course of the operation or teleoperation are stored in the computer and in CD-R devices
for subsequent analysis7 (www.mef.hr/MODERNRHINOLOGY). This can prove
tremendously useful for education as well as in the practice of different surgical
approaches for students, residents, fellows, and even staff physicians.
VR has many applications in computer-aided surgery [13]. The four main
application areas are a) surgical training and rehearsal (for education of surgeons, for
rehearsal of complex surgical procedures), b) surgical planning, c) surgical rehearsal,
and d) surgical delivery
Statistical studies show that physicians are more likely to make errors during their
first several to few dozen surgical procedures. Surgical training may be done on
cadavers, but the problem is a chronic shortage of cadavers for medical research. It
would be helpful if medical training could be performed using a realistic imitation of a
human body inside the computer. Such computer-based training can be used for
minimally invasive surgery, and for open surgery. Training on cadavers has several
drawbacks: a) if a trainee cuts a nerve or a blood vessel in a cadaver nothing will
happen, b) no action can be reversed on cadavers (what is cut is cut), c) dead tissue is
harder, color is altered, and arteries do not pulsate. Advantages of computer simulations
are that the procedures can be repeated many times with no damage to the virtual body,
the virtual body does not have to be dead (many functions of living body can be
simulated for realistic visualizations), and organs can be made transparent and
modeled. The trainee may be informed of mistakes either during or after the surgical
procedure using a multimedia-based context-sensitive help.
In this way, the real surgery and telesurgery procedures can be subsequently
analyzed and possible shortcomings defined in order to further improve operative
treatment. The use of the latest computer technologies enables connection between the
computer 3D spatial model of the surgical field and video recording of the course of
surgery to observe all critical points during the procedure, with the ultimate goal to
improve future procedures and to develop an expert system that will facilitate computer
assisted surgery and telesurgery, with due account of all the experience acquired on
previous procedures. Also, using the computer recorded co-ordinate shifts of a 3D
digitalizer during the telesurgery procedure, an animated image of the course of surgery
can be created in the form of navigation, i.e. the real patient operative field fly-through,
as we have done from the very begining (1998) in our telesurgeries [14].
6. Computer Networks
A component that is essential to the realization of 3D-CAS, Tele-3D-CAS, and VR

systems is a fast computer network. The network is the basis for teleoperation. Fast
computer networks are also the basis for telemedical applications, which may also be
viewed as a kind of teleoperation system.
Following the application of computers to surgery and the connection of diagnostic
devices with computer networks through DICOM protocol, the next step is directed
toward connecting local computer networks with broad range networks, i.e. within a
clinical center, city, country, or even internationally. The establishment of complex,

widespread computer networks across the country offers another significant application
of computer networks in medicine, i.e. telemedicine (distant medical consultation in the
diagnosis and treatment). Current computer networks using ATM technology allow for
very fast and simultaneous communication among a number of physicians for joint
diagnostic or therapeutic consultation. Textual, image, audio and video communication
as well as exchange of operative field spatial models are thus enabled. Patient images
and 3D spatial models can be simultaneously examined by a number of phyisicans,
who can then outline and describe image segments through textual messages, indicator
devices, voice or live image. The course and conclusions of such a consultation can be
stored in computer systems and subsequently explored, employed or forwarded to other
users of the computer assisted diagnostic system.
The use of computer networks in medicine allows for high quality emergency
interventions and consultations requested from remote and less equipped medical
centers in order to achieve the best possible diagnosis and treatment (e.g., surgery). In
addition to this, through consultation with a surgeon, a physician in a remote diagnostic
center can perform appropriate imaging of a given anatomic region, which is of utmost
importance for subsequent operation to be carried out by the consultant surgeon from
the remote hospital center.
7. System Implementation
In 1992, a scientific research rhinosurgical team was organized at the University

Department of ENT, Head & Neck Surgery, Zagreb University School of Medicine and
Zagreb University Hospital Center in Zagreb, and developed the idea of a novel
approach in head surgery. This computer aided functional endoscopic sinus
microsurgery has been named 3D-C-FESS. The first 3D-C-FESS operation in Croatia
was carried out at the Šalata University Department of ENT, Head & Neck Surgery in
May 1994, when a 12-year-old child suffered a gunshot wound in the region of the left
eye. The gunshot wound of the left orbit injured the lower eyelid and conjunctiva of the
left eye bulb, with massive subretinal, retinal and preretinal hemorrhage. The vitreous
chamber was diffusely blurred with blood, and the child was blinded in the injured eye.
Six years after the 3D C-FESS surgery, the left eye function was completely normal,
with normal vision bilaterally.
With support from the University Department of ENT, Head & Neck Surgery,
Zagreb University Hospital Center; Merkur University Hospital; as well as T-Com
Company; InfoNET; and SiliconMaster, in May 1996 the scientific research
rhinosurgical team from the Šalata University Department of ENT, Head & Neck
Surgery organized and successfully conducted the first distant radiologic-surgical
consultation (teleradiology) within the frame of the 3D-C-FESS project. The
consultation was performed before the operative procedure between two distant clinical
work posts in Zagreb (Šalata University Department of ENT, Head & Neck Surgery
and Merkur University Hospital) (outline/network topology).
In 1998, and on several occasions thereafter, the team conducted a number of first-
time tele-3D-computer assisted operations (Fig. 8)—unique procedures not previously
conducted elsewhere in the world [6,12] (www.mef.hr/MODERNRHINOLOGY).
Figure 8. An example of our Tele-3D-C-FESS surgery initially performed in 1998
References
[1] Mladina R, Hat J, Klapan I, Heinzel B. An endoscopic approach to metallic foreign bodies of the
nose and paranasal sinuses. Am J Otolaryngol 16(4) (1995), 276-279.
[2] Rišavi R, Klapan I, Handžiü-ûuk J, Barþan T. Our experience with FESS in children. Int J Pediatric
Otolaryngol 43 (1998), 271-275.
[3] Elolf E, Tatagiba M, Samii M. 3D-computer tomographic reconstruction: planning tool for surgery of
skull base pathologies. Comput Aided Surg 3 (1998), 89-94.
[4] Holtel MR, Burgess LP, Jones SB. Virtual reality and technologic solutions in otolaryngology.
Otolaryngol Head Neck Surg 121 (1999), 181.
[5] Klapan I, Šimiþiü Lj, Rišavi R, Bešenski N, Bumber Ž, Stiglmajer N, Janjanin S. Dynamic 3D
computer-assisted reconstruction of metallic retrobulbar foreign body for diagnostic and surgical purposes.
Case report: orbital injury with ethmoid bone involvement. Orbit 20 (2001), 35-49.
[6] Klapan I, Šimiþiü Lj, Rišavi R, Pasari K, Sruk V, Schwarz D, Barišiü J. Real time transfer of live video
images in parallel with three-dimensional modeling of the surgical field in computer-assisted telesurgery. J
Telemed Telecare 8 (2002), 125-130.
[7] Klapan I, Šimiþiü Lj, Bešenski N Bumber Ž, Janjanin S, Rišavi R, Mladina R. Application of 3D-
computer assisted techniques to sinonasal pathology. Case report: war wounds of paranasal sinuses with
metallic foreign bodies. Am J Otolaryngol 23 (2002), 27-34.
[8] Klimek L, Mosges M, Schlondorff G, Mann W. Development of computer-aided surgery for
otorhinolaryngology. Comput Aided Surg 3 (1998), 194-201.
[9] Mann W, Klimek L. Indications for computer-assisted surgery in otorhinolaryngology. Comput Aided
Surg 3 (1998), 202-204.
[10] Anon J. Computer-aided endoscopic sinus surgery. Laryngoscope 108 (1998), 949-961.
[11] Olson G, Citardi M. Image-guided functional endoscopic sinus surgery. Otolaryngol Head Neck Surg
121 (1999), 187.
[12] Klapan I, Šimiþiü Lj, Rišavi R, Bešenski N, Pasariü K, Gortan D, Janjanin S, Paviü D, Vranješ Ž. Tele-
3D computer assisted functional endoscopic sinus surgery: new dimension in the surgery of the nose and
paranasal sinuses. Otolaryngol Head Neck Surg 127 (2002) 549-557.
[13] Burdea G. Virtual Reality Technology, Wiley, 1994
[14] Klapan I, Vranješ Ž, Rišavi R, Šimiþiü Lj, Klapan D. Computer assisted surgery and telesurgery in
otorhinolaryngology. Ear Nose Throat J, 2005 (in press).
M.J. Roy (Ed.)
IOS Press, 2006
War Related Stress
George NANEISHVILI 1 , Nino OKRIBELASHVILI and Ketevan GIGOLASHVILI

M.Asatiani Research Institute of Psychiatry, Tbilisi Georgia
Abstract. Background. Prolonged armed conflicts in Georgia (1991-93) took place

against a background of extreme social-political tension and economic decline of
the country. Teams for Crisis Assistance investigated the wounded participants of
war actions, who were located in military hospitals.
Methods. A general questionnaire was administered to the wounded, to ascertain
socio-demographic and medical background information. A mental status
examination was conducted. Each subject was given time to talk about physical
and psychological impacts of a traumatic event.
Results. Among 1400 wounded the range of immediate reactions were
considerable: 79.3% of those investigated met criteria for Acute Stress Reaction
(ASR), with 8.9% meeting full criteria for Post-traumatic Stress Disorder
(PTSD). Prompt treatment of trauma survivors with psychotherapy and medication
caused the considerable diminution of separate symptoms (i.e., anxiety,
nightmares, flash backs, intrusive thoughts) in 47% of cases, and the total
reduction in 31% of observed cases, while 22% dropped out from the treatment
plans.
Conclusions: Our findings support the efficacy of early intervention in war-related
stress morbidity.
Key words: Acute Stress Reactions, PTSD, War-Related Stress
Introduction
Each person has an individual threshold for responding to various types of stressors [1].
The range of psychological reactions caused by a traumatic event depends on the type,
magnitude, duration and severity of the stressors, as well as ethno-cultural peculiarities.
1
M.Asatiani Research Institute of Psychiatry, 10 Asatiani St., Tbilisi 0177, Georgia
G. Naneishvili et al. / War Related Stress 265
Extreme traumatic experience, leading to the impairment of defense mechanisms, can

impact all levels of psychological and social functioning and disturbs the individual
bio-psycho-social balance. In 1993, the IFRC in the World Disaster Report proposed
the taxonomy of disasters, in which armed conflicts and displacement are recognized as
long-term man-made disasters. Therefore, armed conflicts, which agitated Georgia in
1991-93 and resulted in the forcible migration of approximately 286,000 people, could
be considered a complex multidimensional phenomenon. So called “civil war” could be
considered a universal complex of stressors that impacts every individual in the society,
and at one end of the continuum of possible responses are manifest acute and chronic
traumatic reactions.
1. Methods/Patients
The study was conducted in a highly selected and vulnerable population. Teams for
Crisis Assistance investigated almost 1400 wounded participants of war actions in the
military hospitals of Tbilisi (Georgia). A general questionnaire for the wounded
assessed socio-demographic factors and medical histories. Socio-demographic
variables included age, gender, marital status, education, occupation, military history,
and trauma history. Medical information collected included medical/surgical history,
substance use, mental status examination, and a Brief Psychiatric Rating Scale. Trained
psychiatrists and clinical psychologists administered the instruments. Observations also
included open-ended psychiatric interviews. Each subject was provided sufficient time
to talk about the physical and psychological impacts of a traumatic event.
2. Results
Most of those studied presented various psycho-pathological symptoms, both neurotic

and psychotic. The range of immediate reactions was considerable: 79.3% met criteria
for acute stress reactions (ASR), while the separate symptoms of Post-traumatic Stress
Disorder (PTSD) were reported in 8.9% of cases. Non-pathological situational
reactions sometimes were manifest as deviant behavior, adaptive-situational reactions,
and psychological crisis. The team members faced definite obstacles: wards were
overloaded, no separate rooms were available for psychotherapy, and patients were
demanding pills. (It is ingrained in the Georgian cultural milieu that every visit to the
doctor must result in “getting pills”), and working hours were unlimited. During the
initial therapeutic sessions, the investigators had to cope with patients’ dissimulation of
the extent of psychological disturbances because of cultural socialization patterns that
reinforce silent endurance as a manifestation of courage in men. By making immediate
decisions, taking into account personal/social resources and skills, and in accordance
with the professional qualification of the observer, patients with acute traumatic
reactions received individualized treatment plans (education about the process of
trauma recovery, individual rational psychotherapy and psycho-correction with
elements of catharsis, axio- and logotherapy) [2,3]. Medication was administered on
occasion. About 53% of the wounded received problem-oriented short-term group
therapy, which was provided to wards of 6-8 patients. Due to the shortage of
psychiatric medication, medicinal treatment was provided at minimal doses with
frequent substitution of drugs. The most common medications offered to the wounded
266 G. Naneishvili et al. / War Related Stress
included antidepressants, benzodiazepines and carbamazepine [4]. Follow-up

assessments at 8 weeks indicate that the immediate attention to trauma survivors with
psychotherapy and medication was associated with considerable, though gradual,
diminution of separate symptoms (i.e., anxiety, nightmares, flash backs, intrusive
thoughts) in 47% of cases, and the total reduction in 31% of observed cases, while 22%
failed to follow up with treatment when the crisis period passed.
3. Discussion
We believe that early intervention in psychological trauma and, particular, in war

related stress, reduces post-traumatic stress morbidity and provides an opportunity to
prevent the progression of conditions into chronic forms of PTSD. Prompt assistance
may well prevent later manifestations and help to lessen potential complications. We
hypothesize that a number of factors might be associated with the high rate of acute
stress reactions (ASR):
1. The investigations were provided among the wounded – the physical trauma, as a
direct mortality threat, and the exposure to the dead destroy a myth of
invulnerability that is the major risk for the development of ASR [5, 6, 7, 8].
2. The military conflict in Georgia occurred against a background of political
destabilization and an unstable military position. Prolonged political conflicts, the
indistinctness of enemy's territory, unclear identification of the enemy, and
frequent rotation of military units, maximizes the destructive impact on personality
and promotes the development of ASR and PTSD.
3. Physical emaciation: The difficulty in delivery of food or inferior nourishment (in
78% of cases), loss of weight about 8-10 kg (reported 46%), disturbances in sleep
stereotype (92% - responded positively) – also creates vulnerability for ASR and
PTSD development [9].
4. Frequent use of drugs (24%) and alcohol for relief of tension reduces the adaptive
potential of the individual [10, 11].
5. The moral situation: During the ethnic conflicts, each soldier has to make his own
decisions, which he has to defend in future. Among those studied, 64%
volunteered, and their motivation for participation in war actions was: "I fight,
because”others” were taking away my motherland". It was a "civil war," requiring
very difficult decisions – on the other side were relatives, ex-neighbors, ex-friends
or simply compatriots. In 75% of individuals, we observed an agonizing feeling
regarding an unwarranted, unjustified war.
6. Lack of life experience: We found that 72% received only secondary education,
56% were single, and 36% were 18-25 years old. The young age, low level of
education [12], and lack of life experience foster difficulties in orientation in new
situations, where one can encounter many unfamiliar feelings to which the brain is
not oriented [13].
7. Lack of military experience: Forty-four percent of those studied went into battle
without any military training. This intensified feelings of being uncertainty,
vulnerability and, lack of protection, as a result, and in turn, future anxiety [14],
uneasiness, and feelings of terror.
While our investigation has many salient findings, it should be noted that this
represents an uncontrolled study, so it may be that some individuals would have
G. Naneishvili et al. / War Related Stress 267
gradually improved over time without our intervention, but the medical literature is
replete with documentation of worsening of stress-related symptoms over time in the
absence of symptoms.
References
[1] F. Neuner, M.Schauer, U. Karunakara, C. Klaschik, C. Robert, Thomas Elbert. Psychological trauma and
evidence for enhanced vulnerability for posttraumatic stress disorder through previous trauma among
West Nile refugees. BMC Psychiatry. 2004; 4: 34.
[2] Onyut LP, Neuner F, Schauer E, Ertl V, Odenwald M, Schauer M, Elbert T. The Nakivale camp mental
health project: building local competency for psychological assistance to traumatised refugees.
Intervention 2004;2:90–107.
[3] Neuner F, Schauer M, Klaschik C, Karunakara U, Elbert T. A comparison of narrative exposure therapy,
supportive counseling, and psychoeducation for treating posttraumatic stress disorder in an african
refugee settlement. J Consult Clin Psychol 2004;72:579–587. doi: 10.1037/0022-006X.72.4.579.
[4] Stein DJ, Zungu-Dirwayi N, van der Linden GJH, Seedat S. Pharmacotherapy for post traumatic stress
disorder (PTSD). The Cochrane Database of Systematic Reviews 2000, Issue 4. Art. No.: CD002795.
DOI: 10.1002/14651858.CD002795.
[5] I.D. Yalom. Existential Psychotherapy. New York: Basic Books, 1980
[6] D. Foy et al. Etiology of PTSD in Vietnam veterans: Analysis of preliminary, military and combat
exposure influences. J Consult Clin Psychol 1987; 43: 643-649
[7] Pitnam R. et al. Prevalence of PTSD in wounded Vietnam Veterans. Am J Psychiatry 1989;146: 667-669
[8] Green BL, Lindy JD, Grace MC, Gleser GC: Multiple diagnosis in posttraumatic stress disorder: the role
of war stressors. J Nerv Ment Dis 1989; 177:329-335
[9] Titchner JL. Post-traumatic decline: A consequence of unresolved destructive drives. In: Figley CR (ed.)
Trauma and Its Wake vol. New York: Brunner/Mazel, 1987
[10] Bond TC. The why of fragging. Am J Psychiatry 1976; 133:1328-1331
[11] Khantzian EJ. The self-medication hypothesis of addictive disorders: Focus on heroin and cocaine
dependence. Am J Psychiatry 1985; 142:1259-1264
[12] Pilisuk M. The legacy of the Vietnam Veterans. J Soc. Issues 1975; 31:3-12
[13] Solomon Z. et al. Exposure to recurrent combat stress: combat stress reactions among Israeli Soldiers in
the Lebanon war. Psychol Med. 1987;17:433-440
[14] SM Southwick, A Morgan, LM Nagy, Bremner D, Nicolaou AL, Johnson DR, Rosenheck R, Charney
DS: Trauma-related symptoms in veterans of Operation Desert Storm: a preliminary report. Am J
Psychiatry 1993; 150:1524-1528
M.J. Roy (Ed.)
IOS Press, 2006
PTSD – Hungarian Lessons Learned

in Afghanistan and Iraq
LTC Zoltan VEKERDI, a1 , LTC Laszlo SCHANDL, Ph.D.b
a
Operational Division, Medical Command, Hungarian Defence Forces,
Budapest Hungary
b
First Department of Internal Medicine, Central Military Hospital,
Hungarian Defence Forces, Budapest, Hungary
Abstract. The authors review conditions of establishment of the Hungarian

Military Medical Contingent. They discuss problems met during the preparation
phase, and briefly describe the curriculum of a pre-deployment training program,
during which mission-oriented foreign language medical training appears as a new
element. They describe the work done by the Contingent and its successful
integration into the multinational medical support system of International Security
Assistance Forces (ISAF) in Afghanistan. They give details on the role of
Hungarian military medical personnel in providing medical support after a terrorist
act against German forces on June 7, 2003, and also the Hungarian role played in
elaboration of a new Mass Casualty Plan of the German Field Hospital deployed in
Kabul, Afghanistan. They focus on stress factors affecting Hungarian soldiers
(both regular ones and medical personnel) deployed in Afghanistan and Iraq, and
coping methods to prevent Post Traumatic Stress Disorders. Finally, the authors
describe opportunities to improve multinational medical co-operation.
Key words. Hungarian Military Medical Contingent, ISAF, Afghanistan, German

Field Hospital, Terror Act, Mass Casualty Care
Introduction
This article gives an overview of the goals and structure of the Hungarian Military
Medical Contingent that was deployed in Kabul, Afghanistan to augment German and
Dutch Medical Treatment Facilities. The authors describe the process of its integration
into Level-2 and Level-3 elements of the mission’s medical support system.
A pivotal motive of these Medical Treatment Facilities, aside from routine medical
support to the troops, is improving readiness, capability and adequate capacity to cope
with possible MASCAL (Mass Casualty) situations. The operational plan of the
German Field Hospital that is summarized here serves this goal. This plan is based on
risk analysis, limitations of capacity, capability and readiness considerations.
Readiness must be assured by education and training of all people involved on all
levels and services. Implementation periods of the MASCAL Plan of the Bundeswehr
1
Corresponding Author: LTC Dr VEKERDI, Zoltan, Operational Division, Medical Command, Hungarian
Defence Forces, 1885 Budapest PO Box 25, Hungary, E-mail: sheltadoc@hotmail.com
Z. Vekerdi and L. Schandl / PTSD – Hungarian Lessons Learned in Afghanistan and Iraq 269
Field Hospital include: the alert process, preparation, reaction phase, after-action
activities, and return to normal work and duty.
The authors give summarized lessons learned during implementation of the
MASCAL plan in exercises and real events.
2. Activities of the Hungarian Military Medical Contingent
2. 1. Legal background
After the overthrow of the Taliban regime, based on United Nations Security Council
Resolution 1386/2001, the International Security Assistance Forces (ISAF) mission
was launched to foster the stabilization process in Afghanistan.
Hungary, based on its Parliament decision 111/2002, decided to contribute to the
ISAF mission with a military medical contingent. The size of this contingent was limited
to not more than 50 persons at a time, and the Hungarian Parliament mandated the
contingent to fulfill its tasks and responsibilities until 31 December 2003.
2.2. Establishment of the contingent
Based on traditionally prominent bilateral co-operation with medical services of the

Bundeswehr and The Netherlands, it was logic to integrate personnel of the Hungarian
Military Medical Contingent (HMMC) into the structure of German and Dutch military
medical treatment facilities already deployed and functioning in the theatre f operation.
From a military point of view this decision was supported by the fact that Germany
and The Netherlands became the lead nations in ISAF mission at the beginning of 2003.
Preparatory works started with inspection of the deployment areas in Kabul in early
January 2003. The Hungarian delegation visited ISAF Headquarters, the Dutch augmented
surgical unit (NATO code: Role2+) at Kabul International Airport, and Bundeswehr Field
Hospital at Camp Warehouse (NATO code: Role3). They collected information on the
work of these units, on tentative tasks and responsibilities and also on conditions of work,
rest, and accommodation of the HMMC personnel to be deployed.
Professional consultations with the German and Dutch parties started in January 2003
to finalise technical details of co-operation. As a result, a military technical agreement was
signed with Germany.
It was mandatory for members of HMMC to be volunteer military people. Since
Hungary is heavily involved in different peacekeeping operations all over the world, the
number of Hungarian military medical specialists deployed at a time to support Hungarian
troops in different missions is approximately 50. Rotation and sustainment of these people
lays quite a burden on the Medical Service of the Hungarian Defence Forces. This is the
reason why medical specialists also from the civilian sector were recruited for this mission.
2.3. Selection and preparation of the personnel
The selection process included analysis of professional training, education and experience,
previous mission assignments, military background and language skills as well. Medical
270 Z. Vekerdi and L. Schandl / PTSD – Hungarian Lessons Learned in Afghanistan and Iraq
examination reviewed health status, physical performance and also psychological features
of the applicants.
After selection, members of HMMC went through normal military training regular for
every Hungarian peacekeeping soldier before deployment. This two-week training
included also a three-day psychological training lead by a professional psychologist. The
aim of the training was to prepare participants to recognise and cope with stress situations,
train for conflict management, and prevent lost days of duty due to psychological reasons.
The training method included both theoretical and practical training in small groups.
Immunization protocol for members of the contingent have followed the matrix used
by Bundeswehr in Kabul.
Personnel of the HMMC were to integrate separately, as individuals, into the
Medical Treatment Facilities deployed and operated by NATO allies. It was this
integration by individual members that made mission-oriented pre-deployment foreign
language medical training (in English and German languages) necessary.
2.4. Integration into the multinational medical support system
The personnel of the HMMC were deployed and rotated by fragments, as positions in
the medical treatment facilities offered for the Hungarian party became vacant. The
largest number of Hungarian military medical personnel deployed at a time was 21.
Most of the Hungarian military medical specialists were assigned to the German Field
hospital and Medical Evacuation Company attached to the field hospital. Two qualified
nurses worked at the Dutch Role2+ facility deployed at Kabul International Airport.
In order to reduce the risk of national donor fatigue during the long sustainment
period, the German field hospital integrated medical specialists of several nations. The
true multinational character of it can be well described through the national percentage
of Medical Officers working in the field hospital and its medical evacuation company
(respectively), which in August 2003 was as follows:
- German 52%, and 70% in the medical evacuation company
- Hungarian 16%, and 30% in the medical evacuation company
- French 16%
- Lithuanian 8%
- Danish 4%
- Bulgarian 4%
2.5. Activities during deployment
The experience gained during the first weeks after deployment of HMMC personnel
proved the correctness of principles followed during the pre-deployment selection
process. We experienced the real physiological effects of the extreme continental
climate of Kabul situated at 1800 meters above see level. Low air pressure, dust storms
and variations in daily temperature combined with heavy fitness programs, without a
proper acclimatization period, to lead to some fatalities among allied soldiers.
The excellent professional readiness of the Hungarian military medical personnel
was a great asset in the process of integration into multinational teams. Daily tasks
quickly became routine activities. This monotony, combined with emotional
deprivation that resulted from confinement to the camp of deployment, became the
main stress factors for the personnel.
Since well-being is an outcome of combined factors of person, environment and

occupation, a variety of measures were recommended and taken to mitigate the above-
mentioned stress factors: team-building activities (professional, national, international
and cultural events), regular physical exercise (a program gradually built up after
proper acclimatization), proper relation of rest and work, access to national news and
media (via Internet and satellite TV), opportunity to contact relatives via cell phone (so
called “morale calls” – calls paid by the Army were introduced later for Hungarian
soldiers deployed to Iraq), controlled incentive trips to the city, a 10-day holiday at
home during a 6-month mission period (paid by Hungarian Defence Forces), food
quality and variety, security measures and conditions of accommodation, meaningful
work, etc.
For reasons of humanitarian assistance, training purposes, and to keep staff of the
field hospital busy, free capacities of the facility under certain conditions were used to
treat local patients. This constant and planned flow of patients fostered team-building
efforts, served as a training method to conserve the manual skills of specialists with a
surgical orientation, helped to establish co-operation between functional areas of the
hospital (which is essential in preparation for possible MASCAL situations) and
provided a meaningful purpose of work for the people involved.
All of the above-mentioned activities fostered successful integration of HMMC
personnel. The real test of effective work and co-operation for the multinational and
multicultural medical units of the German Field Hospital, German Medical Evacuation
Company and the Dutch Surgical Unit deployed at Kabul International Airport was the
management of medical consequences of a terrorist act against German troops on June
7, 2003.
2.6. Terrorist act on June 7, 2003
The terrorist act on June 7, 2003 was the bloodiest committed against German soldiers
since the end of WW II. That Saturday, Afghani suicide bombers attacked the convoy
of German soldiers that were headed to airport after completion of their mission in
Afghanistan, killing four and injuring 29 people.
At approximately 07.50 hours that day a yellow Toyota cab approaching from the
opposite direction crossed the dividing narrow ground stripe of the two-lane road,
lined up and exploded beside the second bus of the convoy full of soldiers. The force of
the explosion knocked the bus into the field across the opposite lane, near a gas station.
The leading car of the convoy alarmed the German Rescue Coordination Centre
that activated for mass casualty situation the German Field Hospital, the Medical
Evacuation Company and the Dutch Surgical Unit. In addition, American and British
allies heard the alarm and joined into rescue operation.
A casualty collection point was established to manage ambulatory casualties at the
scene. To prevent a possible second wave of attack, an armed guard was set up at the
perimeter of the scene. By 09.30 hours all the casualties were evacuated from the scene.
Management of casualties has proven the raison d'Ċtre and effectiveness of
multinational rescue teams.
As a result of activation, in preparation for the mass casualty situation, the field
hospital set up the main and reserve triage areas, redirected regular sick call patients,
and activated reserve intensive and regular care beds. In addition, mass casualty
management areas were set up with the appropriate teams to manage incoming
casualties, reserve stores of medical materials were activated and emergency blood
donation from regular soldiers were organised (“walking blood banks”).
Table 1. The terror act medical consequences in numbers.
Total number of casualties 35 persons

- 33 German soldiers and 2 Afghani people
Number of light and medium severity casualties 25 persons

- All German soldiers
Number of seriously injured casualties 7 persons

- 6 German soldiers and 1Afghani person
Casualties with eye injury 25 persons

- All German soldiers
Enucleation required 3 persons
Lower extremity amputation required 1 person

- German soldier
Total number of dead 6 persons

- 4 German soldiers and 2 Afghani people
Died at the scene 4 persons

- 3 German soldiers and the Afghani suicide
bomber
Died during evacuation from the scene -
Died in the German Field Hospital 2 persons

- 1 German soldier and 1 Afghani person
Based on the above figures it is obvious that not only the casualties themselves, but
also care providers and fellow soldiers required psychological support to cope with
consequences of this trauma situation. As dedicated member of the German contingent,
a field psychologist and two troop priests worked with the affected personnel. Also a
British and an American priest arrived to the field hospital to augment their German
colleagues.
The personnel background of psychological support was present. At the same time,
obviously, this is effective only with efficient language contact (communication
capability) between the participants.
HMMC personnel contributed to rescue and consequence management operation
according to his/her training, education, position and experience from the very first
minute of rescue efforts.
For security reasons (to avoid panic) the Germans turned the cell phone network
off. The commander of the HMMC (the second author of this article) reported to the
homeland commander of HMMC via satellite phone before the arrival of the first
casualties to the field hospital. During the afternoon, the commander of the HMMC
also gave a telephone interview to Hungarian Television to reassure Hungarian public.

He emphasized that there were no Hungarian victims or casualties, and that
consequence management activities were taking place with sustained effort.
The first opportunity to call together members of HMMC and talk about the events
of the day opened late evening. After this staff meeting HMMC personnel filed past the
catafalque of dead fellow German soldiers, and were among the first to sign the book of
final tribute.
All the above-mentioned measures have helped to control the natural reaction of
bereavement and turn it into energy of creativity to augment feeling of group
coherence.
Unlike the Hungarian contingent in Iraq, due to the small number in this HMMC,
no Hungarian psychologist or chaplain were deployed to Afghanistan. If there had been
Hungarian victims or casualties, or if emotional reactions necessitated it, duty
psychologists from Hungary would have arrived to Kabul to support HMMC personnel.
As part of the permanent staff of the Hungarian military transport contingent
deployed later in Iraq, there were both a psychologist and a chaplain included (based on
pre-deployment risk assessment). During the mission period of this contingent only one
soldier was diagnosed and treated for PTSD (after returning to home). His fellow
Hungarian soldier died in a mortar attack committed against the Hungarian convoy in
Iraq.
At the same time -more or less- almost every soldier showed signs of acute stress
reaction after terror attacks against their camp in Iraq (regardless weather he/she was
injured or not in the incident).
2.7. MASCAL plan update with Hungarian contribution
The two pivotal targets of the field hospital mass casualty plan are assurance of
adequate medical response to possible mass casualty situations, and sustainment of
operability of the medical treatment facility.
For a successful operation, and for the survival and sustainment of any military
unit deployed in an operational environment, it is essential to turn lessons learned into
every day routine as quick as possible. This is also the case for the field hospital, where
highly qualified medical personnel are rotated every 3 to 6 months, if not more
frequently. It is critical for frresh personnel to achieve familiarization with the lessons
learned, to acquire and adapt them in protocols for major incident medical management
and to practice them in regular exercises.
Lessons learned during the terrorist event were analysed carefully in several
professional forums. As a result, pre-deployment training programs and the field
hospital MASCAL plan were updated. In August 2003, as the new commander of
HMMC, I arrived to Kabul and became the second Hungarian Clinical Director of the
German Field Hospital shortly afterwards. For the newly arrived staff of the hospital I
compiled a training material in PowerPoint format to familiarise them with the
MASCAL plan of the facility (before they start exercising it) that included lessons
learned.
2.8. Redeployment
According to a resolution of the Hungarian Parliament, the HMMC completed its

mission and was redeployed in December 2003. Part of the contingent’s materials and
equipment remained in the theatre of operation to support Hungarian soldiers who, as
individual contributions to the NATO lead ISAF mission and based on bi-lateral
agreement with Germany arrived and continued to serve in Afghanistan.
After mandatory post-deployment medical examinations, members of HMMC
returned to their original military or civilian place of work, however many civilians –
based on their favourable mission experience - decided to remain in the Army.
3. Discussion
Lessons learned during the organization, establishment and mission activity of the
Hungarian Military Medical Contingent can be summarized as follows:
- Since 1990 this was the first time when Hungarian military medical personnel, as
individuals, separately integrated into a Medical Treatment Facility deployed and
operated by a NATO ally.
- It was this integration by individual members that made mission-oriented pre-
deployment foreign language medical training necessary.
- Successful medical care at a terrorist incident site is considerably influenced by
security of the area (to prevent second wave attacks), by effectiveness of first aid and
buddy aid provided before arrival of medical rescue teams, by triage, first
management and rapid evacuation of casualties.
- In a mass casualty situation, both the method and level of medical care provided for
the sick, wounded or injured by the field hospital changes. That is, medical care
focusing maximally on the needs of individual casualties, and medical support
provided on levels as close as possible to peacetime medical standards, is replaced by
medical care and support focusing on the needs of casualties as a whole contingent
(the best possible care to the largest possible number of casualties) in order to save
life, limb and function.
- In a mass casualty situation, the key factor to sustain continuous operational capability
of the field hospital is rapid, proper, coordinated evacuation of casualties based on
flexible adjustment to the operational needs of the Medical Treatment Facility.
- Proper trauma management of mass casualty situations has the utmost importance in
the prevention of Post Traumatic Stress Disorder.
The risk of traumatic events as a result of enemy activity in operations other than war is
mainly determined by the mission statement of the force (which depends primarily on
levels of political and military ambition).
The Hungarian Parliament did not authorize the Hungarian Defence Forces to
deploy combat units into different theatres of operation. That determined mission,
tasks, responsibilities and consequently –to a great extent- the possible risk exposure to
the troops as well. This may be the logic explanation for the extremely low number of
combat related PTSD patients among Hungarian soldiers.
4. Conclusion
The reader is briefed on the medical support system of the ISAF mission, on challenges, on
system levels that ensure continuity and progressiveness of medical support. The reader
gets an overview of the activation and implementation of the MASCAL Plan of the
German Field Hospital in Kabul with an analysis of lessons learned during exercises and
real events.
After traumatic events (especially after mass casualty situations) acute stress
reactions affect almost every soldier of any nationality concerned or just involved in
incident management. Proper trauma management of mass casualty situations is of
outmost importance in prevention of Post Traumatic Stress Disorder.
The German Field Hospital in Kabul, Afghanistan is a living example of successful
integration of multinational military medical personnel in a peacekeeping / peace-
enforcement operation.
Multinational cooperation however does not mitigate the ultimate national
responsibility over medical support to entire military formations and individual
soldiers, which must include proper psychological and/or psychiatric support as well.
References
[1] ACE Medical Support Principles, Policies and Planning Parameters, ACE Directive 85-8
Supreme Headquarters Allied Powers Europe, Belgium, 1993
[2] Allied Joint Medical Support Doctrine, AJP-4.10
Supreme Headquarters Allied Powers Europe, Belgium, 1999
[3] Guidelines for Medical MASCAL Planning – ISAF, 2002
[4] Kretschmer H, Döller PC, Bialek R, Schüle B: Ratschläge zur Erhaltung der Gesundheit in tropischen
und subtropischen Ländern
[5] Bundesverwaltungsamt, 1999
[6] Medical Training in First Aid, Basic Hygiene and Emergency Care – NATO STANAG 2122, 1991
[7] NATO Medical Handbook
The Committee of the Chiefs of Military Medical Services in NATO (COMEDS) HQ NATO
(IMS/LA&R) Brussels, Belgium, 2001
[8] NATO Principles and Policies of Operational Medical Support – Final Decision on MC 326/2, 2004
[9] Principles of Medical Policy in the Management of Mass Casualty Situation - NATO STANAG 2879
MED (EDITION 3), 1998
[10] Servais O: A katonaorvos és a Genfi Egyezmények
Magyar Honvédség Egészségügyi SzolgálatfĘnökség, 1990
[11] Schandl L: Das Selbstmordattentat am 7.6.2003 – Zusammenarbeit des medizinischen Personals
Wehrmedizin 2003;27(3):22-23
[12] Svéd L, Kopcsó I: A magyar katonaegészségügy a jelenkor válságaiban
Honvédelmi Minisztérium Honvéd Vezérkar Egészségügyi CsoportfĘnökség, 2004
[13] Weidringer JW (red): Katastrophenmedizin – Leitfaden für die ärztliche Versorgung im
Katastrophenfall
Bundesministerium des Innern, 2003
Section VI
Working Groups
M.J. Roy (Ed.)
IOS Press, 2006
Posttraumatic Stress disorder - Diagnostic

and Epidemiological Concerns
NANEISHVILI G., M.Asatiani Research Institute of Psychiatry,

Tbilisi, Georgia
Abstracts. In Cavtat in June, 2005, several international experts convened to

address the key issues in the presentation of PTSD, including diagnostic
instruments, classification, risk factors and co-morbidity, as well as clinical aspects
of secondary and associated posttraumatic symptoms. Here, we summarize the
consensus achieved in discussion between working group members of the group
focusing on “Diagnostic and Epidemiologic concerns".
Keywords. PTSD, Trauma, Stress, Clinical phenomenology, Classification, Co-

morbidity, Risk factors, Secondary and associated posttraumatic symptoms.
Introduction
Posttraumatic stress disorder (PTSD) has been identified in some individuals who have
experienced a physically or emotionally traumatic event that is outside of the range of
normal human experience, such as military combat, rape, natural or manmade
(artificial) disasters. PTSD is diagnosed when certain pathopsychological symptoms
develop after exposure of traumatic events. There are three major symptom categories,
which include: 1) reexperiencing the trauma through dreams or recurrent and intrusive
thoughts; 2) emotional numbing such as feeling detached from others; and 3)
symptoms of arousal such as irritability and exaggerated startle response. The point
prevalence of PTSD in the general population has been estimated to be 0.5% among
men and 1.2% among women. Most men with PTSD have experienced combat. For
women, the most common stressors are rape and physical assault. PTSD may begin
within hours or days after a significant stress, or the onset may be delayed for months
or even years.
1. Formation of the concept of PTSD
Traumatic disorders can arise in response to a large variety of severe stressors. Despite
the diversity of stressors, the concept of an extreme psychological reaction to
catastrophic events was first demonstrated exclusively in the context of war,
specifically as a reaction to combat actions [1]. The concept of traumatic reaction dates
back at least to the time of "the birth of nosological psychiatry", when Griezinger [2]
identified two forms of psychosis, with the first characterized as psychoses caused by
280 G. Naneishvili / Posttraumatic Stress Disorder – Diagnostic and Epidemiological Concerns
emotional turbulence, when “the whole psychic life is accordingly changed ". The
second type includes mental disorders based on intellectual and volitional breaches,
where there is the organic defeat of brain. In the first group Griezinger includes forms
of melancholies caused by heavy emotional influence, in which there is reflected
psychic trauma.
Sommer [3] and other psychiatrists underlined the relationship between psychogenic
reactions and hysteria. They emphasized the existence of a pathological basis in
development of this type of psychosis. Accounts World War I described stupor and
depressive disorders during hostilities among soldiers [4], as well as attacks of panic
and agitation with hallucinations and delusion on the battlefield [5]. Others supplement
these observations, including Kraepelin [6], who coined the term "accidental
psychosis” or “neurosis caused by accident", and Jaspers [7], who defined psychogenic
reactions as "a conflict of personality with ‘unbearable’ reality".
Subsequently, extreme agitation, fright and disorientation have been described
following a variety of other military conflicts. These accounts gave birth to such terms
as "shell shock", "combat neurosis", "battle fatigue", and "traumatic neurosis". More
recently, PTSD was formally recognized and codified in DSM-III [8], and many
authors have expanded upon the initial reports from combat settings to document
similar psychopathology across a wide range of civilian traumas.
2. Clinical Phenomenology and Classification of PTSD.
Posttraumatic Stress Disorder is one of several potential sequelae of exposure to

traumatic stress, including operational stress. Mood and anxiety disorders, psychotic
reactions, sexual disorders, dissociative disorders, and a series of life problems (e.g.,
relationship, vocational, and social problems) are also more common in those exposed
to significant trauma.
PTSD is by definition a reaction to exposure to an event which is outside of normal
human experience. The symptoms of PTSD may initially be considered a normal
human emotional reaction to an abnormal situation, but their persistence, in association
with impairment of function, constitutes a disorder. It should also be emphasize that
there is a wide range of “normal” with regard to the response of various individuals,
and some may even have significant PTSD in response to a trauma that does not pose a
significant threat to their lives. The key is for the event to be perceived by the victim
as traumatic. PTSD represents emotional and cognitive dysfunction of prolonged
duration, but it is well documented that full and complete recovery can be expected,
whether spontaneously or aided by treatment.
Responses in patients with PTSD may be divided into 4 categories:
1. Emotional: Shock, Irritate, Fear, Sorrow, and Indefensibility.
2. Cognitive: Disorientation, Difficulties with concentration, fixed
ideas.
3. Biological: Insomnia, Hyperarousal, and Agitation.
4. Psychological: Progressive restriction of social activities,
Interpersonal conflicts, abuse of alcohol or drugs.
The disorder features the following tenets:
A. Exposure to a traumatic event,
B. Response of fear, helplessness, horror,
D. Re-experiencing of traumatic events (Flashbacks, Recurrent nightmares),
G. Naneishvili / Posttraumatic Stress Disorder – Diagnostic and Epidemiological Concerns 281
E. Avoidance of stimuli associated with trauma,

F. Arousal symptoms.
They are two further detailed in both the Diagnostic and Statistical Manual of Mental
Disorders, 4th Edition (DSM-IV), and the International Classification of Mental
Disorders (ICD-10).
Historically, the first formal criteria for the diagnosis of trauma-related disorders
appeared with DSM-I (1952). These disorders initially were characterized as "traumatic
neuroses", emphasizing the psychoanalytic concept of unconscious defense
mechanisms. DSM-II (1968) supplemented the earlier definition of posttraumatic
syndromes with "transient situational disturbances" and "adjustment reactions", while
DSM-III (1980) was the first to include PTSD. DSM-IV (1994) represented the
provision of clear-cut definitions for the stressor criterion for PTSD. In addition, DSM-
IV detailed primary and secondary symptoms. PTSD is classified by DSM-IV with
code 309.81, as a member of the group of "Anxiety Disorders". The diagnostic criteria
for PTSD according of DSM-IV:
A. The person has been exposed to a traumatic event in which both of the
following were present:
1. the person experienced, witnessed or was confronted with an event or
events that involved actual or threatened death or serious injury.
2. person's response involved intensive fear, helplessness or horror.
B. The traumatic event is persistently reexperienced in one or more of following
ways:
1. recurrent and intrusive distressing recollections of the event,
including images, thoughts or perceptions.
2. recurrent distressing dreams of the event.
3. acting or feeling as if the traumatic event were recurring.
4. intense psychological distress at exposure to internal or external cues
that symbolize or resemble an aspects of the traumatic event.
5. psychological reactivity on exposure to internal or external cues that
symbolize or resemble an aspect of the traumatic event.
C. Persistent avoidance of stimuli associated with traumatic event and numbering
of general responsiveness:
1. efforts to avoid thoughts, feelings or conversations associated with
the trauma,
2. efforts to avoid activities, places or peoples that arouse recollections
of the trauma,
3. inability to recall an important aspect of the trauma.
4. markedly diminished interest or participation in significant activities.
5. feeling of detachment from others.
6. restricted range of affect.
7. sense of a foreshortened future
D. Persistent symptoms of increased arousal:
1. difficulty falling or staying asleep.
2. irritability or outbursts of anger.
3. difficulty concentrating.
4. hypervigilance.
5. exaggerated startle response
E. Duration is more that 1-month.
F. The disturbance caused clinically significant distress in social, occupational or

other important areas of life.
The disorder may be further categorized as acute (duration less than 3 months), chronic
(duration is 3 month or more) or of delayed onset (onset of symptoms is at least 6
months after the trauma)[9].
PTSD is represented within ICD-10 by the code F43.1 in the group of "Reaction to
severe stress, and adjustment disorders"[10]. There are similarities and differences in
the diagnostic criteria between DSM-IV and ICD-10. The similarities include the
clinical picture of the disorder, although psychogenic amnesia (partial or total) is
emphasized only in ICD-10. Duration is less clearly defined in ICD-10.
The diagnosis of PTSD accurately describes the symptoms that result when a person
experiences a short-lived trauma (car-accident, natural disasters, rape). They are
considered traumatic events of time-limited duration. However, chronic traumas may
persist for months to years at a time. Clinicians have found that the current PTSD
diagnosis often does not capture the severe psychological harm that occurs with such
prolonged, repeated trauma. Some investigators believe a new diagnosis, "Complex
PTSD", [11] is needed to describe the symptoms of long-term trauma.
In many nations, ICD-10 Classification is primarily used for reporting and/or
diagnostic purposes, while DSM-IV is used predominantly for research.
The working group discussion addressed new information based on recent research,
including:
–Psychotic features as a subtype of chronic PTSD (particularly based on work done by
Kozaric-Kovacic with Croatian Homeland War veterans);
–The relative significance of flashbacks vs. re-experiencing symptoms;
–The need for future research to address predictors of the risk of mortality;
–For military populations, the questionable validity of an emotional response of “fear,
helplessness and horror” (to be further studied).
3. Problems of co-morbidity
Many studies have documented a high degree of co-morbidity of PTSD with other
mental disorders. For example, the NVVRS [12] found the following rates of
psychiatric co-morbidity among Vietnam veterans with PTSD: Major depression,
15.7%; Panic disorder, 4.9%; Obsessive-compulsive disorder, 8.7%; Alcohol abuse,
22.2%. The VES, [13] conducted by the Centers for Disease Control and Prevention,
also reported high rates of co-morbid depression, GAD and substance abuse among
Vietnam veterans with PTSD compared to veterans without this disorder. High co-
morbidity with somatic disorders suggests a kinship between PTSD and mechanisms of
conversion and dissociation.
4. Risk factors of PTSD
Many studies [14-16] have found evidence of pre-trauma predictors of risk for PTSD.
Such factors include familial psychiatric illnesses, paternal poverty, sexual assault,
childhood behavioral disorders, neuroticism, introversion, prior psychiatric disorders,
and low socio-economic status. Some studies have found that premorbid risk factors
both increase the risk of exposure to trauma as well as the subsequent risk of
developing disabling symptoms from the event.
PTSD rates were three times higher in wounded Vietnam veterans than in non-
wounded combat veterans (20% versus 6,3%) [16]. Epidemiological studies found that
the frequency and severity of PTSD increased in proportion to proximity to the trauma.
The modal form of PTSD for the "on playground" group (i.e./ most exposed) was
severe PTSD (48%); for the "in school group" (i.e., less exposed) it was moderate
PTSD (50%) and the modal reaction for the "not at school" group was no PTSD (55%)
[17].
Debates have continued as to the relative contributions of the trauma itself and the role
of potential predisposing or subsequent events as determinants of PTSD.
An important finding also arose from the MSH study [18]. It was found that premorbid
risk factors became less important as the intensity of the exposure to trauma increased.
When the stress factor impact was most severe, the stressor overrode vulnerability
factors that, at lower levels of trauma exposure had identified higher risk subgroups.
This argument has been important for showing the influence of risk-group variability
and different levels of stress exposure on psychiatric morbidity.
Several studies have shown that the role of the trauma itself was modest at best and
diminished with time. It was overshadowed by premorbid factors as neuroticism,
previous psychiatric history, and previous adverse events.
The validity of pre-trauma risk factors was the subject of extensive discussion. There is
confidence for only two factors:
1. Previous exposure to trauma,
2. Previous history of psychiatric disorders
Additional clarification and future research is indicated for:
1. The role of age as a risk factor of PTSD (vs. self-selection),
2. The positive role of social support and cohesion,
3. The importance of psycho-education and stress inoculation training (i.e.
using VR)
5. Secondary and associated posttraumatic symptoms.
Secondary symptoms are problems that arise because of the posttraumatic re-
experiencing and avoidance symptoms. As time passes after a traumatic experience,
more secondary symptoms may develop. Over time, secondary symptoms can become
more troubling and disabling than the original re-experiencing and avoidance
symptoms. Associated symptoms don't come directly from being overwhelmed with
fear; they occur because of other things that were going on at the time of the trauma.
Depression can develop when a person has loss connected with trauma or when
avoidance of other people leads to isolation. Despair and hopelessness can result when
a person is afraid that he/she will never feel better again. Patients with PTSD may have
their belief system shaken when a traumatic event makes them lose faith that the world
is good and safe place.
Aggressive behavior toward oneself or others can result from frustration over the
inability to control PTSD symptoms. Patients may also become aggressive when other
things that happened at the time of trauma make the person angry. Anger and
aggression can cause occupational, marital and relationship problems, and loss of
active social contacts.
Self-blame, guilt and shame can arise when PTSD symptoms make it hard to fulfill
current responsibilities. Self-blame can cause considerable distress and can prevent a
person from reaching out for help. Sometimes society also blames the victim of trauma.
Patients with PTSD may have relationship problems, and may feel detached or
disconnected from others because they have difficulty feeling or expressing positive
feelings.
Less interest or participation in things the person previously enjoyed, and social
isolation, may result from depression following a trauma and can occur because of
social withdrawal and lack of trust in others. Patients may develop problems with
identity and self-esteem .
Physical health symptoms and medical problems can result from long periods of
physical agitation or arousal from anxiety. For example, an increased rate of mortality
from cardio-vascular disorders was seen in Israel war veterans with PTSD (information
provided by workshop participant Joseph Zohar).
Culturally dependent alcohol and drug abuse may occur when patients with PTSD want
to avoid the bad feelings that result with the disorder's symptoms. Many patients use
alcohol and drugs as a way to try to cope with upsetting trauma symptoms, but it in fact
often leads to more problems. Sixty to eighty percent of Vietnam veterans seeking
PTSD treatment have alcohol use disorders [19]. Veterans over the age of 65 with
PTSD are at increased risk for attempting suicide if they also experience problematic
alcohol use or depression [20].
Conclusions
Trauma is always a catalyst for human behavior. A complex interaction of

environment, biology and mind determines the development of Posttraumatic Stress
Disorder. PTSD is a reaction to an event which is outside of normal human experience.
Combat, natural or artificial disasters, rape, physical attack, robbery and terrorism are
examples of such traumatic events. This type of trauma causes chaos and fills the lives
of those exposed with terror of the unexpected and fear of loss, injury and death. The
essential feature of PTSD is the development of characteristic symptoms following
exposure to an extreme traumatic stressor involving direct personal experience of an
event that involves actual or threatened death or serious injury or other threat to one's
psychical integrity. The past decade has witnessed dramatic increases in psychiatry's
understanding of bio-psycho-social responses to trauma. Psychiatrists assume that early
detection and intervention will prevent the development of chronic forms of PTSD.
References
[1] Grinker R., Spiegel J. Men Under Stress. Philadelphia, PA, Blakiston, 1945
[2] Griezinger W. Uber psychiatriche Reflexactionen. Berlin, 1874
[3] Sommer R., cit."Handbook of Psychiatry", Moscow 1988
[4] Sheickovich M., cit."Handbook of Psychiatry", Moscow 1988
[5] Christoffer A., cit."Handbook of Psychiatry", Moscow 1988
[6] Kraepelin E., Psychiatrie.-6 aufl. – Leipzig: Bart Verlag, 1899
[7] Jaspers K., Allgemeine Psychopatologie. – Berlin; Heidelberg; New York. Springer Verlag, 1965
[8] Diagnostic and Statistical Manual of Mental Disorders, DSM-III. Published by the APA, Washington,
DC, 1980
[9] Diagnostic and Statistical Manual of Mental Disorders, DSM-IV. Published by the APA, Washington,
DC, 1994
[10] The ICD-10 Classification of Mental and Behavioural Disorders, Clinical descriptions and diagnostic
guidelines. WHO, Geneva,1992
[11] Herman J., Trauma and recovery: The aftermath of violence from domestic abuse to political terror. NY,
Basic Books, 1997
[12] Kulka RA, Schlenger WE, Fairbank JA, et al: Trauma and Vietnam War Generation. NY,
Brunner/Mazel, 1990
[13] CDC: Health status of Vietnam veterans: psychological characteristics. JAMA 259:2701-2707, 1988
[14] Card JJ: Epidemiology of PTSD in a national cohort of Vietnam veterans. J Clin. Psychol. 43:6-17, 1987
[15] Davidson JRT, Hudges D, Blazer D, et al: PTSD in the community: an epidemiological study. Psychol
Med 21:1-9, 1991
[16] Herzel JE, Robins LN, McEvoy L: PTSD in general population. New Eng J Med 317:1630,1987
[17] Pynoos RS, Frederick C et al: PTSD in school age children. Arch Gen Psychiatry 12:1057-1063, 1987
[18] Shore JH, Tatum MS et al: Evaluation of mental health effects of disaster. Am J Pub Health 76:76-83,
1986
[19] Evans K, Sullivan J.M. Treating addicted survivors of trauma. NY, Guilford Press, 1995
[20] Kofoed L., Friedman M.J., Peck R. Alcoholism and drug abuse in patients with PTSD. Psychiatric
Quarterly, 64:2.151-171, 1992
M.J. Roy (Ed.)
IOS Press, 2006
Technological challenges in the use of Virtual

Reality Exposure Therapy
Charles VAN DER MAST a,1 , Sinisa POPOVIC b, Dave LAM c,

Gianluca CASTELNUOVO d, Pavel KRAL e, Zeljka MIHAJLOVIC b
a
Delft University of Technology, the Netherlands
b
University of Zagreb, Faculty of Electrical Engineering and Computing, Croatia
c
U.S. Army Telemedicine and Advanced Technology Research Center, Ft. Detrick
Maryland, and University of Maryland School of Medicine, National Study Center for
Trauma and EMS, Baltimore Maryland, USA
d
ATN-P Lab, Instituto Auxologico Italiano, Milan, Italy; Clinical Psychology Lab,
Instituto Auxologico Italiano, Verbania, Italy and Department of Psychology, Catholic
University, Milan, Italy
e
Central Medical Psychology Department, Central Military Hospital, Prague, Czech
Republic
Abstract. This paper describes the result of a discussion in a working group and a
plenary discussion at the NATO Advanced Research Workshop on Novel approaches to
the diagnosis and treatment of posttraumatic stress disorder. Several technological
challenges are presented with regard to the basic functions of a VRET system. Most
challenges are demand-driven and are focused on better ways to support the therapist,
for better and more efficient treatment. Tele-care is one of the most promising but
difficult challenges. The results give directions for both fundamental and practical
research.
Keywords. Virtual reality exposure therapy, agent technology, tele-care, human-

computer interaction., PTSD, Post Traumatic Stress Disorder
Introduction
Virtual reality exposure therapy (VRET) is the result of a close collaboration between
researchers and practitioners of significantly different disciplines, among others, psychiatry,
clinical psychology, psychotherapy, computer science, graphics design, human-computer
interaction, and engineering. The traditional cognitive behavioral therapy (CBT) treatment
1
Corresponding Author: C. van der Mast, Delft University of Technology, Mekelweg 4, 2628 CD Delft, The
Netherlands; E-mail: c.a.p.g.vandermast@ewi.tudelft.nl.
C. van der Mast et al. / Technological Challenges in the Use of Virtual Reality Exposure Therapy 287
process between therapist and patient has been taken as the main paradigm to be supported
by technology in different ways, not in the least by providing interactive immersive worlds
to “play” the treatment process in virtual reality instead of in vivo, as in the behavioral
approach or by imagination, such as in the cognitive framework. It has proven to be the
case that patients are very sensitive to specific multimodal features in the virtual world and
the appropriately accompanying sounds [12]. Medium-level resolution and graphics quality
has proven sufficient in many cases to trigger the specific phobia-related reactions that are
essential in exposure therapy. The effect of locomotion technique on fear has been studied
[20]. In one study [11], treatment using a standard head-mounted display (HMD) -gave the
same results for the treatment of acrophobia as an advanced CAVE system providing
advanced virtual reality systems. Of course this substitutability may be dependent on the
specific type of disorder to be treated. It has been proven in many studies that VRET can
achieve the same results as traditional CBT, but will not outperform it [8]. However, there
are more aspects of CBT which are important other than just exposure. Technology can also
support the therapist in changing in real time to other synthetic worlds in which to expose
the patient, or in recording and replaying sessions in the virtual world for later analysis and
planning the following session [2].
Current VRET systems are mostly developed and used in laboratories where technical
support is available. A few systems are available on the market, but evaluation of practical
use on a larger scale has not yet been reported. To provide full support in clinical situations,
it is essential that VRET systems be feasibly employed in the clinic by several therapists of
a team and without strong and expensive technical support. This usability is important to
enhance the performance of the treatments on the one hand, while on the other hand we
may expect benefits from other support functions besides the VR exposure technique itself
[7]. Interesting new technologies are available to extend a VRET system with new
functions in order to measure and analyze the details of the treatment process for a better
understanding of diagnosis and treatment, as well as for improving the efficiency of the
therapist’s work [16].
In this paper we present the results of a structured brainstorming session on
technological challenges which might assist in enriching and improving all aspects and
functions of VRET we can imagine now. Three of the authors have a technical background
in VRET technology and three have a background in clinical treatment. First we present an
overview of the essential technical and functional components of VRET systems. Second
we present, explain and structure the challenges we found. Finally we will discuss these and
give some final conclusions.
1. Essential components of VRET systems
Most current VRET systems consist of typical functions and components as summarized
below. The system is usually located in one room where both therapist and patient are
together so they can communicate by natural means. If for some reason they are not in the
same room an audiovisual intercom facility should be provided. See Figure 1 for a typical
VRET system in one room with direct communication between therapist and patient.
288 C. van der Mast et al. / Technological Challenges in the Use of Virtual Reality Exposure Therapy
This system is equipped for treating fear of flying. The main functions are the
following. First a device is needed to present the world visually (in stereo or mono) to the
patient [1].
Figure 1. Overview of a typical VRET system in one clinical room [7] and [19].
This computer-generated synthetic world can be presented in an immersive way by a head-

mounted device or it can be projected on one or more screens. However, some intermediate
forms are possible. Augmented reality can be used to superimpose artificial objects, e.g.
animals, on the real world you can see through the HMD. Patients should be able to look
around. If immersive worlds are being presented a tracker system is needed with a sensor
on the patient’s head built in the HMD. Another function is that the patient should be able
to navigate in the virtual world, although it may be to prefer that the therapist takes the
navigation task over from the patient in some situations [20]. For navigation some other
input device is necessary to start and stop navigation in a particular direction. Sometimes
the patient should be able to initiate actions or events or choices within the virtual world,
e.g. as part of tasks to do selections of virtual objects to improve presence. Then we need
stereo sound as an important resource to improve the sense of presence [14] in the virtual
environment. This sound may be dependent on the distance and the direction between the
source of sound and the patient. Another output channel may be servo-controlled
mechanical devices, e.g. to move the aircraft chair to simulate air turbulence during the
flight.
Figure 2. Example of a therapist user interface of a system for treating fear of flying [7].
This may improve the presence, e.g. for treating fear of flying, significantly. Last but
not least we need a user interface for the therapist to control what may or should happen in
the world [7], e.g. lighting condition in the world, the occurrence of turbulence in the
aircraft, the change of crowds in worlds for agoraphobia, see figure 2. We can summarize
all these functions in Figure 3.
two-way communication
visual
audio
action
other patient
therapist VRET-
system
navigation
evaluation
look around
action
measurement
Figure 3. Basic communication functions in a VRET system.
2. Challenges
The following challenges were formulated in the workgroup by the authors, and discussed
during a plenary meeting with all the participants of the NATO workshop. We decided that
it is not reasonable to give a priority to these challenges, as work in many of these areas is
currently ongoing simultaneously in different venues, and any or all of these developments
may be useful, no matter in which order technological advances are made.
2.1. Personalizing the system
A VRET system may be used by many different colleagues from a clinic. Additionally,
each therapist may change over time his or her preferences about using the system for some
specific phobias. This gives a rationale for implementation of the possibility to personalize
the user interface and a part of the main functions of the treatment process by the individual
therapist and to store the applicable parameters. It is conceivable that this personalization
could be extended to prepare for each patient an individual treatment procedure off-line,
including some changes in the worlds, specific for each patient to be treated. This kind of
personalization is an important research goal sometimes referred to as “adaptive” user
interfaces [22]. The possibility of the therapists to “tailor” different versions of the same
virtual environment according to the patient’s needs has been underlined by Castelnuovo
[5].
2.2. Automated support for the therapist
This challenge was emphasized most highly by the workgroup. The first function of a
VRET system is to offer an interactive virtual environment for the patient to experience the
feelings that have to be worked on. But beyond that, the most promising challenge is to
develop support functions for the therapist [2]. By analyzing the treatment process and
composing task models one can recognize and specify steps and modes in the treatment
(see Figure 4). This is an example of a task model. New models have to be developed
describing the task in terms of treatment steps and specific aspects and levels of the
disorder.
Cure
Curepatient
patient
Solve patient
Goals Determine
Determinefear
fear Change exposure
ambiguity
sim.
Procedures
Ask
Askpatient
patientto
to Monitor
Monitorpatient
patient
to
to reportfear
report fear response
response
Sound
T.Controls
T.Screen
P.Posture
Figure 4. ‘Determine fear’ goal decomposition (see [21] for decomposition and explanation of more details).
If it is possible to describe a treatment session in terms of steps to be taken under

supervision by the therapist it may be possible to develop an electronic agent which
provides advice including some rationales to the therapist about the following step(s) in the
actual context of the treatment. It would also seem interesting to provide a planning mode
to the therapist to specify some sequential steps for a session just before it starts. The
general goal is to provide extra explicit knowledge to the therapist about the progress of the
treatment. The agent can obtain its information from built-in procedures which may be
adjusted by the therapist and by measurements of the patient’s physiological condition, e.g.
heart rate and skin conductance. It would be most useful to construct a learning electronic
agent which could learn from an experienced therapist. A junior therapist could use this
“smart” agent to give better treatment in non-critical sessions, under the responsibility and
supervision of an experienced therapist. It would be possible to teach such agents to give
good advice by analyzing individual treatment patterns in specific clinical cases. The advice
might propose the next procedure step or the next navigation or modification of the virtual
world to control the level of fear. Even more measurements can be done by face recognition
[15], [25] and voice recognition since these can indicate levels of stress, fear, and other
emotions [18], [24].
An additional form of support may be considered procedures of computer-supported
self-treatment by the patient. The therapist should be able to specify the procedures and
constraints of these modules for self-treatment. Related to section 3.1, easy-to-use tools
oriented toward non programmers could be useful for providing greater flexibility and
individualization in defining VR scenarios. The therapist could thus individualize
homework scenarios for the patients without the need for the programmer to hard code each
scenario. Individualization of virtual environments is addressed within a currently ongoing
EMMA project [3]. Envisioned VR scenarios driven by the patient’s physiology [23] could
also be useful for patient’s self-treatment during homework sessions.
2.3. Computer-based training
A completely different challenge is the construction of a VRET system for computer-based

training of junior therapists. This could be done using simulated or real patients, or
recorded sessions. The learner could be trained to use the system and to treat different types
of disorders. Simulated patients could include a combination of computer-generated
patients and normal people requested to simulate. Computer-generated patients could model
non-visible changes happening in real patients (e.g. physiological changes), and normal
people could manifest patients’ visible responses.
2.4. Tele-Care
It is both a technical and an organizational challenge to develop a system for tele-treatment

of mental disorders using VRET over the internet. The most serious challenge is to have a
ratio of therapist: patient of more than 1:1. It should be possible to develop a system and a
therapist’s user interface to allow the provision of treatments to more than one patient at the
same time, in different rooms in the same clinic or in different clinics. If one senior and one
junior therapist could treat more than two patients simultaneously, the ratio will improve.
Some experience with tele-treatment of agoraphobia without VR has previously been
reported [13]. In a more general project on tele-care the possibilities of agent support for
tele-care at home has been investigated [8], [17].
2.5. Eye tracking
A challenge that was discussed a lot during the plenary session was the use of an eye
tracking to study how the focus of the patient is oriented during VRET sessions. It is
expected that this may give better insight into what triggers the emotions during the
sessions. This information may be used to adjust the session procedure or the characteristics
of the virtual world online. It was noted that the development of such a capability which
would not require time-consuming and difficult alignment or standardization for each new
patient might be very difficult, but that lessons may be learned from the work previously
done in aviation technology with Heads-Up-Displays and helmet-mounted visual devices.
2.6. VRET experience with the MRI/CT scanner
The most futuristic challenge is to implement a mechanism to allow the use of MRI or CT
scans of the brain during a VRET session. Early steps in this direction have been taken by
devising a fiberoptic magnet-friendly high-resolution wide-field-of-view image delivery
system [9]. Initial tests with functional MRI (fMRI) offer promising results, showing that
the display does not interfere with the brain scans, and that the users can feel the sense of
presence in the virtual environment while being inside the scanner [10]. With state-of-the-
art technology it therefore seems possible to present images of virtual environments to a
person who is within a scanner. Further VRET-fMRI research could address brain patterns
occurring in patients during VR baseline and exposure sessions, compare brain activities of
patients and controls, and so on. The challenge is to conduct research on understanding
optimal treatment schedules, not at standard scanner-mediated treatment in the clinic.
3. Discussion
Most of these challenges were discussed during the plenary workshop without detailed
knowledge about what is going on in other domains. In aviation training and development,
interesting progress is being made which should be looked into, especially with regard to
heads-up displays and helmet-mounted visual instruments. New visualization techniques in
cockpit design using mixed reality may give interesting concepts for improving VRET. In
any case, we need to separate the requirements of basic research from those of clinical
therapy – they have different requirements, goals, and rationales. In general we need the
best clinical feedback during treatment. The goal is to provide the therapist with
information and feedback on the changes that occur, so as to allow him to provide the most
effective treatment. Tools to detect changes in physiological parameters by external
measurement are necessary. Some participants in the plenary session stated that tele-
treatment could be dangerous because these patients are difficult and fragile, but others
reported that tele-care (without VR) of agoraphobia and PTSD [13] works, and is currently
being used safely and effectively. It may prove to be that tele-treatment of PTSD or other
psychiatric disorders is only feasible in some stages (diagnosis and initial therapy) of the
treatment plan. Obviously, all of these alternative potentials require much more research
and development in both the clinical and technological realms to determine their feasibility
and benefits.
4. Conclusion
It is clear that several interesting technological challenges are on the horizon. But we must
remain aware that we need fundamental research on how new technologies can improve the
very personal treatment process supervised by the therapist. This research must be demand
driven by the therapists, and not pushed by technology—The technical ability to do
something does not imply that it is either safe or desirable from a clinical standpoint. We
are just in the early stages of some very interesting developments. They will both improve
our insight in how treatment can be given in the most effective way and how treatment can
be deployed on a large scale more efficiently than with the current means. VRET may play
an important role in these developments.
In our view, an emerging scenario could characterize the future clinical setting: old
(and functional) practices could be integrated and enhanced through new (and promising)
media such as VR. This framework aims at matching “techno” and “psycho” for clinical
purposes [4].
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M.J. Roy (Ed.)
IOS Press, 2006
Novel Approaches for the Integration of

Behavioural Therapy and Virtual Reality
Mariano R. ALCAÑIZ1, Carmen L. JUAN, Beatriz S. Rey, José Antonio Q. LOZANO
Medical Image Computing Laboratory. Technical University of Valencia,
Valencia, Spain
Abstract. In this chapter we describe several technological requirements that must

be considered in order to achieve a practical, efficient, ecological and usable
integration of behavioural therapy and virtual reality (virtual therapy or VT). Some
critical aspects are considered regarding the media form and media content of
virtual therapy applications. Finally, future trends and promising technological
tools used for VT applications are discussed like adaptive displays and augmented
reality interfaces.
Keywords. cognitive behavioural therapy, virtual reality, exposure therapy, mental

disorders
Introduction
The use of Virtual Reality (VR) technology for Behavioural Therapy, also known as
Virtual Therapy (VT) constitutes nowadays a mature scientific area that is being
applied successfully for the treatment of several psychological disorders [1]. Virtual
Therapy (VT), as a clinical applications of VR technology, requires a seamlessly
integration into the daily clinical routine in order to spread its use inside the clinical
community. After a decade of VT development and clinical validation, for achieving
that named integration, it is crucial to analyze the major drawbacks of actual VR
technology for its use in VT systems and to identify some requirements to be
accomplished. In this chapter, we summarize some of these drawbacks and identify
new promising technological fields that will facilitate a practical, efficient, ecological
and usable integration of behavioural therapy and virtual reality.
VR technology for VT can be analyzed from two main perspectives: media form
and media content. Media form refers to the way the stimuli are presented to the patient
and includes the proprieties of the display medium, the extent of sensory information
presented, the degrees of control that users have over positioning their sensors within
the environment, etc.). Media content refers to the content of these stimuli and includes
the objects, actors and events represented by the media and users’ ability to modify
aspects of the virtual environments.
1
Corresponding Author: Mariano Alcaniz. Medical Image Computing Laboratory. Technical University of
Valencia. Camino vera s/n. 46022 Valencia, Spain.
M.R. Alcañiz et al. / Novel Approaches for the Integration of Behavioural Therapy and VR 297
1. Media form aspects
In a Virtual Therapy (VT) system it is crucial that the user can “live” the virtual reality
experience, that is, to achieve a satisfactory and clinically useful sense of presence
within the VT application. Media form characteristics have a significant impact on the
sense of presence in VT. Nobody doubts about the importance of immersion,
interaction and perceptual realism for developing VT applications. However, as a
clinical application, instead of trying to maximize the immersion of the patient using
the most advanced, and sometimes cumbersome, VR technology, it is more important
to establish the drawbacks of VR technology normally used for VT systems and to
identify the tools that are being demanded by the clinicians in order to ensure efficient
and reliable treatments for their patients.
2. Visual devices
Basically, there are two categories of visual devices to be used for VT applications:
Head Based Visual Devices and Stationary Visual Devices.
2.1. Head Based Visual Devices
The Occlusive Head Based Visual Devices, also know like Head Mounted Device
(HMD), is the device that most people associate with Virtual Therapy. These devices
isolate completely the user from the real world. Anything the user needs to see will
must to be generated by the virtual world, including this own body if this was
necessary.
These devices have some screens that they move with the movements of the user
head. These screens are small and lightweight since they are worn or held by the user.
Most of the HMD allow stereoscopic image using, normally, a dual visual output (one
for each eye) system.
Although these devices display the virtual world through the user’s viewpoint, in
these devices it is possible to add some tracking method and, also, some could have it
incorporate in the unit. Tracking the location and orientation of the user head, the HMD
can to be the most intuitive visual interface because, if a user wants to see another side
of an object he will have simply walking to this new side and looking the object.
The main advantages of these devices are the following:

o Low cost for low resolution models
o Can occlude the real world
o Great portability
The main disadvantages of these devices for routine uses with VT applications are:
o Market dependence
o Hygiene problems
o Usability problems (cables, head fitting, FoV)
o Poor ergonomics
o Fragility
298 M.R. Alcañiz et al. / Novel Approaches for the Integration of Behavioural Therapy and VR
2.2. Stationary Visual Devices (Monitor Based and Projection VR)
These devices are known as “stationary” because they are fixed in place, and unlike
previous systems, they can not be moved with the user head movements in the virtual
experience. Basically there are two types:
2.3. Monitor Based Devices
Normally, this visual device is an extension of a simple desktop computer (standard

computer monitor) setup but it may require other additional components like patient
head tracking devices. The main advantages of these devices are the following:
o Inexpensive
o Easy to use
o Higher visual resolution
The main disadvantages of these devices are the following:

o Less immersive (than most other VR visual devices)
o Limited field of view.
Although it has been successfully used for some VT applications [2], the above
mentioned drawbacks constitute severe limitations for VT applications.
2.4. Projection VR
These systems use large screens in order to visualize the virtual experience. This large
visual “surface” is normally created using LCD or DLP projectors. With actual PC
based graphic cards, it is quite easy to set up a large image, stitching together several
images coming from different graphic pipelines. In this sense, it is possible to develop
custom-made large immersive systems that produce a strong immersion. The large
physical dimensions that are necessary for CAVE-based systems and or rear-projected
solutions can be avoided through the use of adequate mirror based set-ups or special
optics, which are becoming standards for LCD/DLP projectors. These visual devices
constitute very natural interfaces for the patient and are quite suitable for a routine
clinical use. The main advantages of these solutions can be summarized as follows:
o Low cost solutions
o No need for big spaces (mini CAVE concept)
o Natural interfaces for the patient. Greater user mobility (few cables)
o Ease of use for clinicians
o Wider FOV
o Better for group viewing
Taking into account these characteristics, projection-based VR systems are the

most promising visual VR device for VT applications.
3. Media content aspects
3.1 Critical issues of media contents
One of the most important characteristics of VT systems is that they allow the patient to
explore and to interact with an artificially created environment. Thus, the patient “has
the feeling” of being in a different place from where they physically are, and this
feeling has labeled a “sense of presence”. As previously stated, media form
characteristics have a significant impact on the sense of presence. Nobody doubts the
importance of immersion, interaction and perceptual realism. However, presence
research has overemphasized them, and sometimes they have been used erroneously to
describe the experience of presence. In some theoretical models, the sense of presence
has been seen as the outcome, or a direct function of immersion. As a result, it has been
assumed that the more inclusive, extensive, surrounding and vivid the VE, the higher
the sense of presence [3].
There have been some attempts to distinguish presence from immersion. Slater
[4,5] defined immersion as an objective description of the technology, while the sense
of presence is a subjective experience and only quantifiable by the user experiencing it.
Presence is essentially a cognitive or perceptual parameter whilst immersion essentially
refers to the physical extent of the sensory information and is a function of the enabling
technology.
Up to now, definitions of presence have been based on cognitive or environmental
aspects. However, it has been demonstrated that presence, like all human experiences,
is influenced by emotions [6]. Emotions play an important role in the way we make our
subjective judgments, we react to the world and we learn things about it. It has been
demonstrated that this variable is especially important in order to generate and enhance
presence in Mental Health applications of VR, e.g., [7]. In this sense, Hoorn, Konijn &
Vand de Veer [8], in a paper entitled “Virtual Reality: Do not augment realism,
augment relevance” argue that VR experience gains more from increased emotional
relevance than from higher realistic solutions. These authors claim that to design VR,
experience instead of technology is the key word, and they recommend that VR
designer focuses on developing features that sustain relevance to the goals and concerns
of the user. According to them, “The sophisticated technology of VR may be powerful
but it is not enough to initiate a reality-experience that is true-to-life. Basic to reality-
experiences that are true-to life is that the experience is emotionally loaded (…). The
basis of emotion psychology is personal meaning: without relevance no emotion
occurs. Thus, VR needs personal relevance for the user to arrive at the intended (total)
involvement as manifested in the experiences of immersion and presence”.Taking into
account this line of thinking, emotions may play a role on the sense of presence. From
this point of view, the focus would lay on designing affectively significant
environments. In order to achieve this, it would be necessary to include elements with
the potential of activating emotions. This is especially true for Clinical Psychology,
because the goal is to achieve important changes in the users.
3.2. Adaptive displays: a key tool for virtual therapy
An adaptive display can be defined as a device that autonomously adjusts its

presentation and actions to better match the immediate goals and abilities of the user.
The system has to monitor several variables, such as user status, tasks and context. The
possibilities depend on the capabilities of the technology that carries the display.
Rothrock et al. [9] identified two types of adaptability depending on the tasks that
the user must perform in the system: interaction and knowledge content. If the user’s
purpose is to execute and control tasks using the system, interaction adaptability would
be required. In this case, a perceptual adaptation is usually made. On the other hand, if
the user’s purpose is to acquire knowledge, the focus would be on content adaptability.
In recent years, interest in adaptive displays has greatly increased, as it is a
technology that can be applied in many different areas. A lot of research has focused on
the technical aspects such as improving resolutions and detail of the displays. Other
research has focused on cognitive aspects such as analyzing the problem of information
overload and the observer’s ability to process the information that is shown.
To achieve a truly adaptive display, i.e., one that automatically adjusts its contents
to the constantly changing state of the observer, requires that the designer be able to
characterize not only the bandwidth required, but also to be able to “impedance match”
the display to the observer, ideally by using non-contact (remote) sensing of the
observer’s cognitive state. One exciting derivative of the clinical work is an adaptive
display that actually shifts within a narrow range of modes according to the
physiological/ cognitive state of the user [10].
Currently, there are research groups that are developing new kinds of sensors and
algorithms that can detect information related to affect. This could be the basis of a new
kind of display that adapts to affect [11].
One of the pioneering works in applying adaptive display technology within VT
applications has been performed within the EMMA (Engaging Media for Mental
Health Applications), an EU funded project.[2] It is representative of the latest category
of adaptive displays. We have developed a virtual reality application whose contents
and aspects change dynamically depending on the emotions of the user. It can be
described as an adaptive display that reacts to affect. This environment is designed to
be used in psychological therapy. The system that has been developed, named “the
book of life”, permits customization of the VE with personnel contents of the patient
and to change dynamically in real time its contents in order to be adapted to the mood
state of the patient.
3.3. The book of life: an adaptive display for virtual therapy
3.3.1. Clinical aspects

The application has been designed to help in the treatment of post-traumatic stress
disorder, adjustment disorder, and bereavement. In each of these conditions, people
have suffered a traumatic experience (e.g. the loss of a loved one, loss of a job, divorce,
rape, etc.). To accomplish our therapeutic goals, a series of emotional objects can be
used and personalized so that they are meaningful to the user and contain the
fundamental elements that the person must confront. The objective is to obtain a
physical representation of personal meanings and the emotions that are related to those
meanings and to study how this strategy helps the person to change. The set of personal
experiences that is created can be used to activate, correct, structure and restructure
those previous experiences. By using them as cognitive-emotional structures, the
therapist can help the patient to structure a new way of processing and integrating past,
present and future experiences.
3.4. General description of the different tools
In the first stages of the therapy, the patient learns how to navigate and interact with the
system by practicing in a neutral environment. The treatment environment is a special
place where patients can feel free to express their emotions and where emotions are
going to have an effect on everything that surrounds them. A series of tools are used in
each session. They are always available in the environment and are selected based on
the therapist’s instructions. For example, if the patient is asked to relive an experience
while speaking to the therapist, the virtual environment will reproduce these feelings in
different forms (such as a dark forest with no exit). Another tool provided by the
system is “the living book”, which has been designed so that the person can reflect
feelings and experiences in it. It contains images, objects and other elements that are
also present in the virtual environment. The objective is to represent the most important
moments, people and situations in the person’s life. Anything that is meaningful for the
patient can be incorporated in the system: photos, drawings, phrases, videos...
Both the therapist and the patient are physically present in a room. The patient
visualizes the virtual environment in a retro-projected screen. The virtual environment
contains a circular room, so the environment outside the room can be visualized from
the inside. The user can navigate both inside the virtual room and outside it (Figure 1).
The patient can select different objects that can appear in different places of the
environment in order to personalize it. The therapist can control the contents that the
user views from another computer, and can make the environment change in real time;
for example, a beach can be changed to a snow-covered town. The therapist can also
create different effects in the environment such as rain, snow, earthquakes...
3.5. Personalization by the patient
The environment includes different systems that interact to allow the patient to express
ideas through different items. The characteristics and positions of these items can be
modified in real time.
4. Object selection
The first customization that the user can make in the environment is the selection of
different objects and elements that can be added to the environment in real time.
Fig. 1. Image of the room from the outside.
A database with different elements can be created for each patient. A graphical
element, the database screen (Figure 2), provides access to the different categories of
objects that can be held and used in the system: sound, video, images, three-
dimensional objects and colours.
Each category is composed of an array of icons that represents objects that are
present in the database. When the patient selects them, they are copied to a temporary
storage tool called the inventory tool, from where the elements can be copied to
different places in the virtual room.
In order to identify the parts of the virtual room where objects can be copied, there
are special objects, called “object holders”, which are distributed throughout the room.
The objects that are in the inventory can be copied into these holders. The effect created
is different depending on the object that is copied. If it is a three-dimensional object, it
is viewed above the object holder (Figure 3). If it is a sound, it will be heard when the
user approaches the object holder. If it is a video, it will be viewed on a small screen
above the object holder when the user approaches it. If it is an image, it will be viewed
in a small screen above the object holder. An object holder can serve as a mixing tool
to combine several elements to form a new more complex element. This is achieved
when different elements from different categories are copied to the same object holder;
thus, an object holder can simultaneously show a 3D object, a video and an image; the
associated sound can be heard when the patient approaches it. Also, if a colour element
is copied to an object holder that already has a 3D object, a coloured light will be
applied to the object. The size of the different elements that are shown in an object
holder can be controlled by the patient.
Fig. 2. The database screen. The object category is shown in the image. The user can select other categories
by pressing the correct tab.
The elements in the object holders can be moved by copying them to the inventory.
This makes them disappear from their current location. Then, they can be copied in
other object holders of the virtual room.
Besides object holders, there are other special elements that are used inside the
virtual room. The most important one is the living book (Figure 3).
Fig. 3. The living book. The title can be read on the upper left corner of the first page. There are different
slots for placing different objects.
The representation of this element is a book that contains pages that represent
different chapters. A title for each chapter can be introduced by using a virtual
keyboard. The living book is the instrument that the patient uses put in order and keep
all the contents that have been analyzed with the therapist during the session. Initially,
the living book is empty. The user can select the elements that will be introduced in
each of the chapters directly from the database screen or from an object holder. The
elements are copied temporarily to the inventory tool, and from there to the different
positions that are available on each page of the living book. The elements are
represented in the living book by means of an icon. Once the elements have been
copied in the book, their order can be changed at any point during the session.
Finally, there is another special element that is used to eliminate objects, the drain.
It is used to destroy the objects that are no longer needed. The interaction with the drain
is similar to the ones that we have described above. When the user drops an element
from the inventory to the drain, the element is deleted from the inventory and can no
longer be used.
5. Emotional discharge system
The emotional discharge system (Figure 4) provides a space that allows the patient to
modify and manipulate the characteristics of the virtual environment and the objects
that are placed in it in accordance with emotions.
Fig. 4. The discharge area. It is composed of three special object holders that allow the user to modify the
objects that are placed above them.
The discharge system has been implemented as three special object holders that are
on the balcony of the virtual room. Patients can modify the shape and the aspect of the
objects that are placed on them with their voices (shouting in a louder or softer way
depending on their emotional state). The size of the objects placed in those special
object holders is modified according to the loudness of the input sound. More than one
object holder can be active at the same time. In this case, the aspect of all the objects
placed over them will change simultaneously.
5.1. Personalization by the therapist
The therapist accompanies the patient during the session and can have an important role
in the customization of the environment.
A special interface has been prepared to allow the therapist to control several
aspects of the appearance of the outer part of the virtual room. The application that
controls this runs on a different computer from the one with the virtual environment.
The commands that the therapist introduces are sent using TCP/IP to the
environment computer, and the appearance of the environment changes depending on
the command that the computer has received. There are five different pre-defined
aspects (Figure 5): a desert, an island, a threatening forest, a snow-covered town and
meadows.
The environments are related to different emotions. For example, the desert can be
related to rage. The island can be shown when the therapist wants to induce relaxation
in the patient. The threatening forest can be related to anxiety. The snow-covered town
can be used during the session when the patient is remembering a sad situation in his /
her life. The meadows can be used to induce happiness in the patient. However, the
specific use that is given to each environment depends on the context of the session and
can be selected by the therapist in real time.
Fig. 5. The different aspects of the virtual environment: the meadows, the desert, the island, the snow-
covered town and the threatening forest.
Apart from this large-scale control (changing the entire aspect of the outer part of
the virtual environment) the therapist can also make small-scale changes. Different
effects can be applied to the environment (Figure 6): a rainbow can appear; it can start
to rain or to snow; an earthquake can be generated; the hour of the day (and the
corresponding illumination) can change...
All these effects can be launched from the same interface, and the therapist can
control both the appearance and disappearance of the effect, as well as the intensity
with which the effect is shown.
6. Augmented reality: a promising field for virtual therapy
Augmented Reality (AR) interfaces suppose a very promising tool for VT applications.
With respect to the occlusive VR interfaces traditionally used for VT, AR offers several
advantages. In AR, the environment is real and the elements that the patient has to use
to interact with the application are real as well. The possibility of an easy integration of
tangible interfaces constitutes a strong advantage for enhancing the sense of presence
(the sensation of being there) and reality judgment (the fact of judging the experience
as real) in VT applications. In AR based VT applications, the patient is seeing his/her
own hands, feet, etc. This is an important aspect for clinical applications of VR. This
situation can be simulated in VR but with more technical difficulties and less effective
clinical results.
Fig. 6. Sad environment with a storm, rain, and snow. The therapist can control the appearance of these
effects at the relevant moments.
6.1. An example of successful use of Augmented Reality based Virtual Therapy
One of the first VT systems using an AR interface has been described in [13]. It
consists in an AR system for treating phobia to cockroaches and spiders. The system
uses a video-see through HMD visualization interfaces and paper based markers for
identification of real elements. The system presents several options for interaction with
the patient:
Appearance of animals: when the system recognized the animal’s marker, it shows the
number of selected animals. The user can increase/reduce the number of animals in 3
or 20.
Movement of animals. The user can select that animals start to move.
Stop movement. The user can select to stop movement.
Initial position. Animals come back to their initial position.
Zoom in/ Zoom out. Animals increase/reduce their size with these options.
Apart from these options, the system includes the possibility that the patient kills
one or several animals. It can be done using two different typical instruments to kill
small animals. The first one is a flyswatter, the program identifies when the flyswatter
marker and the animal’s marker are near and then it kills one or several animals
depends on the number of animals that have been selected. The second instrument is a
typical animal killer. Again, the program identifies when the insecticide marker and the
animal’s marker are near and then it kills one or several animals. In this case the sound
is like when you use a real insecticide. Once one or several animals are died and the
scraper is near the animal’s marker, only one dead animal appears in the middle of the
marker, so the patient or the therapist can take the dead animal to the dustbin.
All these options are included so the patient’s treatment can be progressive. The
therapist chooses in every moment how many animals have to appear, if they have to
move or not, their size, to kill an animal when the patient is prepared and throw it to a
dustbin.
The published initial clinical results of the system are very promising. The system
has helped two patients to overcome the phobia to cockroaches and one patient to
overcome the phobia to spiders. Before the exposure session with the system, patients
were not able: to approach normally to a bowl with an alive animal or to interact with
an alive animal. Following the guidelines of “one-session treatment” from Öst-
treatment [14] and using the AR system in the exposure session, patients experienced a
notable decrease in the degree of fear and avoidance of real animals. After the AR
exposure session patients were able to approach to a real animal, to interact with it and
to kill it by themselves. This reduction in fear and avoidance is maintained because
after two months of the treatment first patient was able to interact and to kill four alive
cockroaches. Apart from that, participants manifested their preference to be treated
with an AR system instead of a treatment with real animals.These results highlight the
importance of AR interfaces for VT applications.
Fig. 7. Two images of the augmented reality system designed for treating phobia to cockroaches and spiders
References
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M.J. Roy (Ed.)
IOS Press, 2006
Posttraumatic Stress Disorder:

Assessment and Follow-up
Paul M.G. EMMELKAMP 1
University of Amsterdam, The Netherlands
Abstract. Research into posttraumatic stress disorder is discussed from the

perspective of clinically relevant measures to be included in future outcome
research. It is concluded that studies into the effects of treatment of posttraumatic
stress disorder should include measures for co-morbidity, impairment and quality
of life. Further, recommendations are made to investigate moderator and mediator
variables affecting outcome of treatment in trauma victims, including social
support, personality traits, and cognitive characteristics. It is recommended to use
theoretically derived variables, rather than available base-line characteristics.
Further, these moderators and mediators should be studied in specific groups of
trauma patients, rather than in patients who have experienced a variety of traumatic
events of varying severity levels
Key words. PTSD, co-morbidity, impairment, outcome, prediction
Introduction
Research into the treatment of acute stress disorder and posttraumatic stress disorder
(PTSD) has accumulated over the past decade. Generally, a number of cognitive
behavioral treatments (CBT; e.g. exposure, cognitive interventions and EMDR) have
shown promise [1,2]. Further, recent studies suggest that writing assignments to
emotionally processing traumatic experiences might be equally effective as CBT [3,4].
Writing assignments have been found to be effective in treating posttraumatic stress
when applied through the Internet [5,6]. Similarly, there is some evidence that virtual
reality exposure may be used as an adjunct to regular CBT treatment [7], but the
evidence is far from conclusive yet [8,9]. Most studies into the effectiveness of
psychological treatment have involved patients who had experienced a variety of
traumatic events of varying severity levels, making results of these studies difficult to
evaluate. Further, the assessment of effectiveness of treatment in these studies is
usually limited to posttraumatic stress symptoms. The effectiveness of treatment on a
number of other - often co-morbid – disorders is usually not evaluated. In addition,
effects of treatment on impairment and quality of life are not established. Finally, most
studies evaluate the effectiveness of treatment with at most 6 months’ follow-up. The
aim of this paper is to discuss and recommend additional measures in outcome research
in addition to measures of posttraumatic stress.
It is important to make a distinction between type of measures: some are useful for
screening, assessment and treatment planning, whereas other measures are suited to
evaluate the effects of treatment, and a few are useful both for treatment planning and
1
Corresponding Author: Paul M.G.Emmelkamp, Department of Clinical Psychology, Roetersstraat 15,
1018 WB Amsterdam; pemmelkamp@fmg.uva.nl. This paper was written while the author was Fellow at
The Netherlands Institute for Advanced Research (NIAS), Wassenaar.
310 P.M.G. Emmelkamp / Posttraumatic Stress Disorder: Assessment and Follow-Up
outcome assessment. Further, different measures may be needed to evaluate the process
of treatment and to predict treatment outcomes than to evaluate the effects of treatment.
1. Rapid Screening
Screening in large populations with an expected low prevalence of PTSD does not
seem to be justified given the large number of 'false positives' that would be
generated. However, screening might be feasible in cases where high prevalence
rates are expected, thus allowing the identification of high-risk individuals who
might benefit from evidence-based brief early interventions. Perhaps the most
studied screening approach to date is that of diagnosing acute stress disorder (ASD)
within 1 month of the traumatic event. Currently, the prevalent view is that the ASD
diagnosis does not have adequate predictive power to predict subsequent PTSD. For
example, in a review of 10 studies which addressed this issue, the proportion of
individuals with acute stress disorder who went on to develop PTSD ranged from
30% to 83% at 6 months follow-up [10]. Further, dissociative symptoms were found
to be rarely endorsed and therefore particularly unhelpful in predicting PTSD [11].
In traumatic events involving a large number of people, the gold standard of
structured interviews by an experienced clinician may be unrealistic. Similarly,
although a number of standardized psychological instruments exist, most are lengthy
and cannot be used as a rapid screening device to identify high-risk groups for PTSD,
depression and substance abuse.
A number of screening instruments, primarily questionnaires, containing traumatic
stress symptoms, have been found to be useful in detecting the presence of PTSD.
Brewin [12] recently reviewed the literature and concluded that the overall mean
diagnostic efficiency was 86.5%. Taken into account the number of items (the
fewer, the better) and the eases of administration, the following questionnaires
appear to have the greatest potential: the Impact of Event Scale (IES), the Trauma
Screening Questionnaire (TSQ) and the SPAN. The IES [13] contains 15 questions
about intrusion and avoidance relative to a specified event, which are answered on a
four-point scale. A disadvantage of the IES scale is that the extended revision has
more items and has not been validated yet. The SPAN test [14] comprises only four
questions: the 'startle', 'physiological upset on reminders', 'anger' and 'numbness'
questions. These four questions are scored for both frequency and severity during
the previous week on scales of 0-4, which scoring is more complicated than is the
case for the TSQ. Finally, the TSQ [15] consists of the ten re-experiencing and arousal
items from the PSS-SR [16], modified to provide only two response options.
Respondents indicate whether or not they have experienced each symptom at least
twice in the past week.
A disadvantage of the short screening instruments discussed above is that they only
focus on posttraumatic stress symptoms. Following the tragic events of 9/11/2001, a
short screening instrument was developed that covered important mental health
symptom domains, mental health functioning, and possible predictive risk factors: The
Pentagon Post Disaster Health Assessment (PPDHA) [17]. The survey consisted of 61
questions, including 17 that were specific to mental health. The survey included 10
questions that pertained to PTSD, depression, anxiety, and alcohol use, as well as 7
additional questions that pertained to key risk or protective factors, functional
impairment, and use of mental health services. Although clinical diagnosis of mental
P.M.G. Emmelkamp / Posttraumatic Stress Disorder: Assessment and Follow-Up 311
disorders was not possible with this screen, high-risk groups for mental health
outcomes could be established.
2. Criteria for Outcome
Posttraumatic stress can be assessed using the Clinician Administered PTSD Scale
(CAPS) [18,19]. This is a widely used structured interview for establishing current or
retrospective diagnosis of PTSD in accordance with DSM-IV criteria [20]. With
adequate training interrater reliability is generally satisfactory [21]. Children's
posttraumatic stress symptoms can be assessed using the 17-item Child PTSD
Symptom Scale (CPSS), which assesses DSM-IV symptoms of PTSD [22]. The scale
can provide measures of both the number and severity of symptoms. In addition, there
is a 7-item scale assessing functional impairment in areas such as relationships,
schoolwork, chores, and hobbies.
A number of studies addressing the effects of treatment in the trauma field rely heavily
on the outcome criterion of still fulfilling the criteria of PTSD or not. While this is
understandable from the perspective of the medical model (one has a disorder or not),
from a psychometric perspective it is hard to defend. As in most other disorders change
can better be conceptualized in dimensional rather than in categorical data. Further,
especially with the current diagnostic criteria of DSM-IV-R, often only a minor change
in one criterion is sufficient to move someone from the PTSD disorder category into
the recovered category. However, many of the patients who at post treatment show only
a minor change in terms of the DSM-IV-R criteria, but in doing so come into the
normal range, will actually still suffer substantially from stress and related complaints.
An example of a dimensional measure to assess posttraumatic stress symptoms is the
Impact of Events Scale [23]. Further, the Harvard Trauma Questionnaire (HTQ) can
also be used to assess posttraumatic stress symptoms in war situations [24].
3. Anxiety, Depression and Suicide
Studies of the impact of psychological trauma on mental health have shown that trauma
not only results in Post Traumatic Stress Disorder (PTSD) but also in other
psychopathology, particularly other anxiety disorders and depression, but this is
neglected in most outcome studies. For example, De Jong et al. [25] assessed the
prevalence of mood disorder, somatoform disorder, post-traumatic stress disorder, and
other anxiety disorders in over 3000 individuals from post conflict communities in
Algeria, Cambodia, Ethiopia, and Palestine. In most countries, PTSD was the most
prevalent disorder in victims of violence associated with armed conflict, but such
violence was a common risk factor for various other disorders (anxiety, depression, and
somatoform disorders) as well.
Post-traumatic stress disorder (PTSD) is frequently comorbid with depression.
One-half to two-thirds of adults with PTSD report a lifetime history of major
depression [26-28]; high co-morbidity has been reported in children and adolescents as
well [29]. Comorbidity of PTSD and depression is associated with more severe
symptoms, higher depression, impulsivity, and more suicide attempts compared to
individuals with PTSD alone [30]. There appears to be a strong connection between
suicidality and the experience of trauma. In a study by Tarrier & Gregg [31] over half
of the sample reported some aspect of suicidality, including ideation (38%), and suicide
plans ( 8.5%). Nearly ten percent of trauma victims had made suicide attempts since the
trauma, which is much higher than in the general population. Both life impairment and
depression were independently and significantly associated with suicidality.
In children, there is considerable evidence that exposure to a traumatic event may
be a major risk for developing not only PTSD [32-34], but other mental disorders as
well. For example, direct exposure to different types of mass traumatic events is
associated with an increase in somatic symptoms, [35] anxiety, and depression, [36]
which are frequently comorbid with posttraumatic stress reactions among youth [37].
Recently, Hoven et al. [38] assessed the prevalence and correlates of probable mental
disorders among New York City, NY, public school students 6 months following the
September 11, 2001, and World Trade Center attack. One or more of 6 probable
anxiety/depressive disorders were identified in 28.6% of all children. The most
prevalent were probable agoraphobia (14.8%), probable separation anxiety (12.3%),
and probable posttraumatic stress disorder (10.6%).
Studies suggest that patients suffering from comorbid PTSD and depression differ
clinically and biologically from individuals with PTSD alone or depression alone.
Some have suggested that PTSD is the primary disorder, with comorbid depression
developing as a secondary reaction [39], but others hold that PTSD is a severe
manifestation of depression. Recently, Sher [30] has suggested that individuals
diagnosed with comorbid PTSD and depression have a separate psychobiological
condition that can be termed “post-traumatic mood disorder”. Nevertheless, most
treatment outcome studies have focused mainly on posttraumatic stress disorder
(PTSD), and have not assessed other mental disorders as well. Further, in most studies
patients with co-morbid psychopathology are often excluded. Thus, it is questionable
whether the results of these studies generalize to PTSD patients with co-morbid
disorders.
4. Substance Abuse
High rates of co-morbid post-traumatic stress disorder (PTSD) and substance abuse
have been reported in a number of epidemiological studies. In a community sample of
substance-abusing women about 42% reported histories of physical assault, and about
47% reported histories of sexual assault. In substance use disorder populations, rates of
30–58% have been reported for lifetime PTSD, and 20–38% for current PTSD [40].
Some research suggests that men may manifest traumatization in different ways than
women, possibly through substance use [41-43]. All too often mental health workers
who are confronted with trauma victims are less familiar with substance assessment
tools and fail to ask for substance abuse, while a number of short, reliable and valid
measures are available.
A number of screening instruments for substance use problems have been
developed, which are particularly useful. The following screening measures require
from 2 to 10 minutes to complete. In screening for alcohol use either the Michigan
Alcoholism Screening Test (MAST) [44] or the Alcohol Use Disorder Identification
Test (AUDIT) [45] can be used. The Drug Abuse Screening Test (DAST) has been
shown to be a valid screener for drug use disorders [46]. The CAGE [47] is a very brief
(4-item) screening tool that focuses on subjective negative consequences of alcohol
abuse. The Dartmouth Assessment of Lifestyle Instrument (DALI) was specifically
developed to detect substance use disorder in acute psychiatric care settings [48]. The
DALI, derived from other screening questionnaires listed above, has excellent interrater
and test-retest reliabilities. The DALI has higher sensitivity and specificity than the
MAST, CAGE, or the DAST and can be used as pretreatment and post treatment
measure.
5. Impairment, Quality of Life and Social Functioning
Impairment and subjective quality of life may be important to assess in trauma victims.
PTSD has been shown to be associated not only with poorer mental and physical health
but also with lower quality of life [49]. Quality of life has been found to be particularly
poor in sexual assault survivors [50,51], war veterans [52], refugees of war [53], and
patients who have experienced multiple traumatic events [54]. In this respect it is of
note that a number of studies found that individuals with subthreshold PTSD also are
severely impaired in social functioning and work [55, 56]. Similarly, children and
adolescents who did not meet full diagnostic criteria of PTSD nevertheless had
impairment associated with sub-threshold symptoms [57,58].
Social functioning has been studied in a number of studies as well. For example,
Bolton et al. [21] assessed young adults who had survived a shipping disaster (the
sinking of the Jupiter in 1988) between 5 and 8 years previously. Survivors with
diagnosable disorder showed poorer psychosocial functioning as compared to controls.
The time course of psychopathology and social functioning remains poorly
understood. In adolescent survivors of the Pol Pot regime in Cambodia, Sack et al. [59]
found that depression, but not PTSD, was associated with significantly poorer global
social functioning. Similarly, in the study of Bolton et al. [21], impaired psychosocial
function was more strongly linked to major depression than to PTSD.
Given the impairment and deficits in social role functioning associated with PTSD,
there is a clear need to assess these domains in treatment outcome studies. In treatment
outcome studies, interpersonal and social role performance can be assessed with the
Adult Personality Functioning Assessment (APFA) for which high inter-rater reliability
and subject-informant agreement have been demonstrated [60], the Manchester Short
Assessment of Quality of Life [61], the Social Adjustment Scale [62], or the Work, or
the Social Adjustment Scale [63].
6. Moderator and Mediators of Treatment Outcome
6.1. Social Support
Social support may offer important protection for mental health in the context of
traumatic events, including violent assaults and the trauma of war [64-66]. Among
Vietnamese refugees who had experienced traumatic war experiences, low social
support was associated with psychiatric disorders [67]. Similarly, in Israeli soldiers
during the Gulf war low social support was associated with psychological distress [68].
In PTSD sufferers in general, and refugees in particular material and social support
may be at least as important as specific psychological or medical interventions [69,70].
The effects of social support and traumatic experiences on mental health in conflict
situations may be different by gender. In a study two years after the war in Kosovo
[71], there remained a high prevalence of posttraumatic stress symptoms, particularly
among women with low social support. Women and persons who experienced more
traumatic events had higher posttraumatic stress scores. Persons with stronger social
support had lower posttraumatic stress scores. Social support had a greater protective
effect for women, whereas traumatic events had a greater detrimental effect on men.
Given the considerable evidence that social support may act as a moderator in
victims of trauma, it might be important to assess social support in victims of trauma in
future studies, not only to assess who are particularly at risk to develop
psychopathology, but also to investigate its role in treatment and relapse. For example,
the finding that debriefing has no or perhaps even a negative effect might be related to
the under use of social support facilities by the victims [72]. Also in outcome studies,
assessment of social support might be important in order to understand why some
patients improve and others do not. After trauma, treatments that facilitate the use of
social support in the natural environment might be more effective than treatments
which do not.
There are a number of social support measures available, but few are brief, and
psychometric characteristics have hardly been investigated. Further, different
components of social support have not been incorporated in most measures.
Timmerman et al. [73] developed a short self-report measure of perceived satisfaction
with social support that is easy to administer: the Social Support Inventory (SSI), which
has good psychometric properties. The SSI contains 20 items and assesses instrumental
support, emotional support, informative support, and social companionship.
6.2. Personality Traits
A number of studies have investigated whether personality traits predict the

development of PTSD, but personality disorder has not been investigated as predictor
of treatment outcome. Generally, neuroticism on its own or in combination with
introversion is related to the severity of post-traumatic stress. Most studies, however,
are retrospective and it is likely that personality assessment post-trauma may be less
reliable and affected by the traumatic experience itself. Not surprisingly, few
prospective studies have been reported. Knezevic et al [74] investigated prospectively
to what extent post-traumatic stress was influenced in civilians who experienced air
attacks in Belgrade, Yugoslavia. Thirteen percent of variance in post-traumatic stress
(IES) at one-year follow-up was explained by personality, but only on intrusions, not
on avoidance. Openness to Experience, one of the ‘Big Five’ personality traits, was the
most significant contributor. Similarly, of the ‘Big Five’ personality traits only
Openness to Experience was found to be significantly related to PTS resulting from
post-intimate stalking [75]. Whether such personality characteristics are related to
treatment outcome deserves to be studied.
6.3. CognitiveChanges
To assess the process of change it might be important to include cognitive measures as

well. The Posttraumatic Cognitions Inventory [76] is particularly useful in this regard. The
PTCI consists of three subscales labeled 'Negative Cognitions About Self (21 items),
'Negative Cognitions About the World' (7 items), and 'Self-Blame' (5 items).
For this purpose more implicit cognitive measures [77] may also be used, such as
the Directed Forgetting Task. It has been suggested that the patient’s memory is fixed
on the traumatic event, as a result of a disturbance of the autobiographic memory. To
retrieve memories, others have to be inhibited. These inhibition mechanisms have been
studied using the Directed Forgetting Paradigm, which measures the capacity to forget
recently processed information and to retain the relevant information [77,78]. However,
when using the Directed Forgetting Task as pre- and post treatment measure, the
instruction should be adapted in that the "remember" or "forget" instruction should be
given after each word.
Changes in these cognitive characteristics may be related to improvement after
treatment. It is particularly interesting to investigate whether patients who improve on
post-traumatic stress measures, but do not improve on these cognitive characteristics
are particularly vulnerable to relapse after treatment.
7. Prognostic Factors and Follow-up
Research on prognostic factors is limited, with different studies often finding different
predictors [2]. This might be partially the result of different groups of trauma victims
studied. Why should we expect that the same variables moderate the effects of
treatment of children who have been sexually abused over the years as those that
moderate the effects of treatment of victims of a single traumatic event, such as a motor
vehicle accident? Thus there is a clear need of studies investigating predictor variables
for specific trauma groups.
Another issue that deserves more attention from researchers in the field is the
identification of exactly what we want to predict. Prediction of dropout of treatment
may be unrelated to prediction of post treatment status, and both may be related only
loosely to relapse and long-term follow-up. Although it is often assumed that patients
who do not get better tend to dropout, research in other areas suggests that the picture is
much more complex and deserves study on its own. Actually, very few studies have
investigated long-term effects of the treatment of trauma victims [2]. Further, it might
well turn out that variables at posttest are better predictors of long-term outcome than
base-line characteristics.
The few studies that investigated prediction of treatment outcome used convenient
predictor variables, which were at hand (e.g. base-line characteristics). To better
understand who will profit from treatment and who will not, other research designs
may be needed. The few studies which have addressed prediction in the context of
treatment studies concern treatment outcome studies in which the comparative
effectiveness of different treatments was evaluated. However, this is not the optimal
design for studies of mediator and moderator variables associated with who will profit
from treatments and who will not, given the limited number of individuals in each
treatment condition and the variety of traumas involved.
Given that different factors might be involved in different traumas it may be
worthwhile to investigate whether one treatment is more effective for some patients and
another treatment for other patients. For example, in ongoing cases of stalking, there
seems little use of trauma-focused exposure [79]. Similarly, it is questionable whether
treatments, which have proven effective in victims of single traumatic events, are
equally effective in polysymptomatic victims of repeated traumatic events.
8. Malingering
PTSD is particularly vulnerable to malingering given the disability benefits often

involved. Recently, there is some concern regarding the validity of combat exposure
reports of veterans seeking treatment for combat-related post-traumatic stress disorder
[80,81]. A significant number of treatment-seeking war veterans may misrepresent their
combat involvement, related to secondary gain incentives (e.g. disability claims). Frueh
et al. [81] verified combat exposure history for 100 consecutive veterans reporting
Vietnam combat in a Veterans Affairs PTSD clinic. Only 41% of the total sample had
objective evidence of combat exposure documented in their military record. There was
virtually no difference between the Vietnam ‘combat’ and ‘no combat’ groups on
relevant clinical variables.
Given that malingering might be involved in a substantial number of cases, there is
a clear need of assessing potential malingering in treatment outcome studies. Although
there is no single or preferred measure to detect malingering among PTSD claimants,
diverse assessment instruments can contribute to the overall effort. The fake-bad
indices of the MMPI were not particularly useful in this respect, but the MMPI-2
appears to do a better job in discriminating malingering PTSD cases from veterans with
combat-related PTSD [82]. Further studies in this area could take into account more
implicit measures like the direct forgetting task [78].
9. Recommendations and Concluding Remarks
What implications should the above considerations have for treatment outcome studies?
Be explicit regarding exclusion criteria and do not exclude a priori individuals
with co-morbid psychopathology.
Assess malingering and exclude patients from treatment outcome studies who
are suspected of malingering.
Assess changes in post traumatic stress symptoms dimensionally, rather than
categorically.
Assess co-morbidity pre and post treatment, most notably other anxiety
disorders, depression including suicidal ideation, and substance abuse.
In children: assess not only internalizing disorders, but externalizing disorders
as well [83].
Assess impairment and quality of life.
Assess effects of treatment over extended period of time, up to four year.
Investigate treatment matching.
Investigate theoretically derived moderator and mediator variables, including
trauma-event related characteristics, premorbid personality characteristics, and
cognitive characteristics.
There is now some consensus in the field that treatments for combat-related PTSD
showed less effect than for PTSD related to other types of trauma. Researchers
investigating moderator and mediator variables affecting treatment outcomes in trauma
victims would do well to use theoretically derived variables, rather than available base-
line characteristics. Further, these moderators and mediators should be studied for
specific groups of trauma patients. In doing so we may become more specific about
which variable is related to successful outcome for groups of patients who have
undergone specific traumas (e.g. war trauma versus rape).
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M.J. Roy (Ed.)
IOS Press, 2006
Author Index
Adler, A.B. 78, 121 Lam, D. 286
Alcañiz, M.R. 296 Lasso de la Vega, N. 183
Baños, R.M. 170, 183 Lončarić, S. 251
Bliese, P.D. 78 Lozano, J.A.Q. 296
Boddam, R. 111 Manson, B. 235
Botella, C. 170, 183 Mantovani, F. 161
Brennen, T. 31 Manzoni, M. 161
Bullinger, A.H. 148 McNerney, P.J. 235
Castelnuovo, G. 161, 286 Mihajlovic, Z. 286
Castilla, D. 183 Molinari, E. 161
Cesa, G. 161 Mück-Šeler, D. 3
Cosic, K. 135 Naneishvili, G. 264, 279
Cukor, J. 219 Okribelashvili, N. 264
Cuvelier, Y. 121 Osma, J. 170
Difede, J.A. 219 Pair, J. 235
Dullea, K. 67 Perpina, C. 170
Emmelkamp, P.M.G. 309 Pivac, N. 3, 42
Gaggioli, A. 161 Popović, S. 87, 135, 286
García-Palacios, A. 170, 183, 196 Quero, S. 183
Geraerts, E. 31 Reisberg, A. 196
Gigolashvili, K. 264 Rey, B.S. 296
Graap, K. 235 Riva, G. 161
Gruzelier, J. 13 Rizzo, A. 235
Guillén, V. 170, 183 Rothbaum, B.O. 205
Hacker Hughes, J.G.H. 121 Roy, M.J. xv, 59
Henigsberg, N. 101 Schandl, L. 268
Hoffman, H. 170, 196, 219 Šimičić, L. 251
Jayasinghe, N. 219 Slamic, M. 135
Jehel, L. 67 Somer, E. 196
Josman, N. 196 Spira, J. 235
Jovanović, T. 87 Thomas, J.L. 78
Juan, C.L. 296 Tichy, V. 121
Judaš, M. 23 van der Mast, C. 286
Klapan, I. 251 Vekerdi, Z. 268
Kostović, I. 23 Weiss, P.L. 196
Kozarić-Kovačić, D. 3, 42, 87 Wiederhold, B.K. 148, 235
Kral, P. 286 Wiederhold, M.D. 148, 235
Kraus, P.L. 59 Wright, K.M. 78

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NOVEL APPROACHES TO THE DIAGNOSIS AND

TREATMENT OF POSTTRAUMATIC STRESS

A. Chemistry and Biology Springer Science and Business Media

Sub-Series E: Human and Societal Dynamics – Vol. 6 ISSN: 1574-5597

Amsterdam • Berlin • Oxford • Tokyo • Washington, DC

© 2006 IOS Press.

Distributor in the UK and Ireland Distributor in the USA and Canada

PRINTED IN THE NETHERLANDS

Local Arrangements and Social Events

Workshop Materials and CDs

Croatian Radiotelevision Reportage Guests

THE UNITED KINGDOM

Novel Approaches to the Diagnosis and

1. Cavtat, June 13–16, 2005

4. PTSD and NATO Operations

Section I. Epidemiology and Pathophysiology of PTSD

Biological Markers in Croatian War Veterans with Combat Related

Section II. Diagnosis and Screening

Efforts to Improve the Diagnosis and Treatment of Posttraumatic Stress

Section III. Management of Posttraumatic Stress Disorder

Pharmacotherapy Research in Posttraumatic Stress Disorder 101

Section IV. Virtual Reality Therapy in the Treatment of Posttraumatic Stress

Scenario Self-Adaptation in Virtual Reality Exposure Therapy for

Section V. Other Aspects of Military Healthcare

Advanced 3D Computer-Assisted Technologies in Improving Patient Telecare 251

Section VI. Working Groups

Posttraumatic Stress Disorder --- Diagnostic and Epidemiological Concerns 279

Author Index 321

Biological Markers in Croatian War

Abstract. Posttraumatic stress disorder (PTSD) is a severe psychiatric illness

Keywords. Combat related Posttraumatic Stress Disorder, War veterans, Blood

Posttraumatic stress disorder (PTSD) is a severe psychiatric disorder, classified as an

1. Materials and methods

history of psychosis, or a history of schizophrenia, schizoaffective disorder or bipolar

1.2. Biochemical determination

1.3. Data analysis

Measures Scores (mean r SD)

Platelet 5-HT concentration did not differ significantly (F=0.069, df=1,152

Groups Plasma cortisol (nmol/)

Platelet MAO activity differed significantly (F=18.903; df=1,208; p<0.001, one-

Plasma lipid levels differed significantly (evaluated by one-way ANOVAs)

Groups Cholesterol Triglycerides HDL LDL (mmol/L)

The noradrenergic system is hyperactive in PTSD, and increased noradrenergic

Theta Synchronisation of Hippocampal and

Keywords. Theta rhythm, hippocampus, brain circuitry, PTSD, hypnosis, EEG-

1. The Theta Rhythm

1.1. Survival Behaviour and the Hippocampus

1.2. Entrainment of Circuitry for Integrating Cognition and Emotion

The hippocampus is involved in circuitry synchronised by the theta rhythm. Non-rhythmic

1.3. Long Range, Top-Down Connectivity

1.5. Summary of the Functional Implications of Theta

• Theta has long been regarded as a signature of hippocampal function,

2.1. The Hippocampus

2.2. Brain Circuitry

• Hippocampal processes involved in PTSD include survival behaviour such as conscious

3. Hypnosis and EEG-Neurofeedback Theta Training

3.1. Neurophysiology of Hypnosis

3.1.1. Hypnotherapy and PTSD

3.2. Elevating the Theta/Alpha Ratio

• Hypnosis is associated with elevated theta, in keeping with internalized top-down

Limbic Circuitry and Posttraumatic Stress

Abstract: The objective of this review is to outline problems which should be

Keywords: amygdala, limbic system, stress, emotional brain