Psychosis Arciniegas

Review Article
Psychosis
Address correspondence to
Dr David B. Arciniegas, Baylor
College of Medicine, 1333
Moursund Street, Houston,
David B. Arciniegas, MD TX 77030,
david.arciniegas@bcm.edu.
Relationship Disclosure:
Dr Arciniegas receives funding
ABSTRACT from the National Institute of
Purpose of Review: Psychosis is a common and functionally disruptive symptom of Mental Health, which in part
supports the development of
many psychiatric, neurodevelopmental, neurologic, and medical conditions and an this work. Dr Arciniegas
important target of evaluation and treatment in neurologic and psychiatric practice. receives royalties from American
The purpose of this review is to define psychosis, communicate recent changes to Psychiatric Publishing, Inc,
Cambridge University Press, and
the classification of and criteria for primary psychotic disorders described in the Demos Medical Publishing, and
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), and receives travel, meeting, and
summarize current evidence-based approaches to the evaluation and management accommodation compensation
from the International Brain
of primary and secondary psychoses. Injury Association.
Recent Findings: The DSM-5 classification of and criteria for primary psychotic disorders Unlabeled Use of
emphasize that these conditions occur along a spectrum, with schizoid (personality) Products/Investigational
Use Disclosure:
disorder and schizophrenia defining its mild and severe ends, respectively. Psychosis is also Dr Arciniegas discusses the
identified as only one of several dimensions of neuropsychiatric disturbance in these unlabeled/investigational use
disorders, with others encompassing abnormal psychomotor behaviors, negative of acetylcholinesterase
inhibitors and antipsychotics
symptoms, cognitive impairments, and emotional disturbances. This dimensional for psychotic symptoms
approach regards hallucinations and delusions as arising from neural systems subserving associated with neurologic
perception and information processing, thereby aligning the neurobiological framework conditions and repetitive
transcranial magnetic
used to describe and study such symptoms in primary psychotic disorders with those used stimulation for auditory verbal
to study psychosis associated with other neurologic conditions. hallucinations in schizophrenia.
Summary: This article provides practicing neurologists with updates on current approaches * 2015, American Academy
to the diagnosis, evaluation, and treatment of primary and secondary psychoses. of Neurology.
Continuum (Minneap Minn) 2015;21(3):715–736.
INTRODUCTION sional misidentification syndromes are

Psychosis is a common and functionally defined and tabulated. The current
disruptive symptom of many psychiat- classification, updated criteria, and ap-
ric, neurodevelopmental, neurologic, proaches to the evaluation of schizophre-
and medical conditions and an impor- nia spectrum and related psychotic
tant target of evaluation and treatment disorders, as well as psychoses in neuro-
in neurologic and psychiatric practice. logic conditions, are reviewed. Practical
This article defines psychosis, commu- guidance on the evaluation and treatment
nicates recent changes to the classifica- of these conditions is drawn from practice
tion of and criteria for primary psychotic guidelines promulgated by the profes-
disorders described in the Diagnostic and sional societies and other international
Statistical Manual of Mental Disorders, organizations, supplemented with find-
Fifth Edition (DSM-5), and summarizes ings published in more recent meta-
current evidence-based approaches to the analyses and systematic reviews.
evaluation and management of primary Psychosis is the defining feature of
and secondary psychoses. The defini- schizophrenia spectrum disorders, a com-
tions of psychosis used in the DSM-5 and mon but variable feature of mood and
International Classification of Diseases, substance use disorders, and a relatively
Tenth Revision (ICD-10) are presented, common feature of many developmental,
and hallucinations, delusions, and delu- acquired, and degenerative neurologic
Continuum (Minneap Minn) 2015;21(3):715–736 www.ContinuumJournal.com 715
Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

Psychosis
KEY POINT
h The American Psychiatric and medical conditions. Across these con- in its classification of mental disorders
Association and the World ditions, psychosis is both a contributor to while deliberately making no attempt
Health Organization disability and a barrier to productivity and to define these terms.8 As a result, the cate-
emphasize the presence participation.1Y4 Psychosis is, therefore, gory of psychotic disorders in the early edi-
of hallucinations without an important target of evaluation and tions of the DSM and in the ICD-9 were
insight or delusions in treatment among patients receiving care overly inclusive and, with respect to clinical,
their current definitions from neurologists and psychiatrists. research, and epidemiologic endeavors,
of psychosis. This article also defines psychosis and ultimately proved impracticable.6,8
reviews the essential clinical features of In their current conceptualization of
primary psychotic disorders and psycho- psychosis, both the APA5 and the World
ses secondary to neurologic conditions. Health Organization8 define psychosis
The criteria for psychotic disorders narrowly by requiring the presence of
included in the DSM-5,5 which have hallucinations (without insight into their
been revised substantially relative to pathologic nature), delusions, or both
the Diagnostic and Statistical Manual hallucinations without insight and de-
of Mental Disorders, Fourth Edition, lusions.6 In both of these current diag-
Text Revision (DSM-IV-TR),6 are a major nostic classification systems, impaired
focus of this review. The revised diag- reality testing remains central conceptu-
nostic criteria for secondary psychoses ally to psychosis. In contrast to earlier
(those due to neurologic or medical diagnostic classification systems, the cur-
conditions, substance use, and medica- rent systems5,8 operationalize impaired
tions) also are reviewed briefly and the reality testing by identifying the symp-
psychoses associated with common neu- toms that provide evidence of such
rologic conditions tabulated. Finally, impairment. Delusions (ie, fixed false
practical and evidence-based suggestions beliefs), by definition, are evidence of
for the evaluation and treatment of impaired reality testing: delusional beliefs
primary and secondary psychotic disor- are ones maintained steadfastly even in
ders are presented. the face of evidence contradicting them
incontrovertibly. Similarly, hallucinations
DEFINING PSYCHOSIS (ie, perceptions occurring in the absence
In early editions of the American of corresponding external or somatic
Psychiatric Association’s (APA’s) Diag- stimuli) are evidence of impaired reality
nostic and Statistical Manual of Men- when the individual experiencing them
tal Disorders (DSM),7 psychosis was is unable to recognize the hallucinatory
defined broadly as ‘‘gross impairment nature of such experiences. Both the cur-
in reality testing’’ or ‘‘loss of ego bound- rent APA5 and the World Health Organi-
aries’’ that interferes with the capacity to zation8 classification systems acknowledge
meet the ordinary demands of life. This that ‘‘formal thought disorder’’ (ie, disor-
approach to defining psychosis empha- ganized thinking, including illogicality,
sized the presence of functional limita- tangentiality, perseveration, neologism,
tions over the symptoms putatively thought blocking, derailment, or some
responsible for them6 and too often combination of these disturbances of
rendered the distinction between psy- thought) is one of several commonly co-
chotic and nonpsychotic mental disor- occurring features of psychotic disorders.
ders ambiguous. Concurrently, the The DSM-55 allows formal thought dis-
International Classification of Diseases, order to supplant hallucinations and
Ninth Revision ([ICD-9], published in delusions in the diagnosis of a psychotic
1975) employed the then-traditional divi- disorder when it is accompanied by
sion between ‘‘neurosis’’ and ’’psychosis’’ grossly disorganized behavior, catatonia
716 www.ContinuumJournal.com June 2015

KEY POINTS
(for schizophrenia, schizophreniform, and ‘‘thought echoes’’ (hallucinations h Hallucination is defined
brief psychotic, and schizoaffective disor- in which the patient hears his or her as a sensory perception
ders) and/or negative symptoms (for thoughts spoken aloud) as ‘‘first-rank’’ in the absence of a
schizophrenia, schizophreniform, and symptoms of schizophrenia. The first two corresponding external
schizoaffective disorders but not brief of these types of auditory hallucinations or somatic stimulus and
psychotic disorder), alone or in combina- have been regarded as so abnormal described according to
tion.8 Since mildly disorganized speech that their presence alone (in the the sensory domain in
is common and diagnostically non- absence of delusions or other thought, which it occurs.
specific, the degree of thought disorder speech, and behavioral disturbances or h Hallucinations may
required to fulfill this DSM-5 criterion negative symptoms) was sufficient to occur with or without
must be of severity sufficient to substan- warrant a diagnosis of schizophrenia insight into their
tially impair effective communication. under the criteria of the DSM-IV-TR6 hallucinatory nature.
For the purposes of this article, the and its predecessors. The absence of insight
term psychosis refers to the presence of Hallucination is distinguished from into a hallucination
defines it as a psychotic
delusions, hallucinations without insight, illusion (misperception of an actual
symptom, that is, a
or both. These symptoms are clearly de- sensory stimulus) and the other dis-
hallucination for which
fined common features of psychosis in turbances of perception or experience reality testing is impaired.
both psychiatric disorders and neurologic described in Table 8-1.10 These per-
conditions. They are captured by informal ceptual phenomena occur in many h Delusions are fixed false
beliefs; they are based
and structured clinical assessments and are neuropsychiatric conditions, including
on incorrect (false)
reasonably amenable to treatment. primary psychiatric disorders, neuro- inferences about reality
logic disorders, medical illnesses, and external to, or about,
Hallucinations substance intoxication and withdrawal oneself and maintained
Hallucination is defined as a sensory states. Some of these perceptual phe- firmly (fixed) despite the
perception in the absence of a corre- nomena (eg, illusions, hallucinations, presentation of
sponding external or somatic stimulus synesthesia, derealization, depersonal- evidence that obviously
and described according to the sensory ization, autoscopy, déjà vu or déjà and incontrovertibly
domain in which it occurs. Hallucina- entendu, jamais vu or jamais entendu) contradicts the belief.
tions may occur with or without insight are also reported by neuropsychiatrically
into their hallucinatory nature. The ab- healthy individuals. Their occurrence is
sence of insight into a hallucination not necessarily pathologic, especially if
defines it as a psychotic symptom, that they occur with preserved insight, they
is, a hallucination for which reality testing are not associated with other disturbances
is impaired. Hallucinations without in- of cognition, emotion, or behavior, and
sight are contrasted with hallucinations they do not compromise personal, social,
that the individual recognizes as unreal. or occupational function.
Examples of hallucinations with preserved
insight include the visual hallucinations Delusions
of migraine aura, sleep transition-related Delusions are fixed false beliefs; they
hypnagogic (while falling asleep) and are based on incorrect (false) inferences
hypnopompic (while waking) hallucina- about reality external to, or about,
tions, and the hallucinated hearing of one’s oneself and maintained firmly (fixed)
name being called that many psychiat- despite the presentation of evidence
rically and neurologically healthy indi- that obviously and incontrovertibly con-
viduals experience occasionally. tradicts the belief. Table 8-2 defines and
Schneider9 described auditory hal- describes the types of delusions com-
lucinations involving hearing voices monly occurring in individuals with
conversing with one another, offering primary and secondary psychotic dis-
running commentary on one’s actions, orders.10 These delusions are often

Psychosis
TABLE 8-1 Disturbances of Perception and Experience in the Differential

Diagnosis of Hallucinationsa
Phenomenon Description
Hallucination Sensory perception in the absence of a stimulus;
described according to the sensory domain in which it
occurs (eg, visual, auditory, tactile, olfactory, gustatory,
nociceptive, themoceptive, proprioceptive, equilibrioceptive);
may be unformed (ie, nonspecific sensory perceptions
within a sensory domain) or formed (ie, people, objects,
voices making comments or commands)
Illusion Misperception of a sensory stimulus; described
according to the sensory domain in which it occurs
(eg, visual, auditory, tactile, olfactory, gustatory,
nociceptive, themoceptive, proprioceptive, equilibrioceptive)
Palinopsia Persistent perception of a visual stimulus after that
stimulus is no longer present (ie, an afterimage)
Synesthesia Perception of a stimulus outside the sensory modality
in which that stimulus is presented (eg, hearing colors,
tasting sounds) or that adds perceptual features not
normally perceived within a sensory modality (eg, black
numbers or letters evoking the perception of color)
Derealization Perceiving/experiencing the external world as unreal
Depersonalization Perceiving/experiencing oneself as detached from
(ie, as if an outside observer of) one’s mental
processes or body
Autoscopy Seeing one’s body from a position outside the body
(ie, out-of-body experience)
Déjà vu Perceiving/experiencing a novel image or
scene as one previously witnessed or experienced
Déjà entendu Perceiving/experiencing a novel sound as one
previously witnessed or experienced
Jamais vu Perceiving/experiencing a familiar image or scene
as unfamiliar
Jamais entendu Perceiving/experiencing a familiar sound as unfamiliar
a
Adapted with permission from Arciniegas DB, Cambridge University Press.10 B 2013 Cambridge
University Press.
divided into two types: ordinary and statements) has an ordinary delusion
bizarre. Ordinary delusions derive from (more specifically, an ordinary perse-
misinterpretation of everyday experi- cutory delusion). Bizarre delusions in-
ences and, as such, are understandable volve phenomena that are physically
but not accepted by other members of impossible or that most people in that
the person’s culture or subculture (ie, person’s culture would regard as en-
are not articles of religious faith). For tirely implausible. The DSM-IV-TR pro-
example, a patient who believes that an vided as an example of bizarre delusion
unknown group of conspirators is the belief that a stranger removed
diverting his savings to a terrorist one’s internal organs and replaced
group despite being presented with them with another person’s organs
evidence to the contrary (eg, bank without leaving any wounds or scars.6

a
TABLE 8-2 Delusions Observed Among Patients With Neuropsychiatric Disorders
Delusion Description
Persecutory Fixed false belief that one is being harmed or that such harm is impending and that the
perpetrators of that harm are causing it intentionally; common examples include the
belief that one is being followed, tricked, spied on, poisoned or drugged, tormented,
ridiculed, cheated, conspired against, or that one’s goals are being obstructed
Grandiose Insightless and unshakable conviction that one possesses special powers, talents,
knowledge, or abilities; is famous (or a famous person or character); or holds a
special relationship to a famous person or deity
Religious Any delusion with religious content, especially beliefs that one is God, an angel, a devil,
the son or daughter of God, a saint, or otherwise deific (subtypes of grandiose delusions)
Referential Fixed false belief that remarks, objects, events, or other phenomena are directed at or are
about oneself
Thought control Fixed false belief that one’s thoughts, feelings, or behaviors are being controlled by
an external force, person, or group
Thought insertion Delusion that thoughts are being inserted into one’s mind (‘‘thoughts are not my own’’)
Thought withdrawal Delusion that an outside force, person, or group is removing or extracting one’s thoughts
Thought broadcasting Delusion that one’s thoughts are being broadcast to others or can be heard aloud by others
Delusional perception Linking a normal percept to a bizarre conclusion (eg, seeing the sunrise signifies to
the patient that he or she is the messiah)
Mind being read Delusion that one’s mind can be or is being read by another person or group;
does not entail ‘‘broadcasting’’ one’s thoughts or that one’s thoughts can be heard
aloud by others; may be a subtype of persecutory (paranoid) delusions
Jealousy Fixed false belief that a spouse or lover is unfaithful; also referred to as
delusion of infidelity
Erotomania Delusion that one is loved by another person (usually one of higher status)
Theft Fixed false belief that one’s valuables are being stolen, often by an unseen thief;
tends to develop in the context of declarative memory impairments (eg, Alzheimer disease)
Phantom intruder Delusion that a stranger, usually unwanted, is in one’s home
Somatic A delusion that pertains to the appearance or functioning (including smell) of one’s
body, usually involving the fixed false belief that one’s body is abnormal, diseased,
or changed in some manner
Parasitosis Fixed false belief that one is infested with insects, bacteria, mites, lice,
fleas, spiders, worms, or other organisms (also known as Ekbom syndromeb)
Nihilistic Delusion that one does not exist or is dead; also described as delusion of negation
a
Adapted with permission from Arciniegas DB, Cambridge University Press.10 B 2013 Cambridge University Press.
b
Ekbom syndrome should not be confused with Willis-Ekbom disease (ie, restless legs syndrome).
Schneider9 described specific types withdrawal and thought insertion. The

of bizarre delusions as ‘‘first-rank’’ presence of bizarre delusions, espe-
symptoms of schizophrenia. (‘‘First- cially of these types, has long been
rank’’ refers to symptoms that, when regarded as so abnormal that their
present, indicate the presence of a presence alone (in the absence of
particular diagnosis [in the case of delusions or other thought, speech,
Schneiderian first-rank symptoms, the and behavioral disturbances or negative
diagnosis of schizophrenia]). These symptoms) was sufficient to warrant a
include delusions of control, including diagnosis of schizophrenia under
thought control, as well as thought DSM-IV-TR and its predecessors.

Psychosis
KEY POINTS
h Delusions are distinct Delusions are contrasted with over- tors may, with sufficient exposure to
from confabulation, valued ideas, which are unreasonable risk-modifying social and environmen-
which refers to the beliefs or ideas that are held with strong, tal factors, be prone to developing
automatic and but not delusional, conviction. When a persistent psychotic symptoms.14Y16
nondeceitful fabrication false belief involves a value judgment, it This psychosis proneness-persistence
of information, usually of may be regarded as delusional only model may explain, at least in part,
an autobiographic or when the judgment made is so extreme the development of hallucinations and
episodic nature, by a that it is not credible. Delusions are delusions across the broad range of
patient with concurrent distinct from confabulation, which refers psychiatric disorders with which they
declarative memory to the automatic and nondeceitful fabri- are associated. It also may yield in-
impairments and
cation of information, usually of an auto- sights into the risk factors for and
executive dysfunction.
biographical or episodic nature, by a patient mechanisms of psychosis associated
h Although delusional with concurrent declarative memory with neurologic conditions. This model
misidentification impairments and executive dysfunc- aligns well with the National Institute
syndromes occur
tion.11 Confabulated information (even of Mental Health (NIMH) Research
commonly among
when fantastic in character) may be Domain Criteria (RDoC) framework,
patients with psychiatric
illnesses, especially
firmly believed in the moment that it is within which phenomena such as de-
primary psychotic offered but is usually soon forgotten lusions and hallucinations are studied
disorders, as many as and, as such, is false but not fixed and, in relation to the operations of under-
20% to 40% occur in hence, not delusional. lying neural systems across the condi-
the context of neurologic Delusional misidentification syn- tions in which they occur, rather than
conditions affecting the dromes. Delusional misidentification in relation to the categorical psychiatric
right hemisphere. syndromes (Table 8-310) share the disorders with which they may be
Accordingly, the theme of doubles (ie, duplication of associated.17,18
presence of these types self, others, or the environment). They In this light, it is not surprising that
of delusions should are associated with impairments in psychosis is listed as a feature of multiple
prompt evaluation for
facial processing and are closely related psychiatric disorders presented in the
potentially treatable
to and sometimes co-occur with redupli- DSM-5. Although psychosis is the defining
or arrestable
neurologic conditions.
cative paramnesia.12,13 Phenomenologically, feature of the schizophrenia spectrum
delusional misidentification syndromes disorders (ie, schizophrenia, schizoaffec-
may be divided into two types: delusional tive disorder, delusional disorder,
hypoidentification (eg, Capgras syndrome) schizophreniform disorder, and brief
or delusional hyperidentification (eg, psychotic disorder), it also occurs in
Frégoli, intermetamorphosis, subjective some people with bipolar disorder
doubles syndromes). Although delusional during either a manic or depressive
misidentification syndromes occur com- episode as well as in some individuals
monly among patients with psychiatric during a major depressive episode
illnesses, especially primary psychotic associated with major depressive dis-
disorders, as many as 20% to 40% occur order. In those conditions, the psy-
in the context of neurologic conditions chotic symptoms (usually delusions)
affecting the right hemisphere.12,13 may be thematically either congruent
Accordingly, the presence of these types or incongruent with the prevailing
of delusions should prompt evaluation mood. Psychotic symptoms (ie, hallu-
for potentially treatable or arrestable cinations without insight, delusions) may
neurologic conditions. develop during either intoxication or with-
drawal from substances and, in some
PRIMARY PSYCHOTIC DISORDERS cases, may become chronic sequelae of
A subset of the population with genetic, prior substance use (substance-induced
epigenetic, and developmental risk fac- psychotic disorder). When individuals

KEY POINT
TABLE 8-3 Examples of Delusional Misidentification and Other h The psychosis

Delusions Involving a Belief That the Identity of a Person, proneness-persistence
Object, or Place Has Been Changed or Replaceda model and Research
Domain Criteria
Syndrome Description approach suggests that
Capgras Delusional belief that a spouse, family member, or the presence of
other familiar individual has been replaced by an hallucinations or
impostor who is physically, but not psychologically, delusions reflects
identical to the replaced person disturbances in the
Frégoli Delusional belief in which the patient believes neural systems underlying
different people are in fact a single person these symptoms regardless
(usually believed to be a persecutor) who changes of the categorical
appearance or is in disguise psychiatric disorder with
Intermetamorphosis A variant of the Frégoli syndrome in which the which they are associated.
patient believes that familiar people and strangers
in the environment swap identities while
maintaining their original appearance
Subjective doubles Delusion that a double of oneself exists
(doppelgänger), carrying out independent
actions; also known as the subjective
Capgras delusion
Clonal pluralization Delusion that there are multiple physically
of the self and psychologically identical copies of oneself
Delusional companions Fixed false belief that nonliving objects
(eg, toys, appliances, cars) are sentient beings
Mirrored Delusion that one’s reflection in a mirror is
self-misidentification someone else
Reduplicative paramnesia Delusion that a familiar person, place, or object
has been duplicated
Cotard Fixed false belief that one or more of one’s organs
or body parts are missing or no longer exist
a
Adapted with permission from Arciniegas DB, Cambridge University Press.10 B 2013 Cambridge
University Press.
with obsessive-compulsive disorder article. Readers are encouraged to

lack insight into the pathologic na- review the relevant sections of the
ture of their obsessions, their obses- DSM-5 and to familiarize themselves
sions are described as delusions. The with the current criteria for these
psychosis proneness-persistence conditions. To help keep readers up-to-
model and RDoC approach suggests date, major changes made to the criteria
that the presence of hallucinations or for psychotic disorders in the transition
delusions reflects disturbances in the from the DSM-IV-TR to the DSM-5 are
neural systems underlying these reviewed in this article.
symptoms regardless of the categorical
psychiatric or neurologic disorder Schizophrenia Spectrum
with which they are associated. Disorders
A complete review of psychosis as The DSM-5 marks a shift from the
it occurs in each of these conditions is presentation of schizophrenia as the
beyond the scope of the present archetypal psychotic disorder to its

Psychosis
KEY POINT
h Disorders along the consideration as one of several psy- use (www.psychiatry.org/File%20Library/
schizophrenia spectrum chotic disorders existing on a spectrum Practice/DSM/DSM-5/ClinicianRated
differ from one another of psychopathology. Disorders along DimensionsOfPsychosisSymptomSeverity.
by the type, number, the schizophrenia spectrum differ from pdf ).19 The provision of this measure
complexity, severity and one another by the type, number, is coupled with the request that clini-
duration of the complexity, severity, and duration of cians and researchers provide further
psychotic symptoms and the psychotic symptoms and associated data on the instrument’s usefulness in
associated features that features that define them. Symptoms of characterizing patient status and im-
define them. schizophrenia spectrum disorders in- proving patient care by submitting
clude hallucinations, delusions, dis- feedback at www.dsm5.org/Pages/
organized thinking (formal thought Feedback-Form.aspx. Given the emerg-
disorder, usually inferred from an in- ing nature of this measure, the DSM-5
dividual’s speech), grossly disorganized encourages, but does not require, using
or abnormal motor behavior (including the Clinician-Rated Dimensions of Psy-
catatonia), and negative symptoms. The chosis Symptom Severity scale to specify
number, complexity, and duration of severity of illness in the schizophrenia
symptoms required for a given diagno- spectrum disorders.
sis increase with movement from the Schizotypal (personality) disorder.
mild to the severe ends of the schizo- At the mild end of the schizophrenia
phrenia spectrum. spectrum disorders is schizotypal dis-
Consistent with this essentially di- order (also known as schizotypal
mensional approach to the evaluation personality disorder). Schizotypal dis-
of psychotic symptoms, the DSM-5 order is characterized by social and
introduced the Clinician-Rated Dimen- interpersonal deficits that reduce the
sions of Psychosis Symptom Severity capacity for, and produce marked
scale in Section III, ‘‘Emerging Mea- discomfort with, close relationships.
sures and Models.’’8,19 This scale is an These deficits are often accompanied by
eight-item measure that rates the se- unusual perceptual experiences (illu-
verity of each symptom that defines sions) and cognitive distortions (ideas of
the schizophrenia spectrum disorders reference, suspiciousness or paranoia,
(hallucinations, delusions, disorganized odd beliefs, or magical thinking that are
speech, abnormal psychomotor behav- held without delusional conviction) simi-
ior, negative symptoms) as well as co- lar to, but less severe than, those experi-
occurring cognitive, depressive, and enced by people with schizophrenia. As
manic symptoms during the week prior noted by Chemerinski and colleagues,20
to assessment on a scale from 0 (not schizotypal disorder and schizophrenia
present) to 4 (present and severe). feature cognitive, social, and attentional
Assessment of this constellation of deficits based in neurodevelopmentally
symptoms with these measures is de- mediated temporal and prefrontal corti-
scribed in the DSM-5 as useful for cal pathology. These deficits are milder
characterizing these conditions, pre- in people with schizotypal disorder than
dicting important aspects of the illness in those with schizophrenia, possibly as a
(eg, cognitive and neurobiological defi- result of preserved capacity in the
cits), informing treatment planning and schizotypal brain to recruit related brain
prognosis, and monitoring symptom se- regions and thereby compensate for
verity over time. The severity of the dis- dysfunctional areas. Additionally, people
orders in this section of the DSM-5 may with schizotypal disorder appear to be
be assessed with this scale, which the less vulnerable to psychosis as a result of
APA has made freely available for clinical the preservation of protective factors

KEY POINT
against the psychotogenic effects of month, with eventual full return to h Although the criteria for
subcortical dopaminergic hyperactivity. premorbid function. Negative symp- schizotypal disorder
Although the criteria for schizotypal toms are not among the diagnostic have not changed
disorder have not changed substantively criteria for this condition. As in the substantively between
between the DSM-IV-TR and DSM-5, the DSM-IV-TR, current specifiers for brief the Diagnostic and
presentation of this condition as both a psychotic disorder include the condi- Statistical Manual of
schizophrenia spectrum disorder and a tion’s relationship to marked stressors Mental Disorders,
personality disorder is a noteworthy (which, if present, define brief reactive Fourth Edition, Text
change in its classification. psychosis) or postpartum onset (during Revision and the
Delusional disorder. Delusional pregnancy or within 4 weeks post- Diagnostic and Statistical
Manual of Mental
disorder encompasses a broader range partum). The DSM-5 adds a specifier
Disorders, Fifth Edition
of the spectrum of psychosis severity for the presence of catatonia, as well as
(DSM-5), the
in the DSM-5 than in the prior edition a coding note directing the use of the presentation of this
of this manual. In both the DSM-IV-TR additional 293.89 code (catatonia asso- condition as both a
and DSM-5, this diagnosis requires the ciated with brief psychotic disorder) to schizophrenia spectrum
presence of one or more delusions indicate this comorbidity. disorder and a personality
lasting at least 1 month in the absence S c h i z o p h r e n i f o r m d i s o r de r . disorder is a noteworthy
of prominent hallucinations (Case 8-1). Schizophreniform disorder represents change in its classification.
If present, hallucinations must be related a point on the spectrum between brief
to the delusional theme (eg, tactile hal- psychotic disorder and schizophrenia.
lucinations of bugs on the skin in a Analogous to changes made to the
patient with delusions of parasitosis). criteria for schizophrenia, this con-
In the DSM-IV-TR, bizarre delusions dition is defined by the presence of
exceeded the criteria for delusional two or more psychotic and related
disorder and were sufficient grounds symptoms (delusions, hallucinations,
for a diagnosis of schizophrenia (even disorganized speech reflecting formal
in the absence of hallucinations, dis- thought disorder, abnormal psychomo-
organized thought or behavior, cata- tor behavior such as grossly disorga-
tonia, or negative symptoms).6 In the nized or catatonic behavior, negative
DSM-5, however, allowance of symptoms)Vat least one of which must
Schneiderian first-rank symptoms to be delusions, hallucinations, or disorga-
suffice for the diagnosis of schizophre- nized speechVlasting at least 1 month
nia has been eliminated. As a result, but less than 6 months. The DSM-5, in
the presence of either ordinary or contrast to the DSM-IV-TR, permits
bizarre delusions (or both) is now making a provisional diagnosis of
consistent with a diagnosis of delu- schizophreniform disorder when a diag-
sional disorder, although the presence nosis must be made before the end of
of bizarre content is used as a specifier this time period (without waiting for
in this diagnosis. possible recovery). It also clarifies the
Brief psychotic disorder. This di- exclusion of schizoaffective disorder,
agnosis is defined by the presence of major depressive disorder, and bipolar
delusions, hallucinations, formal disorder by specifying that no major
thought disorder (ie, disorganized depressive or manic symptoms may
speech), or abnormal psychomotor occur with active-phase psychotic symp-
behavior (grossly disorganized or cat- toms or, if such symptoms have been
atonic behavior), not better explained present, that they have been present
by another mental disorder, substance for a minority of the total active and
use disorder, or medical condition, residual phases of the illness. As with
lasting at least 1 day but less than 1 brief psychotic disorder, an additional

Psychosis
KEY POINT
h The DSM-5 eliminates
the presence of
Case 8-1
A 19-year-old previously healthy man was brought in by his parents for
first-rank hallucinations
evaluation of paranoid ideation. The parents reported that the patient had
or delusions as grounds
always been a loner, worked from home as a computer programmer, and spent
for reducing the
most of his leisure time in his room browsing the Internet, watching detective
number of symptoms
shows on television, and listening to a police scanner. A little over 1 month prior
required for the diagnosis
to presentation, he began refusing to leave his room, keeping the curtains
of schizophrenia.
drawn constantly, and taking copious notes about the comings and goings of his
neighbors. After a week of these new behaviors, his parents asked him to explain
the changes to his routine. He told them that a black sedan had begun parking
across the street from their home each evening and departing early each morning,
leading him to conclude that he was the subject of surveillance by the Federal
Bureau of Investigation. When his parents informed him that the car was recently
purchased by their longtime next-door neighbor and family acquaintance, he then
concluded that the neighbor was the federal agent surveilling him. Despite
repeated attempts to convince him otherwise, including a conversation with
the neighbor, who explained his recent purchase of a luxury car to ease
his long daily commutes, the patient’s paranoid beliefs remained unchanged.
Physical and neurologic examinations were normal, and mental status
examination was remarkable only for the patient’s delusion. Serum laboratory
studies, urine toxicology, and MRI of the brain were normal.
Comment. The patient presented with a nonbizarre delusion as his sole
symptom. The presence of this type of delusion for more than 1 month
in the absence of prominent hallucinations, when not better explained by
a known psychotic disorder or mood disorder with psychotic features and
not attributable to the physiologic effects of a substance or another
medical condition, is consistent with a provisional diagnosis of delusional
disorder (297.1), current severity of delusions: 4 (present and severe).
specifier and related coding note have must be associated with impaired func-
been added to indicate the presence of tioning in one or more major life areas
comorbid catatonia. such as self-care, work, interpersonal rela-
Schizophrenia. The DSM-5 includes tions, or academics.
substantive changes to the diagnostic The DSM-IV-TR permitted diagnosing
criteria for schizophrenia. The core schizophrenia when first-rank delusions
criteria continue to require the pres- or auditory hallucinations occurred in
ence of two or more psychotic and the absence of other symptoms. How-
related symptoms (delusions, halluci- ever, first-rank symptoms are not spe-
nations, disorganized speech reflecting cific to schizophrenia and may occur in
formal thought disorder, abnormal manic and depressive episodes with
psychomotor behavior such as grossly psychotic features, temporal lobe epi-
disorganized or catatonic behavior, lepsy, dissociative identity disorder, and
negative symptoms)Vat least one of other psychiatric conditions.21 Accord-
which must be delusions, hallucina- ingly, the DSM-5 eliminates the pres-
tions, or disorganized speechVthat ence of first-rank hallucinations or
have been present for at least 6 months delusions as grounds for reducing the
(including 1 month, or less if treated number of symptoms required for the
successfully, of active psychotic and re- diagnosis of schizophrenia. This change
lated symptoms). These symptoms also is coordinated with the DSM-5 revised

KEY POINTS
criteria for delusional disorder such criteria are revised in a manner that h In contrast to prior
that patients presenting only with is likely to reduce the frequency with editions of the DSM,
bizarre delusions, and thereby failing which it is diagnosed. schizophrenia subtypes
to meet criteria for schizophrenia, can As in the DSM-IV-TR, the current have been eliminated in
now be diagnosed with delusional diagnostic criteria for schizoaffective the DSM-5.
disorder. As with schizophreniform disorder require an uninterrupted pe- h The DSM-5 eliminates
disorder, clarification of the exclusion riod of illness during which a major schizophrenia subtyping
of schizoaffective disorder, major de- mood episode occurs concurrently in favor of characterizing
pressive disorder, and bipolar disorder with a disturbance meeting Criterion the features of
is offered, and an additional specifier A for schizophrenia (two or more of schizophrenia using the
and related coding note have been the following: delusions, hallucina- Clinician-Rated
added to indicate the presence of tions, disorganized speech reflecting Dimensions of Psychosis
comorbid catatonia. formal thought disorder, abnormal Symptom Severity scale.
In contrast to prior editions of the psychomotor behavior, negative symp-
DSM, schizophrenia subtypes have been toms, at least one of which is delusions,
eliminated in DSM-5. These subtypes hallucinations, or disorganized speech).
(paranoid, disorganized, catatonic, Over the lifetime of the illness, delusions
undifferentiated, residual) were defined or hallucinations also must occur for at
previously by the predominant symptom least 2 weeks in the absence of either a
at the time of a given evaluation. How- manic or depressive episode. This re-
ever, the validity of these subtypes was quirement of a 2-week (or longer) epi-
controversial given their longitudinal sode of psychosis in the absence of mood
instability, overlapping features, and fail- symptoms distinguishes schizoaffective
ure to consistently predict outcomes.22 disorder from either bipolar or depres-
Recognizing these problems and the sive disorders with psychotic features, in
waning use of schizophrenia subtypes which psychotic symptoms occur only
in clinical and research contexts,23 the during mood episodes. Course specifiers
DSM-5 eliminates schizophrenia sub- for bipolar or depressive subtypes of
typing in favor of characterizing the schizoaffective disorder and a new spec-
features of schizophrenia using the ifier for catatonic features are presented
Clinician-Rated Dimensions of Psychosis in the current criteria.
Symptom Severity scale. In contrast to the DSM-IV-TR, how-
Schizoaffective disorder. Defining ever, the DSM-5 requires the presence
schizoaffective disorder has presented of symptoms meeting criteria for manic
challenges to the psychiatric research and/or depressive episodes for the
community.24 Some investigators re- majority (not merely a substantial por-
gard it as variant of schizophrenia in tion) of the total duration of the illness.
which mood symptoms are unusually This criterion requires assessment of
prominent but not unusual in type. mood symptoms over the entire
Others describe it as a mood disorder course of a psychotic illness rather
in which mood episodeYrelated psy- than merely the current period of
chotic symptoms do not fully remit. illness; if mood symptoms are present
Still others view it as the simple co- only for a relatively brief period (eg,
occurrence of two relatively common during only 1 year of a 4-year psychotic
but etiologically distinct psychiatric illness), then a diagnosis of schizophre-
illness types, schizophrenia and a nia is made instead of a diagnosis of
mood disorder. The problem of schizoaffective disorder. The informa-
schizoaffective disorder remains tion requirements needed to confidently
unresolved in the DSM-5, although establish a diagnosis of schizoaffective

Psychosis
KEY POINT
h New in the DSM-5 is the disorder necessitate a fully informed Unspecified schizophrenia spectrum
instruction to use the longitudinal perspective on the totality and other psychotic disorder. The
‘‘unspecified schizophrenia of a patient’s symptoms that often will DSM-5 replaces ‘‘psychotic disorder not
spectrum and other not be arrived at easily, if at all, in many otherwise specified’’ with ‘‘unspecified
psychotic disorder’’ clinical practices. schizophrenia spectrum and other psy-
diagnosis in circumstances Other specified schizophrenia and chotic disorder.’’ As in the DSM-IV-TR,
in which the clinician other psychotic disorders. The DSM-5 this diagnosis applies to presentations
chooses not to specify the introduces this subcategory to provide in which functionally disabling or sub-
reason that the criteria are for the diagnosis of four conditions jectively distressing symptoms character-
not met for another involving psychotic symptoms that do istic of schizophrenia spectrum and
schizophrenia spectrum or not meet full criteria for any of the other psychotic disorders predomi-
psychotic disorder.
schizophrenia spectrum disorders but nate but do not meet full criteria for
nonetheless are issues of clinical con- another condition in this category. It also
cern. Below are examples of clinical applies to presentations about which
presentations to which the ‘‘other insufficient information exists to make
specified’’ designation applies. a more specific diagnosis. New in the
& Persistent auditory hallucinations, DSM-5 is the instruction to use the
denoting the persistent presence ‘‘unspecified schizophrenia spectrum
of auditory hallucinations occurring and other psychotic disorder’’ diagnosis
in the absence of other psychotic in circumstances in which the clinician
features. chooses not to specify the reason that
& Delusions with significant the criteria are not met for another
overlapping mood episodes, which schizophrenia spectrum or psychotic
is most appropriately used when a disorder. The practical usefulness of this
patient otherwise meeting criteria diagnosis is not established.
for delusional disorder also
experiences overlapping mood SECONDARY PSYCHOTIC
episodes for a substantial portion DISORDERS
of the delusional disturbance. The DSM-5 notes the common co-
occurrence of psychotic symptoms (ie,
& Attenuated psychosis syndrome,
hallucinations without insight, delusions)
which describes a condition in
in people with neurocognitive disorders
which psychotic-like symptoms
due to Alzheimer disease, Parkinson
are present but are less severe
disease, diffuse Lewy body disease,
and more transient than in
frontotemporal lobar degeneration,
schizophrenia, and for which insight
Huntington disease, prion disease, cereb-
is relatively maintained.
rovascular disease, traumatic brain in-
& Delusional symptoms in a partner jury, HIV, and substances/medications,
of individual with delusional among others. When psychotic symp-
disorder (formerly named shared toms develop in association with
psychotic disorder, also known as cognitive impairments due to these
folie à deux), a rare condition in conditions, the DSM-5 suggests qualify-
which delusions develop in an ing the neurocognitive disorder diag-
individual who is involved in a close nosis with the specifier ‘‘with behavioral
relationship with an individual with disturbance (psychosis)’’ rather than
prominent delusions. The previously offering a concurrent schizophrenia
unaffected partner’s delusions take spectrum disorder diagnosis. When hal-
on the content of the dominant lucinations or delusions predominate
partner’s delusions. the clinical presentation, are not better

explained by another mental disorder, review, Table 8-425,26 summarizes and
are not merely symptoms of a delirium, comments on the psychotic symptoms
are functionally impairing or distress- associated with more than a dozen
ing, and when there is evidence that neurologic conditions and their possible
their occurrence is pathophysiologically anatomic correlates.
linked to either a neurologic or medical
condition or substance abuse or medica- EVALUATION AND MANAGEMENT
tion, then a diagnosis of ‘‘psychotic disor- Useful direction for the evaluation and
der due to another medical condition’’ or management of patients with schizo-
‘‘substance/medication-induced psychotic phrenia spectrum and related disor-
disorder,’’ respectively, may be made. ders,27 as well as other psychiatric and
A detailed review of the clinical neurologic conditions in which psy-
features of psychosis associated with chotic symptoms developed, is found
neurologic conditions is beyond the in the APA Clinical Practice Guidelines
scope of this review, as the literature (psychiatryonline.org/guidelines).28 The
describing the phenomenology, epide- American Academy of Neurology (AAN)
miology, and putative neurobiology practice parameters and evidence-based
of hallucinations and delusions associated guidelines (www.aan.com/Guidelines)
with neurologic disorders has expanded may also be useful for clinicians evaluating
rapidly over the last 2 decades. As a brief and managing patients with secondary
a,b
TABLE 8-4 Examples of Neurologic Conditions Associated With Psychosis
Condition Typical Symptomsc Anatomic Correlations Comment

Adrenoleukodystrophy Delusions including Temporoparietal This is a rare condition
paranoia white matter and few patients with it
Hallucinations experience psychosis;
including auditory nonetheless, psychosis
may be a presenting
feature of this disorder
Alzheimer disease Delusions, including Medial temporal and Increasingly common as
misidentification temporoparietal areas, illness severity and
syndromes, are the basal forebrain cholinergic duration increase
most common symptoms nuclei leading to cortical
Misidentification syndromes
Hallucinations (visual cholinergic deficit
may be an extension of
more than auditory a variety of cognitive
more than olfactory) impairments such as
anosognosia, visuospatial
dysfunction, or memory
impairment, but the quality
of such problems may, in
some cases, become delusional
AntiYN-methyl-D-aspartate Delusions, hallucinations, Frontotemporal Psychosis occurs in the context of
receptor (anti-NMDAR) catatonia hypermetabolism and associated confusional state,
encephalitis26 occipital hypometabolism decreased level of consciousness,
on positron emission catatonia, behavioral changes,
tomography (PET) dyskinesia, and dysautonomia
Continued on page 728

Psychosis
a,b
TABLE 8-4 Examples of Neurologic Conditions Associated With Psychosis Continued from page 727

Cortical or Delusions Temporoparietal cortex Psychosis appears to be
subcortical stroke or subcortical gray matter more common with right
Hallucinations (visual
temporo-parieto-occipital
more than auditory)
junction lesions; however,
including release
left-sided lesions also producing
hallucinations
Wernicke aphasia may be
associated with psychosis
Risk of psychosis following
stroke may be increased by
cerebral atrophy or ischemic
white matter disease
Diffuse Lewy Hallucinations, Anterior frontal and Visual hallucinations may be a
body disease predominantly visual, temporal cortices including prominent early feature, in
but auditory, olfactory, amygdalae, basal forebrain contrast to Alzheimer disease
and tactile may occur cholinergic nuclei leading to (in which such features are late
cortical cholinergic deficit and less common than delusions)
Delusions and Parkinson disease (in which
such features are late or related
to dopaminergic therapy)
Dopaminomimetic Paranoid ideation, Mesolimbic dopaminergic A common problem following
therapy for paranoid delusions target sites administration of these agents
Parkinson disease Visual hallucinations particularly among patients
and Parkinson with relatively advanced disease;
plus syndromes note, however, that psychotic
symptoms may develop as an
intrinsic feature of Parkinson disease
and other Lewy body diseases
Epilepsy Delusions Medial temporal lobe and Psychosis appears to
associated paralimbic and be more common with
Hallucinations
neocortical network elements left-sided foci
Schizophreniform Although psychosis is typically
psychosis an interictal (or subacute
postictal) problem, partial complex
status and absence status may
be mistaken for psychosis
Fahr disease Delusions including Caudate nucleus, especially The relationship between
(idiopathic basal paranoid delusions medial aspect of the head basal ganglia calcification
ganglia calcification) Hallucinations including of this nucleus (either idiopathic or secondary)
auditory (sometimes is contentious; while paranoia
musical) and complex is more common in patients
visual illusions with basal ganglia calcifications,
the presence of calcifications is not
Thought disorder more frequent than expected in
Schizophreniform the population of patients with
psychosis neuropsychiatric disorders

a,b

Frontotemporal Delusions Disproportionate temporal Psychosis in frontotemporal lobar
lobar degeneration lobe atrophy (temporal degeneration is associated with
lobe variant) TDP-43 type B and FUS pathologies,
and higher with genetic mutations
of C9ORF72 and GRN; in some series,
asymmetric right-sided involvement
is associated with delusions
Ischemic white Delusions Frontal white matter of the More common with extensive
matter disease frontal subcortical circuits or and bilateral disease than with
temporoparieto-occipital single lesions
areas involving auditory or
visual pathways
Hexosaminidase Schizophreniform Subcortical gray matter In adult-onset Tay-Sachs disease,
deficiencies (A: psychosis and cerebellum, as well psychosis occurs commonly and
Tay-Sachs disease, as a lesser degree of diffuse may be the presenting feature
or A and B: cerebral involvement of this condition
Sandhoff disease)
Huntington disease Hallucinations Caudate nucleus, especially Psychiatric symptoms may precede
medial aspect of the onset of motor symptoms, but
Delusions
head of this nucleus delusions are more commonly a late
Schizophreniform feature of the disease; delusions
psychosis and hallucinations commonly
co-occur with depression
Limbic encephalitis Delusion, hallucinations Limbic structures Intracellular, onconeuronal
(paraneoplastic or antigens (Hu, CRMP-5, Ri, Yo, Ma2)
autoimmune)26
Intracellular, synaptic
antigens (GAD, amphiphysin)
Cell surface or synaptic
receptors (NMDAR, AMPAR,
GABA-B R, LGI1, Caspr2, GlyR)
Metachromatic Schizophreniform Temporolimbic, frontal, and Psychosis is a rare feature
leukodystrophy psychosis periventricular white matter of this rare disease
Multiple sclerosis Hallucinations Temporoparietal white Tends to be a relatively late
Thought disorder matter, frontal white matter, feature of the disease and is
or subcortical white matter related to increased plaque
Delusions burden in the areas noted
May wax and wane with acute lesion
formation, inflammation, and
resolution in the relevant areas
Neoplasm Schizophreniform Pituitary or suprasellar area, May result from a range of tumors;
psychosis temporal lobe, limbic-paralimbic laterality of tumor location and
regions, diencephalon and tissue onset of psychosis does not appear
surrounding the third as highly correlated as in some of the
ventricle, and frontal lobes other conditions listed here
Neurodevelopmental tumors
(dermoid tumors, epidermoid
tumors, and teratomas) appear
to confer higher risk of psychosis

Psychosis
a,b

Parkinson disease Delusions (paranoid) Cortical atrophy, May be an idiopathic manifestation
basal forebrain of late disease; associated with
Hallucinations including cholinergic atrophy advanced age, dementia or a
formed visual resulting in cortical premorbid history of schizophrenia,
hallucinations cholinergic deficit and relatively high doses of
prodopaminergic medications
In patients with psychosis early in the
disease or with relatively more minor
motor symptoms, consider diffuse Lewy
body disease as an alternative etiology
In these patients, psychotic
symptoms may result from
dopaminomimetic medications
used to treat motor symptoms
Traumatic Schizophreniform Temporal or frontal lobes More commonly associated with
brain injury psychosis Right hemisphere, left-sided temporal lobe injuries;
Delusions, paranoia, including temporoparietal frontal lesions may be less
and visual hallucinations and frontal areas strongly associated with psychosis
due to traumatic brain injury
Psychotic symptoms due to
right hemispheric injury may
be more specific (eg, delusions
alone) and therefore less
‘‘schizophreniform’’
Wilson disease Hallucinations Putamen and possibly also Psychosis may be the presenting
(hepatolenticular Delusions globus pallidus, thalamus, sign of Wilson disease
degeneration) cortex, and intervening
Schizophreniform white matter The association between
psychosis putaminal copper deposition
and psychosis is contentious,
but may be understood as being
similar to the frontal-subcortical
and limbic-subcortical
aberrations of schizophrenia
TDP-43 = TAR DNA binding protein 43 kDa; FUS = fused in sarcoma; CRMP-5 = collapsin response mediator protein-5; Ma2 =
paraneoplastic Ma antigen 2; GAD = glutamate decarboxylase 1; AMPAR = "-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
receptor; GABA-B = +-aminobutyric acid; LGI1 = leucine-rich, glioma inactivated 1; Caspr2 = contactin associated protein-like 2; FlyR =
glycine receptor.
a
Adapted with permission from McAllister TW, Arciniegas DB, Cambridge University Press.25 B 2013 Cambridge University Press.
b
Childhood disorders, and, in particular, mental retardation, pervasive developmental disorder, autism, and other congenital conditions
may also carry an increased risk of psychosis, but are not included here.
c
Schizophreniform psychosis connotes a condition in which hallucinations, delusions, and thought disorder occurs simultaneously and in a
fashion that closely resembles schizophrenia. When delusions, hallucinations, or thought disorder may arise as independent symptoms,
these terms are listed separately.
psychoses.29 More recent guidelines (www.guideline.gov).31 With regard to

on these topics, including those pro- the application of guidelines to clinical
mulgated in 2013 by the Scottish decision making, the Agency for
Intercollegiate Guidelines Network Healthcare Research and Quality recom-
(SIGN),30 are freely available from the mends using guidelines published within
National Guideline Clearinghouse 5 years of the time at which they are

KEY POINTS
used (www.guideline.gov/about/inclusion- of a subacute or chronic neurologic h When evaluating and
criteria.aspx). Thus, clinicians evaluating condition, neuroimaging (CT or MRI) developing treatment
and developing treatment plans for pa- and EEG may be diagnostically informa- plans for patients with
tients with primary or secondary psycho- tive.27 When the history or examination primary or secondary
ses are encouraged to access guidelines findings suggest the presence of either psychoses, clinicians are
in the National Guideline Clearinghouse delirium or another nonpsychiatric encouraged to access
repository and similar resources,32Y34 cause of psychotic symptoms, relevant guidelines in the
to integrate the guidance they offer serum, urine, and CSF studies should National Guideline
with that presented in relevant profes- be performed. Clearinghouse repository
sional society guidelines (especially With regard to evaluation of the and similar resources to
integrate the guidance
when those guidelines are more than psychosis specifically, patient interview
they offer with that
5 years old), and to supplement all and observation using the Brief Psychiat-
presented in relevant
guidelines with findings presented in ric Rating Scale (BPRS)35 or Positive and professional societies’
subsequently published meta-analyses Negative Syndrome Scale (PANSS)36 as guidelines and to
and systematic reviews. well as interview of a knowledgeable supplement all guidelines
informant using one of the several with findings presented
Evaluation versions of the Neuropsychiatric In- in subsequently
Central to all of the presently avail- ventory (NPI)37 (npitest.net), may be published meta-analyses
able guidelines on the evaluation and useful. Evaluation for manic and de- and systematic reviews.
management of patients with psychosis pressive episodes (current and lifetime) h The DSM-5 directs
is the need to identify the cause of psy- anchored to DSM-5 criteria should be clinicians to interpret
chotic symptoms (in order of priority: performed, as strict adherence to these measures using
delirium, including delirium due to sub- criteria is required to distinguish be- normative data for age
stance intoxication/withdrawal; second- tween schizophrenia mood disorders and for socioeconomic
ary psychoses of neurologic, medical, with psychotic features and schizo- status; as few measures
and substance use disorders; mood dis- affective disorder. The DMS-5 encourages provide socioeconomic
statusYadjusted norms,
orders with psychotic features; schizo- use of the Clinician-Rated Dimensions of
normative data for
phrenia spectrum disorders; and other Psychosis Symptom Severity scale to rate
education may serve as
psychotic disorders) through compre- the severity of both manic and depres- the closest proxy for
hensive neuropsychiatric assessment. Pa- sive symptoms associated with schizo- this adjustment.
tients should be involved in psychiatric, phrenia spectrum and other psychotic
neurologic, and general medical history disorders.19 Cognitive and functional as-
taking to the extent that their clinical sessments, to the extent the patient is
status allows, and, whenever possible, able to participate effectively in them,
collateral and corroborative history also guide diagnosis and treatment plan-
should be obtained from family mem- ning. The DSM-5 directs clinicians to
bers or others knowledgeable about interpret measures using normative data
the patient and from medical records. for age and for socioeconomic status; as
Evaluation for potentially causative or few measures provide socioeconomic
contributory medications (eg, prodo- statusYadjusted norms, normative data
paminergic or anticholinergic agents) for education may serve as the closest
and substance use disorders is essen- proxy for this adjustment. The Clinician-
tial.27 Vital signs and body mass index Rated Dimensions of Psychosis Symp-
measurements, physical, neurologic, and tom Severity scale rates the severity of
mental status examinations, and evalua- cognitive impairment in increments of
tion for substance use should be standard deviations (SD) below the
performed routinely.27 When the history mean for age and socioeconomic status
or examination findings suggest that (0: no impairment; 1: equivocal, between
psychotic symptoms may be the product 0 and 0.5 SD; 2: mild, j0.5 to j1 SD; 3:

Psychosis
KEY POINTS
h Systematic reviews moderate, j1 to j2 SD; 4: severe, less for psychosis that persists despite
and meta-analyses than j2 SD).19 Neuropsychological and stepwise reductions in prodopa-
demonstrate that typical occupational therapy consultations con- minergic medications),52 and limited
(first-generation) and tribute usefully to cognitive and function- for most other neurologic conditions.
atypical (second-generation) al assessments and should be performed While acknowledging the limits of the
antipsychotics are similar when feasible. evidence base for the treatment of
with respect to their psychosis associated with neuro-
beneficial effects on Treatment logic conditions, individual patients
the frequency and Systematic reviews and meta-analyses experiencing secondary psychosis may
severity of hallucinations demonstrate that typical (first-genera- benefit, nonetheless, from judicious
and delusions.
tion) and atypical (second-generation) administration of antipsychotic medica-
h Meta-analyses suggest antipsychotics are similar with respect tions, especially when other medications
that repetitive transcranial to their beneficial effects on the and nonpharmacologic interventions do
magnetic stimulation over frequency and severity of hallucina- not provide adequate relief from psy-
the left temporoparietal
tions and delusions.38,39 Clozapine is chotic symptoms.53,54
region (in the area of
particularly effective in treatment- Whether used to treat primary or
T3-P3 in the International
10-20 System of
resistant populations and reduces sui- secondary psychoses, antipsychotic
Electrode Placement) is an cide risk.39,40 Among patients with treatmentYrelated pretreatment evalua-
effective treatment for schizophrenia, atypical antipsychotics tion of weight; metabolic status; cardiac,
the auditory verbal improve cognition41 and life satisfac- sexual, and neurologic (especially mo-
hallucinations that are tion42 and may modestly contribute to tor) function; and hematologic health
refractory to treatment improvements in functional status.43 as well as periodic monitoring for changes
with antipsychotics. Meta-analyses suggest that repetitive in these areas during treatment is re-
h Acetylcholinesterase transcranial magnetic stimulation (rTMS) commended.27 The specific risks and
inhibitors, adjunctively or over the left temporoparietal region (in parameters requiring monitoring differ
alternatively, may reduce the area of T3-P3 in the International between antipsychotics.38,55 Readers are
psychosis in patients with 10-20 System of Electrode Placement) encouraged to review the manufacturer’s
Alzheimer disease, is an effective treatment for the auditory product information for any specific medi-
Parkinson disease verbal hallucinations that are refractory cation prescribed as well as the recom-
dementia, diffuse Lewy to treatment with antipsychotics.44 How- mendations on antipsychotic medication
body disease, and, to a
ever, rTMS does not appear to be an safety monitoring offered in the report
lesser extent, schizophrenia
effective treatment for other symptoms of the Mount Sinai Conference on the
and related conditions.
of schizophrenia.45 Pharmacotherapy of Schizophrenia,56
h Evidence of benefit Acetylcholinesterase inhibitors, ad- and by the 2013 Scottish Intercolle-
from antipsychotic
junctively or alternatively, may reduce giate Guidelines Network (SIGN).30
treatment of psychotic
psychosis in patients with Alzheimer Among elderly patients with dementia
symptoms is mixed in
patients with psychosis
disease,46 Parkinson disease demen- and psychosis, the benefits of antipsy-
associated with Alzheimer tia,47 diffuse Lewy body disease,48 chotic treatment must be balanced
disease, modest in and, to a lesser extent, schizophrenia against the risk of serious adverse
Parkinson disease (for which and related conditions.49 However, events. Informed consent requires ac-
clozapine and quetiapine antipsychotics remain commonly used knowledgement of the 1.5 to 1.8 times
are the preferred agents to treat psychotic symptoms associated increased mortality associated with anti-
for psychosis that persists with neurologic disorders. Evidence of psychotic treatment in elderly patients
despite stepwise benefit from antipsychotic treatment of with dementia, the risk of which appears
reductions in psychotic symptoms is mixed in pa- similar for both the typical and atypical
prodopaminergic tients with psychosis associated with antipsychotics54 (www.fda.gov/Drugs/
medications), and limited
Alzheimer disease,50,51 modest in DrugSafety/PostmarketDrugSafety
for most other
Parkinson disease (for which clozapine InformationforPatientsandProviders/
neurologic conditions.
and quetiapine are the preferred agents ucm124830.htm).57

KEY POINTS
Psychosocial interventions also are those used to study psychosis associated h While acknowledging
essential elements of the treatment for with other neurologic conditions. the limits of the
patients with primary and secondary Comprehensive neuropsychiatric as- evidence base for the
psychoses, especially during the stable sessment is a prerequisite to the treat- treatment of psychosis
phase of illness.27 These interventions ment of psychotic symptoms, and it associated with
include patient and family education, prioritizes identification of medical, neurologic conditions,
cognitive behaviorally oriented therapies, substance-related, and neurologic individual patients
family interventions, assertive community causes of psychosis over their attribu- experiencing secondary
treatment, social skills training, and tion to psychiatric conditions. The use psychosis may benefit,
supported employment. Additional non- of structured clinical interviews of pa- nonetheless, from
judicious administration
pharmacologic interventions that may tients and knowledgeable informants to
of antipsychotic
reduce contributors to psychotic symp- clarify the character of psychosis and
medications, especially
toms, especially among patients with associated symptoms is recommended when other medications
dementia-associated psychosis, include in guidelines promulgated by the APA and nonpharmacologic
improving sensory function (eg, hearing and similar professional societies. Data interventions do not
aids, eyeglasses), identifying environ- yielded by such interviews establishes a provide adequate relief
mental antecedents to perceptual or cog- baseline for monitoring disease pro- from psychotic symptoms.
nitive misinterpretations, and stimulus gression and against which the effects h Among elderly patients
controls that circumvent misinterpreta- of treatment can be compared. Those with dementia and
tions. Caregiver and family support treatments include pharmacotherapies psychosis, the benefits
also should be provided concurrently and psychosocial interventions, the of antipsychotic
with patient-oriented therapies.58 specific elements of which should fol- treatment must be
low up-to-date guidelines and findings balanced against the
CONCLUSION presented in published meta-analyses risk of serious adverse
Psychosis is a common symptom of and systematic reviews. events and discussion of
many psychiatric, neurodevelopmental, both must be included
in the informed consent
neurologic, and medical conditions and ACKNOWLEDGMENTS
process prior to initiating
is an important target of evaluation and This work was supported in part by the treatment with
treatment in neurologic and psychiatric NIH grant NIMH R01 MH081920-02 antipsychotic medications.
practice. The DSM-5 classification of and the Beth K. and Stuart Yudofsky h Readers are encouraged
and criteria for primary psychotic dis- Chair in Brain Injury Medicine at the to review the manufacturer’s
orders emphasize that these conditions Baylor College of Medicine. product information for
occur along a spectrum, with schizoid any specific medication
(personality) disorder and schizophre- prescribed as well as the
USEFUL WEBSITES
nia defining its mild and severe ends, recommendations on
respectively. Psychosis is also identified American Psychiatric Association. The antipsychotic medication
as only one of several dimensions of American Psychiatric Association (APA) safety monitoring offered
neuropsychiatric disturbance in these has developed the Clinician-Rated Di- in the report of the
disorders, with others encompassing mensions of Psychosis Symptom Sever- Mount Sinai Conference
abnormal psychomotor behaviors, neg- ity scale, an eight-item measure that on the Pharmacotherapy
ative symptoms, cognitive impair- rates the severity of each symptom that of Schizophrenia
ments, and emotional disturbances. defines the schizophrenia spectrum and by the 2013
disorders as well as co-occurring cogni- Scottish Intercollegiate
This dimensional approach regards
tive, depressive, and manic symptoms Guidelines Network.
hallucinations and delusions as arising
from neural systems subserving percep- during the week prior to assessment.
tion and information processing, thereby www.psychiatry.org/File%20Library/
aligning the neurobiological framework Practice/DSM/DSM-5/ClinicianRated
used to describe and study such symp- DimensionsOfPsychosisSymptom
toms in primary psychotic disorders with Severity.pdf

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KEY POINT
The APA offers the Clinician-Rated Dimen- 2. Rabinowitz J, Berardo CG, Bugarski-Kirola D,
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also are essential elements sions of Psychosis Symptom Severity scale and prominent negative symptoms and
of the treatment for without cost for clinical use, but requests functional health, well-being, healthcare-related
patients with primary and that clinicians and researchers provide data quality of life and family burden: a CATIE
analysis. Schizophr Res 2013;150(2Y3):339Y342.
secondary psychoses, on the instrument’s usefulness by submit- doi:10.1016/j.schres.2013.07.014.
especially during the ting feedback at the website below.
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stable phase of illness. dsm5.org/Pages/Feedback-Form.aspx Garre-Olmo J. Psychosis of Alzheimer disease:
prevalence, incidence, persistence, risk
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that provide evidence-based recom- 2013;21(11):1135Y1143. doi:10.1016/
mendations for the assessment and j.jagp.2013.01.051.
treatment of psychiatric disorders. 4. Forsaa EB, Larsen JP, Wentzel-Larsen T, et al.
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psychiatryonline.org/guidelines psychosis in Parkinson disease. Arch Neurol
2010;67(8):996Y1001. doi:10.1001/archneurol.
Agency for Healthcare Research and 2010.166.
Quality. The Agency for Healthcare 5. American Psychiatric Association DSM-5
Research and Quality maintains the Na- Task Force. Diagnostic and statistical manual
tional Guideline Clearinghouse website, a of mental disorders, 5th Edition (DSM-5).
Washington, DC: American Psychiatric
public resource for evidence-based clini- Association, 2013.
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Review Article

Continuum (Minneap Minn) 2015;21(3):715–736.

INTRODUCTION sional misidentification syndromes are

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TABLE 8-1 Disturbances of Perception and Experience in the Differential

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Schneider9 described specific types withdrawal and thought insertion. The

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TABLE 8-3 Examples of Delusional Misidentification and Other h The psychosis

with obsessive-compulsive disorder article. Readers are encouraged to

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Condition Typical Symptomsc Anatomic Correlations Comment

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Condition Typical Symptomsc Anatomic Correlations Comment

Continued on page 729

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Condition Typical Symptomsc Anatomic Correlations Comment

psychoses.29 More recent guidelines (www.guideline.gov).31 With regard to

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phrenia spectrum disorders as well as 12. Edelstyn NM, Oyebode F. A review of

734 www.ContinuumJournal.com June 2015

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39. Foussias G, Remington G. Antipsychotics and Database Syst Rev 2012;1:CD007967.

736 www.ContinuumJournal.com June 2015

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