A Review On Cognitive Impairments in Dep

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Journal of Affective Disorders 106 (2008) 1 – 27

www.elsevier.com/locate/jad

Review
A review on cognitive impairments in depressive and anxiety
disorders with a focus on young adults
Anu E. Castaneda a,b,⁎, Annamari Tuulio-Henriksson a,b , Mauri Marttunen a,c ,
Jaana Suvisaari a,d , Jouko Lönnqvist a,e
a
Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland
b
Department of Psychology, University of Helsinki, Helsinki, Finland
c
Department of Psychiatry, University of Kuopio, and Kuopio University Hospital, Kuopio, Finland
d
Department of Social Psychiatry, Tampere School of Public Health, University of Tampere, Tampere, Finland
e
Department of Psychiatry, University of Helsinki, Helsinki, Finland
Received 23 February 2007; received in revised form 13 June 2007; accepted 13 June 2007
Available online 20 August 2007

Abstract

Background: There is growing evidence for cognitive dysfunction in depressive and anxiety disorders. Nevertheless, the
neuropsychological profile of young adult patients has not received much systematic investigation. The following paper reviews
the existing literature on cognitive impairments in depressive and anxiety disorders particularly among young adults. Additionally,
the focus of young adult age group and the effect of confounding variables on study results are discussed.
Methods: Electronic database searches were conducted to identify research articles focusing on cognitive impairments in depressive
or anxiety disorders among young adults published in English during years 1990–2006.
Results: Cognitive impairments are common in young adults with major depression and anxiety disorders, although their nature
remains partly unclear. Accordingly, executive dysfunction is evident in major depression, but other more specific deficits appear to
depend essentially on disorder characteristics. The profile of cognitive dysfunction seems to depend on anxiety disorder subtype,
but at least obsessive–compulsive disorder is associated with deficits in executive functioning and visual memory. The conflicting
results may be explained by heterogeneity within study participants, such as illness status, comorbid mental disorders, and
medication, and other methodological issues, including inadequate matching of study groups and varying testing procedures.
Limitations: The study is a comprehensive review, but not a formal meta-analysis, due to methodological heterogeneity.
Conclusions: Cognitive impairments are common in major depression and anxiety disorders. However, more research is needed to
confirm and widen these findings, and to expand the knowledge into clinical practice. Controlling of confounding variables in
future studies is highly recommended.
© 2007 Elsevier B.V. All rights reserved.

Keywords: Depression; Anxiety; Neuropsychology; Young adult; Cognitive impairment

⁎ Corresponding author. National Public Health Institute, Department of Mental Health and Alcohol Research, Mannerheimintie 166, 00300 Helsinki,
Finland. Tel.: +358 9 4744 8651; fax: +358 9 4744 8478.
E-mail address: anu.castaneda@ktl.fi (A.E. Castaneda).

0165-0327/$ - see front matter © 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jad.2007.06.006
2 A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.1. Rationale . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.2. Neuropsychological examination in the psychiatric context . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
3. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
3.1. Which cognitive domains are impaired in depressive disorders? . . . . . . . . . . . . . . . . . . . . . . . . . 17
3.1.1. Effects of the subtype of major depressive disorder . . . . . . . . . . . . . . . . . . . . . . . . . . 22
3.1.2. Do cognitive deficits persist after remission of depression? . . . . . . . . . . . . . . . . . . . . . . 22
3.2. Which cognitive domains are impaired in anxiety disorders? . . . . . . . . . . . . . . . . . . . . . . . . . . 22
3.2.1. Deficits in panic disorder, phobias and generalized anxiety disorder . . . . . . . . . . . . . . . . . . 22
3.2.2. Deficits in obsessive–compulsive disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
3.2.3. Deficits in post-traumatic stress disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
4. Discussion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
4.1. Methodological considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
4.2. Conclusions and suggestions for future research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
Role of funding source . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

1. Introduction Gil, 2002) and 52–61% for lifetime (Kessler et al., 2005;
Turner and Gil, 2002) have been reported for mental
The emergence of mental disorders – and the disorders in general, with anxiety disorders, mood
cognitive impairments related to them – in young disorders, and substance use disorders being the most
adulthood may associate with serious and long-lasting prevalent ones. Women are more likely to be diagnosed
psychosocial difficulties. Young adulthood is a key with depressive and anxiety disorders, and men with
period for both prevention and treatment of mental substance use disorders (Aalto-Setälä et al., 2001;
disorders to avoid chronicity of the symptoms (Kessler Feehan et al., 1994; Kessler et al., 2005; Newman
et al., 2005; Newman et al., 1996). This paper reviews et al., 1996; Regier et al., 1993; Turner and Gil, 2002).
the existing literature on cognitive deficits related to Table 1 summarizes the prevalence rates of specific
depressive and anxiety disorders among young adults depressive and anxiety disorders observed in epidemi-
and discusses the impact of confounding variables on ological studies of young adult cohorts in industrial
measurement of neuropsychological functioning. countries. The high prevalence estimates indicate that
depressive and anxiety disorders are major public health
1.1. Rationale problems for this age group.
Only about one third of young adults with mental
Young adulthood is a risk period for the emergence of disorders seek professional help (Aalto-Setälä et al.,
many psychiatric disorders (Kessler et al., 2005; Kim- 2002), and this under-treatment is evident also for
Cohen et al., 2003). The incidence of mental disorders major depression in young adulthood (Haarasilta et al.,
increases from childhood through mid-adolescence and 2003). It has been proposed that the phenomenology
peaks in late-adolescence and young adulthood (New- and nature of depression changes with age (Brodaty
man et al., 1996). The prevalence estimates of mental et al., 2005). Moreover, it has been suggested that early-
disorders are relatively consistent in young adult cohorts onset depression represents a more serious form of the
(in epidemiological studies, defined usually between 18 disorder: It leaves more psychosocial scars (Rohde
and 35 years of age) in industrial countries, using DSM- et al., 1994) and is associated with a greater number of
criteria (APA, 1994): Prevalence estimates of 17–24% comorbid mental disorders (Rohde et al., 1991) than
for 1 month (Aalto-Setälä et al., 2001; Regier et al., late-onset depression. Early- vs. late-onset anxiety
1993), 38–48% for 1 year (Feehan et al., 1994; Kim- disorders have also been hypothesized to be distinct
Cohen et al., 2003; Newman et al., 1996; Turner and forms of the disorders (Hemmings et al., 2004; Tükel
A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27 3

Table 1
Prevalence rates of depressive and anxiety disorders among young adult populations in 1-month, 1-year, and lifetime time frames
DSM-diagnosis 1-month 12-month Lifetime
a, b, c d, e, b, f, g, h, i
Major depressive disorder 2.2–7.7 7.2–16.8 13.5–21.2 b, i, j
Dysthymia 2.2–3.9 a, c 0.1–3.9 d, e, f, h, i 0.5–1.7 i, j
Minor depressive disorder 0.7–1.6 b 1.4–8.2 d, b 7.6–10.3 b
Any depressive disorder 10.8 a 17.4–17.9 d, f N/A
Panic disorder 0.4–1.2 a, c 0.6–3.9 e, f, h, i 2.1–4.4 i, j
Specific phobia N/A 6.1–8.4 e, f, h 13.3 j
Social phobia 1.2 a 1.5–11.1 e, f, h, i 2.5–13.6 k, i, j
Agoraphobia N/A 3.5–4.0 e, f, h 1.1 j
Generalized anxiety disorder 2.3 a 0.9–5.5 e, f, h, i 1.4–6.0 i, l, j
Obsessive–compulsive disorder 1.8 c 2.4–7.1 e, f, h 2.0j
Post-traumatic stress disorder 0.2 a 4.1–8.4 f, i 6.3–11.7 i, j
Anxiety disorder NOS 2.1 a N/A N/A
Any anxiety disorder 6.9–7.7 a, c 26.1 f 15.2–30.2 i, j
a
Aalto-Setälä et al. (2001).
b
Kessler and Walters (1998).
c
Regier et al. (1993).
d
Aalto-Setälä et al. (2002).
e
Feehan et al. (1994).
f
Kim-Cohen et al. (2003).
g
Lindeman et al. (2000).
h
Newman et al. (1996).
i
Turner and Gil (2002).
j
Kessler et al. (2005).
k
Schneier et al. (1992).
l
Wittchen (2002).

et al., 2005). Moreover, having major depressive or as well as for research purposes. In addition, it may be
anxiety disorder in young adulthood may double the possible to differentiate which deficits are illness state-
risk for later substance abuse or dependence (Chilcoat dependent and which are more fundamental trait
and Breslau, 1998; Christie et al., 1988). Having abnormalities or vulnerability markers of certain
depression during early parenting triples the risk for disorders. These findings could have considerable
the offspring to develop an anxiety disorder, major implications for prevention and clinical management
depression or substance dependence (Weissman et al., of these disorders, as cognitive deficits are indeed
2006). These findings implicate that depression and significant factors in affecting individual's ability to
anxiety may impact younger patients more severely function socially and occupationally in everyday life.
than older. Studies of psychiatric disorder-related cognitive
impairments usually report use of well-known stan-
1.2. Neuropsychological examination in the psychiatric dard neuropsychological tests. Among the most used
context test batteries are the Wechsler Adult Intelligence Scale
(WAIS; Wechsler, 1997) and the Wide Range
In the context of psychiatric research, neuropsycho- Achievement Test (WRAT; Jastak and Wilkinson,
logical examination has been increasingly used in 1984), which are used to estimate individual's general
assessing the cognitive dysfunctions that are among intelligence, and the Wechsler Memory Scale (WMS;
the core features of several mental disorders (for a re- Wechsler, 1987), which consists of subtests measuring
view, see Keefe, 1995). In a clinical setting, neuropsy- several subfunctions of memory performance. Also,
chological examination comprises an interview of the the Cambridge Neuropsychological Test Automated
patient's background and present situation, a behavioral Battery (CANTAB; Robbins et al., 1994) and the
observation, and an administration of the neuropsycho- Luria-Nebraska Neuropsychological Battery (LNNB;
logical tests (see Lezak et al., 2004). Information Golden et al., 1985) are among the most used test
obtained from this examination can be used in the batteries to evaluate various components of cognition.
patient's treatment planning, evaluating the efficacy of For measuring verbal memory and learning, the
the treatment, in differential diagnosis in certain cases, California Verbal Learning Test (CVLT; Delis et al.,
4
Table 2
Studies exploring cognitive deficits among young adults with major depressive disorder

Study Sample Age Neuropsychological Main findings Controlled and uncontrolled factors c
(n) a mean test battery b
Diagnostic Patient status Group matching Medication and Comorbid mental Other exclusion Disorder length Disorder severity,
(sd)
criteria treatments disorders criteria phase, and subtype

Basso and NPMDD 31.9 CVLT, FAS, GPT, PMDD group performed DSM-III-R Inpatients No differences in Most were medicated. No group differences No history of No group PMDD group scored
Bornstein (46) (7.3) JLO, TMT, WAIS-R poorer than NPMDD age, gender, PMDD group had in number of comorbid seizure disorders, differences in higher than NPMDD
(1999) PMDD 31.4 (Block design, group in tests of education, race, higher benzotropine disorders or previous recent loss of years since group in Paranoia
(34) (7.3) Vocabulary), verbal abilities (CVLT, prior educational equivalent dosage and or current alcohol or consciousness illness onset (7 (71 vs. 84),
(max 45 WMS_R (Digit FAS, Logical Memory, difficulties, or higher mean dopamine drug abuse. MDD was N 5 min, or other vs. 7 years). Schizophrenia (78
years) Span, Logical Vocabulary), non-verbal presence of blocking rating than a primary diagnosis. neurological vs. 90), and Mania
memory, Visual reasoning (Block Design, metabolic illness. NPMDD group, but disorders. (52 vs. 61). No

A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27


Memory Span, JLO, TMT: B, Visual neither correlated with group differences in
Visual Reproduction) Reproduction), attentional test performance. No depression severity
capacity (Digit Span: other group differences (MMPI-2: Depression:
Forward, Visual Span: in proportion of 82 vs. 84), or other
Backward), and dexterity medicated patients or parts of MMPI-2.
(GPT). Groups did not other medication.
differ in other attentional
tests (Digit Span:
Backward, TMT: A,
Visual Span: Forward).
Depression severity
(MMPI-2: Depression)
correlated negatively with
Visual Reproduction.
Egeland et al. MDD 35.1 CCAP, Dichotic MDD group performed DSM-IV Patient No differences in Most patients were No present alcohol No history of MDD patients 5 MDD patients had
(2003) (50) (8.7) listening test, poorer than CTRL group (SCID) recruitment age, gender, medicated. No or substance abuse. head trauma, had recurrent psychotic symptoms.
SCZ 31.5 DS-CPT (version 7.1), in tests of executive from clinics, education, or differences between MDD patients had neurological MDD. MDD At the time of testing,
(53) (8.4) SCWIT functions (SCWIT) and 31 outpatients concentration medicated and no history of disorder, group had MDD group scored
CTRL 32.9 reaction time and attention and 72 (VSVT). SCZ non-medicated patients hypomanic episodes. developmental longer illness ≥ 21 on MADRS and
(50) (9.0) IQ: WAIS-R (CCAP, DS-CPT). MDD inpatients. group had lower in test performance. CTRL participants dysfunction, or duration than ≥ 18 on HDRS, and
Range: (Picture Completion, group showed reduced IQ than other reported no previous medical illness SCZ group (11 scored higher on
19–51 Similarities) vigilance (CCAP) when groups. or present psychiatric likely to affect vs. 7 years). depression severity
compared to SCZ group; disorders and had nervous system (MADRS: 29 vs. 13;
otherwise SCZ group was never received function. Patients HDRS: 22 vs. 11) and
more impaired than MDD psychiatric treatment. had normal vision lower on schizophrenia
group. Depression severity and hearing. (PANSS: 58 vs. 76)
(HDRS) correlated and general symptom
negatively with vigilance severity (GAF: 46 vs.
(CCAP) in MDD group. 40; BPRS: 44 vs. 52)
Group differences than SCZ group.
remained after symptom
severity (GAF, BPRS)
was covariated in
analysis.
Fossati et al. NPMDD 36.3 Cognitive Estimate, NPMDD group performed DSM-IV Patients were No differences in Most NPMDD Patients had no No neurological N/A MADRS averaged 24
(1999) (20) (9.0) DCST, Grober poorer than CTRL group tested at age, gender, patients and all concurrent diagnoses or general medical and SRRS 22 in
SCZ 33.1 and Buschke's in some tests of executive admission education, or IQ. SCZ patients on Axis II or disorders likely to NPMDD group, in
(14) (7.9) Procedure, Verbal functioning (Category to a hospital. were medicated. psychoactive substance affect cognition. which all NPMDD
CTRL 30.0 fluency, Visual Verbal Fluency, DCST, NPMDD patients use. SCZ patients had patients scored N 20.
(20) (7.2) span, WAIS (Digit Digit Span, Visual Span: had not received no schizoaffective
span), WCST Backward), but when antidepressant disorder and were not
Range: (modified version) medication was covariated medication for depressed at the time
18–45 in analysis, differences in N 2 weeks before of testing. CTRL
IQ: Binois-Pichot Digit Span and Visual Span testing. SCZ patients participants showed no
(Vocabulary) did not remain significant. received higher doses evidence of psychiatric
NPMDD and CTRL groups of antipsychotics than disorders.
did not differ in other tests, NPMDD patients.
e.g., in verbal learning CTRL participants
(Grober and Buschke's received no medication
Procedure). Symptom that could influence
severity (MADRS, SRRS) cognition. Patients had
was not correlated with not received ECT
test performance in within 1 year.
NPMDD group.

A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27


Hill et al. NPMDD 29.0 Cancellation Test, MDD groups performed DSM-III-R PMDD and No differences PMDD and SCH Patients had no No history of N/A SCH group scored
(2004) (14) (10.1) COWAT, CVLT, poorer than CTRL group in or DSM-IV SCH group in age, gender, groups were free of substance dependence neurological higher on symptom
PMDD 25.2 FTT, GPT, JLO, attentive tests (Cancellation (SCID) recruitment IQ, or parental antidepressant or abuse within 6 disorders, head severity (BPRS: 36 vs.
(20) (8.8) SCWIT, TMT, Test, Digit Span, Digit after economic status medication for N 6 months or other injury with loss 44 vs. 51) than MDD
SCH 28.6 WAIS-R (Digit Symbol, TMT: A). PMDD hospitalization (HISP). weeks on average. psychiatric disorders. of consciousness, groups, and higher in
(86) (9.6) Span, Digit Symbol, group performed poorer for a first NPMDD group was CTRL group had no or other medical disorder severity than
CTRL 29.8 Block Design), than CTRL group in tests of lifetime anti-psychotic naïve Axis I disorders (SCID) disorders likely PMDD group, which
(81) (10.6) WCST, WMS-III executive functioning episode and free of or history of psychiatric to affect brain scored higher than
(Visual Reproduction) (COWAT, SCWIT, TMT: B, of psychosis. antidepressant treatment. function. NPMDD group (GAF:
WCST) and motor skills medication for 47 vs. 37 vs. 32). SCH
IQ: WRAT (Reading) (FTT, GPT). PMDD group ≥ 3 weeks before group had more
performed poorer than enrollment. Patients negative symptoms
NPMDD and CTRL groups had not received recent (SANS: 10 vs. 12 vs.
in a test of visual memory or current ECT or 14) than PMDD group,
(Visual Reproduction) and treatment with and PMDD group had
poorer than NPMDD group anticonvulsants or more positive
in tests of visuo-spatial benzodiazepines. symptoms (SAPS: 1 vs.
perception (Block Design, 5 vs. 9) than NPMDD
JLO). MDD groups and group. No patient
CTRL group did not differ group differences in
in verbal memory (CVLT). depression severity
Symptom severity (BPRS) (HDRS: 25 vs. 26
correlated negatively with vs. 21).
general test performance in
PMDD group. BPRS and
SANS were covariated
in analysis.
Mahurin et al. MDD 36.0 TMT Patient groups performed DSM-IV Patients were No differences At the time of testing Patients had no other No history of Duration of HDRS averaged 31 in
(2006) (30) (7.1) poorer than CTRL group in inpatients. in age or MDD patients were Axis I disorders or head trauma with illness averaged MDD group. Length
SCZ 32.9 a test of attentive and MDD group education. un-medicated, and SCZ substance abuse. CTRL accompanying 13 years in of hospitalization
(30) (6.2) executive functioning: they recruitment Gender was patients were receiving group was screened loss of SCZ group. averaged 18 weeks in
CTRL 31.0 were slower in both test from a covariated in neuroleptics. for medical, psychiatric, consciousness, MDD group and
(30) (8.6) parts, and SCZ group hospital's analysis. and cognitive positive findings 14 weeks in SCZ
was yet slower than MDD psychiatric impairment (clinical on brain scan, group at time of
group. SCZ group made unit. interview, MME). neurological testing.
more errors than CTRL diseases, or
group. sensory or motor
impairment that
would interfere
with test
performance.

(continued on next page)

5
6
Table 2 (continued)

Study Sample Age Neuropsychological Main findings Controlled and uncontrolled factors c
(n) a mean test battery b
Diagnostic Patient status Group matching Medication and Comorbid mental Other exclusion Disorder length Disorder severity,
(sd)
criteria treatments disorders criteria phase, and subtype

Merriam et al. MDD 35.5 WCST Patient groups performed DSM-IV N/A No difference in MDD group was No history of substance No history of N/A 5 MDD patients had
(1999) (79) (8.1) (computerized poorer than CTRL group in (SCID) education. MDD un-medicated for dependence and no neurological psychotic features. No
SCH 28.1 version) a test of executive functions, group was older ≥1 month. substance abuse within disorders or head patient group
(47) (8.5) and SCH group performed and SCH group SCH group had never 6 months preceding injury. differences in
CTRL 26.1 yet poorer than MDD group. had lower IQ received antipsychotic testing. depressive symptoms
(61) (7.7) Depression severity (HDRS) (information of medication. Participants (HDRS: 17 vs. 16),
Range: correlated negatively with the measure not had no lifetime history which were assessed

A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27


18–50 most of the WCST indices provided) than of ECT. within 1 week of
in MDD group. other groups. testing. SCH group
Age and IQ scored higher in
were covariated symptom severity
in analysis. (GAF: 57 vs. 30) than
MDD group.
Smith et al. MDD 21.3 BSAT, CVLT, MDD group performed DSM-IV Patient No differences Most patients were N/A N/A Patients had Patients had MDD in
(2006) (42) (1.9) SCWIT, TMT poorer than CTRL group (SCID) recruitment in age, gender, medicated. No patient recurrent MDD. remission for ≥1 month
BPMDD 22.4 in tests of attentive and and from a education, IQ, or group differences in No patient (HDRS with a cut of
(21) (2.8) IQ: NART, WAIS-R executive functions special psychiatric rates of past medication. group score ≤ 8). No group
CTRL 22.2 (Block Design) (TMT) and verbal criteria to clinic. history of CTRL group was differences in differences in
(33) (2.3) short term memory assess deliberate un-medicated. age at onset (15 depression severity
(CVLT). BPMDD bipolar self-harm. vs. 16 years) or (HDRS: 3 vs. 3 vs. 2).
group performed features number of BPMDD group had no
poorer than CTRL depressive history of psychotic
group in verbal episodes features.
memory (CVLT) and (4 vs. 5).
attentive and executive
functioning (BSAT,
SCWIT, TMT).
BPMDD group
performed poorer than
MDD group in tests of
verbal memory and
learning (CVLT)
and executive
functioning (TMT: B).
Stordal et al. NPMDD 35.6 CCAP, COWAT, After controlling the use DSM-IV 28 patients No differences in 3 patients were Patients had no alcohol No neurological Patients had Patients scored a min.
(2004) (45) (8.4) PASAT, SCWIT, TL, of medication and (SCID) were age, gender, un-medicated. The use or drug abuse as a or somatic recurrent MDD. of 18 in HDRS and
CTRL 32.9 VSVT, WAIS-R reaction time (CCAP), inpatients. education, or IQ. of benzodiazepines primary diagnosis. disorders likely MADRS. HDRS
(50) (9.0) (Digit Span which differed and antipsychotic CTRL participants had to affect cognition averaged 22, MADRS
Range: Backward), WCST between groups, medication was no psychiatric illness or lack of 29, GAF 46 and BPRS
19–51 NPMDD group controlled in analysis. known to influence sufficient visual 43 in NPMDD
IQ: WAIS-R (Picture performed poorer than Patients had not cognition or a history and auditory group.
Completion, CTRL group in most received recent ECT. of substance abuse. capabilities to
Similarities) tests of executive perform the tests.
functioning (COWAT,
Digit Span Backward,
PASAT, SCWIT, WCST
(Failure to maintain set)).
Depression severity
(HDRS, MDRS) or
number of depressive
episodes was not correlated
with test performance.
Wang et al. Current 31.0 CVLT No differences in verbal DSM Out-patients No difference in Patients were mainly CTRL participants had N/A Patients were Groups differed in
(2006) NPMDD (10.4) memory and learning and gender. Groups non-medicated. Results no lifetime depression. either currently depression severity
(57) functions appeared undergraduate differed in age. remained after Patients did not have vs. previously (BDI: 16 vs. 6 vs. 1).
Previous 27.0 neither between groups, university excluding the bipolar disorder depressed, or
MDD (8.2) nor between first-episode students. medicated ones from or dysthymia. had single
(42) and recurrent analysis. episode vs.
CTRL 26.9 patients. recurrent
(46) (9.5) depression.
a
BPMDD=Major depressive disorder with bipolar features, CTRL=Control, MDD=Major depressive disorder, NPMDD=Non-psychotic major depressive disorder, PMDD=Psychotic major depressive disorder; SCH=Schizophrenia spectrum disorder,
SCZ=Schizophrenia.
b

A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27


BSAT=Brixton Spatial Anticipation Test, CCAP=California Computerized Assessment Package, COWAT=Controlled Oral Word Association Test, CVLT=California Verbal Learning Test, DCST=Delis Card Sorting Test, DS-CPT=Degraded Stimulus
Continuous Performance Test, FAS=F-A-S Test of Verbal Fluency, FTT=Finger Tapping Test, GPT=Grooved Pegboard Test, IQ=Intelligence quotient, JLO=Judgment of Line Orientation Test, NART=National Adult Reading Test, PASAT=Paced Auditory-Serial
Addition Test, SCWIT=Stroop Color Word Interference Test, TL=Tower of London, TMT=Trail Making Test, VSVT=Victoria Symptom Validity Test, WAIS=Wechsler Adult Intelligence Scale, WCST=Wisconsin Card Sorting Test, WMS=Wechsler Memory Scale,
WRAT=Wide Range Achievement Test.
c
BDI=Beck Depression Inventory, BPRS=Brief Psychiatric Rating Scale, DSM=Diagnostic and Statistical Manual of Mental Disorders, ECT=Electroconvulsive therapy, GAF=Global Assessment of Functioning Scale, HDRS=Hamilton Depression Rating Scale,
HISP=Hollingshead Index of Social Position, MADRS=Montgomery–Åsberg Depression Rating Scale, MME=Mini-Mental Examination, MMPI=Minnesota Multiphasic Personality Inventory, PANSS=Positive and Negative Syndrome Scale for Schizophrenia,
SANS=Scale for the Assessment of Negative Symptoms, SAPS=Scale for the Assessment of Positive Symptoms, SCID=Structured Clinical Interview for DSM, SRRS=Salpétrière Retardation Rating Scale.

7
8
Table 3
Studies exploring cognitive deficits among young adults with panic disorder and social phobia

Study Sample Age Neuropsychological Main findings Controlled and uncontrolled factors c
(n) a mean test battery b
Diagnostic Patient status Group matching Medication and Comorbid mental Other exclusion Disorder Disorder severity,
(sd)
criteria treatments disorders criteria length phase, and subtype

Asmundson PD 35.4 BVRT-F, CVLT, Patient groups performed DSM-III-R Patient No differences in age 1 PD patient received low No evidence of current No significant N/A CTRL group
et al. (18) (9.6) DCT, TMT poorer than CTRL group (a modified recruitment or education. CTRL doses of benzodiazepines; MDD, alcohol or drug medical or central scored lower in
(1995) SP 38.4 in a test of short term version of from an anxiety group performed better otherwise participants had abuse, or comorbid PD neurological anxiety severity
(18) (9.2) verbal learning and SCID) disorder in WAIS-R (Block not received central nervous and SP in patient groups. illnesses, than patient
CTRL 34.9 IQ: WAIS-R (Block memory (CVLT). Groups research Design) than other system affecting medications CTRL participants had pregnancy, groups, which did
(16) (11.0) Design, Picture did not differ in tests of program at a groups; no other for ≥3 weeks. Participants no lifetime or first- smoking in excess not differ from
Completion, visual memory (BVRT-F), hospital. differences in IQ. were not currently attending degree family history of of one-half package each other (BAI:
Similarities, concentration (DCT), or to psychotherapy. psychiatric problems per day, or previous 23 vs. 16 vs. 2).

A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27


Vocabulary) cognitive flexibility (a telephone version of neuropsychological
(TMT). SCID). CTRL group had evaluation.
less depressive
symptoms (BDI: 12 vs.
12 vs. 1) than patient
groups, which did not
differ from each other.
Boldrini et al. PDA 35.9 BFRT, BFSRT, Patient groups performed DSM-IV Patients were No differences in age, Patients received their Patients had no Axis I Patients had no N/A Groups differed in
(2005) (15) (8.6) CBT, COWAT, poorer than CTRL group (SCID: Axis selected from gender, education, IQ, naturalistic treatment; or II comorbidity or history of brain OCD (Y-BOCS: 0
OCD 32.7 Digit Span, in a test of spatial I and II) those or handedness. no-one was receiving substance abuse or injury, brain vs. 23 vs. 0) and
(25) (8.7) ROCFT, WCST memory and learning consecutively benzodiazepines. dependence in the past surgery, anxiety (HARS:
CTRL 29.1 (CBT: Supraspan). admitted to 6 months and scoredb6 neurological 18 vs. 15 vs. 3)
(15) (8.5) OCD group performed outpatient in HDRS. CTRL diseases (including severity.
Range: poorer than CTRL service. participants had no tic disorders), or
18–55 group also in some current or past other active
IQ: RCPM tests of executive psychiatric disorders or medical conditions.
functioning (WCST: alcohol or other
Null sorts), spatial memory substance abuse (a non-
(CBT: Span, ROCFT), patient version of SCID:
and verbal learning Axis I and II). No group
(BFSRT: Intrusions) and differences in depressive
poorer than PDA group symptoms (HDRS: 5
in tests of executive vs. 5 vs. 4).
functioning (WCST: Null
sorts) and verbal learning
(BFSRT: Intrusions).
Groups did not differ in
tests of verbal memory
(BFSRT, Digit Span,),
other executive functions
(COWAT, WCST), or
visual discrimination
(BFRT). No gender
differences were found.
Depression or anxiety
severity (HDRS, HARS)
was not correlated with
test performance. OCD
severity (Y-BOCS:
Obsessions) correlated
negatively with spatial
memory (CBT: Span).
Cavedini PD 36.3 BGT OCD group performed DSM-IV Patient No differences Patients were un-medicated Patients had no other No somatic N/A OCD severity was
et al. (16) (10.9) poorer than other groups (DIS-III-R, recruitment in age, gender, or for ≥2 weeks and were not lifetime Axis I illnesses (a physical assessed in OCD
(2002) OCD 33.7 in a test of decision- computerized consecutively education. receiving any other kind of diagnoses, and CTRL and neurological group (Y-BOCS).
(34) (11.5) making; no differences version) from a hospital. therapy. 4 OCD patients participants had no examination).
CTRL 29.5 were found between were drug-naïve. lifetime diagnoses (Axis
(34) (8.9) PD and CTRL groups. I clinical evaluation).
Cohen et al. SP 34.0 BVRT, MFFT, Patient groups performed DSM-III-R Participant No difference in age. Patients were un-medicated Patients scored b 6 N/A N/A Y-BOCS averaged
(1996) (17) (9.0)TMT, WAIS-R poorer than CTRL group (psychiatric screening from OCD group had lower for ≥2 weeks prior to in HDRS. 23 in OCD group.
Range: (Block Design, in a test of visual retention evaluation) an OCD study IQ than CTRL group; testing.
18–52 Digit Span, (BVRT). SP group program. therefore IQ was
OCD 35.9 Digit Symbol) performed poorer than covariated in analysis.
(65) (9.9) CTRL group in tests of Gender was treated as
Range: visuo-constructional an independent factor.
20–56 functions (Block Design)
CTRL 34.0 IQ: WAIS-R and attention (TMT: A,

A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27


(32) (9.0) (Information) B-A) and poorer than both
Range: other groups in a test of
21–52 executive functioning
(TMT: B). Groups
differed also in short
term verbal memory
(Digit Span) and visual
discrimination (MFFT:
Time), but no more
information of the
difference was provided.
Anxiety measure
(AAS: Anxious, Nervous,
Fearful) was not correlated
with test performance.
Kaplan et al. PD 35.8 Affective Go/No-go PD+MDD group displayed DSM-IV Recruitment Each CTRL participant Patients were un-medicated PD + MDD patients had Participants were N/A PD + MDD group
(2006) (11) (12.1) Task, CANTAB an attentional bias towards (SCID) through local was matched to a at the time of testing. Prior PD as a primary and medically healthy had current MDD.
CTRL1 35.8 (DMS, IES, PRM, negative verbal stimuli radio and patient by gender, age, to study participation, 7 MDD as a secondary (physical Patient groups
(11) (10.7) RVIP, SRM, SS, (Affective Go/No-go Task), newspaper and IQ. To preserve patients had been treated diagnosis. Patients had examinations, scored higher in
PD + 38.3 SWM), CGT had longer decision-making advertisements. the integrity of the with psychiatric medication. no other anxiety or blood and urine depression
MDD (13.6) latencies (CGT), and Patients were matching criteria, PD depressive disorders tests). (MADRS: 13 vs.
(11) made more errors in a outpatients. and PD + MDD groups (SCID). CTRL 0 and 26 vs. 1)
CTRL2 38.7 test of working memory were not directly participants had no and anxiety
(11) (11.9) and visual discrimination compared with each known personal or (HARS: 19 vs. 0
+IQ: WASI (CANTAB: DMS) when other. first-degree family and 24 vs. 1)
(two-subtest compared to matched history of psychiatric severity than
version) CTRL2 group. PD and disorders. CTRL groups.
matched CTRL1 groups
did not differ. Combined
patients and combined
CTRL groups did not
differ in tests of attention,
memory, and executive
functioning (CANTAB,
CGT), but combined
patient group displayed
an attentional bias towards
negative stimuli when
compared to combined
CTRL groups (Affective
Go/No-go Task).

(continued on next page)

9
10
Table 3 (continued)

Study Sample Age Neuropsychological Main findings Controlled and uncontrolled factors c
(n) a mean test battery b
Diagnostic Patient status Group matching Medication and Comorbid mental Other exclusion Disorder Disorder severity,
(sd)
criteria treatments disorders criteria length phase, and subtype

Lautenbacher PD 30.1 TAP (Gesichtsfeld-/ Patient groups responded DSM-IV Patients were No difference in Patients were un-medicated Patients had no additional N/A N/A PD group scored
et al. (2002) (21) (7.7) Neglectprûfung), slower than CTRL group (International recruited gender. PD group was with a washout period of present or lifetime higher in anxiety
MDD 39.0 Wiener-Testsystem in a test of divided Checklist) consecutively at younger than MDD min. 6 days. disorders or comorbid (HARS: 32 vs. 21;
(21) (9.8) (Signal Detection) attention (TAP), but did admission for group. PD and MDD. PAS: 31 vs. 3)
CTRL 34.6 not differ from each inpatient Indications of a change and lower in
(20) (9.1) other. Groups did not treatment in a in the diagnosis during depressive
differ in reaction time psychiatric the inpatient treatment (HDRS: 17 vs. 24)
in a test for selective hospital and led to exclusion. CTRL symptoms than
attention (Wiener- were studied participants had no MDD group.

A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27


Testsystem). within 2 weeks present or lifetime Patients had
after admission. mental disorders. a current diagnosis.
16 PD patients
had agoraphobia.
Lucas et al. PD 34.7 BVRT, SR, WMS-I PD group performed DSM-III-R Patient No differences in age, Participants receiving Patients had no current No history of N/A PD group had
(1991) (25) (10.2) poorer than CTRL group (structured recruitment education, handedness, prescribed medication mood disorders, significant central current PD as a
CTRL 35.0 IQ: WAIS-R in all tests of visual clinical through local number of head were included if they psychotic disorders, neurological primary Axis I
(25) (9.1) (Block Design, learning and memory interview). media. injuries (NHI), or had maintained it for substance abuse, or other illnesses, birth condition, with or
Range: Picture Completion (BVRT, SR, WMS-I) subjective memory ≥1 month. PD group DSM-III-R anxiety stress, learning without
20–60 Similarities, and in some tests of evaluation (SMQ-R). reported more current disorders or a history of disability, or agoraphobia. PD
Vocabulary) verbal long term memory CTRL group use of prescribed bipolar illness, psychosis, previous group scored
(SR, WMS-I). Groups did performed better medication than CTRL or substance dependence. neuropsychological higher in anxiety
not differ in tests of in Picture Completion group. At the time of CTRL participants had evaluation. symptoms (STAI:
concentration (Memory (WAIS-R) than PD testing 11 patients were no current State: 26 vs. 17;
Span, Mental Control). group; no other receiving psychopathology Trait: 30 vs. 17)
Results remained differences in IQ. benzodiazepines and (SCL-90-R) or a history than CTRL group.
essentially the same when 2 other medication. of panic attacks (AQ).
anxiety and depressive PD group scored higher
symptoms (STAI, BDI) in depressive symptoms
were covariated in (BDI: 14 vs. 6) than
analysis and patients CTRL group.
receiving benzodiazepines
were excluded.
a
CTRL=Control, MDD=Major depressive disorder, OCD=Obsessive–compulsive disorder, PD=Panic disorder; PDA=Panic disorder with agoraphobia, SP=Social Phobia.
b
BFRT=Benton Facial Recognition Test, BFSRT=Buschke–Fuld Selective Reminding Test, BGT=Bechara Gambling Task, BVRT=Benton Visual Retention Test, CANTAB=Cambridge Neuropsychological Test Automated Battery, CBT=Corsi Block Tapping
Task, CGT=Cambridge Gamble Task, COWAT=Controlled Oral Word Association Test, CVLT=California Verbal Learning Test, DCT=Digit Cancellation Test, IES=Intradimensional–Extradimensional Shift, IQ=Intelligence quotient, MFFT=Matching Familiar
Figure Test, PRM=Pattern Recognition Memory, RCPM=Raven Colored Progressive Matrices, ROCFT=Rey–Osterrieth Complex Figure Test, RVIP=Rapid Visual Information Processing, SR=Selective Reminding, SRM=Spatial Recognition Memory, SS=Spatial
Span, SWM=Spatial Working Memory, TAP=Testbatterie zur Aufmerksamkeits-prûfung, TMT=Trail Making Test, WAIS=Wechsler Adult Intelligence Scale, WASI=Wechsler Abbreviated Scale of Intelligence, WCST=Wisconsin Card Sorting Test, WMS=Wechsler
Memory Scale.
c
AAS=Affect Analog Scale, AQ=Anxiety Questionnaire, BAI=Beck Anxiety Inventory, BDI=Beck Depression Inventory, DIS=Diagnostic Interview Schedule, DMS=Delayed Match to Sample, DSM=Diagnostic and Statistical Manual of Mental Disorders,
HARS=Hamilton Anxiety Rating Scale, HDRS=Hamilton Depression Rating Scale, MADRS=Montgomery-Åsberg Depression Rating Scale, NHI=Neurological History Interview, PAS=Panic and Agoraphobia Scale, SCID=Structured Clinical Interview for DSM,
SCL=Symptom Checklist, SMQ=Subjective Memory Questionnaire, STAI=State Trait Anxiety Inventory, Y-BOCS=Yale–Brown Obsessive–Compulsive Scale.
Table 4
Studies exploring cognitive deficits among young adults with obsessive-compulsive disorder

Study Sample Age Neuropsychological Main findings Controlled and uncontrolled factors c
(n) a mean test battery b
Diagnostic Patient status Group Medication and Comorbid mental Other exclusion Disorder length Disorder severity
(sd)
criteria matching treatments disorders criteria and phase

Abbruzzese OCD 29.5 FAS, OAT, OCD group made more DSM-III-R OCD group No differences At the time of testing, CTRL group had No history of No patient group Y-BOCS averaged
et al. (25) (8.8) WCST, WST perseverative errors (computerized recruitment in age, gender, OCD patients had no history of documented head differences in age 18 in OCD group.
(1995a) SCZ 29.9 than other groups in version of from an education, or been on fluvoxamine psychiatric illnesses injuries, loss of at onset (23 vs. SCZ patients were
(25) (6.9) one test of executive DIS-R) anxiety handedness. maleate treatment for or alcohol abuse. consciousness, 23 years) or classified as
CTRL 28.8 functioning (OAT), and inpatient unit ≥2 months. SCZ neurosurgical duration of paranoid type.
(25) (5.6) SCZ group performed and SCZ patients had been treatment, or illness (8 vs.
poorer in another tests group from receiving neuroleptics perinatal trauma 7 years).
of executive a hospital for ≥6 months. (a physical and

A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27


functioning (WCST, rehabilitation Patients had not neurological
WST when compared inpatients received examination to
to other groups and service. benzodiazepines in exclude somatic
FAS when compared 2 weeks preceding illnesses). CTRL
to CTRL group). testing. group had no
history of
neurological
illnesses.
Abbruzzese OCD 30.9 WCST Un-medicated OCD DSM-III-R OCD group No differences At the time of 17 patients in OCD No history of Four subgroups No patient group
et al. (33) (10.2) group performed poorer (Diagnostic recruitment in age, gender, testing, patients in group had a comorbid documented head formed within differences in OCD
(1995b) Un- 29.8 IQ: WAIS than OCD group in a Interview from an education, IQ, OCD group had mood disorder. CTRL injuries, loss of OCD group did severity (Y-BOCS:
medicated (7.8) test of executive Schedule) anxiety or handedness. been on fluvoxamine participants had no consciousness, not differ in 27 vs. 28), which
OCD 28.4 functioning. No inpatient maleate treatment for history of psychiatric neurosurgical duration of was assessed in
(14) (5.5) differences in test unit. ≥6 weeks, but had illnesses or alcohol treatment, or illness (12 vs. 5 OCD group before
CTRL performance were not received abuse. perinatal trauma vs. 9 vs. 7 years) beginning of
(33) found between OCD benzodiazepines in (a physical and or age at onset pharmacological
and CTRL groups, 2 weeks and were neurological (23 vs. 25 vs. 24 treatment.
between genders, not undergoing examination to vs. 22 years),
between subgroups of behavioral exclude somatic nor did OCD
checkers, washers, desensitization illnesses). CTRL groups.
mental checkers, and therapy. Patients in group had no
mixed symptoms un-medicated OCD history of
(Y-BOCS) made within group were untreated. neurological
OCD group, or between illnesses.
subgroups of patients
with and without
comorbid mood
disorders made within
OCD group. OCD
severity (Y-BOCS) was
not correlated with
test performance.
Abbruzzese OCD 30.0 OAT, WCST OCD group made more SCZ diagnoses OCD group No differences At the time of testing, CTRL group had no No history of No patient group SCZ severity was
et al. (60) (9.6) perseverative errors in based on recruitment in age, education, OCD patients had history of psychiatric documented head differences in assessed by SANS
(1997) SCZ 31.1 one executive DSM-III-R from an or handedness. been on fluvoxamine illnesses or alcohol injuries, loss of duration of illness and SAPS.
(60) (10.3) functioning test (OAT), (computerized anxiety Groups differed maleate treatment for abuse. consciousness, (9 vs. 9 years) or
CTRL 28.8 and SCZ group in version of inpatient unit in gender. ≥6 weeks. SCZ epilepsy, age at onset (22
(30) (5.4) another (WCST) when DIS-R) and SCZ patients received neurosurgical vs. 23 years).
compared to other group from neuroleptics. Patients treatments, organic
groups. Genders did a hospital had not received illnesses involving
not differ in test rehabilitation benzodiazepines in central nervous

(continued on next page)

11
12
Table 4 (continued)

Study Sample Age Neuropsychological Main findings Controlled and uncontrolled factors c
(n) a mean test battery b
Diagnostic Patient status Group Medication and Comorbid mental Other exclusion Disorder length Disorder severity
(sd)
criteria matching treatments disorders criteria and phase

performance. Paranoid inpatients 2 weeks preceding system or perinatal


SCZ patients made service. testing. traumas (a physical
more perseverative and neurological
errors than non-paranoid examination to
SCZ patients. Duration exclude somatic
of illness was not illnesses). CTRL
correlated with test group had no
performance. history of
neurological

A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27


illnesses.
Cavallaro OCD 30.5 GT, TH, WCST Patient groups made DSM-IV Patient No differences in OCD patients had Patients had no No mental No patient group N/A
et al. (67) (8.9) more moves in a recruitment age or education. been un-medicated multiple diagnoses or retardation or difference in
(2003) SCZ 33.0 problem-solving task from in-and SCZ group for ≥2 weeks and history of drug or history of previous duration of illness
(110) (9.5) (TH) than CTRL group, outpatient included more had not received any alcohol abuse. CTRL neurologic illnesses, (10 vs. 9 years).
CTRL 31.2 with SCZ group hospital males than CTRL other kind of therapy. group had no lifetime brain injury, or
(56) (6.0) performing yet poorer units. group. SCZ patients received DSM-IV Axis I trauma.
than OCD group. OCD antipsychotic diagnoses
group performed poorer medication, but were (computerized version
in a test of decision- not receiving of DIS-R) or history
making (GT) than other anticholinergics or of drug or alcohol
groups. SCZ group made benzodiazepines, nor abuse.
more perseverative scored N 2 in
errors and completed SAEPRS.
fewer stages in another
executive functioning
test (WCST) than other
groups. Genders did not
differ in test
performance.
Gross-Isseroff OCD 34.8 Alternation learning OCD group performed DSM-III-R Patient No differences in Patients were un- HDRS and MADRS Patients had Age at onset 10-item modified
et al. (15) (6.0) task, WCST slower than CTRL group (clinical recruitment age, gender (all medicated for averaged 6 in OCD normal complete averaged 23 years Y-BOCS averaged
(1996) CTRL 34.0 in a test of executive interview) from were female), ≥2 weeks prior to group, with a blood count, and duration of 27 in OCD group
(15) (7.9) functioning (WCST). consecutive education, or IQ. testing. CTRL maximum of 17. urea, electrolytes, illness 12 years and all patients
Range: IQ: Colored OCD group performed admissions participants were OCD patients had no liver function, in OCD group. scored ≥ 15.
21–49 Progressive poorer also in another to an OCD un-medicated. concomitant non- prolactin, and
Matrices or executive functioning outpatient neuropsychiatric, electrocardiogram,
Standard test (Alternation learning clinic. medicated illnesses. and none were
Progressive task), but this difference CTRL participants pregnant or using
Matrices diminished when had no oral contraceptives.
education, which neuropsychiatric A difference in test
correlated with test disorders performance between
performance, was (unstructured genders led to
covariated in analysis. interview). exclusion of males.
OCD severity (Y-BOCS) CTRL participants
correlated negatively had no history of
with executive brain dysfunction,
functioning test brain surgery, or
(Alternation learning any known medical
task) in OCD group. problem at the time
of testing.
Kim et al. OCD 29.8 COWAT, ROCFT, At the first session, OCD DSM-IV OCD group No differences in At the first session, Patients had no history No history of head Illness duration At the first session
(2002) (39) (10.4) TMT, WCST group performed poorer (SCID) recruitment age, gender, or 15 patients and in of alcohol or drug injury or medical or averaged 9 years OCD group scored
CTRL 27.0 than CTRL group in tests from an education. CTRL the follow-up, all abuse. 5 patients had a neurological and age at onset higher in OCD
(31) (8.4) IQ: K-WAIS of immediate and delayed outpatient group performed patients were comorbid MDD, 1 had disorders. 18 years in OCD severity (Y-BOCS:
(Arithmetic, Block visuo-spatial memory clinic. better in Block medicated. 8 patients phobia, and 1 had group. Obsessions: 13 vs.
Design, Digit Span, (ROCFT), verbal fluency Design (K-WAIS) received cognitive bulimia nervosa, but 0; Compulsions:
Picture (COWAT), and attention than OCD group; behavioral therapy. OCD was the primary 12 vs. 0) and
Arrangement, (TMT: A). OCD severity no other No differences in test diagnosis. CTRL depressive (BDI:
Vocabulary) (Y-BOCS) correlated differences in performance between participants had no 20 vs. 6) and
negatively with tests of IQ. originally medicated history of psychiatric anxiety (BAI: 24
attention (TMT: A) and and un-medicated disorders or drug or vs. 6) symptoms
visual memory patients in either alcohol abuse. than CTRL group.
(ROCFT). After a session.
4-month
pharmacological
treatment, OCD group
performed still poorer
than CTRL group in tests

A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27


of immediate and delayed
visuo-spatial memory
(ROCFT) and verbal
fluency (COWAT:
Category).
Kim et al. OCD 26.7 COWAT, LNNB, OCD group performed DSM-IV (SCID) OCD group No differences in 2 OCD patients and No history of alcohol No history of Illness duration Y-BOCS averaged
(2003) (19) (6.9) ROCFT, TMT, poorer than CTRL group recruitment age, gender, all SCZ patients were or drug abuse. CTRL head injury or averaged 8 years 24 in OCD group.
SCZ 29.6 WCST in tests of visuo-spatial from an education, medicated at the time participants had no medical or in OCD group SCZ group was
(22) (7.6) immediate and delayed outpatient handedness, or of testing. history of psychiatric neurological and 6 years in tested after
CTRL 27.6 IQ: K-WAIS memory (ROCFT) and clinic and parental disorders. disorders. SCZ group. remission of the
(21) (9.2) (Arithmetic, Block verbal fluency (COWAT). SCZ group socioeconomic acute psychotic
Design, Digit Span, OCD severity (Y-BOCS) from a status. SCZ group episode and
Picture was not correlated with hospital (10 had lower IQ than averaged 72
Arrangement, test performance in OCD inpatients). CTRL group and in PANSS.
Vocabulary) group. SCZ group therefore IQ was
performed poorer than covariated in
CTRL group in almost analysis.
all of the tests.
Martin OCD 35.4 Working and OCD group performed DSM-III-R N/A No differences OCD patients were HDRS averaged 11 N/A Symptom NIMH (OCD)
et al. (18) (9.6) recognition slower than CTRL group in age, education, un-medicated for in OCD group. duration averaged averaged 8 and
(1995) CTRL 33.7 memory test in memory tasks. OCD or IQ. ≥6 weeks prior 19 years in OCD HARS 11 in OCD
(18) (8.5) severity (NIMH: OCD) to testing. group. group.
IQ: ANART and depressive symptoms
(HDRS) correlated
positively with task
completion time.
Mataix-Cols SRI + 27.8 CAT, CPT-IP, FAS, Groups did not differ in DSM-IV SRI + OCD No differences in SRI + OCD group No current drug abuse No organic No groups No groups
et al. OCD (8.3) RAVLT, SCWIT, any of the tests, even after (semi-structured group age, gender, received SRI or dependence. 11 brain disorders. difference in differences in OCD
(2002) (28) Spatial working excluding patients with interview) included education, medication. 8 SRI- SRI + OCD patients duration of OCD (10-item Y-BOCS:
SRI − 29.3 memory test, TH, comorbidity and more handedness, or OCD patients had and 8 SRI − OCD (11 vs. 12 years). Total: 25 vs. 28;
OCD (8.0) TMT B, WAIS neuroleptics at the time inpatients marital status. never received SRI patients had comorbid Obsessions: 13 vs.
(24) (Block Design, of testing. Treatment than SRI- for OCD and 16 had diagnoses (MDD 14; Compulsions:
Digit Span, Digit naïve patients and those OCD group. finished a washout and/or dysthymia) 12 vs. 14) or
Symbol), WCST in a washout period did period of 2–5 weeks. OCD being the anxiety (STAI
(computerized not differ. Patients on 16 SRI + OCD primary diagnosis and (State): 29 vs. 31)
version) benzodiazepines were patients and dominant disorder for severity assessed
more fluent in CAT, 11 SRI − OCD which treatment was immediately before
IQ: RAPM regardless of whether patients received sought. No group testing.
(12-problem they were on SRI or not. benzodiazepines, and differences in number
version) In SRI-OCD group, 3 SRI + OCD patients of patients with
patients with and 1 SRI − OCD comorbid MDD or

(continued on next page)

13
14
Table 4 (continued)

Study Sample Age Neuropsychological Main findings Controlled and uncontrolled factors c
(n) a mean test battery b
Diagnostic Patient status Group Medication and Comorbid mental Other exclusion Disorder length Disorder severity
(sd)
criteria matching treatments disorders criteria and phase

benzodiazepines had patients received dysthymia or in


shorter reaction times neuroleptics. No depressive symptoms
(CPT-IP), but produced group difference in (BDI: 20 vs. 22).
more perseverative errors number of patients
in executive functioning receiving
test (WCST) than patients benzodiazepines
without. In SRI + OCD and/or neuroleptics.
group, patients with
benzodiazepines had

A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27


longer reaction time
(CPT-IP) than those
without.
Mataix-Cols OCD♂ 27.9 CAT, CPT-IP, FAS, There were no DSM-IV Patients were No differences About half of OCD was a primary N/A No OCD group No OCD group
et al. (33) (7.2) RAVLT, SCWIT, significant main being seen at within gender OCD patients diagnosis and difference in difference in OCD
(2006) OCD♀ 28.9 Spatial working effects of OCD a psychiatric groups in age, were medicated. principal complaint. duration of illness severity (10-item
(23) (9.3) memory test, TH, vs. CTRL groups unit of a education, or No OCD group No OCD group (11 vs. 11 years). Y-BOCS: Total:
CTRL♂ 26.9 TMT B, WAIS when anxiety hospital. No handedness. differences in difference in comorbid 24 vs. 27;
(20) (6.4) (Block Design, severity (STAI) and OCD group medication diagnoses (MDD and Obsessions: 13 vs.
CTRL♀ 29.1 Digit Span, Digit depressive symptoms difference in usage. dysthymia). OCD 13; Compulsions:
(20) (8.6) Symbol), WCST (BDI) were covariated inpatient vs. CTRL groups 12 vs. 14). OCD
(computerized in analysis. There was status (4 differed in depressive vs. CTRL groups
version) only one significant vs. 2). symptoms assessed differed in anxiety
interaction effect immediately before severity assessed
IQ: RAPM between gender and testing (BDI: 20 vs. 21 immediately before
(12-problem group, with OCD♀ vs. 2 vs. 3) and testing (STAI
version) group performing therefore BDI was (State): 27 vs. 32
poorer in a test of covariated in vs. 13 vs. 15),
verbal fluency (FAS) analysis. which was
than other groups. covariated in
OCD severity analysis.
(Y-BOCS) correlated
negatively with tests
of executive
functioning (CAT,
SCWIT) in OCD♀
group.
Moritz et al. OCD 33.2 Creative verbal OCD group performed DSM-IV N/A OCD and CTRL 15 patients were 10 patients were No substantial High HDRS group High HDRS group
(2001) (36) (10.3) fluency, Digit poorer than CTRL (Neuropsychiatric groups, and high un-medicated at diagnosed with neurological had longer scored higher in
CTRL 33.4 Span, TMT, group in tests of Interview for and low HDRS the time of testing. comorbid MDD and disorders (e.g., duration of illness Obsessions than
(36) (9.5) WCST attention and executive DSM-IV and groups did not High and low HDRS 4 with another anxiety stroke, multiple than low HDRS low HDRS group
(computerized functions (Creative medical records) differ in age, groups did not differ disorder. Patients had sclerosis, head group (15 vs. (Y-BOCS: 14 vs.
version) verbal fluency, TMT, gender, education, in number of no history of comorbid trauma, or previous 9 years). 12), but groups did
WCST). Groups did not verbal IQ medicated patients. drug abuse or current brain operations). not differ in
differ in a test of verbal (information of or previous psychotic Compulsions or
short term memory (Digit the test not symptoms. OCD group Total severity
Span). OCD group was provided), or scored higher in (Y-BOCS) or in
divided into subgroups smoking. depressive symptoms number of previous
of high and low depressive (BDI: 22 vs. 3) than hospitalizations.
symptoms (HDRS). High CTRL group. High
HDRS group performed HDRS group scored
poorer than low HDRS higher in depressive
and CTRL groups in one symptoms than low
executive functioning test HDRS group (HDRS:
(WCST) and poorer than 19 vs. 7). High and
CTRL group in another low HDRS groups
one (TMT: B, B-A), did not differ in
when OCD length and number of
severity (Y-BOCS: comorbid anxiety
Obsessions) were disorders.
covariated in analysis.
High HDRS group
performed poorer than
CTRL group also in a
test of creative verbal
fluency. Depressive
symptoms (HRSD)

A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27


correlated negatively
with executive functioning
(WCST), and length of
illness with attentive
performance (TMT: A),
while OCD severity
(Y-BOCS) was not
correlated with test
performance. Patients
with and without MDD
did not differ in test
performance.
Penadés OCD 33.8 ROCFT, SCWIT, OCD group performed DSM-IV OCD No differences 23 patients were No group difference in Patients had no N/A Y-BOCS averaged
et al. (35) (9.4) TMT, WMS-III poorer in tests of visual (SCID) patients were in age, education, un-medicated for depressive symptoms history of traumatic 29 in OCD group.
(2005) CTRL 31.7 (Faces) immediate memory admitted to a handedness, ≥3 previous months (BDI: 9 vs. 7). brain injury or
(33) (5.7) (ROCFT) and executive mental health or IQ. and the rest were Patients did not meet medical or
IQ: WAIS-III functions (SCWIT, TMT, center. medicated in OCD criteria for depression neurological
(Vocabulary) ROCFT). A mediation group. Patients had and had no other disorders (including
effect of organizational not undergone ECT. comorbid current tics and Tourette’s
strategies in deficits in CTRL participants psychiatric diagnosis disorder).
immediate visual memory received no (Axis I or Axis II) or
(ROCFT) was psychopharmacological a history of drug abuse.
demonstrated. Results medication. CTRL participants had
remained after depressive no history of
symptom score (BDI) neuropsychiatric
was covariated in analysis. illnesses.
Visual memory
performance (ROCFT)
correlated negatively with
Compulsions and
positively with Obsessions
(Y-BOCS). Medicated and
un-medicated patients did
not differ in test
performance.
Roh et al. OCD 26.3 COWAT, ROCFT, After 1-year DSM-IV Patient No differences At the first session, No reported alcohol No head injuries, Age at onset OCD severity
(2005) (21) (10.1) TMT, WCST pharmacological treatment, (SCID) recruitment in age, gender, 3 patients were or substance abuse. medical or averaged 18 years decreased during
CTRL 26.0 although OCD group from an education, or un-medicated, and in Patients had no other neurological and disorder the 1-year treatment
(20) (6.8) IQ: K-WAIS showed improvement outpatient IQ. follow-up all patients psychiatric diagnosis, disorders, or duration 8 years in OCD group
(Arithmetic, during follow-up, they still clinic. were medicated with and CTRL participants physical abuse. at the 1-year (Y-BOCS: 27
Block Design, continued to show poorer SRI. In 7 patients had no psychiatric follow-up in vs. 19).
Digit Span, performance than CTRL the treatment response diagnoses. Depressive OCD group.

15
(continued on next page)
16
Table 4 (continued)

Study Sample Age Neuropsychological Main findings Controlled and uncontrolled factors c
(n) a mean test battery b
Diagnostic Patient status Group Medication and Comorbid mental Other exclusion Disorder length Disorder severity
(sd)
criteria matching treatments disorders criteria and phase

Picture group in tests of visual was not favorable and (BDI: 21 vs. 12) and
Arrangement, immediate and delayed they were therefore anxiety (BAI: 27 vs. 15)
Vocabulary) memory (ROCFT), verbal given cognitive- symptoms decreased
fluency (COWAT: behavioral therapy or during the 1-year
Category), attention were treated with treatment in OCD
(TMT: A), and executive additional group.
functioning (WCST). pharmacological
therapies. 13 patients
received antipsychotic

A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27


drugs.
Savage OCD 32.7 MRT, OMO, OCD group performed DSM-IV N/A No differences Patients were free of Patients had no current Patients had no head N/A OCD group scored
et al. (20) (8.7) ROCFT, VVT poorer than CTRL group (SCID) in age, gender, psychotropic MDD or substance abuse injuries or higher than CTRL
(1999) CTRL 31.9 in tests of spatial skills education, IQ, medication for or a history of psychotic neurological group in OCD
(20) (8.7) IQ: WAIS-R (MRT) and visual or handedness. ≥1 month. CTRL episodes or substance disorders (including (Y-BOCS: 21 vs. 0;
(Information, immediate and delayed participants received dependence. CTRL Tourette's MOCI: 14 vs. 3)
Similarities, memory and organizational no psychoactive participants had no syndrome). CTRL and anxiety severity
Vocabulary) strategies (ROCFT). Group medication. psychiatric disorders participants had no (BAI: 12 vs. 3),
difference in immediate (SCID). OCD group neurological which were
visual recall was mediated scored higher in disorders or other assessed in the day
by organizational strategies depressive symptoms significant medical of testing.
(ROCFT). Groups did not (BDI: 11 vs. 3) than illnesses.
differ in tests of shifting CTRL group, which
and maintaining mental was assessed in the
sets (OMO, VVT). day of testing.
Shin et al. OCD 29.3 ROCFT OCD group performed DSM-IV OCD group No differences 14 patients were 3 patients had No medical N/A OCD group scored
(2004) (30) (8.6) poorer than CTRL group (SCID) consisted of in age, gender, medicated at the comorbid MDD, illnesses. Patients higher in anxiety
CTRL 29.8 IQ: WAIS-R in a test of immediate patients who education, or time of testing. obsessive–compulsive had no neurological severity (MOCI: 13
(30) (8.7) (Arithmetic, and delayed visual visited an handedness. CTRL participants personality disorder, or illnesses. vs. 5; BAI: 17
Range: Block Design, memory and organizational OCD clinic. Groups differed received no schizotypal personality vs. 4). BAI was
20–35 Picture strategies. Anxiety severity in IQ, which medication. disorder. CTRL group covariated in
Arrangement, (BAI, MOCI) correlated was covariated had no current or past analysis.
Vocabulary) negatively with test in analysis. psychiatric disorders
performance. The (SCID). No group
mediating effect model difference in depressive
of organizational strategies symptoms (BDI).
on memory revealed that
OCD group had an
apparent visual memory
problem, even when
indirect effect of
organizational strategies
was excluded.
a
CTRL=Control, MDD=Major depressive disorder, OCD=Obsessive–compulsive disorder, SCZ=Schizophrenia, SRI+=Receiving serotonin reuptake inhibitors, SRI−=Not receiving serotonin reuptake inhibitors.
b
ANART=American Version of the Nelson Adult Reading Test, CAT=Category Alternation Test, COWAT=Controlled Oral Word Association Test, CPT=Continuous Performance Test, FAS=F-A-S Test of Verbal Fluency, GT=Gambling Task, IQ=Intelligence
quotient, LNNB=Luria–Nebraska Neuropsychological Battery, MRT=Mental Rotation Test, OAT=Object Alternation Test, OMO=Odd-Man-Out Test, RAPM=Raven Advanced Progressive Matrices, RAVLT=Rey Auditory Verbal Learning Test, ROCFT=Rey-
Osterrieth Complex Figure Test, SCWIT=Stroop Color Word Interference Test, TH=Tower of Hanoi Task, TMT=Trail Making Test, VVT=Visual-Verbal Test, WAIS=Wechsler Adult Intelligence Scale, WCST=Wisconsin Card Sorting Test, WMS=Wechsler
Memory Scale, WST=Weigl's Sorting Test.
c
BAI=Beck Anxiety Inventory, BDI=Beck Depression Inventory, DIS=Diagnostic Interview Schedule, DSM=Diagnostic and Statistical Manual of Mental Disorders, ECT=Electroconvulsive therapy, HARS=Hamilton Anxiety Rating Scale, HDRS=Hamilton
Depression Rating Scale, MADRS=Montgomery–Åsberg Depression Rating Scale, MOCI=Maudsley Obsessive–Compulsive Inventory, NIMH=National Institute of Mental Health, PANSS=Positive and Negative Syndrome Scale for Schizophrenia,
SAEPRS=Simpson and Angus Extra Pyramidal Rating Scale, SANS=Scale for the Assessment of Negative Symptoms, SAPS=Scale for the Assessment of Positive Symptoms, SCID=Structured Clinical Interview for DSM, SRI=Serotonin reuptake inhibitor,
STAI=State Trait Anxiety Inventory, Y–BOCS=Yale–Brown Obsessive–Compulsive Scale.
A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27 17

1987) and the Rey Auditory Verbal Learning Test close to the searched maximum (36 years). Studies with
(RAVLT; Schmidt, 1996) are most commonly used. small sample sizes (n b 10) or inadequate information for
Non-verbal long- and short-term memory is often inclusion criteria were excluded, as well as studies where
measured with the Rey–Osterrieth Complex Figure the depressive patient sample included patients with
Test (ROCFT; Meyers and Meyers, 1995) and the bipolar disorder. The final number of studies which
Benton Visual Retention Test (BVRT; Sivan, 1992). fulfilled all the inclusion criteria was nine for major
The Trail Making Test (TMT; Reitan and Wolfson, depressive disorder (Table 2), two for panic disorder plus
1993), the Wisconsin Card Sorting Task (WCST; five that slightly exceeded the inclusion criteria for age (up
Heaton, 1981), the Stroop Color Word Interference to 60 years in range and 12 in standard deviation) to
Test (SCWIT; Golden, 1978), the Continuous Perfor- complement the scarce data on panic disorder and social
mance Test (CPT; Conners, 2000), the Paced Auditory phobia (Table 3), 15 for obsessive–compulsive disorder
Serial Addition Test (PASAT; Gronwall, 1977), and (Table 4) and five for post-traumatic stress disorder
the Controlled Oral Word Association Test (COWAT; (Table 5).
Benton and Hamsher, 1989) are used to measure
attentive and executive functioning. 3. Results
It is of high relevance to study features that may
associate with and function as mediating factors to 3.1. Which cognitive domains are impaired in depressive
depressive and anxiety disorders in young adulthood. disorders?
Thus far, research has provided very little information
concerning the pattern, nature and extent of cognitive Most of the studies investigating the association
dysfunction involved in mental disorders particularly between depression and cognitive dysfunction have
among young adults. This review aims to aggregate and been conducted among middle-aged and elderly patients
evaluate in detail the existing literature on cognitive (for a review, see Kindermann and Brown, 1997), or
deficits in major depressive and anxiety disorders among among patients regardless of their age (for a review, see
young adult patients. Austin et al., 2001; Veiel, 1997; Zakzanis et al., 1998). In
addition, there are studies with samples defined as young
2. Methods adults, although they may have consisted of, for example,
18–65-year-olds, and accordingly determined all ‘non-
Electronic PubMed and PsycInfo searches were elderly’ individuals as ‘young adults’ mainly to differen-
conducted to identify research articles that focus on tiate them from elderly ones (e.g., Grant et al., 2001; Porter
cognitive findings in depressive or anxiety disorders in et al., 2003). Only few studies (e.g., Smith et al., 2006)
young adulthood and were published in English language explore a clear-cut group of actual young adult patients.
during years 1990–2006. Different forms and combina- Here, as summarized in Table 2, the literature reviewed
tions of the following search terms were used: depression, focuses on the findings among young adults with major
dysthymia, anxiety, panic disorder, phobia, generalized depressive disorder (MDD), since no studies of cognitive
anxiety disorder, post-traumatic stress disorder, obses- dysfunction among young adults with dysthymia or minor
sive–compulsive disorder, neuropsychology, cognitive depressive disorder were found.
deficit/impairment/dysfunction and young adults. In Executive dysfunction seems to be a key factor of
addition, reference lists were screened in order to include young adulthood MDD, since most of the studies have
further relevant studies. To be included, the articles had to found patients to manifest deficits in several subcom-
report use of well-known standard neuropsychological ponents of executive functioning (Egeland et al., 2003;
tests and DSM-criteria for diagnosis (APA, 1994), and to Fossati et al., 1999; Hill et al., 2004; Mahurin et al.,
have included an appropriate control group. Further on, 2006; Merriam et al., 1999; Smith et al., 2006; Stordal
articles were screened in order to identify those fulfilling et al., 2004). MDD in young adulthood seems to relate
the inclusion criterion for age, which, due to the limited also with attentional deficits (Egeland et al., 2003; Hill
number of studies focusing on a clear-cut group of young et al., 2004; Mahurin et al., 2006; Smith et al., 2006),
adults, was kept relatively broad: adult sample mean age short-term and working memory impairment in both
between 18 and 36 years and an age range between 18 and verbal and visual tasks (Fossati et al., 1999), and
51 years. If the age distribution was reported only as a dysfunction in psychomotor skills (Hill et al., 2004).
standard deviation, a maximum of 11 years was defined if Results about verbal memory and learning functions are
the sample mean age was close to the searched median inconsistent. Some studies have observed clear verbal
(27 years) and of 10 years if the sample mean age was memory impairments among depressed patients
18
Table 5
Studies exploring cognitive deficits among young adults with post-traumatic stress disorder
c
Study Sample Age Neuropsychological Main findings Controlled and uncontrolled factors
(n) a mean test battery b
Diagnostic Patient status Group matching Medication Comorbid mental Other exclusion Disorder length Disorder severity
(sd)
criteria and treatments disorders criteria and phase
Gil et al. PTSD 31.7 BT, BVRT-F, Patient groups DSM-III Patient No differences in Patients were Patients showed Patients had no No patient group No patient group
(1990) (12) (9.1) CPT, FEQ, performed poorer recruitment from age or gender. un-medicated no evidence of history of differences in differences in
PCTRL 31.8 ROCFT, VFT, than CTRL group a mental health CTRL group had for ≥2 weeks present or significant head time since the symptom severity
(12) (10.3) WMS (Mental in tests of center outpatient higher IQ than and had not previous trauma. problem began (CGIS: 4 vs.
CTRL 27.5 Control, Paired- organicity (BGT, clinic. PTSD patient groups, undergone alcoholism or (4 vs. 3 years). 4, range: 3–6).
(12) (8.2) Associated BVRT-F, Mental patients were which did not ECT or other substance
Range: Learning) Control), verbal male and differ from each psychosurgery. abuse. CTRL

A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27


20–50 fluency (VFT), involved in battle other. Groups participants had
IQ: Army IQ Test, memory (FEQ, and army differed in no current or
WAIS (Block Paired-Associated traumatic events, education, but previous
Design, Coding, Learning: Hard), terrorist attacks, patient groups psychiatric
Comprehension, and attention and car accidents. did not differ disorders (semi-
Digit Span, Picture (CPT: Hits). PCTRL patients from each other. structured
Completion, PTSD group had MDD, GAD, interview).
Similarities) performed poorer OCD or phobia.
than PCTRL
group in tests of
verbal fluency
(VFT: Letter) and
organicity (BGT).
Groups did not
differ in other
tests of verbal
memory (Paired-
Associated
Learning: Easy),
nonverbal
memory
(ROCFT), and
attention (CPT:
False alarms).
Jenkins PTSD Of all CVLT PTSD group DSM-III-R Trauma-exposed No differences in No use of No trauma- No history of The time since PTSD patients
et al. (15) groups: performed poorer (SCID and groups were age or education. antipsychotic exposed group head injury, assault averaged had current PTSD
(1998) PTSD− 27.7 than other groups modified treatment-seeking CTRL group was or stimulant differences in seizures, 6 years (counted and scored N 107
(16) (6.9) in long term version of rape survivors matched to PTSD drugs. number of blackouts, of both trauma- on MSCR.
CTRL Range: verbal memory. MSCR) from a rape crisis group on gender anxiety disorders hallucinations, exposed groups).
(16) 19–44 center. and handedness (SCID) or or delusions.
on a case-by-case alcoholism
basis. All except (MMAST).
1 trauma-exposed PTSD group
participant were scored higher in
female. depressive
symptoms (BDI)
than other
groups, and
therefore BDI
was covariated
in analysis.
Patients had no
pre-rape
treatment for
psychiatric
illness or
substance abuse.
Jenkins PTSD 28.4 CPT (computerized PTSD group DSM-III-R Trauma-exposed No differences in N/A PTSD group Patients had no The time since PTSD patients
et al. (15) (7.0) version), PASAT, performed poorer (SCID and groups were age or education. scored higher in neurologic assault averaged had current
(2000) PTSD− 27.6 PVSAT (computer- than other groups PTSD treatment-seeking All except 1 depressive disorders pre- 8 years (counted PTSD.

A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27


(16) (5.0) administered), in several tests of interview) rape survivors. trauma-exposed symptoms (BDI: dating the of both trauma-
CTRL 27.0 TMT, WAIS-R auditory (Digit participant were 19 vs. 11 vs. 5) assault. exposed groups).
(16) (8.6) (Digit Span, Digit Span: Total and female. than other groups, Trauma-exposed
Range: Symbol) Backward, and therefore BDI groups were
19–45 PASAT) and was covariated in tested N 3 months
visual (CPT: analysis. No after their
Sequential group differences assault.
learning, Digit in alcoholism
Symbol, TMT: (MMAST: 8 vs. 6
B) attention. vs. 4). Patients
Groups did not had no anxiety,
differ in other affective,
tests of attention schizophrenia
(CPT, Digit Span: spectrum, or
Forward, PVSAT, substance abuse
TMT: A). disorders pre-
dating the assault.
Stein PTSD 33.8 ACT, COWAT, CT, Trauma-exposed DSM-IV Recruitment No differences in No No history of No history of Trauma-exposed PTSD group had
et al. (17) (9.8) CVLT, CVMT, groups performed (CAPS and through posted age, education, or psychotropic psychotic serious brain participants had current PTSD.
(2002) PTSD− 34.5 DVT, PASAT, poorer than SCID) advertisements socioeconomic medication use disorders. injury (with extricated PTSD group
(22) (9.0) ROCFT, SCWIT, CTRL group in and ongoing status. within Substance loss of themselves from scored higher in
CTRL 29.4 TMT, VPA, tests of sustained personal contacts 6 weeks use was consciousness abusive PTSD severity
(22) (10.7) WAIS-III (Digit attention with community before considered mild N 10 min), relationship in (CAPS: 63 vs.
Span, Vocabulary), (PASAT), services in participation. (ASI). PTSD− neurologic time ranging 24; IES-R: 46
WMS-III (Logical executive domestic group had no disorders, from 4 weeks to vs. 22) than
Memory) functioning violence. lifetime PTSD. seizure 2 years before PTSD-group.
(SCWIT), and Trauma-exposed CTRL disorders, enrollment. Trauma-exposed
visual memory participants were participants had learning groups scored
(ROCFT: Copy). female victims of no lifetime disabilities, higher on severity
PTSD group intimate partner exposure to a attention-deficit of intimate partner
performed poorer violence PTSD DSM-IV disorder, or use violence (CTS-2)
than other groups (physical or Criterion A of oral or than CTRL group.
in a test of verbal sexual abuse). stressor, nor had intramuscular
abilities MDD, panic steroids within
(Vocabulary) and disorder, or GAD 4 months
poorer than (SCID). No before
CTRL group in a trauma-exposed participation.
(continued on next page)

19
20
Table 5 (continued)
c
Study Sample Age Neuropsychological Main findings Controlled and uncontrolled factors
(n) a mean test battery b
Diagnostic Patient status Group matching Medication Comorbid mental Other exclusion Disorder length Disorder severity
(sd)
criteria and treatments disorders criteria and phase
test of executive group differences
functions (TMT: in number of
B, B-A). PTSD- lifetime MDD.
group performed PTSD group
poorer than scored higher in
CTRL group in pathological
another test of dissociation
executive (DES-T: 13 vs. 5

A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27


functioning (CT) vs. 1) than other
and in a test of groups. In
long term visual depressive
memory symptoms, PTSD
(ROCFT: scored higher
Delayed). Groups than other groups
did not differ in and PTSD−group
tests of verbal scored higher
memory (CVLT, than CTRL group
Logical Memory, (CES-D: 31 vs.
VPA), verbal 14 vs. 4).
fluency
(COWAT), visual
memory
(VCMT),
attention and
working memory
(ACT, Digit Span,
DVT), and
psychomotor
functioning
(TMT: A).
Symptom severity
(CES-D, DES-T,
CTS-2, IES-R)
was not correlated
with test
performance.
Vasterling PTSD 36.3 CPT, CVMT, LC, PTSD group DSM-III-R and Recruitment No differences in N/A No current No significant The time since PTSD group
et al. (9.8) RAVLT, SCWIT, performed poorer DSM-IV (SCID form the age, gender, (i.e., previous head trauma troops had been scored higher in
(1998) 35.3 WAIS-R than PTSD-group Axis I and enrollment lists education, 3 months) (loss of redeployed PTSD severity
(8.7) (Arithmetic, Digit in tests of verbal borderline and of local military handedness, or alcohol or consciousness averaged than PTSD-group
Span), WCST (RAVLT) and antisocial units that had socioeconomic substance N 30 min), 3.2 years (range: (MSCR: 117 vs.
(19) visual memory modules of been mobilized status. PTSD disorders, central nervous 2.5–4.1 years) 69).
PTSD-(24) IQ: WAIS-R (CVMT) and in Axis II, and for the Operation group included lifetime history system
(Vocabulary) some tests of PTSD Desert Storm. more ethnic of bipolar diseases, or
attention supplement) minorities and or psychotic systematic
(Arithmetic, CPT: had lower IQ than disorders, mood medical
Commissions). PTSD-group. IQ disorders with illnesses.
Groups did not was at first psychotic
differ in other covariated, but symptoms,
attention tests dropped form borderline or
(CPT: Omissions, further analysis, antisocial
LC, SCWIT, since being not personality
WCST, Digit significant. disorders,
Span). subthreshold
manifestations of
PTSD, or PTSD
preceding
military service.

A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27


PTSD-
participants
had no current
mental disorders.
13 PTSD patients
had ≥ 1 current
comorbid mental
disorders,
including
depressive and
anxiety disorders.
No group
differences in
average alcohol
consumption.
a
CTRL=Control, GAD=Generalized anxiety disorder, MDD=Major depressive disorder, OCD=Obsessive–compulsive disorder, PCTRL=Non-traumatized psychiatric control, PTSD=Post-traumatic stress disorder, PTSD−
=Trauma-exposed without PTSD.
b
ACT=Auditory Consonant Trigrams, BT=Bender-Gestalt Test, BVRT=Benton Visual Retention Test, COWAT=Controlled Oral Word Association Test, CPT=Continuous Performance Test, CT=Category Test,
CVLT=California Verbal Learning Test, CVMT=Continuous Visual Memory Test, DVT=Digit Vigilance Test, FEQ=Famous Events Questionnaire, IQ=Intelligence quotient, LC=Letter Cancellation, PASAT=Paced Auditory-
Serial Addition Test, PVSAT=Posner Visual Selective Attention Task, RAVLT=Rey Auditory Verbal Learning Test, ROCFT=Rey-Osterrieth Complex Figure Test, SCWIT=Stroop Color Word Interference Test, TMT=Trail
Making Test, VFT=Verbal Fluency Test, VPA=Verbal Paired Associates, WAIS=Wechsler Adult Intelligence Scale, WCST=Wisconsin Card Sorting Test, WMS=Wechsler Memory Scale.
c
ASI=Addiction Severity Index, BDI=Beck Depression Inventory, CAPS=Clinician Administered PTSD Scale for DSM-IV, CES=Center for Epidemiological Studies, CGIS=Clinical Global Impression Scale, CTS=Conflict
Tactics Scale, DES=Dissociative Experience Scale, DSM=Diagnostic and Statistical Manual of Mental Disorders, ECT=Electroconvulsive therapy, IES=Impact of Event Scale, MMAST=Modified Michigan Alcoholism
Screening Test, MSCR=Mississippi Scale for Combat-Related PTSD, SCID=Structured Clinical Interview for DSM.

21
22 A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27

compared to healthy controls (Smith et al., 2006), cognitive deficits in young adulthood MDD (Basso
whereas other studies report no deficits in this domain and Bornstein, 1999; Egeland et al., 2003; Hill et al.,
(Fossati et al., 1999; Hill et al., 2004; Wang et al., 2006). 2004; Merriam et al., 1999), again with some contradic-
tory results (Fossati et al., 1999; Stordal et al., 2004).
3.1.1. Effects of the subtype of major depressive
disorder 3.2. Which cognitive domains are impaired in anxiety
Cognitive impairment among young adults with disorders?
psychotic depression is more severe across a wide range
of neuropsychological functioning when compared to Relatively little is known about the nature of cognitive
depression severity-matched patients with non-psychotic deficits related to anxiety disorders in general, and among
MDD (Basso and Bornstein, 1999). Furthermore, the young adults in particular. A recent population-based study
pattern of neuropsychological dysfunction in psychotic of 20–64-year-olds demonstrated impairments in verbal
MDD seems to be similar to but less severe than in episodic memory and executive functioning in anxiety
schizophrenia (Hill et al., 2004). These data provide disorders in general (Airaksinen et al., 2005). Moreover,
support for the hypothesis that psychotic depression is a the profile and nature of cognitive dysfunction seemed to
diagnostic entity distinct from non-psychotic MDD and depend on the anxiety disorder subtype. Majority of the
that psychotic MDD may be neuropsychologically more research on cognitive impairments in anxiety disorders
similar to other psychotic disorders than to non-psychotic among young adults has focused on obsessive–compul-
MDD (Kendler et al., 1993). Young adult patients with sive disorder (OCD), whereas much less attention has been
recurrent MDD who, in addition, have some features for paid for other anxiety disorder subtypes.
vulnerability to bipolar disorder (such as a relative with
bipolar disorder) manifest greater cognitive impairment 3.2.1. Deficits in panic disorder, phobias and
than do depressed patients without such features, at least generalized anxiety disorder
in euthymic state (Smith et al., 2006). These results Studies exploring cognitive dysfunction among young
indicate the importance of investigating these patient adults with panic disorder and social phobia are
groups separately when studying cognitive dysfunction, summarized in Table 3. Deficits in divided attention but
and also may explain the discrepancies between some not in selective attention may be present in young adult
earlier studies that have not controlled for these factors. inpatients with severe panic disorder (Lautenbacher et al.,
2002). Asmundson et al. (1995) observed impairments in
3.1.2. Do cognitive deficits persist after remission of panic disorder patients' short-term verbal memory and
depression? learning, but not in visual memory, executive function-
Recent findings suggest some cognitive dysfunction ing, or concentration.
among remitted young adult MDD patients, particularly In the studies slightly exceeding the inclusion criteria
in executive functions and verbal learning and memory for the age range of the present review, panic disorder has
(Smith et al., 2006). This indicates that some cognitive been found to relate with verbal long-term memory
deficits may persist despite clinical recovery and may not impairment (Lucas et al., 1991) and, contradictory to
be simply secondary to mood disturbances in depression. findings of Asmundson et al. (1995), visual memory and
These impairments may represent trait vulnerability learning deficits (Boldrini et al., 2005; Lucas et al., 1991).
markers for MDD, whereas deficits in other domains of However, decision-making (Cavedini et al., 2002), as well
cognitive performance, such as in short-term and as other executive functions (Boldrini et al., 2005) and
working memory, appear to be more state-dependent. concentration (Lucas et al., 1991), were found to be intact
However, there are also contradictory results. Wang et al. in panic disorder in these studies, too. Interestingly, Kaplan
(2006) found no differences in verbal learning and et al. (2006) found that cognitive deficits are associated
memory between currently depressed, previously de- with the presence of comorbid MDD in panic disorder.
pressed, and healthy young adults. As discussed in the No studies about cognitive deficits in social phobia in
Wang et al. paper, this result may be due to the fact that the age group under review were found. However, the
the MDD patients were outpatients with only mild or studies slightly exceeding the present inclusion criteria
moderate depressive symptoms. These data may indicate for age indicate that social phobia relates with deficits in
that impairments in verbal memory and learning are attentive, executive and visuo-spatial functions (Cohen
present only in more severe forms of the disorder. et al., 1996) and in short-term verbal memory and
Moreover, several studies have reported a correlation learning (Asmundson et al., 1995). In the searched age
between depression severity and the magnitude of group, no studies about cognitive functions in specific
A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27 23

phobia or generalized anxiety disorder were found. observed in attention (Gil et al., 1990; Jenkins et al.,
However, studies with older samples (mean age: 38– 2000; Vasterling et al., 1998), short- and long-term
43 years) have not found association between cognitive verbal and visual memory (Gil et al., 1990; Jenkins et al.,
deficits and these disorders (Airaksinen et al., 2005; 1998; Vasterling et al., 1998), and executive functioning
Zalewski et al., 1994), albeit in the study of Airaksinen (Gil et al., 1990; Stein et al., 2002).
et al. this may be due to the small sample size (n = 7) for
generalized anxiety disorder. 4. Discussion

3.2.2. Deficits in obsessive–compulsive disorder The prevalence rates of psychiatric disorders are high
Several recent reviews summarize cognitive deficits in among young adults, with depressive and anxiety disorders
patients with OCD including all ages (see Greisberg and being among the most prevalent ones. However, research
McKay, 2003; Kuelz et al., 2004; Muller and Roberts, has thus far provided very little information of the
2005). The studies focused on cognitive impairments in neuropsychological profile in affective disorders among
OCD among young adults, as summarized in Table 4, have young adults with congruently defined age range.
mainly demonstrated impairments in executive functioning Consequently, in the inclusion of studies for the present
(Abbruzzese et al., 1995a; 1997; Cavallaro et al., 2003; review, the criteria for sample age were defined relatively
Gross-Isseroff et al., 1996; Kim et al., 2002; 2003; Moritz wide-ranging.
et al., 2001; Penadés et al., 2005; Roh et al., 2005; Savage In this review, findings from single studies of
et al., 1999), long- and short-term visual memory (Kim depressive and anxiety disorder-related cognitive deficits
et al., 2002; 2003; Penadés et al., 2005; Roh et al., 2005; were summarized, with a focus on young adults. Although
Savage et al., 1999; Shin et al., 2004), attention (Kim et al., the results are not completely consistent, several conclu-
2002; Moritz et al., 2001; Penadés et al., 2005; Roh et al., sions can be drawn. Neuropsychological dysfunction in
2005) and processing speed (Martin et al., 1995). These young adulthood MDD appears to be mediated by
deficits may persist several months after starting the individual differences and disorder characteristics, with
psychopharmacological treatment with subsequent clinical large variance between the patients. Young adults with
improvement (Kim et al., 2002; Roh et al., 2005). It has severe MDD have cognitive impairments, particularly in
been suggested that impairments in visual memory are executive functioning, but findings on other more specific
caused by a primary executive dysfunction (Penadés et al., deficits vary. The findings reviewed associate with the
2005; Savage et al., 1999), however, other studies have hypothesis of a mild to moderate disruption in prefrontal
demonstrated non-verbal memory deficits in OCD even functions in recurrent MDD (Steele et al., 2007), that may
after excluding the mediating effect of executive function- persist even during remission. MDD with psychotic
ing (Shin et al., 2004). Some studies have found more features is associated with the most severely impaired
executive deficits in non-medicated OCD patients than in neuropsychological functioning. Psychotic MDD seems
medicated ones (Abbruzzese et al., 1995b), while differ- to be neuropsychologically more similar to schizophrenia
ences were not observed in other studies (Mataix-Cols than to non-psychotic MDD, which provides support for
et al., 2002). Also, the presence of comorbid depressive the hypothesis that psychotic depression is a diagnostic
symptoms in OCD may deepen the executive dysfunction entity distinct from non-psychotic MDD, and that it may
(Moritz et al., 2001). Gender may not affect on cognitive be genetically related to schizophrenia (Kendler et al.,
dysfunction in OCD (Mataix-Cols et al., 2006). 1993).
The profile and nature of anxiety-related cognitive
3.2.3. Deficits in post-traumatic stress disorder dysfunction seem to depend on the disorder subtype.
A few reviews on cognitive deficits in post-traumatic Impairments in executive functioning and visual
stress disorder (PTSD) have been published, and they memory appear to be evident in young adulthood
include patients of all ages (see Golier and Yehuda, 2002; OCD. The reviewed data along with the findings that
Horner and Hamner, 2002). The majority of the studies some cognitive deficits may persist even after the
about cognitive deficits in PTSD have investigated improvement of clinical symptoms, support the assump-
combat veterans or prisoners of war with PTSD, and tion of involvement of orbitofrontal–striatal system
therefore the results may not be generalizable to other dysfunction as a possible pathophysiological mecha-
populations. Moreover, the samples have mainly com- nism underlying in OCD (for a review, see Saxena et al.,
prised elderly adults. Five studies in the age group under 2001). Some cognitive deficits appear to be evident in
the present review are summarized in Table 5. Among panic disorder, PTSD and social phobia, too, but the
young adults with PTSD, impairments have been small number of published studies prevents drawing
24 A.E. Castaneda et al. / Journal of Affective Disorders 106 (2008) 1–27

firm conclusions. Few studies on these disorders and progressive disorders, since it may reduce coping
their associations with cognition have focused on a abilities, make the patient more prone to relapse and
clear-cut group on young adults. affect treatment compliance. Future research should
define whether prolongation of remission, and keeping
4.1. Methodological considerations episodes at a mild level, would associate with preserved
cognitive abilities.
There are some significant methodological issues that Furthermore, it remains unclear to what extent
should be taken into account when interpreting the results. cognitive deficits precede the depressive or anxiety
Conflicting findings may be explained by the use of disorder, and to what extent they develop subsequent to
different inclusion criteria of disorder characteristics for disorder onset. Why some patients have severe impair-
patient groups (e.g., subtype, length, age range, severity ments in cognition, some mild, while others remain in
and phase of the disorder). Inclusion of healthy control the normal range, remains unclear, too, and this can be
group may be biased, too. Group comparisons have also solved only by identifying disorder subsets and
been potentially confounded by other comorbid mental characteristics that associate with cognitive impair-
disorders. For example, cognitive deficits in panic disorder ments. Furthermore, it is unclear whether cognitive
and PTSD are strongly associated with comorbidity of dysfunction in depression and anxiety represents state or
MDD (Kaplan et al., 2006) and other disorders (Barrett trait factors, or both, in these disorders. It would be
et al., 1996). In addition, the influence of residual symp- essential to determine whether cognitive deficits are the
toms might confound studies on euthymic patients. An- result of progressive effects over the course of illness or
other common difficulty in this field of research is to whether these deficits precede the onset of illness.
control the complicating effects of medication (Wadsworth Accordingly, prospective studies starting from young
et al., 2005; for a review, see Amado-Boccara et al., 1995) adulthood or even earlier are needed to solve these
and other treatments. Many studies under the present clinically important questions, and to expand the
review have included a clinical control group, which may knowledge into clinical practice.
be of particular interest when evaluating the specificity of
results for a certain disorder. However, for examining the Role of funding source
clinical significance of the disorder symptoms on cognition, This work was supported by The Academy of Finland and the Finnish
the inclusion of a healthy control group is crucial. Graduate School of Psychiatry. Neither had a further role in study design;
The considerable diversity of neuropsychological test in the collection, analysis and interpretation of data; in the writing of the
report; and in the decision to submit the paper for publication.
methods complicates the comparability of results.
Moreover, discrepant outcomes across studies likely
Conflict of interest
reflect the small number of tests administered to
All authors declare that they have no conflicts of interest.
evaluate cognitive status. Furthermore, group-matching
procedures are sometimes inadequate, e.g., lack of
estimated general intelligence. Given the heterogeneous Acknowledgements
nature of depressive and anxiety disorders, another
common methodological shortcoming is the small This work was supported by The Academy of
sample size in many studies. It is possible that negative Finland and the Finnish Graduate School of Psychiatry.
results are due to the lack of statistical power to identify
differences between patients and the control group and References
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