Cognitive Impairment in Affective Psychoses: A Meta-analysis
Emre Bora1,2, Murat Yu ¨cel2,3, and Christos Pantelis2
2Melbourne Neuropsychiatry Centre, Department of Psychiatry,
The University of Melbourne and Melbourne Health, Australia;
3Orygen Youth Health Research Centre, The University of
It has recently been suggested that cognitive impairment
should be included in the diagnostic criteria of schizophre-
nia. One of the main arguments in support of this sugges-
tion has been the hope that cognitive impairment can help
distinguish schizophrenia from bipolar disorder (BD).
However, recent evidence shows that cognitive deficits oc-
cur in BD and persist beyond euthymia. Further, mood dis-
orders with psychotic features might be expected to
manifest greater cognitive impairment, which further com-
plicates the potential to differentiate these disorders. The
goal of the current meta-analysis was to examine the mag-
nitude and characteristics of cognitive impairments in
affective psychoses (AP). A systematic search of the exist-
ing literature sourced 27 studies that met the inclusion cri-
teria. These studies compared cognitive performances of
763 patients with AP (550 BD and 213 major depressive
disorder) and 1823 healthy controls. Meta-regression
and subgroup analyses were used to examine the effects
of moderator variables. Meta-analyses of these studies
showed that patients with AP were impaired in all 15 cog-
nitive taskswith large effect sizes for most measures. There
were no significant differences between the magnitude of
impairments betweenthe BD and majordepressive disorder
stroop task, verbal learning, and category fluency, reflect-
ing impairments in elementary and complex aspects of at-
tentional processing, as well as learning and memory. In
general, the pattern of cognitive impairments in AP was
similar to reported findings in euthymic patients with
BD, but relatively more pronounced.
Key words: schizophrenia/psychosis/bipolar disorder/
Cognitive impairment is one of the cardinal features of
schizophrenia with affected patients typically performing
0.8–1.5 SDs below the level of healthy controls across
many cognitive domains.1–4According to the results of
several meta-analyses, the most pronounced cognitive
deficits in schizophrenia are in digit symbol coding, ver-
bal learning, and general IQ (each with large to very large
effect sizes).1–4Cognitive deficits are prevalent in schizo-
phrenia with up to 80% of patients being cognitively im-
clinically relevant because they are considered to contrib-
ute to social impairments and treatment outcome in
schizophrenia.6,7Recently, severe cognitive impairment
was proposed to be part of the diagnostic criteria for
schizophrenia in the Diagnostic and Statistical Manual
of Mental Disorders (Fifth Edition) (DSM-V) and Inter-
national Classification of Diseases, Eleventh Revision
One of the arguments raised in favor of including cog-
nitive impairment within the diagnostic criteria for
schizophrenia is the potential that it can help to discrim-
inate schizophrenia from affective psychoses (AP).5
However, there is also evidence for persistent cognitive
deficits in bipolar disorder (BD), which complicates
the potential utility of cognitive impairment to differen-
tiate between these disorders.8,9For example, several
meta-analyses have recently examined cognitive deficits
in euthymic BD and found medium to large effect size
impairments for several domains that have also been
found to be impaired in schizophrenia including response
inhibition, verbal memory, category fluency, set-shifting
ability, and sustained attention.10–12Still, some authors
suggest that the severity and frequency of cognitive im-
2 disorders. For example, it has been suggested that there
are differing patterns of cognitive deficits in the major
psychoses, with deficits being less persistent and variable
in BD compared with schizophrenia.5,13
Psychotic symptoms are one of the factors that are
likely to contribute to the cognitive deficits observed in
mood disorders. A single meta-analysis confirmed that
patients with psychotic depression are cognitively more
impaired compared with their nonpsychotic counter-
parts.14Studies that investigated the effect of psychotic
cognitive deficits are
1To whom correspondence should be addressed; Melbourne
Neuropsychiatry Centre, Department of Psychiatry, The Univer-
sity of Melbourne and Melbourne Health, Alan Gilbert Building
NNF Level3,Carlton3053,Australia; tel:61-3-8345-5611,fax:61-
3-8345-5610, e-mail: firstname.lastname@example.org.
? The Author 2009. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.
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Schizophrenia Bulletin Advance Access published September 18, 2009
features on cognitive deficits in BD found less consistent
findings: while some studies reported more severe cogni-
tive deficits in working memory, verbal memory, and ex-
ecutive functions, others did not find a between-group
difference.15–18There is emerging evidence indicating
that cognitive deficits are quite common in AP. For ex-
ample, a recent study reported that 84% of the schizo-
phrenia patients, 58.3% of psychotic major depression
(MDP) patients, and 57.7% of psychotic bipolar patients
were cognitively impaired (1 SD below healthy controls
in at least 2 domains).19Moreover, a meta-analytic study
comparing the cognitive performances of schizophrenia
imately 0.5 SD lower than BD patients.20However, BD
samples in these studies included a mixture of psychotic
and nonpsychotic patients. A recent meta-analysis con-
cluded that differences between schizophrenia and AP
(psychotic depression and psychotic bipolar disorder
[BDP]) might be even smaller.21Furthermore, results
of this meta-analysis suggested that cognitive differences
between schizophrenia, schizoaffective disorders, and
AP are driven by a subgroup of schizophrenia patients
who are predominantly male and have severe negative
To our knowledge, meta-analytic methods have not
been used to estimate the magnitude and pattern of cog-
nitive impairments in AP compared with healthy con-
trols. This may be relevant for the discussions related
to inclusion of cognitive impairment criteria for schizo-
phrenia and other psychiatric disorders. The goal of
the current meta-analysis was to examine the magnitude
and BDP). Additional aims were to examine the effect of
potential moderator variables on cognitive performance
of patients with AP, including clinical variables (duration
of illness, age of onset, and symptomatic status of the
sample) and key demographic variables (gender, age,
Potential articles were identified through a literature
search in PubMed, Scopus, Psychinfo, and EMBASE
in the period between 1987 and May 2009. For the liter-
ature search, combinations of the following keywords
were used: bipolar disorder, manic-depress*, mania, de-
press*, psychosis, affective psychosis, cognit*, neuropsy-
cholog*. The last 2 terms were also replaced with the
keywords describing cognitive domains (attention, exec-
utive, or memory). The reference lists of the published
articles were also cross-referenced and reviewed.
The following criteria were used to select studies for
review: (1) assessed cognitive abilities using reliable neu-
ropsychological testing methods and were published in
English peer-reviewed journals (2) reported test scores
effect sizes for group comparisons (3) compared adult
patients with AP (depression or BD with current psy-
mood episode) (ICD-9, ICD-10, DSM-III, DSM-III-R,
or DSM-IV) with healthy controls. If there were several
relevant articles based on a single sample, studies with
a larger sample were selected. Studies that examined cog-
nitive deficits of late-onset depression were excluded be-
cause the pathophysiology of late-onset depression is
probably different from young-onset cases.
In addition to cognitive data, we recorded information
concerning the sample characteristics and potential mod-
erator variables. The clinical variables included diagno-
sis, age of onset, and duration of illness. We also
coded whether samples included first-episode (FE) or
multi-episode patients. Strictly euthymic patients were
coded as well. Demographic variables included means
and SDs of age and years of education for both groups.
Gender was coded as percentage of males. We also coded
whether the studies included a schizophrenia control
sample in addition to healthy subjects because one could
hypothesize that sites conducting research only in affec-
tive patients could misdiagnose some schizophrenia
patients as psychotic mood disorder patients. Further,
we coded the studies that included an affective control
group without a history of psychosis. We made an at-
tempt to code variables related to medication and posi-
tive and negative symptoms; however, because very few
studies reported comparable data, we did not use these
data for further analyses.
tabase searches. In the first instance, abstracts and titles
of articles were reviewed to identify relevant studies and
eliminate the studies that obviously failed to meet inclu-
sion criteria. This resulted in 101 articles that were exam-
ined further. Of these, 43 studies investigated the
cognitive profile of AP. Thirteen further studies were
excluded because they did not provide sufficient data
to calculate effect sizes, did not include a healthy control
group, or investigated cognitive deficits of late-life de-
pression. The remaining 30 studies were checked for sam-
ple overlap. Three studies were excluded because they
were based on the same sample used in other studies.
This resulted in 27 studies included in the analysis, which
are summarized in table 1.15–18,22–44In these studies,
patients were diagnosed with DSM-III, DSM-III-R,
DSM-IV, or ICD-10. In most of the studies, a structured
clinical interview was used(table 1). Fifteen of these stud-
ies included BDP patients, 7 of these studies included
MDP patients, and 5 studies included both BDP and
reported separate scores for BDP and MDP groups, so it
was possible to obtain 17 BDP-control and 9 MDP-
control comparisons. Seven of the studies included
FE samples with psychotic mood disorders based on
E. Bora et al.
Table 1. Studies included in the current meta-analysis
Gruzelier et al22
21 AP (9 BDP,
12 MDP), 29
Sex, edu DSM-III PSE,
Nelson et al23
13 MDP, 14 HCAge DSM-III-R
Morice et al24
20 BDP, 34 HCDSM-III
Most in remission
but no further
Coffman et al25
30 BDP, 52 HCSex DSM-III-R
No informationCurrent IQ
Rossi et al26
40 BDP, 64 HCDSM-III-R
Ilonen et al27
28 MDP, 30 HC Age, edu DSM-IV
Schatzberg et al2811 MDP, 23 HC SexDSM-III-R
Zubieta et al29
15 BDP, 15 HC Sex, edu,
Euthymic Premorbid IQ
Seidman et al30
15 BDP, 94 HCSex, age,
DSM-III-R History of
Cognitive Impairment in AP
Table 1. Continued
StudySample Matched Diagnosis
Wiegand et al31
17 AP (13 BDP
and 4 MDP), 17
Sex, age DSM-IV SCIDHistory of
Inpatient manic or
Premorbid IQ 0.47
Fitzgerald et al32
18 AP (13 BDP
and 5 MDP), 31
all patients are
Hill et al33
14 MDP, 81 HCSex, age,
Politis et al34
16 MDP, 20 HC SexDSM-IV SCIDLast episode
Badcock et al35
14 BDP, 33 HCDSM-IV SCID Last episode
Manic episodePremorbid IQ0.82
Glahn et al36
11 BDP, 32 HC DSM-IV SCID History of
a few patients
Gomez et al37
29 MDP, 25 HC Sex, age,
DSM-IV SCIDLast episode
E. Bora et al.
Table 1. Continued
Study SampleMatched Diagnosis
Ayres et al38
72 AP (41 BDP
and 31 MDP),
AgeDSM-IV SCID History of
UnclearLetter fluency 0.26
Glahn et al17
34 BDP, 35 HC SexDSM-IV SCIDHistory of
Bora et al16
40 BDP, 30 HCSex, age DSM-IV SCID History of
Euthymic Letter fluency
Selva et al15
18 BDP, 26 HC Sex, age DSM-IV SCAN
Mixture of manic
seem to have
Szoke et al39
52 BDP, 48 HCAge DSM-IV DIGSHistory of
Cognitive Impairment in AP
Table 1. Continued
Study SampleMatched Diagnosis
35 BDP, 35 HCSex, age,
DSM-IV SCIDHistory of
EuthymicLetter fluency 0.47
Basso et al18
24 BDP, 24 HC DSM-III-R Last episode
Severe mania Letter fluency0.61
Wang et al41
23 MDP, 53HC Sex ICD-10Last episode
Category fluency 1.27
Hill et al42
22 BDP, 21 MD,
DSM-IV SCIDLast episode
35 BDP, 274 HC Sex, edu ICD-10 PSE,
75 BDP, 280 HC Sex, ageDSM-IV SCID History of
Note: BD, bipolar disorder; BDP, psychotic bipolar disorder; DSM, Diagnostic and Statistical Manual of Mental Disorder; SCID,
Structured Clinical Interview; SADS, Schedule for Affective Disorders and Schizophrenia; FE, first episode; ICD, International
Classification of Diseases, Tenth Revision; MDP, psychotic major depression; HC, healthy controls; AP, affective psychosis; HC,
healthy controls; DIGS, diagnostic interview for genetic studies; SCAN, schedules for clinical assessment in neuropsychiatry; PSE,
present state examination; TMT, trail making test; CPT, continuous performance test; WCST, Wisconsin card sorting test; cat,
category; per, perseveration; ES, effect size (Cohen D).
E. Bora et al.
structural clinical assessment. Diagnoses of the FE
patients were BDP31,32,38,42,43and/or MDP.27,32,33,38,42
Psychosis was defined as psychotic symptoms during cur-
rent/lastmoodepisode in 14studies and ashistory ofpast
psychotic mood episodes in another 13 studies (table 1).
studies included currently psychotic patients in acute
mood episodes and 5 AP studies included currently non-
psychotic patients who were euthymic. In another 9 stud-
ies, the AP group included a mixture of symptomatic
(depressive or manic) and euthymic patients and all these
studies included some patients with current psychosis (ta-
ble 1). There was no information about current psychotic
or mood symptoms in 2 studies. Fifteen of these 27 stud-
ies also included BD or MD groups without a history of
psychosis15–18,23,27,28,33,34,36,37,39–41,44; however, we only
included the psychotic samples (current or history) in
Our primary goal was to analyze individual measures
rather than broader cognitive constructs like executive
functioning, because we aimed to compare cognitive im-
pairment in AP with the findings in remitted BD and
schizophrenia. Fifteen individual neuropsychological
variables were included in the study. Similar to other
meta-analyses in BD and schizophrenia, we combined
data across very similar tests in some instances. For ex-
ample, we combined different tasks of immediate verbal
memory such as the Rey Auditory Verbal Learning Test
and the California Verbal Learning Test. The same ap-
proach was used for delayed verbal memory tests. Differ-
ent IQ measures were combined as well, and the digit
symbol coding test and its variants were combined under
the symbol coding measure. Table 2 lists the 15 cognitive
measures we used in this meta-analysis and their referen-
ces.45–54We also summarized the findings for these tasks
from other meta-analyses conducted in schizophrenia
and remitted BD.1–4,10–12
However, we still combined individual tasks under 6
cognitive domains of the MATRICS (Measurement
and Treatment Research to Improve Cognition in
Schizophrenia) because there were not a sufficient num-
ber of studies to examine individual tests in BDP and
MDP separately.55We also calculated a summary mea-
sure, ‘‘global cognition,’’ by averaging the effect sizes
from each cognitive domain.
For each cognitive test, an effect size and standard error
was calculated. Effect sizes for each cognitive variable
Table 2. Cognitive variables included in the current meta-analysis and effect sizes of the impairments for these tasks in remitted bipolar
disorder and schizophrenia based on previous meta-analyses
Cognitive VariablesIndividual Tests Remitted Bipolar Disorder10–12
WAIS IQ and shorter forms
Vocabulary, NART, Wechsler Adult
Trail making A47
DSST and its variants0.7–0.8
Babcock story recall
Wechsler logical memory
Visual memory recall51
Trail making B47
TOVA, Conners’ CPT 0.80.9–1.2
Digit span backwards45
Note: NART, National adult reading test; DSST, Digit symbol substitution test; RAVLT, Rey Auditory Verbal Learning Test; CVLT,
California Verbal Learning Test; TOVA, test of variables of attention; WAIS, Wechsler Adult Intelligence Scale.
Cognitive Impairment in AP
from each study were calculated as the mean difference
between APandhealthy control performancedivided by
the pooled SD. Effect sizes were weighted using the in-
verse variance method. We used a random-effects
model. When multiple tests were reported for one cog-
nitive measure, one combined effect size was calculated
for these tests. Whenever patients with AP performed
more poorly than healthy controls, we reported be-
tween-group differences as positive effect sizes. There-
fore, the effect sizes for the relevant variables were
multiplied by ?1. Homogeneity of the resulting mean
weighted effect sizes was tested using the Q test. Publi-
cation bias was assessed by graphically examining fun-
nel plots and using Egger test. Meta-analyses were
performed using MIX software.56
The effects of moderator variables on observed be-
yses and meta-regressions. We used subgroup analyses
for examining the effect of diagnosis (BD or depression),
absence/presence of a schizophrenia control group, FE/
multi-episode samples, definition of psychosis, and cur-
rent psychosis on the magnitude ofpatient-control differ-
ences. We also calculated homogeneity statistics Qwand
Qbet. Qbetwas used to test the significance of differences
Table 3. Analyses of potential moderators of effect size for cognitive deficits in AP
ControlAP ES95% CI
Sch control þ/?
Sch control þ
Sch control ?
Definition of psychosis
Last episode psychotic
History of psychosis
BDP or MDP
BDP or MDP
BDP or MDP
BDP or MDP
BDP or MDP
BDP or MDP
BDP or MDP
Note: Abbreviations are explained in the first footnote to table 1. k, number of studies; AP, number of patients with diagnosis of
affective psychoses; Control, number of control subjects.
aFour different BDP or MDP samples from 2 studies.
bTwo different samples from a single study.
*P < .001, **P = .06.
E. Bora et al.
in effect size magnitude between moderator subgroups,
analogously to the F statistic. Meta-regression analyses
were usedtoestimatethe impactof between-groupdiffer-
ences of age (26 studies), gender (27 studies), and
education (21 studies) on cognitive impairment in AP.
The effects of age of onset (14 studies) and duration
of illness (14 studies) were also examined using meta-
regression. We were not able to analyze the effects of
medication and symptoms on cognitive deficits because
most of the studies did not report relevant data. Meta-
regression analyses were conducted in SPSS 11.0. These
weighted generalized least squares regressions were
performed by using the macros written by David
B. Wilson (http://mason.gmu.edu/;dwilsonb/ma.html).
Meta-regression analyses performed with random-
effects modelling were performed using the restricted-
significance level set at P < .05.
The 27 studies included in the meta-analysis compared
the cognitive performances of 763 patients with AP
(550 BDP and 213 MDP) and 1823 healthy controls.
The patient and control groups were matched for age
(d = 0.14, ?0.05 to 0.33, z = 1.47, P = .14) and gender
(48.4% of controls and 45.1% of the patients were males;
RR = 1.08, CI = 0.99–1.19, z = 1.73, P = .08). There was
a small but significant between-group difference for ed-
ucation. Specifically, patients were less well educated (d =
0.21, CI = 0.04–0.39, z = 2.35, P = .02) than controls.
There was no significant effect of diagnosis on any of
the 6 cognitive domains and global cognition (table 3).
Patient-control differences were not significantly differ-
ent for MDP and BDP. Studies that had a schizophrenic
control group were not more impaired than the studies
that did not. The definition of psychosis did not signifi-
cantly influence the magnitude of the cognitive deficit in
AP (table 3). While FE samples were also impaired com-
pared with controls, the magnitude of this deficit was sig-
nificantly smaller than multi-episode patient-control
dividual task analyses because there were no sufficient
In all the 15 analyses conducted for individual cogni-
tive measures, AP patients performed more poorly than
were large (d > 0.8). A medium degree of impairment was
found for 2 measures (visual memory and letter fluency),
while the degree of impairment for premorbid IQ and
current IQ was small. The largest effect size was found
for symbol coding (d = 1.02).
The Q tests revealed significant heterogeneity for 7 of
the tasks (stroop, symbol coding, Wisconsin card sorting
test [WCST] perseveration/category, category fluency,
verbal memory delayed/immediate). Several studies sig-
nificantly contributed to heterogeneity. The study of
Selva et al15significantly contributed to heterogeneity
for symbol coding, stroop, category fluency, and the
WCST perseveration/category and after removal of
this study, Q test results became insignificant for all these
measures (d values after removal were 0.91, 0.91, 0.94,
Table 4. Mean weighted effect sizes for individual tasks for AP and control differences
Test Studies, n
zPQ test P
Symbol coding6 5051841.020.67–1.37 5.74
<.001 .01 0.88
Stroop7 434 2230.97 0.66–1.27 6.15
Category fluency9 528 2900.96 0.71–1.207.68
Verbal memory immediate9 561 2780.950.65–1.256.21
WCST per8 393 2580.950.69–1.27 5.87
CPT6 208 133 0.930.73–1.138.76
<.001 .69 0.92
Trail making A9 344 2360.910.75–1.0711.22
Verbal memory delayed 10 5872960.900.60–1.205.94
WCST cat7 3111930.870.58–1.175.87
Trail making B 10 3922880.850.70–0.99 11.32
<.001 .53 0.21
Digit span backwards6 392288 0.830.60–1.076.88
Letter fluency9499 2910.690.53–0.86 8.17
<.001 .27 0.06
Visual memory4125 900.680.43–0.935.27
IQ5 2811330.440.10–0.772.54 .01 .050.45
Premorbid IQ8 5361900.310.09–0.522.76.005 .200.55
Note: Abbreviations are explained in the first footnote to table 1. d, effect size (Cohen D).
Cognitive Impairment in AP
0.80, and 0.74, respectively). The study of Basso et al. sig-
nificantly contributed to heterogeneity of delayed and
immediate verbal memory, and Q tests were nonsignifi-
cant after removal of this study (d values were 0.80
and 0.83). There was no evidence for a significant publi-
cation bias for any of the tasks.
Effect of Moderator Variables
When the between-group comparisons were restricted to
BDP, effect sizes were very similar to the ones obtained
for the combined AP group (table 5). To examine the ef-
fect of current mood and psychotic symptoms on cogni-
tive impairment in AP,we compared the meaneffectsizes
of studies that included psychotic patients with acute
mood episodes (d = 0.75, CI = 0.56–0.95, z = 7.6, P <
.001) and nonpsychotic euthymic patients (d = 0.69, CI =
0.50–0.88, z = 7.1, P < .001). Current symptoms did
not significantly influence the severity of the cognitive
dysfunction (Qbet= 027, P > .05). We repeated this anal-
ysis by excluding FE patients because only the currently
psychotic group included FE patients. This analysis con-
firmed that currently psychotic patients (d = 0.85, CI =
0.60–1.09, z = 6.8, P < .001) were not significantly more
impaired than euthymic patients (Qbet= 1.41, P> .05).
Meta-regression analyses did not reveal any significant
relationships between cognitive deficits and demographic
confounders (age, gender, and education) except for a re-
lationship between duration of education and 3 cognitive
measures. The patients who had a shorter duration of ed-
ucation than controls had a more pronounced deficit in
letter fluency (z = 2.38, P = .02), WCST categories (z =
2.31, P = .02), and the stroop (z = 2.23, P= .03). Differ-
ences in age ofillness onset and duration ofillness didnot
significantly contribute to the results.
To our knowledge, this is the first meta-analysis to exam-
ine the magnitude of cognitive deficits in AP. The current
meta-analysis combined results from 27 studies consist-
ing of 763 patients with AP and 1183 healthy controls
and found large effect size impairments for most of the
measures. Patients performed at least 0.8 SD lower
than controls on 11 of 15 cognitive measures with the
largest effect sizes being observed for symbol coding,
stroop interference, and verbal learning and category
In general, the pattern of cognitive impairment in AP
was similarto findingsreported ineuthymic patients with
BD, despite being minimally more pronounced.10–12For
some measures (eg, verbal and visual memory, stroop,
WCST per, premorbid IQ), the observed between-group
differences were about 0.2 SD higher than the results
reported for BD-control comparisons. Digit symbol cod-
ing was relatively more differentially affected in AP com-
pared with remitted patients with BD (1.02 vs 0.75). One
reason for the minimal increased severity of cognitive im-
pairment in AP might be explained by the influence of
psychosis. Another reason might be the effect of symp-
toms on cognitive impairment in AP because many
patients in these samples were not assessed in a remitted
phase of the illness. This is an important issue because
some authors believe that cognitive impairments in AP
Table 5. mean weighted effect sizes for individual tasks for bipolar disorder and control differences
Test Studies, n
zPQ test P
Symbol coding5 461 1621.110.75–1.47 6.00
<.001 .03 0.67
CPT4 105 104 0.980.74–1.22 7.95
Trail making A7 296 1960.96 0.79–1.1410.68
WCST per8 363 2300.950.63–1.27 5.87
<.001 .001 0.05
Stroop5 386 183 0.940.53–1.354.52
Verbal memory immediate7 521 238 0.900.54–1.25 4.94
Digit span backwards4 337231 0.900.53–1.284.71
Category fluency7 450238 0.870.59–1.156.18
WCST cat7 298 1820.870.58–1.165.87
Trail making B8 344 2480.830.66–1.09.74
Verbal memory delayed8 5392560.810.50–1.13 5.13
Letter fluency8474 2620.690.51–0.89 7.23
Visual memory3 102 790.670.39–0.944.79
IQ4 215 990.520.14–0.892.68.01 .070.39
Premorbid IQ6488 1500.250.01–0.502.02 .04 .230.94
Note: Abbreviations are explained in the first footnote to table 1.
E. Bora et al.
are nonpersistent symptoms of the illness.5In this study,
a preliminary analysis suggested that the magnitude of
cognitive impairment was very similar in euthymic and
currently psychotic AP. These findings are in line with
previous meta-analyses that found substantial impair-
ment in remitted BD patients.10–12However, these find-
ings do no rule out a significant role for symptoms in the
cognitive impairment of psychotic depression because
there are no controlled studies in patients with remitted
major depression who also have a history of psychosis.
Other factors like severity of illness and number of
mood episodes could also contribute to cognitive impair-
ment, but we were not able to examine the effect of these
variables due to lack of reported data.57,58Long-term
effects of antipsychotics could also play a role because
psychotic patients are likely to use these medications
deficits for many of the measures in AP are comparable
with the impairments reported for schizophrenia.1–4The
severity of impairments in executive functions, sustained
attention, and working memory are all similar to those
observed in schizophrenia. This result could have impli-
cations for the inclusion of cognitive impairment in the
diagnostic criteria for psychoses in DSM-V. However,
there are other factors that should be considered in inter-
preting these findings. Most importantly, cognitive defi-
cits could worsen in AP but not in schizophrenia during
acute episodes and psychotic episodes. If schizophrenia
patients differ from AP when they are nonpsychotic,
this would suggest that these 2 diagnostic entities are
somewhat discrepant with regard to cognitive impair-
ment. Our previous meta-analysis, which examined stud-
ies comparing cognitive functioning in schizophrenia and
AP, provide relevant data regarding this issue.21That
meta-analysis suggested that cognitive differences be-
tween schizophrenia and AP were very minimal in
both inpatient and outpatient samples. However, further
research is clearly needed to investigate the effect of
symptomatic status on the observed differences between
schizophrenia and AP.
Findings of the current meta-analysis also suggest that
impairments in several cognitive domains in AP are not
as pronounced as those in schizophrenia. For example,
previous meta-analyses conducted in schizophrenia
reported more substantial global intellectual impairment
in schizophrenia. This result is consistent with studies
that found IQ deficits to be apparent before the onset
of psychosis in schizophrenia but not in mood disor-
ders.59,60Symbol coding tasks, a measure of information
processing efficiency, were also more impaired in schizo-
phrenia. This is interesting in light of a recent meta-anal-
ysis, which found that symbol coding impairment was
processing inefficiency may be the central feature of
many of the higher order cognitive deficits observed in
schizophrenia.3These deficits might be related more
to schizophrenia-specific brain abnormalities and, con-
sistent with this idea, both low IQ and information pro-
cessing inefficiency have been reported to be associated
with gray matter abnormalities.61
of the findings in AP is the effect of diagnosis. AP groups
consisted of a mixture of BDP and MDP patients. Our
results indicate a similar level of cognitive impairment
when results were analyzed separately in patients with
BDP. Moreover, MDP-control and BDP-control differ-
ences were not significantly different. However, these
results should be interpreted with caution because the
number of studies that included patients with psychotic
depression were relatively small. Studies that compare
cognitive performance of patients with psychotic depres-
sion and BDP are important in order to show possible
differences between these groups. To date, only a few
studies compared the cognitive functioning of these
groups, and they have not provided any evidence for
between-group cognitive differences.19,62
The current study does not provide any information
regarding longitudinal progression of cognitive deficits
from early to chronic phases of illness. Only 6 of the stud-
ies included in the meta-analysis investigated cognitive
impairment in FE patients with AP.27,31,32,38Like the
cognitive impairments in FE patients with AP. However,
the magnitude of these deficits was significantly less than
in that multi-episode patients. Very few studies have in-
vestigated cognitive deficits in individuals at high risk for
psychosis, providing some evidence for cognitive deficits
prior to the onset of psychosis.64,65Previous cross-
sectional and longitudinal studies in schizophrenia inves-
tigated cognitive impairments in different phases of ill-
ness from preonset to FE and chronic stages.66–68
A similar approach should be applied to cognitive re-
search of AP and mood disorders. The outcome of this
research is also relevant to examining the developmental
model suggested by Murray et al because this model sug-
gests a shared genetic predisposition (and shared neuro-
biological markers) between BD and schizophrenia and
schizophrenia-specific additional neurodevelopmental
One of the limitations of the current meta-analysis
was the lack of data about potential moderator factors
in some studies. One of these factors was antipsychotic
treatment, which can clearly influence the observed
cognitive deficits in AP. On the one hand, antipsy-
chotics could be expected to moderately improve cog-
nitive deficits in AP because atypical antipsychotics
have been shown to be moderately beneficial for cogni-
tive deficits in schizophrenia.69,70On the other hand,
antipsychotics could be associated with poorer cogni-
tive deficits functioning in AP: Patients with more se-
vere prognosis and more severe and acute symptoms
Cognitive Impairment in AP
could be treated with larger doses of antipsychotics. In
line with this possibility, some authors reported an as-
sociation between poorer cognition and antipsychotics
in BD.58,71However, we were unable to examine the in-
fluence of this variable because very few studies reported
between-studies comparable data. Also, age of onset and
duration of illness are among a number of other variables
that could have an impact on cognitive impairments in
AP. We analyzed the effect of these variables on cognitive
impairments and did not find any significant influence of
beinterpretedwithcaution because onlysomeofthe stud-
ies reported these variables.
The results of the current meta-analysis might have im-
portant implications regarding current discussions about
the inclusion of cognitive impairment as a criterion in
diagnostic criteria for schizophrenia.5First, together
with the meta-analyses in remitted BD, they show that
cognitive deficits are characteristic features of nonschiz-
ophrenic psychoses. Some of these observed impairments
are similar in severity compared with those observed in
schizophrenia, and in some others, schizophrenia
patients are moderately more impaired. These results ar-
impairment criteria in the diagnosis of schizophrenia can
increase our ability to differentiate between schizophre-
nia and BD. Our results could be interpreted as being
in line with the hypothesized psychosis continuum be-
tween schizophrenia, BD, and depressive disorder.72,73
Second, results of these studies suggest that there might
be deficits in some cognitive domains that can be rela-
tively more specific to schizophrenia such as processing
speed and global intelligence.
In conclusion, the findings ofthe current meta-analysis
confirm that cognitive impairment is also a common
characteristic of AP. This indicates the necessity of inves-
done in schizophrenia (ie, longitudinal and FE studies).
Future research efforts regarding management of cogni-
tive deficits should also target patients with AP because
these deficits are likely to be associated with functional
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NHMRC Clinical Career Development Award (ID:
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