Schizophrenia Bulletin Advance Access published September 23, 2009
Schizophrenia Bulletin
doi:10.1093/schbul/sbp094
Cognitive Impairment in Schizophrenia and Affective Psychoses: Implications for
DSM-V Criteria and Beyond
Emre Bora1,2, Murat Yücel2,3, and Christos Pantelis2
2
Melbourne Neuropsychiatry Centre, Department of Psychiatry,
The University of Melbourne and Melbourne Health, Australia;
3
Orygen Youth Health Research Centre, The University of
Melbourne, Australia
It has recently been suggested that the diagnostic criteria of
schizophrenia should include specific reference to cognitive
impairments characterizing the disorder. Arguments in
support of this assertion contend that such inclusion would
not only serve to increase the awareness of cognitive deficits
in affected patients, among both clinicians and researchers
alike, but also increase the ‘‘point of rarity’’ between
schizophrenia and mood disorders. The aim of the current
article is to examine this latter assertion in light of the re-
cent opinion piece provided by Keefe and Fenton (Keefe
RSE, Fenton WS. How should DSM-V criteria for schizo-
phrenia include cognitive impairment? Schizophr Bull.
2007;33:912–920). Through literature review, we explore
the issue of whether cognitive deficits do in fact differenti-
ate the major psychoses. The overall results of this inquiry
suggest that inclusion of cognitive impairment criteria in
Diagnostic and Statistical Manual of Mental Disorders
(Fifth Edition) (DSM-V) would not provide a major ad-
vancement in discriminating schizophrenia from bipolar
disorder and affective psychoses. Therefore, while cognitive
impairment should be included in DSM-V, it should not dic-
tate diagnostic specificity—at least not until more compre-
hensive evidence-based reviews of the current diagnostic
system have been undertaken. Based on this evidence, we
consider several alternatives for the DSM-V definition
of cognitive impairment in schizophrenia, including (1)
the inclusion of cognitive impairment as a specifier and
(2) the definition of cognitive impairment as a dimension
within a hybrid categorical-dimensional system. Given
the state of current evidence, these possibilities appear to
represent the most parsimonious approaches to the inclu-
1
To whom correspondence should be addressed; Melbourne
Neuropsychiatry Centre, Department of Psychiatry, The
University of Melbourne and Melbourne Health, Alan Gilbert
Building NNF Level 3, Carlton 3053, Australia; tel: 61-3-8345-
5611, fax: 61-3-8345-5610, e-mail: boremre@gmail.com
Ó The Author 2009. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.
For permissions, please email: journals.permissions@oxfordjournals.org.
1
sion of cognitive deficits in the diagnostic criteria of schizo-
phrenia and, potentially, of mood disorders.
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Key words: schizophrenia/psychosis/bipolar disorder/
depression/cognition
Introduction
Cognitive deficits are common and clinically relevant
features of schizophrenia and are important indices of
functional and treatment outcomes in patients.1–8 There
is a growing consensus regarding the importance of incor-
porating cognitive deficits into the major diagnostic sys-
tems, including Diagnostic and Statistical Manual of
Mental Disorders and International Classification of Dis-
eases. Recently, it has been suggested that the diagnostic
criteria for schizophrenia should specifically include a cri-
terion pertaining to cognitive ability. One such possibility
would require ‘‘a level of cognitive functioning suggesting
a consistent severe impairment and/or a significant de-
cline from premorbid levels considering the patient’s ed-
ucational, familial and socioeconomic background.’’1,6
Clearly, inclusion of such a criterion would increase
the awareness of the importance of cognitive dysfunction
in schizophrenia and would ideally lead to routine admin-
istration of brief cognitive assessment tools by clinical
providers. There is little doubt that this represents a desir-
able outcome that would help stimulate the development
of new treatment methods and promote better manage-
ment of cognitive impairments in this disorder.
The advantages of this approach have been thoroughly
discussed in 2 recent opinion articles by Keefe6 and by
Keefe and Fenton.1 One of the main arguments support-
ing the inclusion of cognitive impairment as a diagnostic
criterion is the expectation that such qualification of the
clinical picture would help define a ‘‘point of rarity’’ be-
tween schizophrenia and closely associated affective dis-
orders. Keefe and Fenton1 discuss the existing literature
on cognitive differences between schizophrenia and bipo-
lar disorder (BD) and conclude that these 2 clinical enti-
ties may be cognitively separable. Moreover, Keefe and
Fenton.1 suggest that schizoaffective (SA) disorders may
also be cognitively differentiated from BD. However, we
E. Bora et al.

disagree with this contention on the basis of the available

literature, including the results of our own recent meta-
analytic studies in each of these disorders. This issue is of
critical importance as the outcome of this discussion will
impact on the awareness and understanding of the nature
of cognitive impairment in schizophrenia and affective
disorders among both research and clinical communities
alike. How then should we define cognitive impairment in
schizophrenia? What are the consequences of different
definitions of cognitive impairment to the development
of valid diagnostic systems? And what should be done re-
garding the recognition of cognitive impairment in affec-
tive disorders?

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In this article, we first discuss the evidence regarding
cognitive distinctions that discriminate schizophrenia
from mood disorders in the context of the reviews pro-
vided by Keefe and Fenton.1 We provide an updated
viewpoint on this issue due to the inclusion of several
meta-analyses focusing on cognitive deficits in affective
disorders that have been published since the Diagnostic
and Statistical Manual of Mental Disorders (Fifth Edi-
tion) (DSM-V) meeting on deconstructing psychosis,
upon which Keefe and Fenton1 based their recent
work. Our group has also conducted 3 relevant meta-
analyses that further elaborate and help to characterize
the cognitive profile of BD, affective psychoses, and their
distinction from the cognitive profile of schizophrenia.
Our second objective will be to discuss alternative
approaches to the inclusion of cognitive impairment in
the diagnostic classification of schizophrenia and affec-
tive disorders.
Diagnostic Differences in Cognition
Cognitive Deficits in Schizophrenia, Affective Psychoses,
and Remitted BD
A number of meta-analyses have examined the magni-
tude of cognitive impairment in schizophrenia.2–5 Large
effect sizes (ESs; between 1.0–1.5; see figure 1a), repre-
senting robust impairments, have been reported across
a multitude of cognitive domains, including current
IQ, category fluency, verbal memory, sustained atten-
tion, and response inhibition. In particular, the symbol
coding task yields some of the most robust impairments,
with very large ESs reported (between 1.5–1.6).
Several meta-analyses have also examined cognitive def-
icits in remitted BD.9–11 Results of the most recent of these
studies is summarized in figure 1a and 1b.11 It should be
noted that while figure 1a and 1b substantially differ from
the relevant figure presented by Keefe and Fenton,1 this is
due to the inclusion of more updated information, includ-
ing the results of recent meta-analyses, rather than inclu-
sion of additional individual studies. As can be seen in
these figures, pronounced deficits (ESs between 0.70–
0.86) in verbal memory, response inhibition, sustained at-
tention, executive functions, working memory, and sym-
2
Fig. 1. Effect Sizes of Cognitive Deficits in Schizophrenia, Affective
Psychoses, and Euthymic BD.
bol coding are in evidence. A meta-analysis undertaken
by our group (Bora et al17) additionally examined cogni-
tive differences between patients with affective psychoses
(BD or major depressive disorder [MDD] with history of
psychosis) and healthy controls. In this analysis, impair-
ment in symbol coding was found to be the most robust
deficit in patients with affective psychoses (ES of 1.0),
alongside large impairments in a number of other domains
including response inhibition, verbal learning, and cate-
gory fluency. Interestingly, when the analysis was re-
stricted specifically to psychotic BD, the magnitude and
pattern of impairments remained very similar.
These results suggest that cognitive impairment is ap-
parent not only in schizophrenia but also in affective psy-
choses and BD. Comparing across the 3 groups, very
similar profiles and levels of impairment are apparent
in a number of the reported cognitive domains. The
most notable difference between these groups appears
to be a greater general impairment in patients with
schizophrenia, particularly given indices of current and
premorbid IQ, symbol coding, and category fluency.
Diagnostic Differences in Severity of Cognitive
Impairment
One prominent argument supporting the inclusion of
cognitive impairment in the diagnostic criteria of

schizophrenia has been the suggestion that cognitive def-
icits are more severe in this disorder than in BD. A recent
meta-analysis investigating this issue concluded that cog-
nitive deficits in schizophrenia were indeed about 0.3–0.6
ES greater across a number of cognitive domains as com-
pared with BD.12 This between-group difference was
found to be most pronounced for verbal fluency, working
memory, verbal and visual memory, mental speed, and
executive control (ES = 0.4–0.6). However, these differ-
ences were not sufficiently large to differentiate the 2 dis-
orders because an average difference of ES of 0.5 would
indicate that 31% of patients with BD would perform
worse than the average patient with schizophrenia.12
Furthermore, it could be argued that differences be-
tween schizophrenia and psychotic mood disorders
may be even smaller in magnitude due to evidence sug-
gesting that psychosis might have a negative impact on
cognition in BD.13–16 In a recent meta-analysis, we exam-
ined cognitive differences between major psychoses by
comparing the cognitive functioning of patients with
schizophrenia, SA disorder, and affective psychoses
(BD or MDD patients with a history of psychotic fea-
tures).17 The most pronounced differences between
schizophrenia and psychotic mood disorders were in
the domains of verbal learning and current IQ (approx-
imately 0.4 ES), while the between-group differences for
working memory, processing speed, executive control,
and verbal fluency were minimal (0.2–0.3 ES). In this
meta-analysis, demographic variability of the schizophre-
nia cohort investigated between studies was also found to
be an important determinant of the extent of the between-
group differences. Specifically, studies that included
a greater proportion of male patients and patients with
more severe negative symptoms, as compared with the
affective psychosis group, were more likely to find be-
tween-group cognitive differences. Associations between
cognitive deficits, negative symptoms, and younger onset
of the illness were also apparent. These findings could be
explained in 3 ways: Firstly, they may simply reflect a gen-
eral gender bias in cognition. Secondly, consistent with
dimensional approaches, there may be a simple gradient
of severity running across the major psychoses. If this
were the case, poor cognition and more severe negative
symptoms would be more common in schizophrenia
due to the fact that a patient with a poor prognosis
receives a diagnosis of schizophrenia. However, one po-
tential argument refuting this view contends that gender
does not appear to be a marker of poor prognosis in BD
or major depression.18–20 Moreover, there is little evi-
dence that cognitive impairment in males with affective
disorders is of any greater magnitude than their female
counterparts. Additionally, a meta-analytic review did
not find any negative effect of an increased male ratio
in BD.11,21 Finally, these results might suggest that the
observed group differences between schizophrenia and
affective psychoses were driven by a subgroup of schizo-
Cognition and DSM-V
phrenia patients (more commonly males) with a poor
prognosis. If this were the case, there would be no sub-
stantive evidence to support the notion that magnitude of
cognitive impairment can differentiate between affective
psychoses and most schizophrenia patients.
Cognitive Impairment and Clinical State
Keefe and Fenton1 argue that one of the main differences
between the cognitive profiles of schizophrenia and mood
disorders is the more state-dependent nature of cognitive
deficits in the latter. For that reason, it was suggested that
cognitive impairment criteria should emphasize the con-
sistency of cognitive deficits in schizophrenia in order to
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increase the point of rarity between the disorders.
There is sufficient evidence showing long-term stability
of cognitive deficits in schizophrenia.22–24 Also, a signif-
icant number of longitudinal studies have examined the
relationship between symptomatic improvement and
cognition in schizophrenia, and, as Keefe and Fenton1
have suggested, these studies do not support a substantial
association between improvements in symptoms and re-
covery of cognitive functioning.24–27 For example, in the
recent European First Episode Schizophrenia Trial
study, which included 498 first-episode patients with
schizophrenia or schizophreniform disorder, cognitive
improvement, and symptoms were only weakly corre-
lated.26 This is also the case for chronic schizophrenia
patients, and a recent meta-analysis of longitudinal stud-
ies did not find a significant effect of changes in symp-
toms on cognitive improvements.27
However, the results of previous meta-analyses clearly
demonstrate that cognitive impairment also persists
throughout euthymic states in BD.9–11 While only
a few longitudinal studies have examined cognitive defi-
cits in BD, recent evidence suggests that cognitive impair-
ment might also be stable over the long term.28,29 These
results, as in schizophrenia, suggest that cognitive impair-
ment is not simply a by-product of other symptom
domains in BD. The findings of recent studies in unaf-
fected first-degree relatives of BD also suggest that cog-
nitive impairment might be a trait-related feature of
BD.10,11,30,31 Unlike BD, however, there is less evidence
for cognitive impairments in remitted patients with a his-
tory of depression.32 Further studies are needed to exam-
ine cognitive deficits in remitted patients with major
depression, especially psychotic depression because there
is clear evidence showing that the cognitive profiles of
patients with psychotic depression are unique in compar-
ison with those of their nonpsychotic counterparts.33 We
believe that evidence at least in BD argues against the
utility of using stability of cognitive impairment as
a tool for increasing the point of rarity between schizo-
phrenia and mood disorders. However, we share Keefe
and Fenton’s1 opinion regarding the importance of
emphasizing the consistency of cognitive impairments
when operationalizing the impairment criteria because
3
E. Bora et al.
symptomatic patients with either schizophrenia or BD
could still elicit relatively greater impairments in some
cognitive domains when compared with their remitted
states (despite the fact that cognitive improvement is
not correlated with change in symptom scales).34–38
For example, working memory has been shown to im-
prove following recovery of acute psychosis in both con-
ditions.37
Prevalence of Cognitive Impairments in Schizophrenia and
Mood Disorders
Without doubt, cognitive impairment is a common and
cardinal feature of schizophrenia, with more than 80% of
patients showing significant impairment (according to a 1
SD impairment criterion).1 However, studies investigat-
ing cognitive impairment in affective disorders also pro-
vide evidence for a substantial prevalence of such deficits.
As detailed above, in BD, the negative ES across several
cognitive domains is approximately 0.8.11 Similarly, in
a recent meta-analysis, we examined the magnitude of
neuropsychological impairment in affective psychoses
(MDD or BD with psychotic features), yielding
a mean impairment ES of approximately 1 SD across sev-
eral cognitive domains. Given such evidence, if a 1.0 SD
impairment criterion were to be applied, almost 40% of
remitted BD patients and half of patients with affective
psychoses would meet criteria for impairment (figure 2).
The results of a recent study undertaken by Reichenberg
et al39 corroborate our estimations. In this study, the
authors defined cognitive impairment as 1 SD below nor-
mal in 2 or more cognitive domains, resulting in 84% of
their schizophrenia patients, 58.3% of psychotic major
depression patients, and 57.7% of psychotic BD patients
meeting impairment criteria. These results suggest that
there is a significant overlap between the major psychoses
when 1 SD is used as the diagnostic threshold.
As discussed by Gold,40 one alternative approach to
increasing the diagnostic specificity of cognitive impair-
Fig. 2. Prevalence of Cognitive Impairment in Schizophrenia,
Affective Psychoses, and Euthymic BD.
4
ment would be to use a more conservative criterion (eg 2
SDs below the norm). Gualtieri and Morgan41 reported
that only 30% of patients with BD and 4% of normal con-
trols fell below the 2 SD impairment threshold in at least
2 cognitive domains. However, more stringent criteria
would also decrease the sensitivity of detecting cognitive
impairments in clinical populations. Even in the severely
impaired sample of Wilk et al,42 only half of the patients
performed below 2 SDs from the norm. In fact, results of
meta-analyses conducted in schizophrenia would esti-
mate that an even smaller percentage of patients would
meet impairment criteria given such a stringent thresh-
old.2–5 However, use of a more stringent cognitive im-
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pairment criterion would also effectively cause
a division of schizophrenia into 2 entities (cognitively im-
paired and cognitively unimpaired).
Early Cognitive Decline in Schizophrenia
There is evidence indicating that subjects who later de-
velop schizophrenia have cognitive impairment during
their childhood and adolescence.43,44 However, there is
less evidence for a similar premorbid intellectual impair-
ment in affective disorders.43,44 While few studies have
compared premorbid intellectual impairments in patients
who later develop schizophrenia or BD, most of these
studies report premorbid IQ impairments only in the
schizophreniform group.43–45 There is also evidence of
early progressive preonset cognitive impairment from
childhood to late adolescence in schizophrenia.1,46 As dis-
cussed by Keefe,6 these findings are somewhat specific to
schizophrenia, with a general lack of similar evidence re-
garding preonset intellectual impairments in affective dis-
orders.1
Nevertheless, early cognitive decline may not differen-
tiate between schizophrenia and affective psychoses due
to the fact that IQ deficits in early adolescence are ob-
served only in a subgroup of patients who later go on
to develop schizophrenia.47,48 The most compelling study
regarding premorbid IQ in schizophrenia is based on
a population-based cohort of 555 326 adolescents who
were assessed prior to recruitment into the army.48 In
this study, while 1856 of these adolescents (76% male)
were later diagnosed with schizophrenia, only 33% had
low IQ (<85) prior to illness onset. Also, among patients
with apparently normal IQ, a subgroup (23%) still had
lower than expected intellectual capacity based on a dis-
crepancy between actual and expected IQ scores. Never-
theless, according to this study, only half of the patients
could be considered to have had a premorbid intellectual
impairment. Furthermore, this ratio was probably an
overestimate because the study sample was biased toward
inclusion of more severe cases and male patients. These
findings suggest that while early cognitive decline is po-
tentially specific to schizophrenia, it is not common
enough to reliably differentiate between most cases of
schizophrenia and affective psychoses.

Summary of Case for Diagnostic Differences in Cognition
As discussed above, defining the severity and prevalence of
cognitive impairment would not help to differentiate
schizophrenia from other major psychoses due to the sig-
nificant overlap of cognitive performance between syn-
dromes. Further, because early intellectual decline is
a characteristic limited to a subgroup of patients with
schizophrenia, it would also serve little use in differentiat-
ing between these disorders. Emphasizing stability of the
cognitiveimpairment wouldnotbea solutioneither,ascog-
nitive deficits persist regardless of symptom state in both
schizophrenia (ie, following resolution of first-rank symp-
toms) and BD (ie, during periods of euthymia). Therefore,
we suggest that introducing cognitive impairment as an in-
clusion criterion for diagnostic purposes would not serve to
increase the point of rarity between the major psychoses.
How to Define Cognitive Impairment in Schizophrenia?
Keefe and Fenton’s Proposal
As Keefe and Fenton1 have suggested, it could still be desir-
able to include cognition in the diagnostic criteria of schizo-
phrenia as this may effectively increase the awareness of
cognitive dysfunction in clinical practice. Inclusion of cogni-
tive impairment criteria could also pave the way for research
efforts to focus more explicitly on treatment avenues target-
ing cognitive remediation. The emphasis that Keefe and
Fenton1 place on recognizing the stability of cognitive def-
icits over time and the importance of decline from premorbid
levels of cognitive functioning is also important.
Keefe and Fenton’s1 recommendations regarding the in-
clusion of cognitive characteristics in the diagnostic crite-
ria of schizophrenia could be interpreted in several ways.
Firstly, they may have considered cognitive impairment as
a gateway criterion for the diagnosis of the disorder. One
potential problem with this approach, however, is that it
would result in the reclassification of substantial numbers
(depending on the severity of impairment incorporated in
the definition) of schizophrenia patients who would no
longer meet diagnostic criteria for the disorder. Con-
versely, it is also possible that Keefe and Fenton1 only con-
sidered adding cognitive impairment as a criterion within
section A of DSM-V. This change would not necessarily
influence the diagnosis of patients with cognitive impair-
ment. However, for those patients who were cognitively
intact, it would be more difficult to satisfy criteria for
the disorder (eg, if 3 clinical symptoms were required as
compared with the current 2). This approach would still
lead to a reclassification of some, but not all, patients
with schizophrenia who were not cognitively impaired.
Alternative Approaches for Inclusion of Cognitive
Impairment in Schizophrenia
To our knowledge, the psychosis working group for
DSM-V is not advocating the inclusion of cognition as
Cognition and DSM-V
part of the diagnostic criteria for schizophrenia. How-
ever, there may be several alternative ways to include cog-
nitive impairment in the diagnostic classification of
schizophrenia. One approach would involve the use of
cognitive impairment as a specifier, rather than an inclu-
sion criterion. This is similar to the current practice used
in obsessive-compulsive disorder of further classifying
the syndrome using insight as a specifier. Moreover,
within such a system, cognitive impairment could be
further defined as ‘‘moderate’’ (1 SD impairment in at
least 2 domains) or ‘‘severe’’ (2 SD impairments in at least
2 domains). This approach would increase attention to,
and awareness of, cognitive deficits in schizophrenia
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without causing diagnostic shifts.
A second alternative would involve adoption of a di-
mensional approach to clinical classification. While
replacing the categorical classification system with a di-
mensional approach represents one possibility to refining
the current diagnostic system, such a radical option is un-
likely to be accepted at this stage. However, a more fea-
sible change is one in which the classification system is
based on a hybrid model of categorical and dimensional
approaches. In both alternatives, cognitive impairment
would be represented as one of the dimensions within
the system. In a hybrid system, a patient meeting diagnos-
tic criteria for schizophrenia would be further defined
according to the severity of their symptoms within differ-
ent dimensions (such as positive and negative symptoms
and cognitive impairment). Akin to using cognitive im-
pairment as a specifier, this approach would prevent di-
agnostic shifts based on cognitive impairments.
We contend that, at this stage, DSM-V should cer-
tainly include cognitive impairment in the diagnostic clas-
sification of schizophrenia but through means that would
not exclude cases based on their relatively preserved cog-
nitive abilities. We suggest that incorporating cognitive
impairment either as a specifier or as a dimension within
a hybrid classification system would provide the most ap-
propriate means of satisfying this agenda. Additionally,
in line with Keefe and Fenton,1 the state independent na-
ture of the cognitive deficits should be emphasized, and
the severity of the impairment should be clearly defined.
Looking to the future, the addition of cognitive impair-
ment as an inclusion criterion for schizophrenia should
not be considered until such time as there is consistent
evidence for a specific impairment that can differentiate
between the major psychoses. At present, it is unlikely
that cognitive impairment can help to differentiate
schizophrenia from mood disorders based on current di-
agnostic boundaries. This does not necessarily mean that
we should consider major psychoses, including affective
psychoses and schizophrenia as a unitary concept. The
potential utility of cognitive testing as a tool to better un-
derstand heterogeneous entities within the major psycho-
ses and schizophrenia should be tested rigorously. While
historically there has been some suggestion that poor
5
E. Bora et al.
functioning schizophrenia cases should be differentiated
from patients with better prognoses (ie, type 1 and 2 schizo-
phrenia),49,50 these subtypes have been thought to lack val-
idity and stability.50 More recently, it has been proposed
that there exists a ‘‘deficit’’ schizophrenia subtype, which
appears to be a more reliable diagnosis.51 Indeed, ‘‘deficit’’
schizophrenia patients are more cognitively impaired
(approximately 0.5 ES) as compared with their nondeficit
counterparts.52 However, a 0.5 SD difference in cognitive
ability still indicates a significant overlap in the cognitive
performance of both groups and limits its utility in distin-
guishing between subtypes. Also, this category does not
adequately represent schizophrenia patients with poor
prognoses because only 15%–20% of all cases would be
classified into this category.50 Future neurobiological
and clinical research, as well as developments in genetics,
could lead to a more effective subtyping of schizophrenia
and mood disorders. In that case, the inclusion of specific
cognitive criteria may be helpful in distinguishing between
subtypes of these disorders. Alternatively, cognitive defi-
cits could prove to be a common dimension of all major
psychoses that differ only in relative severity.
Finally, we suggest that cognitive impairment should
also be considered as a specifier of BD and psychotic de-
pression. There is already sufficient evidence supporting
the stability and persistence of cognitive deficits in euthy-
mic patients with BD, and currently available literature
points toward consistent cognitive impairment in late-
onset depression.53 Inclusion of a cognitive specifier or
dimension, at least as a research norm, could lead to in-
creased attention to cognitive deficits in mood disorders,
which in turn may help to differentiate between syn-
dromes within the mood disorders spectrum.
Funding
National Health and Medical Research Council
(NHMRC) Program Grant (ID: 566529 to C.P.).
NHMRC Clinical Career Development Award (ID:
509345 to M.Y.). Melbourne Neuropsychiatry Centre
to E.B.
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