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2010 The Authors

Bipolar Disorders 2010: 12: 351363 Journal compilation 2010 John Wiley & Sons A/S
BIPOLAR DISORDERS

Consensus Article

The International Society for Bipolar


DisordersBattery for Assessment
of Neurocognition (ISBD-BANC)
Yatham LN, Torres IJ, Malhi GS, Frangou S, Glahn DC, Bearden CE, Lakshmi N Yathama, Ivan J
Burdick KE, Mart nez-Aran A, Dittmann S, Goldberg JF, Ozerdem A, Torresa,b, Gin S Malhic, Sophia
Aydemir O, Chengappa KNR. The International Society for Bipolar Frangoud, David C Glahne, Carrie E
DisordersBattery for Assessment of Neurocognition (ISBD-BANC). Beardenf, Katherine E Burdickg,
Bipolar Disord 2010: 12: 351363. 2010 The Authors. Anabel Martnez-Aranh, Sandra
Journal compilation 2010 John Wiley & Sons A S.
Dittmanni, Joseph F Goldbergj,
Aysegul Ozerdemk, Omer Aydemirl
Objectives: Although cognitive impairment is recognized as an
important clinical feature of bipolar disorder, there is no standard and K N Roy Chengappam
cognitive battery that has been developed for use in bipolar disorder
research. The aims of this paper were to identify the cognitive measures
from the literature that show the greatest magnitude of impairment
in bipolar disorder, to use this information to determine whether the
Measurement and Treatment Research to Improve Cognition in
Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB),
developed for use in schizophrenia, might be suitable for bipolar
disorder research, and to propose a preliminary battery of cognitive tests
for use in bipolar disorder research.

Methods: The project was conducted under the auspices of the


International Society for Bipolar Disorders and involved a committee
that comprised researchers with international expertise in the cognitive
aspects of bipolar disorder. In order to identify cognitive tasks that
show the largest magnitude of impairment in bipolar disorder, we
reviewed the literature on studies assessing cognitive functioning
(including social cognition) in bipolar disorder. We further provided
a brief review of the cognitive overlap between schizophrenia and
bipolar disorder and evaluated the degree to which tasks included
in the MCCB (or other identied tasks) might be suitable for use doi: 10.1111/j.1399-5618.2010.00830.x
in bipolar disorder.
Key words: battery bipolar cognition
executive function mania memory
Results: Based on evidence that cognitive decits in bipolar disorder
neurocognitive neuropsychology
are similar in pattern but less severe than in schizophrenia, it was judged
that most subtests comprising the MCCB appear appropriate for use in Received 10 November 2008, revised and
bipolar disorder. In addition to MCCB tests, other specic measures of accepted for publication 14 April 2010
more complex verbal learning (e.g., the California Verbal Learning Test)
or executive function (Stroop Test, Trail Making Testpart B, Wisconsin Corresponding author:
Card Sorting Test) also show substantial impairment in bipolar disorder. Lakshmi N. Yatham, MBBS, FRCPC, MRCPsych
Division of Mood Disorders
Conclusions: Our analysis reveals that the MCCB represents a good Department of Psychiatry
starting point for assessing cognitive decits in research studies of The University of British Columbia
bipolar disorder, but that other tasks including more complex verbal UBC Hospital
learning measures and tests of executive function should also be 2255 Wesbrook Mall, Detwiler Pavilion
considered in assessing cognitive compromise in bipolar disorder. Vancouver, BC, V6T 2A1, Canada
Several promising cognitive tasks that require further study in bipolar Fax: 604-822-7922
disorder are also presented. E-mail: yatham@interchange.ubc.ca

Aliations and disclosure information for all authors are listed before the references.

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Yatham et al.

Development of a standardized neuropsycholog-


Introduction
ical battery would be benecial for bipolar disorder
Cognitive impairment is increasingly recognized as research for several reasons. First, adoption of a
a core feature of bipolar disorder (1) that is present common set of cognitive outcome measures could
in both acutely symptomatic as well as remitted facilitate interpretation of ndings across sites.
states. Although the magnitude of cognitive Currently, interpretation of discrepant ndings
impairment is likely inuenced by variables such across studies may be obscured by the use of
as medication and residual mood symptoms, these dierent measures by dierent investigators. The
factors do not appear to account fully for the use of a common set of measures across studies
neuropsychological impairments observed in remit- would decrease the variability associated with the
ted patients, leading to the proposition that cog- use of dierent measures across studies, thus
nitive impairment reects both state and trait facilitating integration and interpretation of nd-
features of the illness (2). Cognitive decits ings across studies. A further advantage is that
observed in patients are also present in rst-degree data can be more readily pooled across sites, thus
unaected relatives, which suggests that these increasing sample size and the ability to detect
decits may at least partly reect a genetic diathesis meaningful ndings or relationships among vari-
to the illness (3, 4). Cognitive decits also impact ables (e.g., meta-analysis). Finally, the adoption of
upon psychosocial and functional outcome (57) a common battery could have utility across a range
and are increasingly recognized as critical targets of important research contexts, including investi-
for treatment or rehabilitative eorts in patients gation of the relationship between bipolar
diagnosed with the illness. cognition and underlying brain structure and
Given the prevalence and adverse psychosocial function, psychosocial functional outcome meas-
impact of cognitive dysfunction in the illness, it is ures, clinical symptoms and phenotypes, genetic
imperative that appropriate cognitive measures be variables, and benecial or untoward eects of
used to improve our understanding of the nature, treatments.
severity, and correlates of cognitive decits in the In response to the need to assess the feasibility of
illness and to develop eective therapeutic strate- adopting a cognitive battery for use in bipolar
gies that target this cognitive compromise. Ideally, disorders research, the International Society for
this should involve the use of cognitive measures Bipolar Disorders (ISBD) established a committee
that have been validated in patients with bipolar of experts, chaired by Lakshmi Yatham, and
disorder. However, no standard research battery entrusted it with the task of summarizing the
exists for measuring cognition in bipolar disorder cognitive literature on bipolar disorder and, based
or measuring change in cognition following an on this literature, proposing a preliminary battery
intervention. This is in stark contrast to develop- for use in research studies of bipolar disorder.
ments in other psychiatric disorders, such as schizo- Given evidence of the overlap between neuropsy-
phrenia, in which cognitive researchers developed a chological functioning in bipolar disorder and
common battery for clinical trial purposes schizophrenia and that the MCCB had already
[Measurement and Treatment Research to Improve been established for clinical trials research in
Cognition in Schizophrenia (MATRICS) Consen- schizophrenia, a central aim was to evaluate
sus Cognitive Battery (MCCB)] (8) through the whether the MCCB or its components might also
MATRICS initiative (reviewed below). The lack of be suitable for use in bipolar disorder. The specic
consensus about what specic cognitive measures or goals of this paper were thus: (i) to identify, based
collection of measures should be used in research on the cognitive literature in bipolar disorder, the
studies of bipolar disorder can in part be traced to cognitive measures that show the greatest impair-
the relative infancy of this eld. Additionally, ment in bipolar disorder; (ii) to evaluate the degree
contemporary cognitive research in bipolar disorder to which the MCCB includes comparable measures
is diverse, and the needs of individual researchers that were identied above; and (iii) to propose a
often dictate the use of varying tasks designed for preliminary battery for use in bipolar disorder.
unique purposes. Despite this, there are many
research applications in which the goal may be to
Process
obtain a generic index of cognitive functioning using
measures that have been shown to detect cognitive Given the nature and scope of the task, the ISBD
impairments associated with the illness. In such executives and the chair of the committee agreed
cases, incorporation of a common standardized that the committee membership should include
battery for bipolar disorder would be useful and or researchers with broad expertise in bipolar disorder
warranted. as well as cognition. Thus, nominations for the
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committee membership were sought from research- studies indicate that patients with bipolar disorder
ers who published on cognitive aspects of bipolar show moderate to large impairments on tests of
disorder. The nal list of members included psychi- attention, processing speed, explicit memory, and
atrists and neuropsychologists from dierent parts several aspects of executive function. Table 1
of the world, in keeping with the ISBD mandate. provides a summary of the specic neuropsycho-
Cognitive tasks that show the greatest impair- logical measures that show the largest patient-
ment in bipolar disorder were identied from control eect size dierences across this literature
review of existing meta-analytic studies that calcu- and thus serve as primary candidates for inclusion
lated patient-control eect size dierences in cog- in a bipolar cognitive battery.
nitive functioning. This was judged to be the most
eective way of assessing the magnitude of cogni-
Beyond meta-analytic findings
tive impairment across tasks, as this type of data
analysis summarizes results across multiple studies. Executive function represents a multifaceted con-
Recognizing that the meta-analytic data exclude struct that has been frequently implicated in
less frequently studied cognitive measures that may bipolar disorder and measured using a wide range
nevertheless have some relevance to bipolar disor- of tasks without a single gold standard. While
der, we also identied promising tasks in two other medium-to-large eect sizes have been detected for
broad domains that are frequently implicated in measures of certain aspects of executive function,
bipolar disorder, namely executive function and especially response-inhibition and set-shifting tasks
emotion processing social cognition. Several tasks (see Table 1), not all executive functions are
were identied that show preliminary relevance to equally impaired in bipolar disorder patients,
bipolar disorder but that require further study. which highlights the importance of conceptualizing
In addition, we briey summarized the literature executive function as a constellation of multiple
comparing neuropsychological functioning in higher-order cognitive processes. Cognitive tasks
bipolar disorder and schizophrenia, again with an that probe distinct components of executive func-
emphasis on published meta-analytic work. We tionor are known to rely on well-dened neural
also briey described the MCCB, a consensus circuitryare needed to better disentangle some of
cognitive battery that was recently designed for these key processes. For example, the Hayling
clinical trials research in schizophrenia. In light of Sentence Completion Test (HSCT) (15) is a meas-
the recognized overlap in neurobiology, genetics, ure of inhibitory control, known to be subserved
risk factors, and clinical features, including neuro- by the ventral prefrontal cortex (VPFC), which
psychological functioning in both disorders (911), requires subjects to nish incomplete sentences
we evaluated the degree to which the MCCB may using contextually relevant (part A) or contextually
be applicable to bipolar disorder. irrelevant (part B) words. Remitted bipolar disor-
The potential utility of the MCCB for bipolar der patients show substantial impairment on
disorder was assessed by comparing the overlap this task (eects of 1 SD or greater, relative to
between the tasks identied from the review of the healthy controls) (16, 17), indicating decits in
literature on bipolar disorder and the measures inhibitory control which may relate to VPFC
included in the MCCB. A given MCCB measure dysfunction. Consistent with these ndings, using
demonstrating impairment in bipolar disorder was the Cambridge Neuropsychological Test Auto-
judged a stronger candidate for inclusion into a mated Battery (CANTAB) intra-dimensional
bipolar battery than an MCCB measure without extra-dimensional (IDED) set-shifting task,
such evidence. We also considered the possibility McKirdy et al. (18) found that euthymic bipolar
that cognitive domains or measures not included in disorder patients and schizophrenia patients
the MCCB might also be suitable for use in bipolar showed comparable decits in extra-dimensional
disorder. Finally, the psychometric properties, set-shifting and reversal learning, cognitive func-
cultural bias, ease, and simplicity of administration tions which rely on VPFC integrity. Tests of
were also considered in the nal task selection. strategy and planning (e.g., the Tower of London),
although complex, also involve an inhibitory
control component and show moderate eects in
Cognitive deficits in bipolar disorder: meta-analytic
bipolar disorder patients versus controls (11). Such
findings
measures have typically been omitted from meta-
Four recent meta-analyses by independent groups analyses of cognition in bipolar disorder, as there
have been conducted examining neuropsychologi- are few studies and very few have employed
cal decits in remitted patients with bipolar disor- identical tasks. In addition, the computerized
der relative to healthy controls (4, 1214). These Balloon Analogue Risk Task (BART) is a measure
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Yatham et al.

Table 1. List of candidate cognitive tests for inclusion in the bipolar disorder battery based on existing meta-analytic data

No. of
meta-analyses Effect size
Cognitive domain MCCB comparison Neuropsychological test including measure range

Attention/vigilance Included Continuous Performance Test


Hits omissions 3 0.580.83
Reaction time 2 0.600.62
Processing speed Included Trail Making Testpart A 4 0.520.71
BACS-Symbol Coding WAIS Digit Symbol 4 0.590.84
Included Category Fluency 2 0.871.09
Executive/working Trail Making Testpart B 4 0.550.99
memory Stroop Test 4 0.630.76
Wisconsin Card Sorting Test
Categories 4 0.520.69
Perseverative errors 3 0.700.88
COWA (letter fluency) 4 0.340.60
WAIS Number Letter Digit Span Backwards 4 0.541.02
Sequencing
Verbal learning Hopkins Verbal Learning CVLT or RAVLT
and memory TestRevised (HVLT-R) Learning 3 0.810.90
Immediate recall 4 0.730.82
Delayed recall 4 0.710.85
Visual learning Brief Visuospatial Rey Osterreith Complex Figure 2 0.590.62
and memory Memory TestRevised and WMS Visual Reproduction
(BVMT-R) Delayed Recall

Effect sizes for these measures represent the range of values reported across four existing meta-analyses. Only measures with ranges
including an effect size value of at least 0.5 were included. The MCCB column indicates whether a given test is included in the
Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB).
BACS = Brief Assessment of Cognition in Schizophrenia; WAIS = Wechsler Adult Intelligence Scale; COWA = Controlled Oral Word
Association; CVLT = California Verbal Learning Test; RAVLT = Rey Auditory Verbal Learning Test; WMS = Wechsler Memory Scale.

of risk-taking propensity (19) and thus may cap- Table 2. Promising cognitive tests that may be relevant to bipolar disorder
ture important phenotypic variance associated with Primary cognitive
faulty decision making in bipolar disorder. How- Test abilities involved
ever, only one study to date has used this task in
bipolar disorder patients (20). Bipolar disorder Hayling Sentence Completion Inhibitory control
Test (HSCT)
patients with alcohol abuse showed dierential CANTAB IDED Mental set shifting,
impairment on this task and, notably, failed to reversal learning
adjust their performance after popping balloons. In Tower of London (and variants) Planning, inhibition,
summary, decision making and response inhibition working memory
represent behavioral manifestations of a common Balloon Analogue Risk Task (BART) Decision making risk
taking
underlying biological mechanism, possibly linked Theory of Mind Advanced Test Theory of mind
to VPFC dysfunction (21). Table 2 provides a
summary of several tasks that represent promising CANTAB IDED = Cambridge Neuropsychological Test Auto-
tasks for potential future use in bipolar disorder mated Battery intra-dimensional extra-dimensional set-shifting
but at the same time require further study in this task.
disorder.
assess the ability to evaluate the emotional state
of others (facial aect recognition or discrimina-
Emotional processing and social cognition
tion paradigms). The term social cognition refers
Emotional processing and social cognition are to a complex set of processes subserving adaptive
complex, multidimensional psychological domains social interaction; these involve representation of
that are increasingly implicated in bipolar disorder internal somatic states, knowledge about the self
(22). However, this broad area has not been and others, and interpersonal motivations (23).
suciently studied to provide rm conclusions, More traditional tests of social cognition assess
and there are no meta-analytic studies summariz- participants mentalising abilities (theory of mind
ing this body of work in bipolar disorder. Emo- tests) or attitudes to societal values (23). Another
tional-processing paradigms include tasks that category of paradigms examines the interaction
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between cognition and emotion and mostly inappropriate meanings. Although bipolar disor-
includes tests of aective decision making. These der patients underperformed in this task (Cohens
require participants to use information about d = 0.55), the eect was moderated by sustained
reward-punishment contingencies in strategy for- attention. These results are somewhat encouraging
mation. A brief review of bipolar disorder studies in terms of pursuing further studies while under-
assessing emotion processing and social cognition scoring the need to clarify both the magnitude of
follows. the eect size of social cognition decits in bipolar
disorder in respect to each of the available tasks
and the relationship of social cognition to other
Emotion processing (facial affect processing)
dimensions of cognitive function such as general
Studies that examined facial aect processing in intellectual ability and attention.
bipolar disorder required participants to either
match facial identities according to the aect
Affective decision making
displayed (matching paradigms) or to name the
aect displayed (labelling paradigms). Facial iden- Tests developed to assess aective decision making
tity perception was found to be intact (eect size focus on the eect of reward and punishment on
consistently < 0.18 in all studies) in bipolar action selection. The most popular paradigms are
disorder patients both in remission (2426) and the Iowa Gambling Task (IGT) (37) and the
when in episode (2729). Facial aect recognition Cambridge Gamble Test (CGT) (38). Both involve
also appears intact in euthymic bipolar disorder simulated gambling where optimal performance is
patients (25, 26, 30, 31) with negligible or small based on participants ability to weigh short-term
eect size. The same also applies to potential gains against potential long-term losses. Their
dierential decits between dierent basic emo- main dierence relates to the fact that in the
tions. Harmer et al. (30) reported that recognition CGT participants are given explicit information
of disgust was facilitated in bipolar disorder about their odds of winning or losing at each trial
patients, but this nding was never replicated while in the IGT they are not.
either in euthymic (25, 31) or symptomatic patients There are three studies that have examined
(28, 32). aective decision making using the IGT in mania
(39, 40) and remission (21, 40) in a sample
collectively totalling 63 patients. Both Clark et al.
Theory of mind
(39) and Yechiam et al. (40) reported that manic
Currently there are six studies, recently reviewed by patients underperformed compared to controls.
Bora et al. (33), on social cognition (theory of However, the eect size of this dierence was 0.8 in
mind) that have specically focused on bipolar the former study and 0.11 in the latter. Further-
disorder. These studies involved a total of 206 more, there was no evidence in any study that
bipolar disorder patients who varied widely in their bipolar disorder patients systematically favoured
symptomatic status and were generally poorly more high-risk choices than controls. The dier-
matched to controls in terms of potential socio- ence in performance was attributable to more
demographic confounders (33). Among remitted erratic behaviour both in acutely ill and in remitted
samples, two of three studies showed signicant patients (21, 40). There are ve studies that have
dierences favoring controls over patients. How- used the CGT to examine manic (n = 18) (41) or
ever, across all samples no two studies used depressed (4144) bipolar disorder patients (cumu-
identical types or versions of social cognition tasks. lative total n = 112) compared to controls. All
Eect sizes for individual studies are either small or studies consistently reported that patients, regard-
moderate (< 0.7), with the exception of the study less of polarity, showed impaired risk-adjustment
by Sarfati et al. (34), where an eect size of 1.2 was (however, eect size was < 0.5), meaning that they
noted. This nding is likely unreliable given the were slower than controls to increase their bets as
small sample of patients (n = 10), their acutely the odds of winning became more favourable.
manic presentation at the time of testing, and their In summary, despite the central role of mood
lower general intellectual ability compared to the dysregulation to mood disorders, there are large
controls. In the largest study to date, Lahera et al. gaps in our evidence base in relation to emotional
(35) examined 75 euthymic bipolar disorder processing and social cognition in bipolar disorder.
patients and 48 demographically matched controls. Both the number of relevant studies and their
They used the Theory of Mind Advanced Test (36), sample sizes are small, thus preventing a robust
which requires subjects to make inferences both consensus to emerge. With the possible exception
about false beliefs deceptions and hidden of the Theory of Mind Advanced Test (Table 2),
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Yatham et al.

none of the tests reviewed shows particular prom- signicant cognitive decits are present early in the
ise in reliably dierentiating bipolar disorder course of illness (58). Third, meta-analyses indi-
patients from controls, particularly in remitted or cated that patients with bipolar disorder generally
euthymic patients, thus suggesting the need to perform better than patients with schizophrenia
develop new paradigms in this area. (11, 52). However, when comparisons are to a
more homogeneous subset of studies that matched
patient groups on clinical and demographic char-
Toward a candidate cognitive battery for bipolar
acteristics, the eect-size dierences between
disorder
groups were somewhat attenuated in magnitude
Bipolar disorder is recognized as a heterogeneous (52). Figure 1, based on Stefanopoulou et al. (11),
disorder, and the variable clinical presentation portrays the standard mean dierence between
extends to the cognitive domain. Although far patients with bipolar disorder and healthy com-
from conclusive, there is preliminary evidence that parison subjects and between patients with schizo-
patients with a diagnosis of bipolar I disorder (45, phrenia and healthy comparison subjects on a
46), a history of psychotic symptoms (4750), or number of common neuropsychological tests. The
increased illness burden (e.g., increased number of gure clearly shows that one area where individ-
prior hospitalizations, number of previous mood uals with bipolar disorder and those with schizo-
episodes, duration of illness) (51) may have more phrenia dier is IQ: while bipolar disorder is
severe cognitive decits. The implication of this associated with mild to moderate reductions in IQ,
cognitive heterogeneity is that a suitable cognitive those in schizophrenia are severe. Otherwise, the
battery for bipolar disorder should be able to cognitive dierences between schizophrenia and
detect the range of cognitive impairment observed bipolar disorder can best be described as quanti-
in the illness. Tables 1 and 2 provide a summary of tative rather than qualitative in nature.
cognitive tasks that have either been shown to be
impaired in a wide range of patients with bipolar
The MATRICS project
disorder (Table 1) or that show promising rele-
vance to bipolar disorder (Table 2). With these The MATRICS committee was formed, with
tasks in mind, we now turn to a discussion of the funding from the National Institute of Mental
cognitive overlap between schizophrenia and bipo- Health and additional guidance from the U.S.
lar disorder followed by the MATRICS project. Food and Drug Administration, to support the
development of pharmacological agents to treat
cognitive decits in patients with schizophrenia
Cognitive functioning in schizophrenia and bipolar
(59). A comprehensive review of the literature
disorder
identied seven separable cognitive domains that
Two recent meta-analyses compared cognitive have been shown to be reliably impaired in patients
performance in bipolar disorder and schizophrenia with schizophrenia (60). Next, the committee met
to healthy subjects (11) or to each other (52). Three and nominated a wide array of standardized
conclusions can be drawn from these reviews and cognitive measures with high psychometric quality,
other previous work. First, individuals with schizo- and specic tasks were chosen to comprise the beta
phrenia have profound cognitive impairments on a version of the MCCB (61). After testing the beta
wide variety of measures (53, 54). These decits version in a common sample and evaluating each
appear to be similar in severity in rst-episode test on several properties, including test-retest
patients and in patients with well-established illness reliability, utility as a repeated measure, practical-
(55), suggesting the presence of early cognitive ity, and tolerability (62), a nal consensus battery
decits associated with the illness (56). Against this was agreed upon by the panel (Table 3). The nal
background of generalized decit, verbal memory, version of the MCCB was then administered to 300
executive functioning, and processing speed may be community volunteers across ve sites in the U.S.
dierentially impaired. Second, patients with bipo- for purposes of co-norming and standardization
lar disorder are impaired on a wide variety of (63).
cognitive domains during acute mood episodes (2),
and decits in declarative memory, executive con-
Is the MCCB suitable for use in bipolar disorder?
trol of attention, response initiation, and inhibition
persist during remission (see Table 1). It is unclear The MCCB has now been implemented in several
if the cognitive decits in bipolar disorder represent ongoing studies of patients with schizophrenia;
a trait vulnerability or develop during the course of however, there are no published data using this
the disorder (57), although recent work suggests battery in bipolar disorder. Beyond the extensive
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ISBD-BANC

Verbal fluency
Stroop Test
WCST perseverative errors
WCST categories
Trail making B
Trail making A
CVLT recognition
CVLT long delay
CVLT learning
NART
Performance IQ
Verbal IQ
Full-scale IQ

0 0.5 1 1.5 2
Patients with bipolar disorder Patients with schizophrenia

Fig. 1. Eect size dierences in cognitive functioning between patients with either bipolar disorder or schizophrenia and healthy
controls, based on Stefanopoulou et al. (11). WCST Wisconsin Card Sorting Test; CVLT = California Verbal Learning Test;
NART = National Adult Reading Test.

Table 3. Cognitive measures included in the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery and their
potential utility for bipolar disorder

Cognitive domain Neuropsychological test Bipolar utility

Speed of processing Brief Assessment of Cognition in Schizophrenia High


(BACS): Symbol Coding
Category Fluency: Animal Naming High
Trail Making Testpart A High
Attention vigilance Continuous Performance TestIdentical Pairs (CPT-IP) High
Working memory Wechsler Memory Scale3 Letter-Number Sequencing Likely
Wechsler Memory Scale3 Spatial Span Likely
Verbal learning Hopkins Verbal Learning TestRevised Likely
Visual learning Brief Visuospatial Memory TestRevised High
Reasoning and problem solving Neuropsychological Assessment Battery (NAB): Mazes Unclear
Social cognition Mayer-Salovey-Caruso Emotional Intelligence Test Unclear
(MSCEIT): Managing Emotions

and rigorous process undertaken to devise this MCCB (64) suggests that future translational work
battery, there are several additional advantages will be made easier by inclusion of the MCCB
that could be associated with using the MCCB in subtests in current data collections.
patients with bipolar disorder. Given the expected There are also several potential disadvantages to
widespread use in large-scale trials of patients utilizing the MCCB in studies of patients with
with schizophrenia, adoption of the MCCB in bipolar disorder. As the MCCB was designed with
bipolar disorder would greatly facilitate the ability schizophrenia in mind, it is unclear whether the
to compare treatment eects on cognitive function- MCCB would be suciently sensitive to detect the
ing between patients with schizophrenia and bipolar less severe cognitive decits noted in bipolar
disorder. In addition, the MATRICS initiative disorder patients. Moreover, the MCCB was
has now completed translation of the MCCB into developed for use primarily in clinical trials, so
eight languages (German, Spanish-Spain, Spanish- its use in broader research applications in bipolar
LatinAmerica,Chinese,Russian,Hindi,Norwegian, disorder is unknown. Finally, despite the fact that
and Japanese), with several other translations decits in executive function are frequently impli-
underway, making this battery useful for interna- cated in bipolar disorder, the MCCB includes few
tional collaborations (http://www.matrics.ucla.edu/ executive functioning measures, and the ones
matrics-ct/home.html). Finally, the ongoing devel- included (Neuropsychological Assessment Battery:
opment of neuroscience-based and preclinical bat- Mazes) have generally not been studied in bipolar
teries that will parallel or complement the existing disorder.
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Yatham et al.

So how well does the MCCB meet the needs for analytic studies summarizing data from more
assessing cognition in research studies of bipolar complex verbal list learning measures (see Table 1).
disorder? There is a substantial empirical basis for This study also reported patient-control eects
proposing that all the MCCB subtests comprising sizes of approximately 0.59 and 0.67 for BVMT-R
the domains of processing speed and attention vig- immediate and delayed recall, respectively, and
ilance would be highly suitable for bipolar disor- these values fall within the range observed on other
der, as these tests (or nearly identical versions) can nonverbal memory tests in bipolar disorder (see
be found in Table 1. Although the domains of Table 1). This cursory analysis suggests that the
working memory and learning memory are highly HVLT-R, but not the BVMT-R, may show
implicated in bipolar disorder [(49, 65) (also see reduced sensitivity to detecting learning memory
Table 1)], the specic tests chosen to reect these diculty relative to other tests. In rounding out the
functions in the MCCB [Letter-Number Span, evaluation of remaining MCCB tests for use in
Spatial Span, Hopkins Verbal Learning Test bipolar disorder, the utility of the Mazes and
Revised (HVLT-R), and Brief Visuospatial Mayer-Salovey-Caruso Emotional Intelligence
Memory TestRevised (BVMT-R)] have not been Test (MSCEIT) subtests appears to be less certain,
extensively studied in bipolar disorder. Thus, until as these measures of reasoning problem solving
further research conrms the expected utility of and social cognition have not been suciently
these tests, these MCCB subtests should be con- studied in bipolar disorder to date.
sidered likely candidates for a bipolar battery. One To summarize, of the 10 major subtests that
concern is that the learning memory measures make up the MCCB battery, 5 can be considered to
included in the MCCB (HVLT-R, BVMT-R) may have high utility for use in bipolar disorders,
be less complex or dicult than the tests that have another 3 are estimated to have likely utility, and
been typically used to identify learning memory the remaining 2 can be considered to have uncer-
decit in bipolar disorder. For example, most tain utility (Table 3).
studies on verbal learning in bipolar disorder have
used the California Verbal Learning Test [(CVLT)
Proposed preliminary battery for bipolar disorder
(66)] (46, 6773), which, under some conditions,
may be better able to detect learning diculties Based on available data suggesting that most of the
than the HVLT-R, particularly in less impaired subtests in the MCCB have at least likely utility in
patients (74, 75). In one of the few prior studies detecting cognitive impairments in bipolar disor-
that compared bipolar disorder patients to healthy der, our qualied conclusion is that the MCCB is a
controls on the two learning memory tests from promising starting point for a bipolar disorder
the MCCB (HVLT-R, BVMT-R), Schretlen et al. research cognitive battery. A summary of the most
(76) reported patient-control eects sizes of highly recommended MCCB subtests for inclusion
approximately 0.42 and 0.67 for HVLT-R learning into a proposed preliminary cognitive battery for
and delayed recall scores. These values are lower bipolar disorder is provided in Table 4. Existing
than the range typically reported in the meta- cognitive research in bipolar disorder (Table 1)

Table 4. Final proposed cognitive battery for bipolar disorder

MCCB Subtest Duration


Cognitive domain Neuropsychological test subtest type (min)

Speed of processing Brief Assessment of Cognition in Schizophrenia Yes Core 3


(BACS): Symbol Coding
Category Fluency: Animal Naming Yes Core 2
Trail Making Testpart A Yes Core 2
Attention vigilance Continuous Performance TestIdentical Pairs (CPT-IP) Yes Core 13
Working memory Wechsler Memory Scale3 Letter-Number Sequencing Yes Core 6
Wechsler Memory Scale3 Spatial Span Yes Core 5
Verbal learning memory Hopkins Verbal Learning TestRevised Yes Substitute 5
Verbal learning memory California Verbal Learning Test No Substitute 10
Visual learning Brief Visuospatial Memory TestRevised Yes Core 5
Executive function Stroop Test No Core 5
Trail Making Testpart B No Core 5
Wisconsin Card Sorting Test No Optional 20

The remaining Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery
(MCCB) subtests [Neuropsychological Assessment Battery (NAB): Mazes; Mayer-Salovey-Caruso Emotional Intelligence Test
(MSCEIT)] may also be considered optional measures. Their use is encouraged in order to further data collection in bipolar disorder.

358
ISBD-BANC

also suggests that several non-MCCB tests with version conrm comparable impairment in this
large patient-control eect sizes should also be population.
strongly considered for inclusion into a proposed The nal proposed battery and the estimated
bipolar disorder battery. Specically, we propose duration of each subtest are provided in Table 4.
that the Stroop Test (77) and Trail Making Test In sum, the xed components of the proposed
part B (TMT-B) (78) should be included as core battery include the subtests from the MCCB and
subtests based on their brevity, ease of administra- the Stroop Test and TMT-B, and the exible
tion, adequate reliability and repeatability, coverage components include the use of either the HVLT-R
of executive functioning, and likely international or CVLT, as well as the optional inclusion of the
utility (79, 80). Similarly, the Wisconsin Card WCST.
Sorting Test (WCST) (81) also represents a well-
established measure of executive functioning and
Conclusion and future directions
demonstrates some utility in an international con-
text (80, 82). Nevertheless, based on its relatively The task of the ISBD Cognition Committee was to
lengthy administration time, its marginal reliability, summarize the existing literature on cognitive
and its limited utility in a test-retest context (79), we functioning in bipolar disorder, to identify
propose that the WCST be considered an optional cognitive measures that show maximal impairment
or supplemental test that should be utilized by the in bipolar disorder, to evaluate the suitability of
investigator based on specic needs. the MCCB for use in bipolar disorders, and to
Another question that will have to be considered propose a preliminary cognitive battery that could
by the individual researcher is whether to use the be applicable for international use in bipolar
HVLT-R or a test such as the CVLT as the disorders research. The proposed ISBD Battery
primary verbal learning measure within the de- for Assessment of Neurocognition (ISBD-BANC)
scribed battery. The HVLT-R may be a valid represents a preliminary cognitive battery that
option when the research study involves a direct would be expected to have utility across a range
comparison between schizophrenia and bipolar of the multiple neuropsychological research con-
disorder or, owing to the six alternate forms, when texts in the eld of bipolar disorders. The battery
there is a need to assess learning repeatedly across would be appropriate for broad research applica-
more than two time periods. Another advantage of tions where a screening of cognitive abilities is
using the HVLT-R is that it may more directly required or where repeated assessments are neces-
allow for comparison between verbal and visual sary (e.g., treatment eects, clinical trials).
learning on the HVLT-R and BVMT-R, which Even though the selection of the proposed
were co-normed during the MCCB development battery was largely based on considerable knowl-
process. Moreover, the CVLT is limited with edge regarding the neuropsychology of bipolar
regard to translation into other languages and disorder that has emerged in the past decade, there
potential for international utility. is still a great deal that is not known. While the
On the other hand, the costs of using the HVLT- current proposal is based on a summary of
R in place of the CVLT may include loss of empirical research and the committee members
sensitivity to detect verbal learning memory prob- knowledge derived from their own research
lems in bipolar disorder and consequent loss of the clinical expertise, it does not represent an empirical
ability to detect change in cognitive function across validation of a battery for this patient population.
repeated assessments. Further advantages of the Rather, the proposed battery represents a collec-
CVLT include the tests high reliability and exist- tion of established individual tests that the
ence of an alternate form for repeat testing (66, 83). committee has deemed appropriate for use in
The use of the CVLT in place of the HVLT-R may bipolar disorder research. Thus, unlike eorts like
be warranted when comparisons with schizophre- MATRICS, we have not conducted a prospective,
nia will not be made, when the goals of an psychometrically validated study on our clinical
individual study require maximal sensitivity to population of interest. Therefore, the present eort
verbal learning memory decit, or when the study should be considered a preliminary step toward
emphasizes detection of change in verbal learn- delineating a core set of cognitive tasks that have
ing memory across only two time points. Finally, likely relevance to bipolar disorder. We anticipate
although it may be assumed that the revised that these tasks and their respective functional
version of the CVLT (CVLT-2) (84, 85) would be domains, as complex or multifaceted as they may
equally appropriate to use in bipolar disorder be, will be worthy of further study, delineation,
as the original version, this conclusion should and parcellation. In some instances, the proposed
remain tentative until new studies using the revised measures may turn out to be highly relevant
359
Yatham et al.

clinical targets for treatment and rehabilitative University Medical School, Izmir, lDepartment of Psychiatry,
eorts and may thus be considered as appropriate Celal Bayar University Medical School, Manisa, Turkey,
m
Department of Psychiatry, Western Psychiatric Institute and
outcome measures. Other included tasks may be Clinic, University of Pittsburgh Medical Center, Pittsburgh,
discovered to have less utility in the future. In PA, USA.
addition to conducting future prospective bipolar
disorder research using tasks from the proposed
battery, future research should aim to further Disclosures
validate these measures in dierent languages and Over the past two years, LNY has received research grant
varying cultural contexts. funding from AstraZeneca, Bristol-Myers Squibb, and Servier;
Although the broad areas of emotion process- and has been a speaker and or a member of the advisory
boards and has received honoraria from Merck, Sano,
ing social cognition are likely to represent aspects AstraZeneca, Servier, Bristol-Myers Squibb, Eli Lilly & Co.,
of psychological function that are relevant to and Janssen. GSM has received funding for research, has served
bipolar disorder, our review suggests that a specic on a number of international and national pharmaceutical
test that shows unequivocally strong impairment in advisory boards, and has been in receipt of honoraria for talks
bipolar disorder has yet to emerge from these at sponsored meetings worldwide involving the following
companies: AstraZeneca, Eli Lilly & Co., Janssen-Cilag,
areas. Regardless, in the course of our review we Lundbeck, Organon, Pzer, Ranbaxy, Servier, and Wyeth.
have identied some of the more promising tasks AM-A has received research funding from the Spanish Ministry
comprising these broad domains (Table 2) and of Science and Innovation. JFG has served on speakers bureaus
suggest that future work should evaluate dier- or has received lecture honoraria from AstraZeneca, Eli Lilly &
ent versions of these tasks to assess their appli- Co., GlaxoSmithKline, Janssen-Cilag, Merck, and Pzer, and
has served on the advisory board for Eli Lilly & Co. IJT, SF,
cability to bipolar disorder. It is hoped that future DCG, CEB, KEB, SD, AO, OA, and KNRC have no conicts of
research in these areas will isolate specic measures interest to disclose.
that may be included in future versions of the KNRC, as co-editor of Bipolar Disorders, did not participate in
proposed or other cognitive batteries for bipolar any editorial decisions to accept or reject this paper or in
disorder. choosing any referees, which was overseen by the senior editor,
who had no conicts of interest in adjudicating the manuscript.
Ultimately, wider adoption of a common set of
standardized procedures will lead to presentation
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