REVIEW ARTICLEPSYCHIATRY

published: 08 August 2013
doi: 10.3389/fpsyt.2013.00087

Cognitive impairment in bipolar disorder andschizophrenia: a systematic review
Paul A. Vöhringer 1,2,3 *, Sergio A. Barroilhet 2,4 , Andrea Amerio 2,5 , Maria Laura Reale 2,6 , Katherine Alvear 7 ,Derick Vergne 2 and S. Nassir Ghaemi 8,91

Unidad de Trastornos del Ánimo, Clínica Psiquiátrica, Departamento de Psiquiatria, Facultad Medicina, Hospital Clínico Universidad de Chile, Santiago, Chile
Mood Disorders Program, Tufts Medical Center, Boston, MA, USA
3
Harvard School of Public Health, Boston, MA, USA
4
Escuela de Psicología, Universidad de los Andes, Santiago, Chile
5
Section of Psychiatry, Department of Neuroscience, University of Parma, Parma, Italy
6
Department of Psychiatry, Parmenio Piñero Hospital, Buenos Aires, Argentina
7
Universidad Diego Portales, Santiago, Chile
8
Tufts University School of Medicine, Boston, MA, USA
9
Director Mood Disorders Program, Tufts Medical Center, Boston, MA, USA
2

Edited by:
Pablo A. Gaspar, Hospital Clinico de la
Universidad de Chile, Chile
Reviewed by:
Joseph H. Callicott, National Institutesof Health, USA
Bernhard J. Mitterauer,
Volitronics-Institute for Basic
Research Psychopathology and Brain
Philosophy, Austria*Correspondence:
Paul A. Vöhringer , Mood Disorders
Program, Tufts Medical Center, 800
Washington Street #1007, Boston,
MA 02111, USAe-mail: pvohringer@
tuftsmedicalcenter.org

Aims: Previous comparisons of cognitive decline among patients with bipolar disorder (BD)and schizophrenia (SZ) have found somehow quite similar profiles of deficits, but results
have varied between studies. Therefore an extensive and thoughtful systematic review ofthe matter is warranted.
Methods: Studies were found through systematic search (PubMed) following PRISMA
guidelines. To be included, studies must have assessed the following cognitive functions:executive functions, memory, IQ, attention-concentration, and perceptuomotor function.
In order to make comparison between the two entities, studies should include BD patientswith operationally defined euthymia, schizophrenic patients in remission, and third groupof healthy control patients. Comparisons were made after controlling for years of schoolingand residual affective symptoms.
Results: We found that overall both SZ and BD patients present deficits on all neurocognitive measures compared to healthy controls. In particular, SZ patients show more severe
and pervasive cognitive deficits while BD patients present a milder and more confined
impairment. In addition, evidence from the literature suggests that SZ and BD patients
share a similar cognitive impairment profile with different degrees of deficits.Therefore, thedifference between the two groups seems to be more quantitative (degree of deficit) rather
than qualitative (profile), supporting a dimensional approach to the two clinical entities. Limitations of the present review includes the impossibility to control for effects of medication,
varying time required for assessment across studies, illness diagnosis reliability, and course
severity.
Conclusion: Patients with BD might exhibit a cognitive impairment that could be similar to SZ in terms of their profile, although patients with SZ may have more severe andwidespread impairments.
Keywords: systematic review, cognitive impairment, schizophrenia, bipolar disorder, working memory

INTRODUCTION
In his landmark paper “The Diagnosis and Prognosis of Dementia
Praecox” presented in Heidelberg in 1898 (1), German psychiatrist
Emil Kraepelin discussed the results of his methodical observationof patients by stating that in dementia praecox “The prognosis,
however, is really by no means simple. Whether dementia praecox
is susceptible of a complete and permanent recovery . . . is still very
doubtful, if not impossible. But improvements are not at all unusual. . .. It is a more serious matter that in most of these cases the improvement is only temporary, and that such patients are in great danger

www.frontiersin.org

of relapsing sooner or later, without any particular cause, and thengenerally suffer more serious injury from their illness.” He distinguished dementia praecox from an apparently less severe course
illness that was reported in 13% of his patients. The idea that an
illness with a course potentially severe as dementia praecox and a“spontaneous recovery” was difficult to accept in the nineteenth
century Germany psychiatry. In addition Kraepelin saw Dementia
Praecox as a “disease process in the brain, involving the cortical neurones [and brought about] by an autointoxication . . . as a result of
a disorder of metabolism” (2).

August 2013 | Volume 4 | Article 87 | 1

Vöhringer et al.

Although the course of illness, as understood by Kraepelin,pointed to a differentiate Manic Depressive Insanity (current bipolar disorder – BD) from Dementia Praecox (current Schizophrenia – SZ) in terms of degree of cognitive deterioration (Dementia),
research in the last decade has begun to shed some light into thelong term course of BD. In addition, they have also reported that in
BD different cognitive domains deteriorate in remarkable similar
ways as SZ. In other words, although Kraepelin’s great insight has
led to the proper qualitative differentiation between these remarkably similar illnesses, recent prospective observational studies (3)have shown that BD and SZ share similar dimensional characteristics in terms of neurocognitive domains. Data from recent
meta-analysis conducted in BD and SZ are in line with these findings. Depp et al. and Fett et al. reported a similar mean correlation
between overall neurocognitive ability and everyday functioning(4, 5). Mann-Wrobel et al., similarly though less severely thanin SZ (6), reported a broadly generalized cognitive impairment
in euthymic BD patients with verbal ability as a possible areaof preserved performance (7). Neuropsychological deficits represent a core feature of BD and SZ; however, their onset andprogression differ between diagnostic groups. (8). For instance,
although cognitive deterioration can appear from the outset inboth disorders, in BD, as compared to SZ, it follows a progressive
longitudinal worsening related to the number and the intensity ofmood episodes (9). This might reflect different brain structuraland functional alterations related to BD exacerbations. Imaging
studies have shown alterations in regions related to emotional andcognitive functioning. A meta-analysis by Bora et al showed graymatter reductions are more circumscribed to these areas whencontrolling by gender. Modest differences between both disorders
were found, with SZ patients showing higher dorsomedial and dorsolateral prefrontal cortex affectation compared with BD (10). In
functional studies frontal-subcortical structures show abnormalities in both disorders with common hyper-activation of emotional
limbic regions in relation to prefrontal-cortical regions. In addition, BD has shown more pronounced chronic hypo-activation ofventral-medial regions (11). The end result of this apparent connectivity abnormality may result in a glutamatergic transmission
excess in key memory and processing regions with concomitant
excitotoxicity and neurocognitive sequelae in BD (12). Moreover,modern techniques in molecular biology and neuroanatomical
immunocytochemistry have established that both disorders shareneuronal pathological markers in brain areas as hippocampus that
correlate with neurocognitive sequelae (13, 14).
The aim of this systematic review is twofold: (i) describe andcompare the neuropsychological dysfunction between BD and SZ
patients as addressed by included studies; (ii) investigate the courseof illness to better differentiate and predict onset and progressionof these two disorders.

METHODS
To identify studies reporting cognitive impairment in BD and
SZ we searched PubMed database for the period between
2008/01/31 and 2013/01/31, following PRISMA guideline recommendations (15). We combined the search strategy of freetext terms and exploded MESH headings as following: [((SZAND bipolar AND control) AND (neurocogniti∗ OR cognitive

Frontiers in Psychiatry | Schizophrenia

Cognitive comparison between bipolar disorder and schizophrenia

OR neuropsycholog∗ )) NOT (Gen∗ (MeSH Major Topic) OR
Neuroimag∗ (MeSH Major Topic))]. Additional studies were identified by reviewing the references of each article found, method
deemed appropriated by recent articles seeking similar objectives as ours (4, 10). The search cutoff date was the last day ofJanuary 2013. Criteria for inclusion in this study were:(a) publication Full text available in English, (b) inclusion of a BD groupwith operationally defined euthymia, a schizophrenic group inremission and a healthy comparison group (studies that did not
directly compare the three groups were excluded), (c) recruitmentof adult population (18 years or older), (d) meta-analysis, controlled clinical trial, systematic reviews, comparative study, andrandomized controlled trial, (e) assessment of the following cognitive functions: executive functions, memory, IQ or educational
level, attention-concentration, and perceptuomotor function. Key
words and application of inclusion/exclusion criteria resulted
in 18 papers. Additionally we performed a second search using
the algorithm (“premorbid” OR “pre-morbid” OR “at risk” OR“prodrom”) AND (schizoph∗ AND bipolar) AND (cognition OR
neurocogniti∗ OR neuropsycholog∗ ) AND [Meta-Analysis(ptyp)
OR Randomized Controlled Trial(ptyp) OR Review(ptyp) AND“last 5 years” (PDat)]. This algorithm yielded to one additional
review (8) with same aims as ours. Additional 22 records wereidentified trough bibliographic cross-referencing. After removing 1 duplicate study, 39 records were screened. Application ofinclusion/exclusion criteria resulted in exclusion of 29 studies: 16
were out the search interval dates, 2 lacked either schizophrenic or
euthymic bipolar group, and 1 lacked of a control group, 3 werefocused on differential neuroimaging. 2 were focused on genetics,
and 4 on the effect of treatment alternatives (CBT, Befriending,
ECT, and Ziprasidone), 1 studied only bipolar patients and discussed comparatively with SZ. As shown in Table 1, key words
and application of inclusion/exclusion criteria finally resulted in
10 papers.
Two reviewers extracted all data independently (Sergio A. Barroilhet and Paul A. Vöhringer). Discrepancies between reviewers
were resolved through discussion until consensus was reached.

RESULTS
Findings from studies that analyzed the cognitive profile ofpatients with SZ and BD when compared with healthy controls(HC) are summarized in Table 2.
Reviewed studies found that overall both SZ and BD patients
present deficits on almost all neurocognitive measures comparedto HC, with few exceptions in some domains (16, 17) for somesample comparisons (18, 19). In particular, SZ patients show more
severe and pervasive cognitive deficits while BD patients present
a milder and more confined impairment (20). In addition, evidence from the literature suggests that SZ and BD patients sharea similar cognitive impairment profile with different degrees of
deficits. Therefore, the difference between the two groups seems
to be more quantitative (degree of deficit) rather than qualitative(profile), supporting a dimensional approach to the two clinicalentities (21).
With regard to the course of the disease, authors report that in
BD patient’s cognitive deficits persist during periods of euthymia,
which implies that cognitive deficits are not uniquely associated

August 2013 | Volume 4 | Article 87 | 2

Vöhringer et al.

Cognitive comparison between bipolar disorder and schizophrenia

Table 1 | Included studies.
Study

Sample characteristics

Barrett et al.

SZ (SZ = 44, SZA = 2, age = 29)

Global intellectual functioning: WASI two-test version, vocabulary, and matrix reasoning(17) in

BD/mania (n = 32, age = 37)

Verbal attention and working memory (digit span forward/backward from WMS)

Lewandowski

HC (n = 67, mean age = 32)

et al. (8)Materials

Spatial attention: Corsi Block-Tapping Test
Verbal memory: paired associates WMS
Visual memory: ROCFT
Response inhibition and attentional set shifting: Hayling and Brixton Tests
Verbal fluency: COWATT
Language: Perin’s Spoonerisms
Callosal function: TFL

Brissos et al.
(16)

SZ remitted (n = 23, mean age = 37)
BD type I euthymic (n = 30, mean age = 36)
HC (n = 23, mean age = 37)

Attention and mental control: WMS digit span
Perceptual-motor skills: SDMT and TMT-A
Executive functions: SCT and SCWT, TMT-B, and ToH
Verbal fluency: COWA
Verbal abstraction: WAIS: comprehension and similarities subtests
Visuo-spatial attention: Bell’s Test
Memory function: WAIS: information subtest, WMS: logical memory

Brissos et al.

SZ remitted (n = 35, mean age = 40)

Attention and mental control: mental tracking, digit span forward (WMS), Bell’s Test

(20)

BD type I euthymic (HPS+ = 44, mean

Processing speed: Symbol Digit Modalities Test, TMT-A

age = 39; HPS− = 35, mean age 38)

Executive functions: Digit Span backward, SCT and SCWT, TMT-B, ToH,HC (n = 50, mean age = 34)

COWAT – animal naming
Test of verbal fluency: WAIS-R comprehension and similarities subtests
Verbal memory: WAIS-R – information subtest, WMS – logical memory

Gogos et al.
(24)

SZ non-psychotic (n = 38, mean age = 43)
BD euthymic (n = 40, mean age = 42)

Immediate memory/learning, visuo-spatial ability, language, attention, and delayed
memory: RBANS domain scores and total score

HC (n = 43, mean age = 41)
Joshua et al.
(18)

SZ not acute phase (n = 39, mean age = 42)
BD not acute phase (n = 40, mean age = 42)

Executive functioning (response initiation, response suppression, and an error pattern):
HSCT

HC (n = 44, mean age = 41)
Rossell andBatty (25)SZ (n = 32, mean age = 36)
BD/mania (n = 28, mean age = 39)

Word comprehension across grammatical categories, i.e., nouns, verbs, and adjectives

HC (n = 32, mean age = 37)
Sanchez-Morla

BD (n = 73, mean age = 44)

Executive function. Concept formation and shifting: WCST. Planning and problem

et al. (23)(BD I = 55, BD II = 18)

solving: ToH. Verbal fluency: COWAT. Semantic fluency: Animal Naming Test
Executive control: TMT-B and SCWT. Verbal working memory: WAIS-R digit subtest,

SZ (n = 88, mean age = 39)
HC (n = 67, mean age = 44)

digits backward. Sustained attention. Degraded stimulus CPT
Verbal learning and memory: CVLTVisual memory: ROCFT

Simonsen et

SZ (n = 102, mean age = 32)

Verbal learning and memory: Logical Memory Test (WMS-III) and CVLT-II, with sub scoreal. (19)

SZA (n = 27, mean age = 34)

measures of verbal learning and recall

BD I or II (n = 136, mean age = 36)

Processing speed: Digit Symbol Test WAIS-III

BD with psychosis = 75

Working memory: Digit Span Test – backward (WAIS-III) and WM-MA

HC (n = 280, mean age = 36)

Verbal fluency: Verbal Fluency Test (D-KEFS), with measures of phonetic fluency,
semantic fluency, and semantic fluency set shift
Interference: Color Word Interference Test (D-KEFS), with subscore for interference
control and interference set shift(Continued)

www.frontiersin.org

August 2013 | Volume 4 | Article 87 | 3

Vöhringer et al.

Cognitive comparison between bipolar disorder and schizophrenia

Table 1 | Continued
Study

Sample characteristics

Materials

Wobrock et al.

SZ first episode (n = 11, mean age = 30)

Deficits in attention, speed processing, and psychomotor performance: RT1 single(22)

SZ chronic (n = 13, mean age = 35)

stimulus and RT3 compound stimulus (subtests of the WTS)
Divided attention task: “Geteilte Aufmerksamkeit” (subtest of TAP)BD (n = 18, mean age = 42)
HC (n = 23, mean age = 30)

Psychomotor performance and speed: ZVT, a test similar to the TMT-A
Attention and working memory: digit span task “Zahlennachsprechen” (a subtest of the
HAWIE), working memory test “Arbeitsgedächtnis” (subtest of the TAP)
Visuo-spatial working memory: Corsi Block-Tapping Test (of WTS battery), Test of Spatial
Recognition Memory (CANTAB)
Verbal learning and memory: VLMT, similar to the CVLT
Non-verbal learning capacity: NVLT, subtest of WTS
Verbal fluency: RWT
Deficits in concept formation, cognitive flexibility, and executive functions: WCST and
TOLIntermodal comparison: “Intermodaler Vergleich” (subtest of the TAP). Interference:“Stroop” task (subtest of the WTS), word (Stroop-LI) and color (Stroop-BI) interference
conditions

Zanelli et al.
(28)

SZ (n = 65, mean age = 27)
BD (n = 37, mean age = 28)

Learning and memory: RAVLT, visual reproduction subtest of the WMS–R
Executive functions and working memory: TMT-B; LNST, RCPM series AB and B

OP (n = 46, mean age = 29)

Attention, concentration, and processing speed: TMT-A and WAIS-R digit symbol subtest

Depressive psychosis (n = 39, mean

Language: WAIS-R category fluency (semantic and letter fluency tasks)

age = 37)

Visual-spatial perception and organization: set A of RCPM and WAIS-R Block Design

HC (n = 177, mean age = 37)

Verbal intelligence: WAIS-R vocabulary and comprehension subtests

HC, healthy controls; SZ, schizophrenia; BD, bipolar disorder; SZA, schizoaffective disorder; SZF, schizophreniform disorder; HPS+, with history of psychosis; HPS−,
without history of psychosis; OP, other psychotic disorders (persistent delusional disorders, acute and transient psychotic disorders, other non-organic psychotic
disorders, and unspecified non-organic psychosis).
CANTAB, Cambridge Neuropsychological Test Automated Battery; COWAT, Controlled Oral Word Association Test; CPT, Continuous Performance Test; CVLT, California
Verbal Learning Test; D-KEFS, Delis–Kaplan Executive Function System; DP, Depressive Psychosis; HSCT, Hayling Sentence Completion Test; LNST, Letter-Number
Span Test; NVLT, “Non-verbaler Lerntest”; RAVLT, Rey Auditory Verbal Learning Test; RBANS, Repeatable Battery for the Assessment of Neuropsychological Status;
RCPM, Raven’s Colored Progressive Matrices; ROCFT, Rey–Osterrieth Complex FigureTest; RT1, “Reaktionstest” single stimulus; RT3, “Z” compound stimulus; RWT,
“Regensburger Wortflüssigkeits-Test”; SCT, Stroop Color Test; SCWT, Stroop Color-Write Test; TFLT, Tactile Finger Localization Test; SDMT, Symbol Digit Modalities
Test; TAP, “Aufmerksamkeitsprüfung” test battery; TMT-A, Trail Making Test part A; TMT-B, Trail Making Test part B; ToH, Hanoi Towers Test; TOL, Tower of London Test;
VLMT, “Verbaler Lern und Merkfähigkeitstest”; Voc, WAIS Vocabulary subtest; WAIS-R/-III, Wechsler Adult Intelligence Scale (Revised/Third Edition); WASI, Wechsler
Abbreviated Scale of Intelligence; WCST, Wisconsin Card Sorting Test; WM, working memory; WM-MA, Working Memory-Mental Arithmetic Test; WMS, Wechsler
Memory Scale; WTS, Wiener Test System; ZVT, “Zahlenverbindungstest.”

with the clinical manifestations of BD. In this context, neurocognitive impairment would be considered a trait rather than astate-specific feature.
EXECUTIVE FUNCTIONS

Cognitive flexibility, inhibitory control, working memory andfluency, among others, were considered.
To analyze executive functions authors used tests that assess
cognitive flexibility through attention shifting tasks (Trail Making
Test – Part B; TMT-B, Brixton Spatial Anticipation Test; BSAT, Wisconsin Card Sorting Test; WCST) and tests that assess inhibitory
control through selective attention tasks (Stroop Color Test; SCT,
Stroop Color-Write Test; SCWT, Hayling Sentence Completion
Test; HSCT).
With regard to cognitive flexibility, SZ patients showed more
perseverative responses with poorer WCST scores as compared toBD patients and HC after adjusting for gender, age, and durationof education (p = 0.002 and 0.026, respectively) (22).

Frontiers in Psychiatry | Schizophrenia

Brissos et al., Joshua et al., Sanchez-Morla et al., reported that
BD patients performed intermediately between SZ patients and
HC on stimulus inhibition and speed information processing (16,18, 23).
Studies investigating working memory used a variety of different tests (Attention Test Battery; TAP, Digit Spam Test; WAISIII, Working Memory-Mental Arithmetic Test; WM-MA). They
showed that SZ patients performed poorly as compared to HC(19, 22). In addition, Sanchez-Morla et al. emphasize significant
differences between SZ and BD patients with worse results inthe former group (Digits Backward – WAIS-R: 4.5 (±1.9) and
4.9 (±1.9), respectively, p < 0.003; after adjusting for age, yearsof education, gender, subclinical depressive symptomatology, andpremorbid IQ) (23).
Similar trends were reported when analyzing verbal fluency;
SZ patients performing worse relative to HC (Verbal Fluency
Test, D-KEFS: phonetic: 37.8 (±12.3) vs. 44.9 (±10.8), semantic: 39.0 (±10.6) vs. 48.1 (±8.4), set shifting: 12.0 (±2.5) vs. 14.7

August 2013 | Volume 4 | Article 87 | 4

www.frontiersin.org

Executive functions and(24)

Gogos et al.

BD patients persisted during
the entire course of thememorySZ < BD, HC on visuo-spatial

extended amount of timeattention focused for anthat required keeping

found using different tests

euthymia. Similar results

disease including periods ofAttention deficits in SZ and

SZ < BD, HC on delayedand delayed memory

SZ = BD on attention

SZ < HC on attention

memory/learning

Matched for IQ(Continued)

functioning

overall cognitive

SZ < BD, HC on

during euthymia

SZ, BD < HC on language

impairment

strongly related with poor
selective attention

cognitive

deficient inhibitory control,with more severe

not associatedinterpreted as a proxy of

not IQ

BD HPS+ was

qualitative differences)

Not assessed

Controlled for
educational level,

SZ and HC

between pt withsignificantly, BD

in incongruent tasks is

SZ < BD < HC on immediate

SZ > BD HPS+, HPS−, HC in
slowness and perseveration

Not assessed

functions (only quantitative, notmemory function

Not assessed

entire course of the diseasesignificance

SZ, BD < HC on verbal

BD pt persisted during thedifferences didn’t reach statisticalprocessing speed, executive

Attention deficits in SZ andbetween SZ pt and HC although

SZ < BD < HC on mental control,

processing

BD pt performed intermediately(20)

intermediately

perceptual-motor skills

automatic and attentional

and information processing(16)

Brissos et al.

pt performed

BD, SZ < HC on

SZ < BD, HC on simple

No differences

BD, SZ < HC in stimulus inhibition,

Brissos et al.

including periods of euthymia

deficits

the two groups

callosal functioning

Although not“pattern” ofcompared to HC
BD > SZ inintermediate results between

inhibition, verbal fluency andcurrent IQ score

IQ = BD: similar

current IQ scores

BD pt are reported to have

SZ < BD < HC on response

et al. (8)“preserved”

premorbid andperformances by first episodeNotes

episodeLewandowski

IQ

SZ withNo differences

functions

Perceptuomotor

BD and SZ pt

BD, SZ < HC, impaired in

Attention

disclosed lower

functioning and language by first

Memoryverbal and visual memory

BD, SZ < HC, impaired on executive(17) inlanguage

Barrett et al.

Study

Table 2 | Findings.

Vöhringer et al.
Cognitive comparison between bipolar disorder and schizophrenia

August 2013 | Volume 4 | Article 87 | 5

Frontiers in Psychiatry | Schizophrenia
groups presented similar
performance with difficulties
in identifying the correct word
meaning in the presence of

retrieval (more executive task)

SZ = BD = HC on word

comprehension across grammaticalcategories (depend on executive

regulation)

Batty (25)entire course of the disease
euthymia

Verbal Memory Tests

SZ = BD on executive control,

BD pt persisted during thesemantic fluency

SZ vs. BD: mixed results inworking memory

SZ, BD < HC
Attention deficits in SZ andincluding during periods ofand delayed visual memory

SZ < BD: executive control, verbal

et al. (23)planning and problem solving, andSZ < BD < HC in immediate

SZ, BD < HC on all tasks

Sanchez-Morlaalternatives

recognition, both clinical

SZ < BD, HC on the semantic

Rossell anderrors

SZ > BD, HC on semantically relateddifferences with either SZ or control)

Not assessed

Controlled for IQ

SZ, BD < HC

Controlled for IQ

SZ

and different frommatched for IQ,

BD and HC(Continued)

psychosis

without historyof psychosis = BD

BD with history

functioning in BD

visual memory

memory andexecutive, verbal

correlated with

Duration of illness

word meanings

and categorize

ability to organizea shortfall in

SZ and BD show

differ, from HC

scored in the middle with ns.

Not assessed

functioning
BD group did not

Not assessed

executive

differences with either SZ or control)

SZ, BD < HC on semantic

measures ofscored in the middle with ns.

SZ > HC on response errors (BDimpaired on all

SZ group was

dysfunction)
SZ > HC on response latency (BDControlled for IQ

significantly

Not assessed

Not assessed

Not assessed

Notes

performance (overall executive

IQ

SZ < BD, control on overall HSCT

Perceptuomotor(18)

Attention

Joshua et al.

MemoryfunctionsExecutive functions andlanguage

Study

Table 2 | Continued

Vöhringer et al.
Cognitive comparison between bipolar disorder and schizophrenia

August 2013 | Volume 4 | Article 87 | 6

www.frontiersin.org<HC on psychomotor

episode <HC on attention

SZ pt have decreased verbal
learning and memory
performances as compared toHC. BD pt are reported tohave intermediate results
between the two groups

on speed, verbal fluency, and verbal

working memory

With regard to cognitive flexibility,

SZ pt showed more perseverative

responses with poorer WCST

scores as compared to BD pt and(22)

SZ pt showed

reported withregard to current
IQ

learning and category fluency, andon the TMT-B

WAIS-R, Wechsler Adult Intelligence Scale Revised; WCST, Wisconsin Card Sorting Test.

TMT-A, Trail Making Test part A; TMT-B, Trail Making Test part B; HDRS, Hamilton Depressive Rating Scale; YMRS, Young Mania Rating Scale; SCWT, Stroop Color-Write Test; CPT, Continuous Performance Test;

HC, healthy controls; SZ, schizophrenia; BD, bipolar disorder; SZA, schizoaffective disorder; SZF, schizophreniform disorder; Pt, patients; NART, National Adult Reading Test; SDMT, Symbol Digit Modalities Test;

BD < HC on category fluency

OP < HC on verbal learninggroups wereDP < HC on measures of verbal

between clinical

SZ < HC on the Letter-Number Span

Test

the rest
Similar pattern

fluencypoorerchronic showed

SZ acute andperformance thansignificant poorer

examined studies

Not assessedto HC in allmeasures

BD and HC

performance thanshowed a poorer

SZ pt overalldesignBD < HC on measures of category

delayed verbal memory

to HC

results comparedsignificant poorer

SZ pt showed

results comparedand comprehension, digit symbol,(28)

performancecompared to psychotic BD pt

Test – WAIS-III scores as

showed lower Dygit Symbol

speeding. In particular, SZ pt

measures of processing

performed poorly than HC on

letter-number span, and block

SZ < BD on measures of vocabulary

Zanelli et al.

SZ < BD < HC in overall

SZ pt chronic and first episode

SZ pt chronic and first

Both first episode and chronic

SZ chronic and first episode <HC

Wobrock et al.

BD < HC on measures ofon all measures

between them. Other pt with athe two groups

performed poorer

HC

performed poorly

differences were shown

intermediate results between

from digit symbol where theyhistory of psychosis (SZ, SZA)

psychosis

compared to HC. No significant

BD pt are reported to haveneurocognitive subscores, aparthistory ofperceptuomotor functions as

and memory

All patients with a

BD HPS− = HC on all

Controlled for IQ

non-psychotic pt reported lower

SZ < BD, HC

Both psychotic and

Not assessed<BD, HC on verbal learning

SZ, SZA, BD with psychosis

Notes

SZ, SZA, BD HPS+, <BD, HPS−,IQ

HC on set shifting verbal fluency

Perceptuomotoral. (19)

Attention

Simonsen et

MemoryfunctionsExecutive functions andlanguage

Study

Table 2 | Continued

Vöhringer et al.
Cognitive comparison between bipolar disorder and schizophrenia

August 2013 | Volume 4 | Article 87 | 7

Vöhringer et al.

(±2.7), p < 0.001, after adjusting for demographic variables, current symptom measures, and illness course variables) (19). BD
patients performed intermediately between the two groups (17).
MEMORY

There is strong evidence that both first episode and chronic SZ
patients have decreased verbal learning and memory performances
as compared to HC. BD patients are reported to have intermediate
results between the two groups (17, 19, 22–25).
In particular, a study conducted in Australia on 32 SZ and 28 BD
patients explored the semantic retrieval (Generate condition) andthe semantic recognition (Forced choice condition): SZ patients
performed significantly poorer compared to HC on semantic
retrieval (MRC Oxford Psycholinguistic Database Generate condition total score: 49.7 (±20.4) and 74.1 (±17.8), respectively,
p < 0.001; after adjusting for premorbid IQ) (25). Similar findings were reported in other studies (26, 27). On the contrary, BDpatients did not present significant impairment. With regard tosemantic recognition, both clinical groups presented similar performance with difficulties in identifying the correct word meaning
in the presence of alternatives (MRC Oxford Psycholinguistic
Database Forced choice condition total score: 72.7 (±16.0) and75.1 (±17.0), respectively vs. 88.0 (±5.6) in HC, p < 0.001; after
adjusting for premorbid IQ) (25).
Sanchez-Morla et al. examined visual memory on 88 SZ and 73
BD patients using Rey-Osterreith Complex Figure Test (ROCFT).
They found significant differences in immediate and delayed visualmemory among the three groups, with BD patients performingintermediately between SZ patients and HC (23).
IQ

Several studies analyzed premorbid IQ in SZ and BD patients using
tests based on measures of current ability though to be relatively
insensitive to brain dysfunction (17, 23).
Patients affected by SZ showed significant poorer results compared to HC in all examined studies (22, 28). Two studies showedthat BD patients disclosed lower scores compared to HC (Vocabulary Subtest – WAIS-R: 103.8 (±19.5) and 108.9 (±17.8), respectively, p < 0.0001; National Adult Reading Test – NART IQ: 103.29(±11.88) and 107.74 (± 9.98), respectively, p < 0.05) (17, 23). Similar pattern between clinical groups were reported with regard tocurrent IQ (17, 28).
ATTENTION

Some authors reported that attention deficits in SZ and BD
patients persisted during the entire course of the disease including
during periods of euthymia (16, 23, 24, 29, 30).
Researchers described similar degree of sustained attention
impairment in SZ and BD patients. In particular, a study conducted in Spain in 2009 measured – using the Continuous Performance Test (CPT) – lower number of hits and a longer reaction
time in both SZ and BD patients as compared to HC (CPT:hits: 26.2 (±10.4), 30.7 (±8.7), and 34.6 (±6.2), respectively,
p < 0.037; Furthermore, the reaction time was longer for SZ and
BD compared with HC (ms): 550 (±94), 540 (±98), and 480(±65), respectively, p < 0.0001; after adjusting for the effect ofage, years of education, gender, subclinical depressive symptomatology, and premorbid IQ) (23). Others reported similar finding
Frontiers in Psychiatry | Schizophrenia

Cognitive comparison between bipolar disorder and schizophrenia

using different tests that required keeping attention focused for an
extended amount of time (Repeatable Battery for the Assessmentof Neuropsychological Status; RBANS, Subtest Attention, Digit
Spam, and Coding) (24).
Based on results of the Stroop Test, Brissos et al. described
increased slowness and perseveration in incongruent tasks in SZ
patients as compared to BD patients (with or without history ofpsychotic symptoms) and HC and interpreted it as a proxy ofdeficient inhibitory control, strongly related with poor selective
attention (20).
PERCEPTUOMOTOR FUNCTIONS

Simonsen et al. divided the BD study population in psychotic andnon-psychotic subjects. Both categories reported lower perceptuomotor functions as compared to controls. No significant differences were shown between them. Other patients with a historyof psychosis (SZ, schizoaffective disorder) performed poorly thanHC on measures of processing speeding. In particular, SZ patients
showed lower Dygit Symbol Test – WAIS-III scores as comparedto psychotic BD patients [56.1 (±14.5) and 63.7 (±16.2), respectively, p < 0.001; after adjusting for demographic variables, current
symptom measures, illness course variables]. These results are consistent with findings from Brissos et al. that, using different tests,
revealed a significant worse performance for SZ patients relativeto HC [Symbol Digit Modalities Test – SDMT: 30.6 (±11.71) and56.4 (±14.82), respectively, p < 0.001; Trail Making Test part A –TMT-A: 78.8 (±50.76) and 38.0 (±15.34), respectively, p < 0.001;
after adjusting for sex, age, educational level, Hamilton Depressive Rating Scale – HDRS, Young Mania Rating Scale – YMRS, ascovariates) (20). Evidence from Germany supported such patterns
reporting lower performances for both first-episode and chronic
SZ patients as compared to HC (22).

DISCUSSION
Overall, patients with BD exhibit neurocognitive impairment
qualitatively similar to but quantitatively less pronounced thanpatients with SZ. In a general sense, it seems that while emotional and interpersonal difficulties in childhood reflect a generalpredisposition to adult psychiatric illness, early developmental
impairments in psychomotor, language, and cognitive function
show some specificity to SZ outcomes and are not seen in those
who later develop BD. (31)A previous meta-analysis showed that SZ patients demonstrateworse cognitive performance than BD patients in most domains,with substantial heterogeneity. This study focused on performancedifferences between patients groups, without normal controls, thus
deviations from the norm were not analyzed (32). The courseof cognitive impairment also differs between groups: premorbid
cognitive impairment is present early in life in SZ (often childhood/adolescence), preceding onset of psychosis, but cognitive
impairment typically does not occur until later in adulthood in
BD, after many years of mood episodes (8).
Despite overlap between BD and SZ in genetics and phenomenology of psychosis (31), these cognitive impairment data indicatethat BD and SZ are different in severity and course of cognition.
During adulthood, BD patients have shown impairment onneuropsychological measures sensitive to frontal lobe dysfunction
during the adolescence, usually before the diagnosis is made. This
August 2013 | Volume 4 | Article 87 | 8

Vöhringer et al.

may suggest the presence of some kind of neurodevelopmental vulnerability, expressed initially as attentional deficits or comorbidity
with attention deficit-hyperactivity disorder (33). Nevertheless,there is lack of systematic studies regarding time varying patterns
upon developmental deficits, starting on pre-morbid stage, andcontinuing during the illness phases of both conditions. Regarding
specific domains of cognitive impairment, in SZ working memory
was impaired, while in BD attention was impaired (34)The usual clinical symptomatology showed by these illnesses
can also modify cognitive functioning. For instance, severity ofnegative symptoms in SZ may have some correlation with poor
neurocognitive performance, while on the contrary, severity ofdepressive symptoms in BD showed no association with performances on any neuropsychological test (28). A high level ofnegative symptomatology might be seen as predictor of worse
response (17, 19); there are prior data suggesting that negative
symptoms had strong predictive capacity of neurocognitive outcomes associated with measures of executive functioning andselective attention, but not associated with visual or verbal learning and memory, verbal fluency, or processing speed (35). Further,changes in depressive symptoms were correlated with poorer verbal fluency, while no relationship between manic symptoms andneuropsychological performance was detected (36).
Evidence suggests that patients were usually taking psychiatric medication while cognitively assessed, eventually biasing themeasure of differences between groups. This lack of clean assessment, impede drawing any definitive conclusion of the effectsof medication on cognitive function. One study suggested thepresence of the pharmacological treatment over cognitive functioning. (37) concluded that schizophrenic patients in polypharmacy had significantly lower cognitive functions than those in
the second-generation antipsychotics monotherapy (37). Additionally, moderate improvement was found in cognitive test performance of patients on their first episode of SZ treated withsecond-generation antipsychotics (38). Similarly, untreated bipolar patients showed better cognitive performance than patients on
atypical antipsychotics (39).
Interesting evidence on the effect of psychopharmacologic
agents over cognitive function has been developed with lithium.
Studies suggest that cognitive deficits are not explained by thismedication, but by the condition itself (15, 40). With respect toother drugs, cognitive side effects may occur as a direct consequence of the mechanism of action of the psychotropic agent, or
indirectly through side effects such as sedation (41). Nevertheless,post-onset neuropsychological evaluation may be confounded by
medication, making it difficult to comment about the relevanceof neuropsychological deficits when talking about the etiology ordevelopment of these conditions. We think that further randomized research on drug naive patients should clarify the role ofmedication on cognitive deficits. Moreover, typically early models
for the etiology of psychotic illnesses focused on dopamine neurotransmission because of the powerful antipsychotic action of
dopamine antagonists giving support to the so-called dopamine
hypothesis of psychosis. Nevertheless, recent evidence increasingly
supports a primarily glutamatergic dysfunction in this condition, where dopaminergic disbalance is a secondary effect. (42)
In fact, a more recent model for the pathophysiology of SZ and
BD involves a pathophysiologic mechanism by which the cognitivewww.frontiersin.org

Cognitive comparison between bipolar disorder and schizophrenia

decline is representing the core of the clinical morbidity andin this context impairment of glutamate and more specificallyN -methyl-d-aspartate (NMDA) function has been considered ofmajor importance. Given that astrocytes are crucial in controlling
glutamate homeostasis, seems to logical to assign a major role to
glial–neuronal interactions in the pathophysiology of the cognitive
decline in these conditions (43)
Few studies evaluated psychosocial function of patients. Whenassessed, verbal memory impairment seemed to correlate witha poorer psychosocial functionality. Furthermore, BD patientsscored lower than SZ patients; we thought that depressive or sub
threshold depressive symptoms might play a role on these results.
Executive function had a directly positive effect on psychosocial
adjustment in both patients with BD and SZ. There were positive correlations between insight and executive function among
subjects with SZ and BD, suggesting that the ability to recognize
their own experiences of illness seems to be the first step to developing an effective strategy for supplementing their deficiencies in
psychosocial adjustment (44). The possibility of a shared general
cognitive impairment might yet be possible as an explanation, due
to comparable qualitative scores shown by the two conditions; nevertheless these abnormalities oftentimes are larger in SZ patients.
Following the same vein, a study suggests the existence of a continuum between SZ and affective disorders but with substantial
difference between the courses of their cognitive deficits, being
more severe in SZ and milder in BD (28). On the other hand,a study contradicts this theory suggesting that BD patients usually present impaired performance on multiple cognitive domains,
whereas their first-degree relatives shown performances comparable to HC on most cognitive tasks (3) additional research iswarranted in order to reach a sound conclusion on this matter.
Evidence regarding the effect of past psychotics symptoms on
the neurocognitive performance remains unclear. A study foundsimilar performance in all BD patients; no differences were founddepending on the history of the disease (16). On the contrary,
there is evidence concluding that patients with a psychotic bipolar condition represent a group that is neurocognitive closer tothe SZ than the non-psychotic bipolar subjects. This study was
carried out with symptomatic patients and therefore this clinicalcondition may confound these results (19).
The overall homogeneity among these findings argues favorably for the validity of a milder neuropsychological impairment
in BD compared with SZ and yet other considerations like theeventual cognitive continuum between BD and SZ, the role ofpsychotropic medication, the pre-morbid deficit and the possible
effect of psychotic symptomatology over the neuropsychologicalstatus remains unclear.
Limitations of the present systematic review includes heterogeneity of samples and assessments, the impossibility to control
for acute or chronic effects of medication, varying time required
for assessment across different studies, illness diagnosis stability,
and course severity. Another limitation to be considered pertains
with the time limit that was set up for the systematic review. In
effect, to gain novelty about the selected studies, search time was
set up with year 2008 as the lower limit and important papers
about glial research have appeared before the 2008, thus some relevant evidence regarding this pathophysiological mechanism may
be left out of the overall search.
August 2013 | Volume 4 | Article 87 | 9

Vöhringer et al.

REFERENCES
1. Adityanjee,
Aderibigbe
YA,
Theodoridis D, Vieweg VR.
Dementia praecox to schizophrenia: the first 100 years. Psychiatry
Clin Neurosci (1999) 53(4):437–48. doi:10.1046/j.1440-1819.
1999.00584.x
2. Decker HS. The psychiatric worksof Emil Kraepelin: a many-faceted
story of modern medicine. J Hist
Neurosci (2004) 13(3):248–76. doi:
10.1080/09647040490510470
3. Jabben N, Arts B, Krabbendam L,
van Os J. Investigating the association between neurocognitionand psychosis in bipolar disorder:
further evidence for the overlap
with schizophrenia. Bipolar Disord(2009) 11(2):166–77. doi:10.1111/
j.1399-5618.2009.00663.x
Epub2009/03/10,
4. Depp CA, Mausbach BT, Harmell
AL, Savla GN, Bowie CR, Harvey
PD, et al. Meta-analysis of theassociation between cognitive
abilities and everyday functioningin bipolar disorder. Bipolar Disord(2012) 14(3):217–26. doi:10.1111/
j.1399-5618.2012.01011.x
Epub2012/05/03,
5. Fett AK,Viechtbauer W, Dominguez
MD, Penn DL, van Os J, Krabbendam L. The relationship between
neurocognition and social cognition with functional outcomesin schizophrenia: a meta-analysis.
Neurosci Biobehav Rev (2011)35(3):573–88.
doi:10.1016/j.
neubiorev.2010.07.001
Epub2010/07/14,
6. Dickinson D, Ramsey ME, Gold JM.
Overlooking the obvious: a metaanalytic comparison of digit symbol coding tasks and other cognitive measures in schizophrenia. ArchGen Psychiatry (2007) 64(5):532–
42. doi:10.1001/archpsyc.64.5.532
Epub 2007/05/09,
7. Mann-Wrobel MC, Carreno JT,
Dickinson D. Meta-analysis ofneuropsychological
functioningin euthymic bipolar disorder:
an update and investigation ofmoderator variables. Bipolar Disord(2011) 13(4):334–42. doi:10.1111/
j.1399-5618.2011.00935.x
Epub2011/08/17,
8. Lewandowski KE, Cohen BM,
Ongur D. Evolution of neuropsychological dysfunction during the course of schizophrenia and bipolar disorder. Psychol
Med (2011) 41(2):225–41. doi:
10.1017/S0033291710001042 Epub
2010/09/15,
9. Robinson LJ, Ferrier IN. Evolution of cognitive impairment

Cognitive comparison between bipolar disorder and schizophrenia

in bipolar disorder: a systematic
review of cross-sectional evidence.
Bipolar Disord (2006) 8(2):103–
16. doi:10.1111/j.1399-5618.2006.
00277.x Epub 2006/03/18,
10. Bora E, Fornito A, Yucel M, Pantelis C. The effects of gender ongrey matter abnormalities in major
psychoses: a comparative voxelwise meta-analysis of schizophrenia
and bipolar disorder. Psychol Med(2011) 11:1–13.
11. Drevets WC, Price JL, Furey ML.
Brain structural and functional
abnormalities in mood disorders:
implications for neurocircuitry
models of depression. Brain Struct
Funct (2008) 213(1–2):93–118.
doi:10.1007/s00429-008-0189-x
Epub 2008/08/16,
12. Yildiz-Yesiloglu A, Ankerst DP.
Neurochemical alterations of thebrain in bipolar disorder andtheir implications for pathophysiology: a systematic review of
the in vivo proton magnetic
resonance spectroscopy findings.
Prog Neuropsychopharmacol Biol
Psychiatry (2006) 30(6):969–95.
Epub 2006/05/09.
13. Chambers JS, Perrone-Bizzozero
NI. Altered myelination of the
hippocampal formation in subjects with schizophrenia andbipolardisorder.
NeurochemRes(2004)
29(12):2293–302.
doi:10.1007/s11064-004-7039-x
Epub 2005/01/28,
14. Tkachev D, Mimmack ML, Ryan
MM, Wayland M, Freeman T,
Jones PB, et al. Oligodendrocyte
dysfunction in schizophrenia andbipolar disorder. Lancet (2003)
362(9386):798–805. doi:10.1016/
S0140-6736(03)14289-4
Epub2003/09/19.
15. Liberati A, Altman DG, Tetzlaff J,
Mulrow C, Gotzsche PC, Ioannidis
JP, et al. The PRISMA statement
for reporting systematic reviews andmeta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ (2009)339:b2700. doi:10.1136/bmj.b2700
Epub 2009/07/23,
16. Brissos S, Dias VV, Carita AI,
Martinez-Aran A. Quality oflife in bipolar type I disorderand schizophrenia in remission:clinical and neurocognitive correlates. Psychiatry Res (2008)
160(1):55–62.
doi:10.1016/j.
psychres.2007.04.010
17. Barrett SL, Mulholland CC, Cooper
SJ, Rushe TM. Patterns of neurocognitive impairment in first-episodebipolar disorder and schizophrenia. Br J Psychiatry (2009)

Frontiers in Psychiatry | Schizophrenia

195(1):67–72. doi:10.1192/bjp.bp.
108.054874
18. Joshua N, Gogos A, Rossell S. Executive functioning in schizophrenia:
a thorough examination of performance on the Hayling Sentence
Completion Test compared to psychiatric and non-psychiatric controls. Schizophr Res (2009) 114(1–3):84–90. doi:10.1016/j.schres.2009.
05.02919. Simonsen C, Sundet K, Vaskinn A,
Birkenaes AB, Engh JA, Faerden A,
et al. Neurocognitive dysfunction in
bipolar and schizophrenia spectrum
disorders depends on history of psychosis rather than diagnostic group.
Schizophr Bull (2011) 37(1):73–83.
doi:10.1093/schbul/sbp034
20. Brissos S, Dias VV, Soeiro-deSouza MG, Balanza-Martinez V,
Kapczinski F. The impact of ahistory of psychotic symptoms on
cognitive function in euthymic
bipolar patients: a comparison
with schizophrenic patients andhealthy controls. Rev Bras Psiquiatr(2011) 33(4):353–61. doi:10.1590/
S1516-44462011000400008 Epub
2011/12/23,
21. Craddock N, Owen MJ. Rethinking psychosis: the disadvantages ofa dichotomous classification now
outweigh the advantages. World Psychiatry (2007) 6(2):84–91. Epub
2008/02/01,
22. Wobrock T, Ecker UK, Scherk
H, Schneider-Axmann T, Falkai
P, Gruber O. Cognitive impairment of executive function asa core symptom of schizophrenia. World J Biol Psychiatry (2009) 10(4 Pt 2):442–51.
doi:10.1080/15622970701849986
Epub 2008/07/09,
23. Sanchez-Morla EM, Barabash A,
Martinez-Vizcaino V, TabaresSeisdedos R, Balanza-Martinez
V, Cabranes-Diaz JA, et al. Comparative study of neurocognitive function in euthymic
bipolar patients and stabilized
schizophrenic patients. Psychiatry Res (2009) 169(3):220–8.
doi:10.1016/j.psychres.2008.06.032
Epub 2009/09/18.
24. Gogos A, Joshua N, Rossell SL.
Use of the Repeatable Battery
for the Assessment of Neuropsychological Status (RBANS) to
investigate group and genderdifferences in schizophrenia andbipolar disorder. Aust N Z J
Psychiatry (2010) 44(3):220–9.
doi:10.3109/00048670903446882
Epub 2010/01/07,
25. Rossell SL, Batty RA. Elucidating
semantic disorganisation froma word comprehension task:
do patients with schizophrenia
and bipolar disorder show differential processing of nouns,
verbs and adjectives? Schizophr Res (2008) 102(1–3):63–8.
doi:10.1016/j.schres.2008.04.008
Epub 2008/05/23,
26. Marvel CL, Schwartz BL, Isaacs
KL. Word production deficits
in schizophrenia. Brain Lang
(2004) 89(1):182–91. doi:10.1016/
S0093-934X(03)00366-3
Epub2004/03/11.
27. Woods SP, Weinborn M, Posada C,
O’Grady J. Preliminary evidence for
impaired rapid verb generation inschizophrenia. Brain Lang (2007)
102(1):46–51. doi:10.1016/j.bandl.
2006.11.005 Epub 2006/12/13,
28. Zanelli J, Reichenberg A, Morgan K,
Fearon P, Kravariti E, Dazzan P, et al.
Specific and generalized neuropsychological deficits: a comparisonof patients with various firstepisode psychosis presentations.
Am J Psychiatry (2010) 167(1):78–85.
doi:10.1176/
appi.ajp.2009.09010118
Epub 2009/12/03,
29. Clark L, Kempton MJ, ScarnaA, Grasby PM, Goodwin GM.
Sustained attention-deficit confirmed in euthymic bipolar disorder but not in first-degree relatives of bipolar patients or euthymic
unipolar depression. Biol Psychiatry (2005) 57(2):183–7. doi:10.
1016/j.biopsych.2004.11.007 Epub
2005/01/18,
30. Ozdel O, Karadag F, Atesci FC,
Oguzhanoglu NK, Cabuk T.
Cognitive functions in euthymic
patients with bipolar disorder. Ann
Saudi Med (2007) 27(4):273–8.
doi:10.4103/0256-4947.51487 Epub
2007/08/09,
31. Murray RM, Sham P, Van Os J,
Zanelli J, Cannon M, McDonald
CA. developmental model for similarities and dissimilarities between
schizophrenia and bipolar disorder. Schizophr Res (2004) 71(2–3):
405–16. doi:10.1016/j.schres.2004.
03.002
32. Krabbendam L, Arts B, van Os
J, Aleman A. Cognitive functioning in patients with schizophrenia and bipolar disorder:
a quantitative review. Schizophr
Res (2005) 80(2–3):137–49. doi:
10.1016/j.schres.2005.08.004 Epub
2005/09/27,
33. Meyer SE, Carlson GA, Wiggs
EA, Martinez PE, RonsavilleDS, Klimes-Dougan B, et al. A
prospective study of the association among impaired executive

August 2013 | Volume 4 | Article 87 | 10

Vöhringer et al.

functioning, childhood attentional
problems, and the developmentof bipolar disorder. Dev Psychopathol (2004) 16(2):461–76.
doi:10.1017/S095457940404461X
Epub 2004/10/19.
34. Diwadkar VA, Goradia D, Hosanagar A, Mermon D, Montrose DM,
Birmaher B, et al. Working memory and attention deficits in adolescent offspring of schizophrenia or bipolar patients: comparing vulnerability markers. Prog
Neuropsychopharmacol Biol Psychiatry (2011) 35(5):1349–54. doi:
10.1016/j.pnpbp.2011.04.009 Epub
2011/05/10,
35. Lewandowski KE, Cohen BM,
Keshavan MS, Ongur D. Relationship of neurocognitive deficits todiagnosis and symptoms acrossaffective and non-affective psychoses. Schizophr Res (2011) 133(1–3):212–7. doi:10.1016/j.schres.2011.
09.004 Epub 2011/10/15,
36. Chaves OC, Lombardo LE, Bearden CE, Woolsey MD, Martinez
DM, Barrett JA, et al. Association of clinical symptoms andneurocognitive performance inbipolar disorder: a longitudinal
study. Bipolar Disord (2011) 13(1):
118–23. doi:10.1111/j.1399-5618.
2011.00888.x Epub 2011/02/16,
37. Hori H, Yoshimura R, Katsuki
A, Hayashi K, Ikenouchi-Sugita
A, Umene-Nakano W, et al.

www.frontiersin.org

Cognitive comparison between bipolar disorder and schizophrenia

Several prescription patterns ofantipsychotic drugs influencecognitive functions in Japanesechronic schizophrenia patients. Int
J Psychiatry Clin Pract (2012)16(2):138–42.
doi:10.3109/
13651501.2011.631018
Epub2011/12/06.
38. Davidson M, Galderisi S, Weiser
M, Werbeloff N, Fleischhacker
WW, Keefe RS, et al. Cognitiveeffects of antipsychotic drugs infirst-episode schizophrenia andschizophreniform
disorder:arandomized, open-label clinical
trial (EUFEST). Am J Psychiatry(2009) 166(6):675–82. doi:10.
1176/appi.ajp.2008.08060806 Epub
2009/04/17,
39. Torrent C, Martinez-Aran A, Daban
C, Amann B, Balanza-Martinez V,
del Mar Bonnin C, et al. Effects
of atypical antipsychotics onneurocognition in euthymic bipolar patients. Compr Psychiatry(2011) 52(6):613–22. doi:10.1016/
j.comppsych.2010.12.009
Epub2011/02/08,
40. Lopez-Jaramillo C, Lopera-Vasquez
J, Ospina-Duque J, Garcia J, Gallo
A, Cortez V, et al. Lithium treatment
effects on the neuropsychological
functioning of patients withbipolar I disorder. J Clin Psychiatry (2010) 71(8):1055–60.
doi:10.4088/JCP.08m04673yel
Epub 2010/04/07,

41. Harvey PD, Hassman H, Mao L,
Gharabawi GM, Mahmoud RA,
Engelhart LM. Cognitive functioning and acute sedative effectsof risperidone and quetiapine
in patients with stable bipolar I
disorder: a randomized, doubleblind, crossover study. J Clin
Psychiatry (2007) 68(8):1186–94.
doi:10.4088/JCP.v68n0804
Epub2007/09/15,
42. Gaspar PA, Bustamante ML, Silva H,
Aboitiz F. Molecular mechanisms
underlying glutamatergic dysfunction in schizophrenia: therapeutic
implications. J Neurochem (2009)
111(4):891–900.
doi:10.1111/j.
1471-4159
43. Kondziella D, Brenner E, Eyjolfsson EM, Sonnewald U. How
do glial-neuronal interactions
fit into current neurotransmitter hypotheses of schizophrenia? Neurochem Int (2007)
50(2):291–301.
doi:10.1016/j.
neuint.2006.09.006
44. Yen CF, Cheng CP, Huang CF,
Ko CH, Yen JY, Chang YP, et al.
Relationship between psychosocial
adjustment and executive function
in patients with bipolar disorderand schizophrenia in remission:
the mediating and moderating
effects of insight. Bipolar Disord(2009) 11(2):190–7. doi:10.1111/
j.1399-5618.2008.00650.x
Epub2009/03/10,

Conflict of Interest Statement: S. Nassir Ghaemi has received a research grantfrom Pfizer. Neither he nor his family
holds equity positions in pharmaceutical corporations. The other authors
declare that the research was conductedin the absence of any commercial or
financial relationships that could beconstrued as a potential conflict ofinterest.
Received: 01 May 2013; paper pending
published: 01 June 2013; accepted: 29 July
2013; published online: 08 August 2013.
Citation: Vöhringer PA, Barroilhet SA,
Amerio A, Reale ML, Alvear K, Vergne
D and Ghaemi SN (2013) Cognitive impairment in bipolar disorder and schizophrenia: a systematic
review. Front. Psychiatry 4:87. doi:
10.3389/fpsyt.2013.00087
This article was submitted to Frontiers in
Schizophrenia, a specialty of Frontiers in
Psychiatry.
Copyright © 2013 Vöhringer, Barroilhet , Amerio, Reale, Alvear, Vergne andGhaemi. This is an open-access article distributed under the terms of theCreative Commons Attribution License(CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor
are credited and that the original publication in this journal is cited, in accordancewith accepted academic practice. No use,
distribution or reproduction is permitted
which does not comply with these terms.

August 2013 | Volume 4 | Article 87 | 11