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Articles   |    
Neuropsychological Impairments in Schizophrenia and Psychotic Bipolar Disorder: Findings from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) Study
S. Kristian Hill, Ph.D.; James L. Reilly, Ph.D.; Richard S.E. Keefe, Ph.D.; James M. Gold, Ph.D.; Jeffrey R. Bishop, Pharm.D.; Elliot S. Gershon, M.D.; Carol A. Tamminga, M.D.; Godfrey D. Pearlson, M.D.; Matcheri S. Keshavan, M.D.; John A. Sweeney, Ph.D.
Am J Psychiatry 2013;170:1275-1284. doi:10.1176/appi.ajp.2013.12101298
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Dr. Keefe has received investigator-initiated research funding support from the Department of Veterans Affair, the Feinstein Institute for Medical Research, GlaxoSmithKline, NIMH, Novartis, Psychogenics, the Research Foundation for Mental Hygiene, and the Singapore National Medical Research Council; he has received honoraria from or served as a consultant or advisory board member for Abbott, Amgen, Astellas, Asubio, BiolineRx, Biomarin, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, EnVivo, Helicon, Lundbeck, Merck, Mitsubishi, Novartis, Otsuka, Pfizer, Roche, Shire, Sunovion, Takeda, and Targacept; he receives royalties for the BACS testing battery and the MATRICS Battery (BACS Symbol Coding), and he is a shareholder in NeuroCog Trials. Dr. Gold receives royalties for the BACS. Dr. Bishop has received research support from Ortho-McNeil Janssen. Disclosures for Dr. Tamminga, as a Deputy Editor of the American Journal of Psychiatry, were published in the January issue. Dr. Pearlson has served on an advisory panel for Bristol-Myers Squibb. Dr. Keshavan has received research support from Sunovion and GlaxoSmithKline. Dr. Sweeney has been on advisory boards for Bristol-Myers Squibb, Eli Lilly, Pfizer, Roche, and Takeda and has received grant support from Janssen. The other authors report no financial relationships with commercial interests.

Supported in part by NIMH grants MH078113, MH077945, MH077852, MH077851, MH077862, MH072767, and MH083888.

From the Department of Psychology, Rosalind Franklin University of Medicine and Science, Chicago; Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago; Department of Psychiatry, Duke University Medical Center, Durham, N.C.; Department of Psychiatry and Maryland Psychiatric Research Center, University of Maryland, Baltimore; Department of Pharmacy Practice, University of Illinois, Chicago; Department of Psychiatry, University of Chicago Medicine, Chicago; Departments of Psychiatry and Pediatrics, University of Texas Southwestern Medical Center, Dallas; Department of Psychiatry, Yale University, New Haven, Conn.; and Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center, Boston.

Address correspondence to Dr. Hill (scot.hill@rosalindfranklin.edu).

Copyright © 2013 by the American Psychiatric Association

Received October 11, 2012; Revised January 10, 2013; Accepted February 14, 2013.

Abstract

Objective  Familial neuropsychological deficits are well established in schizophrenia but remain less well characterized in other psychotic disorders. This study from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium 1) compares cognitive impairment in schizophrenia and bipolar disorder with psychosis, 2) tests a continuum model of cognitive dysfunction in psychotic disorders, 3) reports familiality of cognitive impairments across psychotic disorders, and 4) evaluates cognitive impairment among nonpsychotic relatives with and without cluster A personality traits.

Method  Participants included probands with schizophrenia (N=293), psychotic bipolar disorder (N=227), schizoaffective disorder (manic, N=110; depressed, N=55), their first-degree relatives (N=316, N=259, N=133, and N=64, respectively), and healthy comparison subjects (N=295). All participants completed the Brief Assessment of Cognition in Schizophrenia (BACS) neuropsychological battery.

Results  Cognitive impairments among psychotic probands, compared to healthy comparison subjects, were progressively greater from bipolar disorder (z=–0.77) to schizoaffective disorder (manic z=–1.08; depressed z=–1.25) to schizophrenia (z=–1.42). Profiles across subtests of the BACS were similar across disorders. Familiality of deficits was significant and comparable in schizophrenia and bipolar disorder. Of particular interest were similar levels of neuropsychological deficits in relatives with elevated cluster A personality traits across proband diagnoses. Nonpsychotic relatives of schizophrenia probands without these personality traits exhibited significant cognitive impairments, while relatives of bipolar probands did not.

Conclusions  Robust cognitive deficits are present and familial in schizophrenia and psychotic bipolar disorder. Severity of cognitive impairments across psychotic disorders was consistent with a continuum model, in which more prominent affective features and less enduring psychosis were associated with less cognitive impairment. Cognitive dysfunction in first-degree relatives is more closely related to psychosis-spectrum personality disorder traits in psychotic bipolar disorder than in schizophrenia.

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FIGURE 1. Global Neuropsychology Scores on the Brief Assessment of Cognition in Schizophrenia (BACS) for Probands With Schizophrenia, Depressed or Manic Schizoaffective Disorder, and Psychotic Bipolar Disordera

a Cognitive function compared with test norms in four proband groups and the healthy comparison group. Schizophrenia probands demonstrated significantly greater global neuropsychological deficits than bipolar probands; schizoaffective probands were intermediate and differed from the two primary diagnostic groups.

FIGURE 2. Neuropsychological Profiles on the Brief Assessment of Cognition in Schizophrenia (BACS) for Probands With Schizophrenia, Depressed or Manic Schizoaffective Disorder, and Psychotic Bipolar Disordera

a The patterns of subtest performance on the Brief Assessment of Cognition in Schizophrenia indicate a similar profile of cognitive dysfunction across psychotic disorders.

FIGURE 3. Neuropsychological Performance on the Brief Assessment of Cognition in Schizophrenia (BACS) in Probands With Schizophrenia, Depressed or Manic Schizoaffective Disorder, and Psychotic Bipolar Disorder Compared With Healthy Comparison Subjects, Across the Schizophrenia-Bipolar Dimensiona

a Consistent with a dimensional model of psychosis, cognitive performance declines progressively as affective symptoms become less prominent and psychotic features more pronounced and pervasive.

FIGURE 4. Neuropsychological Performance on the Brief Assessment of Cognition in Schizophrenia (BACS) in Psychosis-Free Relatives of Schizophrenia and Psychotic Bipolar Probands and Healthy Comparison Subjects

a All relatives of schizophrenia probands (with cluster A or cluster B traits and without; the former was defined as being one criterion from meeting the diagnostic threshold for a disorder in the cluster) exhibited significant levels of cognitive impairment compared to healthy comparison subjects (p<0.001).

b Cognitive performance differed significantly between bipolar proband relatives with cluster A or cluster B traits and healthy comparison subjects (p<0.001).

c Cognitive performance in relatives with cluster A or cluster B traits did not differ significantly within or across disorders.

d Cognitive performance did not differ significantly between relatives of bipolar probands without elevated cluster A or cluster B traits and healthy comparison subjects.

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TABLE 1.Demographic and Clinical Data for Healthy Comparison Subjects and Probands With Schizophrenia, Depressed or Manic Schizoaffective Disorder, and Psychotic Bipolar Disorder
Table Footer Note

a MADRS=Montgomery-Åsberg Depression Rating Scale; WRAT-4=Wide-Range Achievement Test, 4th edition; PANSS=Positive and Negative Syndrome Scale; YMRS=Young Mania Rating Scale.

Table Footer Note

b Healthy comparison group > bipolar group > schizophrenia group and both schizoaffective groups.

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c Healthy comparison group > schizophrenia group and both schizoaffective groups; bipolar group > schizophrenia group and schizoaffective depressed subtype group.

Table Footer Note

d Disproportionate number of males in the schizophrenia group.

Table Footer Note

e Disproportionate number of African-Americans in the schizophrenia group.

Table Footer Note

f Bipolar group < schizophrenia group and both schizoaffective groups.

Table Footer Note

g Schizoaffective manic subtype group > bipolar, schizophrenia, and schizoaffective depressed subtype groups.

Table Footer Note

h Both schizoaffective subtype groups > bipolar group and schizophrenia group.

Anchor for Jump
TABLE 2.Demographic Data, History of Psychosis, and Personality Traits for Healthy Comparison Subjects and First-Degree Relatives of Probands With Schizophrenia, Depressed or Manic Schizoaffective Disorder, and Psychotic Bipolar Disorder
Table Footer Note

a Healthy comparison group < relatives of schizophrenia probands.

Table Footer Note

b Healthy comparison group > relatives of schizophrenia and schizoaffective manic subtype probands; relatives of bipolar probands > relatives of schizoaffective manic subtype probands.

Table Footer Note

c Relatives of schizophrenia probands < healthy comparison group and relatives of bipolar probands. WRAT-4=Wide-Range Achievement Test, 4th edition.

Table Footer Note

d Disproportionate number of males in the healthy comparison group.

Table Footer Note

e Disproportionate number of Caucasians among relatives of bipolar probands.

Anchor for Jump
TABLE 3.Familiality Estimates for Wide-Range Achievement Test, 4th Edition (WRAT-4) Reading Test and Brief Assessment of Cognition in Schizophrenia (BACS) Battery (composite and subtests)
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