Patients with schizophrenia show a deficit in cognitive ability compared to estimated premorbid and familial intellectual abilities. However, the degree to which this pattern holds across psychotic disorders and is familial is unclear. The present study examined deviation from expected cognitive level in schizophrenia, schizoaffective disorder, and psychotic bipolar disorder probands and their first-degree relatives. Using a norm-based regression approach, parental education and WRAT-IV Reading scores (both significant predictors of cognitive level in the healthy control group) were used to predict global neuropsychological function as measured by the composite score from the Brief Assessment of Cognition in Schizophrenia (BACS) test in probands and relatives. When compared to healthy control group, psychotic probands showed a significant gap between observed and predicted BACS composite scores and a greater likelihood of robust cognitive decline. This effect was not seen in unaffected relatives. While BACS and WRAT-IV Reading scores were themselves highly familial, the decline in cognitive function from expectation had lower estimates of familiality. Thus, illness-related factors such as epigenetic, treatment, or pathophysiological factors may be important causes of illness related decline in cognitive abilities across psychotic disorders. This is consistent with the markedly greater level of cognitive impairment seen in affected individuals compared to their unaffected family members.
Bibliographical noteFunding Information:
Dr. Tamminga has received support from Intracellular Therapies (ITI, Inc.), PureTech Ventrues, Eli Lilly Pharmaceuticles, Sunovion, Astellas, Merck (ad hoc consulting), International Congress on Schizophrenia Research (unpaid volunteer), NAMI (unpaid volunteer), American Psychiatric Association (Deputy Editor), and Finnegan Henderson Farabow Garrett & Dunner, LLP. Dr. Keefe has received investigator initiated support from the Department of Veteran's Affair, Feinstein Institute for Medical Research, GlaxoSmithKline, National Institute of Mental Health, Novartis, Psychogenics, Research Foundation for Mental Hygiene, Inc., and the Singapore National Medical Research Council. Dr. Keefe has received honoraria, served as a consultant, or advisory board member for Abbvie, Akebia, Amgen, Astellas, Asubio, AviNeuro/ChemRar, BiolineRx, Biomarin, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, EnVivo, Helicon, Lundbeck, Merck, Mitsubishi, Otsuka, Pfizer, Roche, Shire, Sunovion, Takeda, Targacept. Dr. Keefe is a shareholder in Sengenix and NeuroCog Trials, Inc. and receives royalties from the BACS testing battery and the MATRICS Battery (BACS Symbol Coding). Dr. Keshavan has received support from Sunovion and GlaxoSmithKline. Dr. Sweeney has received support from Takeda, BMS, Roche, and Eli Lilly and research funding from Janssen. The other authors have no disclosers at this time.
This study was supported in part by NIMH grants MH078113 , MH077945 , MH077852 , MH077851 , MH077862 , MH072767 , and MH083888 . We thank Gunvant K. Thaker for his collaboration, design, and implementation of this study.
- Brief assessment of cognition in schizophrenia
- Cognitive decline
- First-degree relatives
- Premorbid cognition
- Psychotic disorders