Neurocognitive Functioning as Intermediary Phenotype and Predictor of Psychosocial Functioning Across the Psychosis Continuum: Studies in Schizophrenia and Bipolar Disorder

Objective: Neurocognitive functioning may represent an indicator of genetic risk and poor outcome in both schizophrenia and bipolar disorder. In this study, shared and nonshared characteristics in the cognitive domain in both disorders were analyzed to determine to what degree neurocognitive functioning may represent a predictor of the familial vulnerability and poor functioning that schizophrenia spectrum disorders and bipolar disorder share.

Method: Neurocognition, psychopathology, and psychosocial functioning were assessed in samples of patients with a schizophrenia spectrum disorder (n’ ‰=’ ‰345) and bipolar disorder (n’ ‰=’ ‰76) meeting
DSM-IV criteria, first-degree relatives of both patient groups (n’ ‰=’ ‰331 and n’ ‰=’ ‰37, respectively), and healthy controls (n’ ‰=’ ‰260 and n’ ‰=’ ‰61, respectively). Multiple regression models were used to investigate the effect of group status on neurocognition and to explore associations between cognition, symptoms, and psychosocial functioning in the 2 groups. The schizophrenia spectrum study sample was recruited between September 2004 and January 2008, and the bipolar study sample was recruited between June 2004 and July 2007.

Results: Cognitive deficits were more severe and more generalized in patients with a schizophrenia spectrum disorder compared to patients with bipolar disorder; cognitive alterations were present in relatives of patients with schizophrenia spectrum disorders
but not in relatives of bipolar patients. The association between neurocognitive dysfunction and psychosocial functioning was more generalized in schizophrenia spectrum disorders than in bipolar disorder; for both disorders, associations were only partly mediated by symptoms.

Conclusions: The evidence for cognitive dysfunction as a marker of familial vulnerability is stronger for schizophrenia than for bipolar disorder. Although the presence of multiple cognitive deficits is shared by the 2 groups, the severity of cognitive deficits and its consequences appear to partly differ between schizophrenia and bipolar disorder, which is in line with a model that implies the specific presence of a neurodevelopmental impairment in the former but not in the latter.

J Clin Psychiatry 2010;71(6):764-774

Submitted: October 30, 2008; accepted February 2, 2009.

Online ahead of print: January 26, 2010 (doi:10.4088/JCP.08m04837yel).

Corresponding author: Lydia Krabbendam, PhD, Department of Psychiatry and Neuropsychology, Maastricht University, PO Box 616 (VIJV), 6200 MD Maastricht, The Netherlands ([email protected]).