Abstract
Background: Most data sets currently included in genomic analyses of schizophrenia are comprised of case–control design that focuses on diagnostic categorization on those who meet diagnostic criteria for schizophrenia and of healthy participants. A hallmark of schizophrenia is impaired cognitive functioning. The goal of the study was to examine cognitive endophenotypes in 3 large-scale consortia that differ in recruitment and assess the pattern of neurocognitive performance across consortia. Methods: The 3 consortia were family based with different sampling strategies. The Multiplex Investigation of Multigenerational families (MGI) included Caucasian families with at least 2 first-degree relatives with schizophrenia spectrum disorders. The Project Among African-Americans to Explore Risks for Schizophrenia (PAARTNERS) included African American families—affected sibling pairs, TRIOs, or multiplex. The Consortium on the Genetics of Schizophrenia (COGS) included families with a proband, unaffected sibling and both parents (COGS-1) as well as a case–control design (COGS-2). The Penn computerized neurocognitive battery (CNB), based on tasks administered in functional neuroimaging, was administered across consortia. The CNB measures performance accuracy and response time in several domains including: Executive Functions, Episodic Memory, Complex Cognition, Social Cognition and Sensori-Speed. Results: Across consortia, probands with schizophrenia showed a similar pattern of neurocognitive deficits in performance accuracy and speed implicating frontotemporal impairment. Notably, family members manifested mild impairment, intermediate between probands and controls. The neurocognitive parameters were heritable and met established criteria for endophenotypes. Conclusion: Quantitative neurocognitive measures are endophenotypes that can be administered in large-scale consortia and integrated in genomic analyses. Such efforts can advance the understanding of the neurobiology of schizophrenia and be evaluated in treatment studies.
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