Relative risk for cognitive impairments in siblings of patients with schizophrenia

Background: Patients with schizophrenia have impairments in several domains of cognition, including working memory/executive function, verbal memory, language, oculomotor scanning/psychomotor speed, and general intelligence. Impairments have also been found in unaffected siblings, suggesting they co uld be heritable. To assess the suitability of cognitive dysfunction for us e in genetic studies, we estimated relative risk (lambda) in a large cohort of siblings. Methods: One hundred forty-seven patients with schizophrenia, 193 of their siblings, and 47 control subjects were studied using a neuropsychological t est batters,, which included intelligence quotient (IQ), Wide Range Achieve ment Test, Wisconsin Card Sort, Wechsler Memory Scale (revised), California Verbal List Test, Trails A and B, and Letter and Category Fluency. Relativ e risk was estimated using a cutoff score of 1 SD below the control mean. Results: As expected, patients performed markedly worse than control subjec ts on all tests except the Wide Range Achievement Test. Siblings had impair ed performance on the Wisconsin Card Sort and Trails B, with trends for red uction (p = .01-.05) on the California Verbal List Test and Letter Fluency. Relative risk to siblings was elevated on the Trails B (lambda = 4.0) and California Verbal List Test (lambda = 2.8). Trends (p = .01-.05) for increa sed lambda were also seen for Wisconsin Card Sort, Letter Fluency, Wechsler Memory Scale and decline in IQ (lambda = 1.74-2.4). Correlations between t ests of different cognitive junctions were weak, indicating they measure re latively independent processes. Conclusion: Unselected siblings of patients with schizophrenia have impairm ents in several cognitive domains. Relative risk scores were in the moderat e range, suggesting a significant genetic component. Impairments on one tes t only weakly predicted impairments on other tests. Thus, cognitive phenoty pes identify distinct, familial traits associated with schizophrenia. Using this dimensional approach to subdividing schizophrenia may reduce the clin ical and genetic heterogeneity of schizophrenia and improve the power of ge netic studies, (C) 2001 Society of Biological Psychiatry.