Familial aggregation of clinical and neurocognitive features in sibling pairs with and without schizophrenia

Abstract

Objective Neurocognitive impairment was found to be heritable in individuals with schizophrenia and their relatives. However, the heritability of neurocognitive measures in families with and without schizophrenia has not been directly compared. In this study, we examined the genetic structure of clinical and neurocognitive measures in sibling pairs with and without schizophrenia to test the hypothesis that the familial aggregation of such measures may be altered by having schizophrenia. Method A total of 278 subjects including patients with schizophrenia and their non-psychotic full siblings, healthy controls, and their full siblings were recruited. Heritability was estimated for working memory, episodic memory, executive function and attention, as well as clinical features, such as positive, negative and disorganization symptoms. Results Many clinical and cognitive domains were impaired in subjects with schizophrenia and their non psychotic siblings. Negative symptoms, working memory, episodic memory and executive function, but not positive, disorganization symptoms and attention, were found to be significantly heritable in all sibling pairs. However, the heritability of working memory function was significantly ( χ 2 (d.f. = 6) = 13.9, p = .031) decreased in proband sibling pairs (h 2 = .38) as compared to control sibling pairs (h 2 = .95). Significant genetic correlations were observed between negative symptoms and the cluster of working memory, episodic memory and executive function. Conclusions Several neurocognitive measures were heritable in sibling pairs with and without schizophrenia. However, schizophrenia reduced the heritability of working memory, perhaps due to disease-related environmental or genetic factors. Evidence for potential pleiotropy will inform future phenotypic studies.