DISC1 is associated with prefrontal cortical gray matter and positive symptoms in schizophrenia

Abstract

Background DISC1 is considered a susceptibility gene for schizophrenia and schizoaffective disorder, but little is known regarding the potential mechanisms through which it may confer increased risk. Given that DISC1 plays a role in cerebral cortex development, polymorphisms in this gene may have relevance for neurobiological models of schizophrenia that have implicated cortical deficits in its pathophysiology. Methods We investigated whether the DISC1 leu607phe polymorphism was associated with prefrontal gray matter volumes using magnetic resonance imaging in a cohort of patients with schizophrenia (N=19) and healthy volunteers (N=25) and positive and negative symptoms in 200 patients with schizophrenia. Results Among patients and healthy volunteers, phe carriers (N=11) had significantly less gray matter in the superior frontal gyrus and anterior cingulate gyrus compared to leu/leu homozygotes (N=33). Further, among patients left superior frontal gyrus gray matter volume was significantly negatively correlated with severity of hallucinations. In addition, patients who were phe carriers (N=144) had significantly greater severity of positive symptoms (hallucinations) compared to patients who were leu/leu homozygotes (N=56). Discussion These findings implicate DISC1 in variation of prefrontal cortical volume and positive symptoms, thus providing a potential mechanism through which DISC1 may confer increased risk for schizophrenia or schizoaffective disorder.