Unsuppressed Striatal Activity and Genetic Risk for Schizophrenia Associated With Individual Cognitive Performance Under Social Competition

Abstract

Abstract Background and Hypothesis Social competition affects human behaviors by inducing psychosocial stress. The neural and genetic mechanisms of individual differences of cognitive-behavioral response to stressful situations in a competitive context remain unknown. We hypothesized that variation in stress-related brain activation and genetic heterogeneity associated with psychiatric disorders may play roles towards individually differential responses under stress. Study Design A total of 419 healthy subjects and 66 patients with schizophrenia were examined functional magnetic resonance imaging during working memory task including social competition stressors. We explored the correlation between stress-induced brain activity and individual working memory performance. The partial least squares regression was performed to examine the genetic correlates between stress-related activity and gene expression data from Allen Human Brain Atlas. Polygenic risk score (PRS) was used to assess individual genetic risk for schizophrenia. Study Results Greater suppression of bilateral striatal activity was associated with better behavioral improvement in working memory manipulation under social competition (left: rPearson = −0.245, P = 4.0 × 10−6, right: rPearson = −0.234, P = 1.0 × 10−5). Genes transcriptionally related to stress-induced activation were linked to genetic risk for schizophrenia (PFDR < 0.005). Participants with decreased accuracy under social competition exhibited higher PRS of schizophrenia (t = 2.328, P = .021). Patients with schizophrenia showed less suppressed striatal activity under social stress (F = 13.493, P = 3.5 × 10−4). Conclusions Striatal activity change and genetic risk for schizophrenia might play a role in the individually behavioral difference in working memory manipulation under stress.