Unsuppressed Striatal Activity and Genetic Risk for Schizophrenia Associated with Individual Cognitive Performance under Social Competition

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.