Social Cognition and Functional Connectivity in Schizophrenia and Early Psychosis

Individuals with schizophrenia (SZ) experience pervasive, treatment-resistant impairments in social cognition that contribute to poor functional outcomes. However, the mechanisms of social cognitive dysfunction in SZ remain poorly understood, which impedes the design of novel interventions to improve outcomes. This pre-registered project examines the representation of social functioning in the brain’s functional architecture across early psychosis (EP) and SZ. The study contains two parts: a confirmatory and an exploratory portion. In the confirmatory portion, we identified specific resting-state brain connectivity disruptions evident in EP and SZ. We performed a seed-based connectivity analysis using brain regions associated with social cognitive dysfunction in SZ (based on a published review) to test whether aberrant functional connectivity observed in SZ was also present in EP. In the exploratory portion, we assessed the out-of-sample generalizability and precision of resting state connectivity-based predictive models of social cognition. We used machine learning to predict social cognition from whole-brain connectomes and established the generalizability of these brain-behavior relationships with out-of-sample testing and cross-validation (to handle confounding variables). Results reveal significant decreases between the left inferior frontal gyrus and intraparietal sulcus that were evident in SZ but not EP. This connectivity profile is significantly associated with social cognition/functioning in both SZ and EP. Null predictive modeling results reveal the importance of out-of-sample evaluation, proper null hypothesis testing, and confound removal procedures. Overall, this work provides insights into the brain's functional architecture in SZ and EP. This work suggests that IFG-IPS connectivity profiles could be an important prognostic biomarker of social impairments and may be a target for future interventions focused on improved treatment outcomes related to social functioning.