Social Cognition and Functional Connectivity in Early and Chronic Schizophrenia.

Background: Individuals with schizophrenia (SZ) experience impairments in social cognition that contribute to poor functional outcomes. However, mechanisms of social cognitive dysfunction in SZ remain poorly understood, which impedes the design of novel interventions to improve outcomes. In this preregistered project, we examined the representation of social cognition in the brain's functional architecture in early and chronic SZ.

Methods: The study contains 2 parts: a confirmatory and an exploratory portion. In the confirmatory portion, we identified resting-state connectivity disruptions evident in early and chronic SZ. We performed a connectivity analysis using regions associated with social cognitive dysfunction in early and chronic SZ to test whether aberrant connectivity observed in chronic SZ (n = 47 chronic SZ and n = 52 healthy control participants) was also present in early SZ (n = 71 early SZ and n = 47 healthy control participants). In the exploratory portion, we assessed the out-of-sample generalizability and precision of predictive models of social cognition. We used machine learning to predict social cognition and established generalizability with out-of-sample testing and confound control.

Results: Results revealed decreases between the left inferior frontal gyrus and the intraparietal sulcus in early and chronic SZ, which were significantly associated with social and general cognition and global functioning in chronic SZ and with general cognition and global functioning in early SZ. Predictive modeling revealed the importance of out-of-sample evaluation and confound control.

Conclusions: This work provides insights into the functional architecture in early and chronic SZ and suggests that inferior frontal gyrus-intraparietal sulcus connectivity could be a prognostic biomarker of social impairments and a target for future interventions (e.g., neuromodulation) focused on improved social functioning.