Social Determinants of Health and Neurobiology Across the Schizophrenia Course

Importance: Individuals with schizophrenia-spectrum psychotic conditions (SSPCs) are disproportionately exposed to adverse social determinants of health (SDOHs). These exposures drive health inequity in schizophrenia and are consistently linked to earlier illness onset, greater symptom severity, and poorer long-term outcomes. The brain-based mechanisms through which structural disadvantage becomes biologically embedded are not well characterized. Objective: To examine structural, functional, neurochemical, and plasticity brain changes associated with SDOHs with, or at risk for, SSPCs. Evidence Review: PsycInfo, PubMed, and Web of Science databases were searched from database inception until January 2026 to identify original, empirical studies that reported on the association between SDOHs (early life adversity, social disconnection, racism/discrimination, poverty, food insecurity) and neurobiological measures (brain structure, brain function, neurochemical, neuroplasticity) in individuals across the schizophrenia spectrum. Quality assessment scores using the Joanna Briggs Institute Checklist weighed the impact of individual study findings on the overall outcome summary. Findings: The systematic literature search yielded 14 500 articles, with 114 articles meeting full inclusion criteria. Most articles examined early life adversity (n = 95) with the remaining articles focused on social disconnection (n = 13), racism/discrimination (n = 4), poverty (n = 2), and food insecurity (n = 1). Regarding brain measures, 83 articles reported on structural brain measures, 23 on functional brain measures, 10 on neurochemical measures, and none on neuroplasticity. Together, these studies recruited 10 921 participants across the schizophrenia spectrum (high schizotypy n = 250; familial high-risk n = 1825; clinical high-risk for psychosis n = 3538; first-episode psychosis n = 1169; recent-onset psychosis n = 506; chronic schizophrenia n = 3754). Strong evidence that greater exposure to adverse SDOHs may be associated with neurobiological abnormalities, including cortical thinning, regional brain volume reduction, decreased structural connectivity and functional activation, and abnormal neurochemical levels was found. Conclusions and Relevance: These findings support the hypothesis that social adversity becomes biologically embedded, providing evidence for an intermediary link between SDOHs and clinical outcomes in SSPC. Integrating neuroscience with social epidemiology can advance psychosis prevention, refine treatment, and address structural drivers of mental health disparities.