Social withdrawal and hippocampal volume among adolescents at clinical high risk for psychosis and healthy comparisons: The moderating role of neighborhood residential stability

Abstract

Objective Hippocampal volume (HV) reductions are a nonspecific marker of psychiatric vulnerability, including risk for psychosis. However, the behavioral and contextual factors that shape this association remain poorly understood. This study examined whether social withdrawal, a behavioral risk factor for psychosis, is associated with HV in adolescents, and whether neighborhood residential stability moderates this relationship. Methods Participants included 166 youth at clinical high risk for psychosis (CHR-P) and 41 healthy comparisons (ages 12-19, 40.1% female, 51.2% White non-Hispanic) from the North American Prodrome Longitudinal Study Phase 2. Clinicians assessed social withdrawal via the Premorbid Adjustment Scale. We derived residential stability measures from the 2010-2014 5-year American Community Survey estimates. Using linear mixed-effects models, we tested cross-sectional associations between bilateral HV and social withdrawal. Follow-up models tested the interaction between social withdrawal and neighborhood residential stability. Results Greater social withdrawal was associated with reduced bilateral HV in both univariable (left: β = -0.180, 95% CI = -0.316 to -0.044; right: β = -0.189, 95% CI = -0.317 to -0.060) and multivariable models (left: β = -0.169, 95% CI = -0.313 to -0.026; right: β = -0.154, 95% CI = -0.296 to -0.012). Notably, this association was moderated by neighborhood residential stability (left: interaction β = 0.217, 95% CI = 0.064 to 0.370; right: interaction β = 0.191, 95% CI = 0.048 to 0.333). Conclusions Social withdrawal may reflect neurodevelopmental vulnerability in adolescence, and neighborhood stability may buffer this risk. These findings underscore the value of integrating both behavioral and contextual factors into early risk detection and intervention efforts.