Associations of social determinants of health, allostatic load, and brain age gaps in adolescence

Social determinants of health (SDOH) are fundamental drivers of behavioral outcomes; however, their impact on adolescents’ brain age gap (BAG)—an integrated neural marker reflecting deviations from normative brain maturation and potential brain plasticity—remain poorly understood. Moreover, the biological mechanisms underlying the effects are unknown. We conducted a prospective cohort analysis using magnetic resonance imaging (MRI) data from the Adolescent Brain Cognitive Development study (T1: n = 7330, 46.9% female, 55.2% White; diffusion tensor imaging (DTI): n = 6963, 46.7% female, 55.9% White; resting-state functional MRI (rs-fMRI): n = 6482, 47.3% female, 56.3% White; multimodal MRI: n = 6334, 47.2% female, 56.7% White), and applied XGBoost regression models to estimate T1, DTI, rs-fMRI, and multimodal BAGs, separately. We then used Bayesian multilevel models to examine the associations among SDOH, BAG, allostatic load, lifestyle factors, and mental health phenotypes. We found that positive SDOH (e.g., reduced exposure to industrial pollutants, high educational quality, and socioeconomic advantages) were associated with smaller BAGs, which indicate promoted brain plasticity; negative SDOH (e.g., number of early childhood education centers, unemployment rate, sexism, and racism) were associated with larger BAGs, which reflect lower brain plasticity. Allostatic load mediated the associations between SDOH and BAGs. Adequate nutritional intake amplified the effects of regional educational attainment on enhancing brain plasticity through reduced allostatic load. Only the larger rs-fMRI BAG predicted increased depression two years later. These findings underscore the critical roles of SDOH in shaping brain aging and highlight allostatic load as a key intervention target for promoting optimal brain development and mental health.