Abstract
BACKGROUND: Neighborhood environments are increasingly recognized as important determinants of mental health, yet the biological pathways linking neighborhood stressors to depressive symptoms remain underexplored. This study examined whether metabolic and inflammatory biomarkers are involved in the longitudinal association between perceived neighborhood physical disadvantage and depressive symptoms among older adults. METHODS: We analyzed longitudinal data from the Health and Retirement Study (HRS, 2006-2016), a nationally representative cohort study of older adults. The neighborhood environment was measured using a four-item physical disadvantage scale. Depressive symptoms were assessed with the eight-item CES-D scale. Four biomarkers were examined: hemoglobin A1c (HbA1c), C-reactive protein (CRP), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL). Cross-lagged panel models were performed to assess longitudinal pathways, with and without covariate adjustment. RESULTS: Perceived neighborhood physical disadvantage and depressive symptoms were reciprocally associated over time. Greater perceived neighborhood physical disadvantage was associated with higher subsequent HbA1c (B = 0.01, 95% CI: 0.01, 0.03), and higher HbA1c was associated with higher subsequent depressive symptoms (B = 0.05, 95% CI: 0.01, 0.09). CRP was associated with later depressive symptoms (B = 0.03, 95% CI: 0.01, 0.06), but was not associated with prior neighborhood physical disadvantage. No significant associations were found for TC or HDL. DISCUSSION: HbA1c was associated with both perceived neighborhood physical disadvantage and later depressive symptoms. These findings highlight the importance of considering neighborhood context alongside glycemic regulation in understanding depression risk among older adults.