Accelerated biological aging (GOLD BioAgeDiff) and depressive symptoms in US adults: NHANES 2005-2018

BACKGROUND: Accelerated biological aging may link depressive symptoms with broader somatic morbidity, yet associations with mortality-validated phenotypic aging metrics remain understudied. We examined the association between Gompertz Law-Based Biological Age Difference (GOLD BioAgeDiff) and depressive symptoms in U.S. adults. METHODS: NHANES 2005-2018 participants (≥18 years) with complete PHQ-9 and biomarker data were analyzed. GOLD BioAgeDiff was defined as biological age minus chronological age. Survey-weighted logistic regression evaluated moderate-to-severe depressive symptoms (PHQ-9 ≥10), and linear regression evaluated continuous PHQ-9 scores. Primary models adjusted for sociodemographic and behavioral factors; fully adjusted models additionally included BMI, physical activity, diabetes, and coronary heart disease. RESULTS: Among 14,318 adults, 1228 had PHQ-9 ≥10. Each 1-SD increase in GOLD BioAgeDiff (≈5.05 years) was associated with higher odds of moderate-to-severe depressive symptoms in the primary model (OR 1.14, 95% CI 1.06-1.24; P = 0.001), attenuated in the fully adjusted model (N = 13,760; OR 1.09, 95% CI 1.00-1.19; P = 0.063). GOLD BioAgeDiff was also associated with higher PHQ-9 scores (primary β = 0.25, 95% CI 0.14-0.36; P < 0.001; fully adjusted β = 0.15, 95% CI 0.04-0.26; P = 0.009). Spline analyses showed borderline evidence of deviation from linearity in the primary model (P = 0.067) but no evidence supporting nonlinearity in the fully adjusted model (P = 0.396). Exploratory subgroup analyses suggested possible heterogeneity by CHD and smoking status. LIMITATIONS: Cross-sectional design limits temporality and causal inference. CONCLUSIONS: Higher GOLD BioAgeDiff was associated with greater depressive symptom burden. Estimates were attenuated after cardiometabolic adjustment, and subgroup findings require cautious interpretation and longitudinal confirmation.