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

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.

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.

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.

Cross-sectional design limits temporality and causal inference.

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.