Fig. 2. Forest plot summaries of linear mixed-effects models examining associations between depression, anxiety severity and epigenetic age acceleration (EAA) (n = 672 observations).

a Associations between depressive symptoms and EAA across epigenetic clocks. b Associations between anxiety symptoms and EAA across epigenetic clocks. Principal component-based ages were calculated for first and second generations. Results were rounded into three decimals. Points represent standardized regression coefficients (i.e., the estimated change in EAA, in SD units, per 1-SD increase in depression or anxiety, or for comparisons based on clinical cutoffs (e.g., GDS ≥ 5; GAI ≥ 8). Error bars represent 95% confidence intervals (CIs). An asterisk (*) indicates statistical significance (p < 0.05). For Model 3 and Model 6 (fully adjusted models), bootstrapped CIs are shown. p values for the fully adjusted models were corrected for multiple testing using the Benjamini–Hochberg procedure (see Methods). The vertical dashed line denotes the null. Model 1: Crude model; Model 2: Model adjusted for demographic and health covariates (sex, education, marital status, ethnicity, housing type, number of chronic diseases, BMI) Model 3: Model 2 further adjusted for lifestyle covariates (physical activity, social activity, alcohol consumption, smoking status) Model 4: Crude model with symptoms categorized into clinical cutoff (GDS ≥ 5; GAI ≥ 8). Model 5: Model 4 adjusted for demographic and health-related covariates; Model 6: Fully adjusted model with symptoms operationalized using the clinical cutoff.