The interaction and joint effects of the hemoglobin-to-red cell distribution width ratio and the triglyceride-glucose index (TyG) on depressive symptoms among residents of Nanjing City, along with the mediating role of TyG: a population-based study o

To investigate the mediating role of the triglyceride-glucose (TyG) in the association between the hemoglobin-to-red cell distribution width ratio (HRR) and depressive symptoms (DS), and to analyze the interaction and joint effects of HRR and TyG on DS. Based on cross-sectional data from 181,752 adult residents in Nanjing City (2020-2024), multivariable logistic regression, restricted cubic spline, and mediation analysis were used to assess the relationships of HRR and TyG with DS. HRR showed a nonlinear negative correlation with DS (Q4 vs. Q1: OR = 0.01, 95% CI 0.01-0.02), while TyG exhibited a nonlinear positive correlation (Q4 vs. Q1: OR = 6.22, 95% CI 5.64-7.15). Mediation analysis revealed heterogeneity in the proportion of the HRR - DS association mediated by TyG (Q1: 11.81%; Q3: -42.37%). A significant additive interaction between HRR and TyG on DS was observed (RERI = -7.59, 95% CI -8.18 to -7.00), but no significant multiplicative interaction. Joint analysis indicated that the HRR_Q1 + TyG_Q4 group had the highest DS risk (OR = 8.00, 95% CI 7.80-8.10), while the HRR_Q4 + TyG_Q1/Q3 groups showed the strongest protective effects (OR ≈ 0.04). The combined HRR + TyG model demonstrated significantly superior predictive performance compared to individual biomarkers (AUC = 0.861). TyG partially mediates the HRR-DS association, and HRR and TyG jointly influence DS risk through antagonistic effects. The combined model (HRR + TyG) may serve as an efficient biomarker panel for screening high-risk DS populations. Targeting improvements in iron metabolism and insulin resistance may provide novel strategies for DS prevention and management.