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<p>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.</p><p></p>

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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 of 181,752 participants

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  • 发表日期：

    2025年10月17日

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  • Mingfei Jiang,
  • Xiaoran Li,
  • Yong Lu

摘要

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.