Abstract / Summary
Abstract Background : The relationship between metabolic syndrome (MetS) and incident depression and anxiety remains unclear. This study prospectively examined whether MetS increases the risk of new-onset depressive and anxiety disorders. Methods : This prospective cohort study included 316,263 participants from a large population-based cohort, with MetS defined according to NCEP ATP III guidelines. Multivariable Cox regression models estimated the association of MetS and its five components with outcomes. Restricted cubic splines were applied to explore dose-response relationships, and mediation analyses assessed the potential role of nine inflammatory markers. Results : Over a median follow-up of 14.07 years, 13,714 depression and 13,903 anxiety incident cases were identified. MetS was associated with increased risks of depression (HR 1.27, 95% CI 1.22–1.32) and anxiety (HR 1.17, 95% CI 1.12–1.21), with clear dose-response relationships (all P trend < 0.001). Further RCS analysis revealed a J-shaped association between SBP and depression. Among individual components, reduced HDL-C showed the strongest positive association with depression (HR 1.31, 95% CI 1.26–1.36) and anxiety (HR 1.20, 95% CI 1.15–1.24). The combination of elevated WC and reduced HDL-C demonstrated the highest risk for depression (HR 1.30, 95% CI 1.24–1.36) and anxiety (HR 1.20, 95% CI 1.14–1.26). Mediation analyses indicated that leukocyte and neutrophil counts explained 7.0% of the MetS-depression association and 12.0–14.0% of the MetS-anxiety association. Subgroup analyses revealed stronger associations in participants aged under 58 years and those with higher education. Conclusions : Our findings suggest that MetS, particularly the phenotype characterized by central obesity and dyslipidemia, may serve as a modifiable risk marker for depression and anxiety. The partial mediation by inflammatory markers supports the role of systemic low-grade inflammation in linking metabolic dysfunction to mental disorders, highlighting the potential value of integrating metabolic and inflammatory screening into mental health risk assessment.