Depression Mediates the Association Between Ambient Air Pollution and Gastrointestinal/Liver Diseases: A Nationwide Cohort Study in China

Background The escalating burden of gastrointestinal (GI) and liver diseases poses a critical public health challenge, with emerging evidence implicating air pollution as a modifiable risk factor. However, the mechanistic pathways, particularly the mediating role of depression in the pollution-disease nexus, remain underexplored. This study investigates the longitudinal associations between ambient air pollution exposure and GI/liver diseases in a nationwide cohort, with a focus on quantifying depression’s mediating effects. Methods Utilizing data from the China Health and Retirement Longitudinal Study (CHARLS, 2011–2020; n = 18,755), we evaluated the impact of long-term exposure to PM₁, PM₂.₅, PM₁₀, SO₂, CO, NO₂, and O₃ on incident GI/liver diseases. Multivariable-adjusted Cox proportional hazards models incorporated demographic, socioeconomic (region, education, retirement status), and lifestyle (smoking, drinking) covariates. Mediation analysis assessed the proportion of total effects mediated by depression (CESD-10 scores). Results Chronic exposure to PM₁ (HR = 1.33, 95% CI: 1.29–1.37), PM₂.₅ (HR = 1.29, 1.26–1.33), PM₁₀ (HR = 1.28, 1.25–1.32), SO₂ (HR = 1.63, 1.59–1.68), CO (HR = 1.47, 1.43–1.51), and NO₂ (HR = 1.27, 1.23–1.30 ) per interquartile range increase was significantly associated with elevated disease risk, whereas O₃ exhibited protective effects (HR = 0.77, 0.74–0.79). Depression mediated 4.0–11.3% of pollution effects, with the highest mediation observed for O₃ (11.3%) and lowest for SO₂ (4.0%). Stratified analyses revealed heightened vulnerability in rural residents, individuals with lower education, and Northeastern populations. Conclusions This study pioneers the identification of depression as a mediator linking air pollution to GI/liver diseases in a nationally representative cohort. The findings advocate for integrative policies targeting air quality improvement and mental health interventions to alleviate the dual burden of environmental and psychological morbidity.