Volatile organic compound exposure and depression risk: insights from individual, mixture, and sex-stratified analyses

BACKGROUND: Volatile organic compounds (VOCs) are ubiquitous environmental pollutants associated with a range of adverse health outcomes. However, the relationship between VOC exposure and mental health, particularly depression, remains insufficiently explored. This study aimed to evaluate the association between individual and mixed VOC exposures and the risk of depression in a representative U.S. population. METHODS: We analyzed data from 5,618 NHANES participants (2012–2020). Urinary VOC metabolites were measured as exposure biomarkers. Multivariable logistic regression models estimated associations across exposure quartiles and on continuous scales. Restricted cubic spline and threshold analyses were used to explore potential nonlinear exposure–response associations. To assess combined effects of multiple chemicals, we applied weighted quantile sum (WQS) regression and quantile g-computation. Stratified analyses were also performed. RESULTS: In fully adjusted models, participants in the highest quartile versus lowest showed significantly higher odds of depression for multiple VOCs, and continuous analyses yielded consistent positive associations. RCS models identified nonlinear dose-response for ATCA and AMCC with thresholds at 4.44 ng/mL (ATCA ≥ 4.44: OR, 1.26, 95% CI, 1.04–1.54) and 4.52 ng/mL (AMCC ≥ 4.52: OR, 1.33, 95% CI, 1.11–1.58). Stratified analyses showed significant VOC–depression associations in women but not in men. Mixture analyses confirmed a positive mixture–depression association overall (OR, 1.39, 95% CI, 1.15–1.67) that was stronger in females (OR, 1.68, 95% CI, 1.29–2.18). CONCLUSION: This study provides robust epidemiological evidence linking both individual and combined VOC exposures to an increased risk of depression, with notable sex-specific differences. These findings underscore the importance of environmental chemical exposures in mental health and highlight the urgent need for targeted public health interventions, particularly among vulnerable female populations.