Environmental VOC exposure and mental health.

Volatile organic compounds (VOCs) are major atmospheric pollutants with potential neurotoxic effects, yet their impacts on population-level mental health remain understudied. Here, we develop an integrative framework that combines the Community Multiscale Air Quality (CMAQ) model, epidemiological analysis, and network toxicology to assess the mental health risks of ambient VOC exposure across China. We simulated the spatiotemporal distribution of 33 VOC species at a 36 km × 36 km resolution using CMAQ, driven by the Weather Research and Forecasting (WRF) model. Ground-based observations and satellite-derived formaldehyde validated model performance. Applying these model-based exposure estimates to a national psychiatric cohort of 9195 inpatients, we observed significant associations between short-term VOC exposure and elevated serum interleukin-6 levels (per IQR increase in total VOC: β = 0.09, 95% CI: 0.03, 0.16), particularly for oxygenated VOCs such as formaldehyde (β = 0.14, 95% CI: 0.06, 0.22) and methacrolein (β = 0.06, 95% CI: 0.01, 0.11). Network toxicology predicted high blood-brain barrier permeability (probability > 0.9) for most VOCs and identified 43 overlapping genes linked to both VOC exposure and major depressive disorder, enriched in neuroinflammatory and synaptic signaling pathways. Our findings provide multidimensional evidence linking ambient VOC exposure to neuroinflammatory responses and potential mental health risks, supporting the need for broader VOC monitoring and mechanistic research.