Long-term Individual and Joint Exposure to Multiple Ambient Air Pollutants Associated with Progression Trajectory of Neuropsychiatric Multimorbidity: Multi-state Transition Analysis

Considering the fact that air pollution is frequently linked to neuropsychiatric disorders, we initially examined how long-term individual and joint exposure to PM2.5, NO2 and NO relates to neuropsychiatric multimorbidity (NPM)'s temporal trajectory, encompassing depression, anxiety disorder and dementia, based on the UK Biobank cohort. Annual mean air pollution concentrations of PM2.5, NO2, and NO were estimated using the land use regression model, and joint exposure to air pollution reflected by air pollution score (APS) was calculated by principal components analysis. Multi-state models assessed air pollution's impact on transitions from health to first neuropsychiatric disorder (FND), then to NPM and mortality. 414,705 participants were included. Over the course of a 12.7-year median follow-up, 32,460 (7.8%) individuals developed FND, 7074 (21.8%) further developed NPM, and totally 25,094 (6.1%) died. Transitions from baseline to FND and mortality increased by 9.4% (7.9%, 11.0%) and 7.1% (5.1%, 9.0%), respectively, for each interquartile range increase of PM2.5. The corresponding increases were 8.2% (6.1%, 10.3%) and 9.2% (6.1%, 11.4%) for NO2, 7.5% (5.5%, 8.4%) and 6.5% (4.6%, 8.4%) for NO, as well as 8.9% (7.4%, 10.4%) and 7.9% (6.1%, 9.8%) for APS. Notably, the risks of transitions from FND to NPM increased by 3.5% (0.3%, 6.6%) for PM2.5. After dividing FND into three specific diseases, we found that PM2.5, NO, and APS had impact on the transition from anxiety to NPM. Older participants, males, insomniacs, and the impoverished exhibited greater susceptibility to the identified risks. Our findings emphasize that reducing concurrent exposure to multiple air pollutants can potentially mitigate the onset and advancement of NPM, particularly in susceptible populations.