Long-Term Air Pollution, Genetic Susceptibility, and the Risk of Depression and Anxiety: A Prospective Study in the UK Biobank Cohort

Background: Depression and anxiety are two mental disorders that are often comorbid. However, the associations of long-term air pollution exposure with depression and anxiety remain inconclusive. Objective: We conducted a cross-sectional and prospective study to examine the associations of ambient exposure to particulate matter (PM) with a diameter of ≤2.5μm (PM2.5), ≤10μm (PM10), and 2.5–10μm (PMcoarse), nitrogen oxides (NOx), and nitrogen dioxide (NO2) with the risk of depression and anxiety in the UK Biobank. Methods: This study included 398,241 participants from the UK Biobank, 128,456 of whom participated the 7-y online mental health survey. A total of 345,876 individuals were free of depression and anxiety at baseline; of those, 16,185 developed incident mental disorders during a median of 8.7 y of follow-up. Depression and anxiety were assessed using hospital admission records and mental health questionnaires. Associations of air pollution with prevalent and incident mental disorders were examined using logistic regression and Cox regression models, respectively. Results: Elevated levels of the five air pollutants were associated with higher odds of mental disorders at baseline. Levels of four pollutants but not PMcoarse were also associated with higher odds and risks of mental disorders during follow-up; specifically, hazard ratios [HR, 95% confidence interval (CI)] of an interquartile range increase in PM2.5, PM10, NOx, and NO2 for incident mental disorders were 1.03 (95% CI: 1.01, 1.05), 1.06 (95% CI: 1.04, 1.08), 1.03 (95% CI: 1.01, 1.05), and 1.06 (95% CI: 1.04, 1.09), respectively. An air pollution index reflecting combined effects of pollutants also demonstrated a positive association with the risk of mental disorders. HR (95% CI) of incident mental disorders were 1.11 (95% CI: 1.05, 1.18) in the highest quintile group in comparison with the lowest quintile of the air pollution index. We further observed that the associations between air pollution and mental disorders differed by a genetic risk score based on single nucleotide polymorphisms previously associated with genetic susceptibility to mental disorders in the UK Biobank cohort. Discussion: To our knowledge, this research is one of the largest cohort studies that demonstrates an association between mental health disorders and exposure to long-term air pollution, which could be further enhanced by genetic predisposition. https://doi.org/10.1289/EHP10391