The Association between Multiple Environmental Exposures and Symptoms of Generalized Anxiety Disorder in a Prospective, US-Based Cohort Study

BACKGROUND: Emerging evidence has implicated built and natural environmental exposures in the etiology and exacerbation of anxiety symptoms. OBJECTIVES: Our objective was to assess individual and joint associations between neighborhood socioeconomic status (nSES), walkability, greenness, fine particulate matter (PM_2:5 ), nitrogen dioxide (NO₂ ), and temperature and generalized anxiety disorder (GAD) symptoms. METHODS: We included 81,897 participants of the Nurses’ Health Study II. GAD symptoms were measured in 2013 and 2017 using the seven-item Generalized Anxiety Disorder scale (GAD-7). Walkability and nSES z-scores were calculated at the census tract level. Summer and annual average greenness were measured using Normalized Difference Vegetation Index (NDVI) at 270 m and 1,230 m buffer sizes. 1-, 3-, and 12-month averages of particulate matter with an aerodynamic diameter of <2:5 micrograms (PM_2:5 ), nitrogen dioxide (NO₂ ), and temperature were predicted using spatiotemporal models. Exposures were measured at the residential level. Longitudinal logistic and generalized estimating equations (GEE) models estimated odds ratios (OR) and 95% confidence intervals (CIs) for clinically relevant GAD symptoms (GAD-7 ≥5 points). We assessed effect modification by nSES, summer NDVI (1,230 m), and select covariates. We employed quantile g-computation to assess the association between environmental exposure mixtures and GAD symptoms more directly. RESULTS: In single-exposure models, summer NDVI (e.g., for 1,230 m, OR = 0:96; 95% CI: 0.94, 0.98), NO₂ (e.g., for 12-month average NO₂, OR = 1:03; 95% CI: 1.01, 1.04), 12-month average temperature (OR = 1:05; 95% CI: 1.03, 1.07), and walkability (OR = 1:02; 95% CI: 1.01, 1.03) were associated with GAD symptoms. In the joint-exposure model, nSES (OR = 0:96; 95% CI: 0.95, 0.98) and summer NDVI were associated (OR = 0:92; 95% CI: 0.88, 0.96); all other associations were attenuated. Associations with summer NDVI (1,230 m), temperature, and NO₂ were modified by nSES, with stronger associations in socioeconomically deprived areas. DISCUSSION: In this population, higher levels of summer greenness and nSES may be protectively associated with GAD symptoms, whereas medium-and long-term NO₂ exposure, long-term temperature, and walkability are adversely associated with GAD symptoms. Socioeconomically deprived areas may bear additional risks. The results of the quantile g-computation analysis suggest that environmental exposures may act antagonistically with one another in relation to GAD symptoms. https://doi.org/10.1289/EHP14458.