Association of PFAS, Metals, Phthalate and Organophosphate Metabolites with Depression Among U.S. Adults

Depression is a major public health concern, and evidence continues to show that environmental toxicants may contribute to its development. This study evaluated the association between depressive symptoms and per- and polyfluoroalkyl substances (PFAS), heavy metals, phthalates, and organophosphate metabolites using data from NHANES 2017-2018. Depressive symptoms were measured with the Patient Health Questionnaire-9 (PHQ-9). Environmental exposure variables were analyzed using multivariable linear regression and Bayesian Kernel Machine Regression (BKMR). All models adjusted for demographic, socioeconomic, behavioral, and clinical covariates. In multivariable linear regression models adjusted for demographic, socioeconomic, behavioral, and clinical covariates, higher urinary dimethylphosphate concentrations were significantly associated with increased depressive symptom scores (β = 0.15; 95% CI: 0.04, 0.27; p = 0.0098). Mono-(2-ethylhexyl) phthalate (MEHP) was also positively associated with PHQ-9 scores (β = 0.001; 95% CI: 0.0003, 0.0019; p = 0.0043). Because environmental mixtures tend to follow non-linear patterns, BKMR analysis was run. BKMR analyses indicated that organophosphate metabolites exhibited the greatest overall contribution to depressive symptoms (group posterior inclusion probability = 0.7875), with diethylphosphate emerging as the most influential individual exposure within the group (conditional PIP = 0.7211). Exposure-response functions suggested non-linear and threshold relationships for several metabolites. These findings identify specific organophosphate and phthalate metabolites as potential contributors to depressive symptoms and support the importance of evaluating chemical mixtures rather than single exposures. Additional longitudinal studies are needed to clarify temporal relationships and to inform public health efforts aimed at reducing exposure to organophosphate pesticides and endocrine-disrupting chemicals.