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

Highlights: Public health relevance—How does this work relate to a public health issue? Depression is a major public health concern, and this study evaluates whether exposure to common environmental chemicals is associated with depressive symptoms in the U.S. population. The analysis examines PFAS, metals, phthalates, and organophosphate metabolites that are widely present in food, consumer products, and indoor environments. Public health significance—Why is this work of significance to public health? Specific organophosphate and phthalate metabolites were associated with higher PHQ-9 scores, indicating potential environmental contributions to depressive symptoms. Mixture modeling showed that organophosphate metabolites had the strongest overall contribution, highlighting the importance of evaluating combined chemical exposures rather than individual compounds alone. Public health implications—What are the key implications or messages for practitioners, policy makers and/or researchers in public health? Environmental exposures should be considered in public health research and surveillance related to mental health outcomes. The findings support efforts to reduce population-level exposure to neurotoxic and endocrine-disrupting chemicals and highlight the need for longitudinal studies to clarify temporal relationships. 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.