Sex specificity in associations between exposure to a mixture of per and poly-fluoroalkyl substances and anxiety among US adults

Background: Exposure to per and poly-fluoroalkyl substances (PFAS) is suggested to interfere with the central nervous system that may affect mental health. Studies on the relationships between exposure to PFAS mixtures and anxiety in humans are rare. This study aimed to evaluate the associations between single and combined exposure to PFAS and anxiety among adults.

Methods: Data were extracted from the National Health and Nutrition Examination Survey (NHANES, 2007-2012). Six serum PFAS concentrations were accessed including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), PFOS (perfluorooctanesulfonic acid), PFHxS (perfluorohexane sulfonate), PFDA (perfluorodecanoic acid), Me-PFOSA-AcOH (2-(N-methylperfluorooctanesulfonamide) acetic acid). The anxiety state was defined through the questionnaire responses of the participants. Weighted logistics regression was used to calculate their odds ratio (OR) and corresponding confidence interval (95% CI) that assessed the relationship between PFAS exposure and anxiety. Moreover, Two different statistical methods including quantile-based g-computation (Qgcomp), and Bayesian kernel machine regression (BKMR) were employed to investigate the overall effects of PFAS mixtures on anxiety.

Results: The effects of specific PFAS exposure on anxiety varied by sex. In male participants, one-unit increase in PFDA (OR = 0.62; 95%CI: 0.44, 0.88), PFOA (OR = 0.60; 95%CI: 0.41, 0.87), PFNA (OR = 0.68; 95%CI: 0.46, 0.96) concentrations were inversely linked to anxiety. In female participants, a one-unit increase in PFOA (OR = 1.50; 95%CI: 1.05, 2.14) concentration was associated with anxiety. Analysis of Qgcomp demonstrated that PFAS mixtures were negatively associated with anxiety in males (OR = 0.85; 95%CI: 0.74, 0.99), and were positively associated with anxiety in females(OR = 1.16; 95%CI: 1.01, 1.33). Analysis of BKMR suggested that PFAS mixtures were negatively associated with anxiety in the males, while its associations with anxiety were positive in the females.

Impact: Although a growing number of studies have focused on the relationship between PFAS and anxiety, most have been performed based on animal observations rather than human populations, and the combined effects of PFAS mixtures on anxiety have not been evaluated. To address these gaps, this study first explored the associations between individual PFAS and PFAS mixture exposures and anxiety among US adults. Using data from the National Health and Nutrition Examination Survey, we demonstrated that co-exposure to a mixture of PFAS was negatively associated with anxiety in males, and its association was contrary in females.