Per- and polyfluoroalkyl substances (PFAS), perceived stress, and depressive symptoms in a prospective cohort study of black women

Abstract

Background: Per- and polyfluoroalkyl substances (PFAS) are endocrine-disrupting chemicals with neurotoxic properties. PFAS have been associated with depressive symptoms among women in some studies, but little research has evaluated the effects of PFAS mixtures. Further, no study has investigated interactions of PFAS-depression associations by perceived stress, which has been shown to modify the effects of PFAS on other health outcomes.

Objective: In a prospective cohort study of reproductive-aged Black women, we investigated associations between PFAS and depressive symptoms and the extent to which perceived stress modified these associations.

Methods: We analyzed data from 1499 participants (23-35 years) in the Study of Environment, Lifestyle, and Fibroids. We quantified concentrations of nine PFAS in baseline plasma samples using online solid-phase extraction-liquid chromatography-isotope dilution tandem mass spectrometry. Participants reported perceived stress via the Perceived Stress Scale (PSS-4; range = 0-16) at baseline and depressive symptoms via the Center for Epidemiologic Studies Depression Scale (CESD; range = 0-44) at the 20-month follow-up visit. We used Bayesian Kernel Machine Regression to estimate associations between PFAS concentrations, individually and as a mixture, and depressive symptoms, and to assess effect modification by PSS-4 scores, adjusting for confounders.

Results: Baseline perfluorodecanoic acid concentrations were associated with greater depressive symptoms at the 20-month follow-up, but associations for other PFAS were null. The PFAS were not associated with depressive symptoms when evaluated as a mixture. The association between the 90th percentile (vs. 50th percentile) of the PFAS mixture with CES-D scores was null at the 10th (β = 0.03; 95 % CrI = 0.20, 0.25), 50th (β = 0.02; 95 % CrI = -0.16, 0.19), and 90th (β = 0.01; 95 % CrI = 0.18, 0.20) percentiles of PSS-4 scores, suggesting perceived stress did not modify the PFAS mixture.

Conclusion: In this prospective cohort study, PFAS concentrations-assessed individually or as a mixture-were not appreciably associated with depressive symptoms, and there was no evidence of effect modification by perceived stress.

Keywords: Black women; Depression; EDCs; Mixtures; PFAS; Stress.

Figure 1.

Schematic illustrating the timing of CES-D measurement for participants in the SELF cohort (n=1,499). We imputed scores for participants that completed the CES-D at the 40-month (5.4%) or 60-month visit (1.8%). We also imputed scores for participants that did not have the CES-D measured at any follow-up visit (4.5%)

Figure 2.

Associations of plasma PFAS concentrations and PSS-4 scores with CES-D scores in the (A) multivariable linear regression model and (B) BKMR model (for an increase from the 25^th to 75^th percentiles, holding all other mixture components at their 25^th, 50^th, or 75^th percentiles). Both models were adjusted for age, educational attainment, annual household income, employment status, marital status, BMI, smoking status, alcohol consumption, and parity (n=1,499). The multivariable linear regression model was also co-adjusted for all plasma PFAS concentrations and PSS-4 scores. PFAS were ln-transformed for BKMR and multivariable linear regression models; ln-transformed PFAS and PSS-4 scores were z-standardized for the BKMR model. Beta coefficients from the multivariable linear regression model were back-transformed to percent (%) differences in CES-D scores per doubling in plasma PFAS concentrations or point increase in PSS-4 scores.

Figure 2.

Associations of plasma PFAS concentrations and PSS-4 scores with CES-D scores in the (A) multivariable linear regression model and (B) BKMR model (for an increase from the 25^th to 75^th percentiles, holding all other mixture components at their 25^th, 50^th, or 75^th percentiles). Both models were adjusted for age, educational attainment, annual household income, employment status, marital status, BMI, smoking status, alcohol consumption, and parity (n=1,499). The multivariable linear regression model was also co-adjusted for all plasma PFAS concentrations and PSS-4 scores. PFAS were ln-transformed for BKMR and multivariable linear regression models; ln-transformed PFAS and PSS-4 scores were z-standardized for the BKMR model. Beta coefficients from the multivariable linear regression model were back-transformed to percent (%) differences in CES-D scores per doubling in plasma PFAS concentrations or point increase in PSS-4 scores.

Figure 3.

Associations of varying percentiles (10^th—90^th) of the PFAS mixture (PFHxS, PFOS, PFOA, PFNA, PFDA, MeFOSAA) with CES-D scores, compared to the 50^th percentile of the PFAS mixture, when PSS-4 scores were held at their 10^th, 50^th, and 90^th percentiles, respectively. Models were adjusted for age, educational attainment, annual household income, employment status, marital status, BMI, smoking status, alcohol consumption, and parity (n=1,499). Plasma PFAS concentrations scores were ln-transformed and z-standardized; PSS-4 scores were z-standardized.