Environmental Toxicant Exposure and Depressive Symptoms

Abstract

Importance: Recognizing associations between exposure to common environmental toxicants and mental disorders such as depression is crucial for guiding targeted mechanism research and the initiation of disease prevention efforts.

Objectives: To comprehensively screen and assess the associations between potential environmental toxicants and depressive symptoms and to assess whether systemic inflammation serves as a mediator.

Design, setting, and participants: A total of 3427 participants from the 2013-2014 and 2015-2016 waves of the National Health and Nutrition Examination and Survey who had information on blood or urine concentrations of environmental toxicants and depression scores assessed by the 9-item Patient Health Questionnaire (PHQ-9) were included. Statistical analysis was performed from July 1, 2023, to January 31, 2024.

Exposures: Sixty-two toxicants in 10 categories included acrylamide, arsenic, ethylene oxide, formaldehyde, iodine, metals, nicotine metabolites, polycyclic aromatic hydrocarbons, volatile organic compound (VOC) metabolites; and perchlorate, nitrate, and thiocyanate.

Main outcomes and measures: An exposome-wide association study and the deletion-substitution-addition algorithm were used to assess associations with depression scores (PHQ-9 ≥5) adjusted for other important covariates. A mediation analysis framework was used to evaluate the mediating role of systemic inflammation assessed by the peripheral white blood cell count.

Results: Among the 3427 adults included, 1735 (50.6%) were women, 2683 (78.3%) were younger than 65 years, and 744 (21.7%) were 65 years or older, with 839 (24.5%) having depressive symptoms. In terms of race and ethnicity, 570 participants (16.6%) were Mexican American, 679 (19.8%) were non-Hispanic Black, and 1314 (38.3%) were non-Hispanic White. We identified associations between 27 chemical compounds or metals in 6 of 10 categories of environmental toxicants and the prevalence of depressive symptoms, including the VOC metabolites N-acetyl-S-(2-hydroxy-3-butenyl)-l-cysteine (odds ratio [OR], 1.74 [95% CI, 1.38, 2.18]) and total nicotine equivalent-2 (OR, 1.42 [95% CI, 1.26-1.59]). Men and younger individuals appear more vulnerable to environmental toxicants than women and older individuals. Peripheral white blood cell count mediated 5% to 19% of the associations.

Conclusions and relevance: In this representative cross-sectional study of adults with environmental toxicant exposures, 6 categories of environmental toxicants were associated with depressive symptoms with mediation by systemic inflammation. This research provides insight into selecting environmental targets for mechanistic research into the causes of depression and facilitating efforts to reduce environmental exposures.

Figure 1.. Adjusted Association Between Environmental Toxicants (62 Exposures) and Depressive Symptoms in 3427 Adults (Exposome-Wide Association Study Analysis)

AAMA indicates 2-carbamoylethylmercapturic acid; AMCC, methylcarbamoylmercapturate; CEMA, cyanoethyl mercapturic acid; CYMA, N-acetyl-S-(2-cyanoethyl)-l-cysteine; DHBMA, dihydroxy-butyl-mercapturic acid; GAMA, carbamoyl-2-hydroxyethylmercapturate; HEMA, 2-hydroxyethylmercapturic acid; HPMA, hydroxypropylmercapturic acid; HPMMA, 3-hydroxy-1-methyl-propylmercapturic acid; MA, mandelic acid; MHA, methylhippuric acid; MHBMA, monohydroxybutenyl-mercapturic acid; PAH, polycyclic aromatic hydrocarbon; TNE-2, total nicotine equivalent-2; and VOC, volatile organic compound.

Figure 2.. Adjusted Association Between Environmental Toxicants (62 Exposures) and Depressive Symptoms in 3427 Adults (Exposome-Wide Association Study Analysis) Stratified by Age and Sex

2,2DCVMA indicates N-acetyl-S-(2,2-dichlorovinyl)-l-cysteine; AAMA, 2-carbamoylethylmercapturic acid; AMCC, methylcarbamoylmercapturate; ATCA, 2-aminothiazoline-4-carboxylic acid; BMA, benzylmercapturic acid; BPMA, N-acetyl-S-(n-propyl)-l-cysteine; CEMA, cyanoethyl mercapturic acid; CYMA, N-acetyl-S-(2-cyanoethyl)-l-cysteine; DHBMA, dihydroxy-butyl-mercapturic acid; GAMA, carbamoyl-2-hydroxyethylmercapturate; HEMA, 2-hydroxyethylmercapturic acid; HPMA, hydroxypropylmercapturic acid; HPMMA, 3-hydroxy-1-methyl-propylmercapturic acid; MA, mandelic acid; MHA, methylhippuric acid; MHBMA, monohydroxybutenyl-mercapturic acid; PAH, polycyclic aromatic hydrocarbon; PGA, polyglutamic acid; PHEMA, poly(2-hydroxyethyl methacrylate); PMA, phenylmercapturic acid, TNE-2, total nicotine equivalent-2; and VOC, volatile organic compound.

Figure 3.. Mediation of Association Between Environmental Toxicants and Depressive Symptoms by Inflammation Biomarkers

AAMA indicates 2-carbamoylethylmercapturic acid; AMCC, methylcarbamoylmercapturate; ATCA, 2-aminothiazoline-4-carboxylic acid; BMA, benzylmercapturic acid; BPMA, N-acetyl-S-(n-propyl)-l-cysteine; CEMA, cyanoethyl mercapturic acid; CYMA, N-acetyl-S-(2-cyanoethyl)-l-cysteine; DHBMA, dihydroxy-butyl-mercapturic acid; HPMA, hydroxypropylmercapturic acid; HPMMA, 3-hydroxy-1-methyl-propylmercapturic acid; MA, mandelic acid; MHBMA, monohydroxybutenyl-mercapturic acid; PAH, polycyclic aromatic hydrocarbon; PGA, polyglutamic acid; PNT, perchlorate, nitrate, and thiocyanate; TNE-2, total nicotine equivalent-2; VOC, volatile organic compound; and WBC, white blood cell.