{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T22:16:17Z","timestamp":1793484977199,"version":"4.5.0"},"reference-count":50,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec id=\"ab-zoi240651-4\"><jats:title>Importance<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi240651-5\"><jats:title>Objectives<\/jats:title><jats:p>To comprehensively screen and assess the associations between potential environmental toxicants and depressive symptoms and to assess whether systemic inflammation serves as a mediator.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi240651-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi240651-7\"><jats:title>Exposures<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi240651-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>An exposome-wide association study and the deletion-substitution-addition algorithm were used to assess associations with depression scores (PHQ-9\u2009\u22655) 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.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi240651-9\"><jats:title>Results<\/jats:title><jats:p>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 <jats:italic>N<\/jats:italic>-acetyl-<jats:italic>S<\/jats:italic>-(2-hydroxy-3-butenyl)-<jats:sc>l<\/jats:sc>-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.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi240651-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2024.20259","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T15:07:08Z","timestamp":1720019228000},"page":"e2420259","source":"Crossref","is-referenced-by-count":108,"title":["Environmental Toxicant Exposure and Depressive Symptoms"],"prefix":"10.1001","volume":"7","author":[{"given":"Jianhui","family":"Guo","sequence":"first","affiliation":[{"name":"Institute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Garshick","sequence":"additional","affiliation":[{"name":"Pulmonary, Allergy, Sleep, and Critical Care Medicine Section, Medical Service, Veterans Affairs Boston Healthcare System and Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifei","family":"Si","sequence":"additional","affiliation":[{"name":"Peking University Sixth Hospital Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqi","family":"Tang","sequence":"additional","affiliation":[{"name":"Institute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyao","family":"Lian","sequence":"additional","affiliation":[{"name":"Institute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Child and Adolescent Health, School of Public Health, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petros","family":"Koutrakis","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2024,7,3]]},"reference":[{"issue":"2","key":"zoi240651r1","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/S2215-0366(21)00395-3","article-title":"Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.","volume":"9","author":"GBD 2019 Mental Disorders Collaborators","year":"2022","journal-title":"Lancet Psychiatry"},{"issue":"9","key":"zoi240651r2","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1017\/S0033291717003336","article-title":"Socio-economic variations in the mental health treatment gap for people with anxiety, mood, and substance use disorders: results from the WHO World Mental Health (WMH) surveys.","volume":"48","author":"Evans-Lacko","year":"2018","journal-title":"Psychol Med"},{"issue":"6","key":"zoi240651r4","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1001\/jamapsychiatry.2019.0010","article-title":"Identifying modifiable risk factors of mental health disorders\u2014the importance of urban environmental exposures.","volume":"76","author":"Kioumourtzoglou","year":"2019","journal-title":"JAMA Psychiatry"},{"issue":"4","key":"zoi240651r5","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/S2215-0366(18)30060-9","article-title":"Social determinants of mental disorders and the Sustainable Development Goals: a systematic review of reviews.","volume":"5","author":"Lund","year":"2018","journal-title":"Lancet Psychiatry"},{"issue":"6","key":"zoi240651r6","doi-asserted-by":"publisher","first-page":"3381","DOI":"10.1007\/s11357-023-00913-3","article-title":"Exposome and unhealthy aging: environmental drivers from air pollution to occupational exposures.","volume":"45","author":"Pandics","year":"2023","journal-title":"Geroscience"},{"issue":"140","key":"zoi240651r7","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1183\/16000617.0034-2016","article-title":"The exposome concept: a challenge and a potential driver for environmental health research.","volume":"25","author":"Siroux","year":"2016","journal-title":"Eur Respir Rev"},{"issue":"2","key":"zoi240651r8","doi-asserted-by":"publisher","first-page":"25001","DOI":"10.1289\/EHP9889","article-title":"The interplay of environmental exposures and mental health: setting an agenda.","volume":"130","author":"Reuben","year":"2022","journal-title":"Environ Health Perspect"},{"issue":"7","key":"zoi240651r9","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aax0903","article-title":"Nature and mental health: an ecosystem service perspective.","volume":"5","author":"Bratman","year":"2019","journal-title":"Sci Adv"},{"issue":"9","key":"zoi240651r10","doi-asserted-by":"publisher","first-page":"13089","DOI":"10.1007\/s11356-021-16692-3","article-title":"Association among urinary polycyclic aromatic hydrocarbons and depression: a cross-sectional study from NHANES 2015-2016.","volume":"29","author":"Rahman","year":"2022","journal-title":"Environ Sci Pollut Res Int"},{"issue":"3","key":"zoi240651r11","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1007\/s40572-020-00280-7","article-title":"A scoping review of non-occupational exposures to environmental pollutants and adult depression, anxiety, and suicide.","volume":"7","author":"Dickerson","year":"2020","journal-title":"Curr Environ Health Rep"},{"issue":"4","key":"zoi240651r12","doi-asserted-by":"publisher","first-page":"315","DOI":"10.5487\/TR.2010.26.4.315","article-title":"Toluene induces depression-like behaviors in adult mice.","volume":"26","author":"Yang","year":"2010","journal-title":"Toxicol Res"},{"issue":"21","key":"zoi240651r13","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1001\/jama.2019.17576","article-title":"Neglecting major health problems and broadcasting minor, uncertain issues in lifestyle science.","volume":"322","author":"Ioannidis","year":"2019","journal-title":"JAMA"},{"issue":"1","key":"zoi240651r14","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/s41386-020-00851-0","article-title":"Using the exposome to understand environmental contributors to psychiatric disorders.","volume":"46","author":"Burkett","year":"2021","journal-title":"Neuropsychopharmacology"},{"issue":"6476","key":"zoi240651r15","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1126\/science.aay3164","article-title":"The exposome and health: where chemistry meets biology.","volume":"367","author":"Vermeulen","year":"2020","journal-title":"Science"},{"issue":"10","key":"zoi240651r16","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1176\/appi.ajp.2020.19111158","article-title":"An exposure-wide and mendelian randomization approach to identifying modifiable factors for the prevention of depression.","volume":"177","author":"Choi","year":"2020","journal-title":"Am J Psychiatry"},{"issue":"3","key":"zoi240651r17","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.bpsgos.2022.05.005","article-title":"Estimating the association between exposome and psychosis as well as general psychopathology: results from the ABCD Study.","volume":"2","author":"Pries","year":"2022","journal-title":"Biol Psychiatry Glob Open Sci"},{"key":"zoi240651r18","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1016\/j.bbi.2020.07.037","article-title":"Anxiety and depression in COVID-19 survivors: role of inflammatory and clinical predictors.","volume":"89","author":"Mazza","year":"2020","journal-title":"Brain Behav Immun"},{"key":"zoi240651r19","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/j.bbi.2018.10.012","article-title":"Inflammation as a predictor of disease course in posttraumatic stress disorder and depression: a prospective analysis from the Mind Your Heart Study.","volume":"75","author":"Eswarappa","year":"2019","journal-title":"Brain Behav Immun"},{"issue":"6","key":"zoi240651r20","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1016\/j.cell.2021.01.043","article-title":"Hallmarks of environmental insults.","volume":"184","author":"Peters","year":"2021","journal-title":"Cell"},{"issue":"18","key":"zoi240651r21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2221097120","article-title":"High fried food consumption impacts anxiety and depression due to lipid metabolism disturbance and neuroinflammation.","volume":"120","author":"Wang","year":"2023","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"15","key":"zoi240651r22","doi-asserted-by":"publisher","first-page":"7820","DOI":"10.3390\/ijms22157820","article-title":"Copper, iron, and manganese toxicity in neuropsychiatric conditions.","volume":"22","author":"Tarnacka","year":"2021","journal-title":"Int J Mol Sci"},{"key":"zoi240651r23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.175634","article-title":"Omega-3 fatty acids prevent nicotine withdrawal-induced exacerbation of anxiety and depression by affecting oxidative stress balance, inflammatory response, BDNF and serotonin metabolism in rats.","volume":"947","author":"Amiry","year":"2023","journal-title":"Eur J Pharmacol"},{"issue":"1","key":"zoi240651r24","doi-asserted-by":"publisher","first-page":"5624","DOI":"10.1038\/s41467-020-19335-2","article-title":"Application of an analytical framework for multivariate mediation analysis of environmental data.","volume":"11","author":"Aung","year":"2020","journal-title":"Nat Commun"},{"issue":"1","key":"zoi240651r25","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1186\/s12940-017-0310-9","article-title":"Construction of environmental risk score beyond standard linear models using machine learning methods: application to metal mixtures, oxidative stress and cardiovascular disease in NHANES.","volume":"16","author":"Park","year":"2017","journal-title":"Environ Health"},{"issue":"18","key":"zoi240651r27","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.1001\/jama.282.18.1737","article-title":"Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study: primary care evaluation of mental disorders: patient health questionnaire.","volume":"282","author":"Spitzer","year":"1999","journal-title":"JAMA"},{"issue":"12","key":"zoi240651r28","doi-asserted-by":"publisher","first-page":"1848","DOI":"10.1289\/EHP172","article-title":"A systematic comparison of linear regression-based statistical methods to assess exposome-health associations.","volume":"124","author":"Agier","year":"2016","journal-title":"Environ Health Perspect"},{"key":"zoi240651r29","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2021.145025","article-title":"Chronic environmental contamination: a systematic review of psychological health consequences.","volume":"772","author":"Schmitt","year":"2021","journal-title":"Sci Total Environ"},{"issue":"6","key":"zoi240651r30","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1192\/bjp.bp.109.065912","article-title":"Cigarette smoking and depression: tests of causal linkages using a longitudinal birth cohort.","volume":"196","author":"Boden","year":"2010","journal-title":"Br J Psychiatry"},{"key":"zoi240651r31","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2020.173010","article-title":"Unique, long-term effects of nicotine on adolescent brain.","volume":"197","author":"Leslie","year":"2020","journal-title":"Pharmacol Biochem Behav"},{"issue":"6","key":"zoi240651r32","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1038\/npp.2008.220","article-title":"Nicotine exposure during adolescence induces a depression-like state in adulthood.","volume":"34","author":"I\u00f1iguez","year":"2009","journal-title":"Neuropsychopharmacology"},{"issue":"1","key":"zoi240651r33","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s12940-017-0210-z","article-title":"Early-life exposure to air pollution and greater use of academic support services in childhood: a population-based cohort study of urban children.","volume":"16","author":"Stingone","year":"2017","journal-title":"Environ Health"},{"key":"zoi240651r34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2023.114770","article-title":"Association of polycyclic aromatic hydrocarbons exposure with child neurodevelopment and adult emotional disorders: a meta-analysis study.","volume":"255","author":"Zhen","year":"2023","journal-title":"Ecotoxicol Environ Saf"},{"issue":"8","key":"zoi240651r35","doi-asserted-by":"publisher","first-page":"731","DOI":"10.3390\/antiox9080731","article-title":"Integrated hypoxia signaling and oxidative stress in developmental neurotoxicity of benzo[a]pyrene in zebrafish embryos.","volume":"9","author":"Lin","year":"2020","journal-title":"Antioxidants (Basel)"},{"issue":"Pt B","key":"zoi240651r36","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.108259","article-title":"RGFP966 is protective against lipopolysaccharide-induced depressive-like behaviors in mice by inhibiting neuroinflammation and microglial activation.","volume":"101","author":"Bian","year":"2021","journal-title":"Int Immunopharmacol"},{"issue":"1","key":"zoi240651r37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3109\/15563659008993472","article-title":"Neurotoxicological evaluation of hospital sterilizer workers exposed to ethylene oxide.","volume":"28","author":"Estrin","year":"1990","journal-title":"J Toxicol Clin Toxicol"},{"issue":"24","key":"zoi240651r38","doi-asserted-by":"publisher","first-page":"9566","DOI":"10.3390\/ijms21249566","article-title":"Beyond the mind-serum trace element levels in schizophrenic patients: a systematic review.","volume":"21","author":"Baj","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"24","key":"zoi240651r39","doi-asserted-by":"publisher","first-page":"16006","DOI":"10.1021\/acs.est.0c05331","article-title":"Depression and anxiety associated with exposure to fine particulate matter constituents: a cross-sectional study in North China.","volume":"54","author":"Shi","year":"2020","journal-title":"Environ Sci Technol"},{"issue":"5","key":"zoi240651r40","doi-asserted-by":"publisher","first-page":"536","DOI":"10.3390\/ijerph14050536","article-title":"Chronic exposure to uranium from gestation: effects on behavior and neurogenesis in adulthood.","volume":"14","author":"Dinocourt","year":"2017","journal-title":"Int J Environ Res Public Health"},{"key":"zoi240651r41","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2022.119211","article-title":"Physical activity reduces the role of blood cadmium on depression: a cross-sectional analysis with NHANES data.","volume":"304","author":"Tian","year":"2022","journal-title":"Environ Pollut"},{"issue":"3","key":"zoi240651r42","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1159\/000209349","article-title":"Major depression, antidepressant medication and the risk of obesity.","volume":"78","author":"Patten","year":"2009","journal-title":"Psychother Psychosom"},{"issue":"2","key":"zoi240651r43","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.mehy.2006.01.047","article-title":"Rapid recovery from major depression using magnesium treatment.","volume":"67","author":"Eby","year":"2006","journal-title":"Med Hypotheses"},{"issue":"3","key":"zoi240651r44","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/0048-9697(84)90065-2","article-title":"Metabolism of arsenocholine in mice, rats and rabbits.","volume":"34","author":"Marafante","year":"1984","journal-title":"Sci Total Environ"},{"issue":"4","key":"zoi240651r45","doi-asserted-by":"publisher","first-page":"269","DOI":"10.21307\/ane-2017-061","article-title":"Developmental neurotoxicants and the vulnerable male brain: a systematic review of suspected neurotoxicants that disproportionally affect males.","volume":"77","author":"Kern","year":"2017","journal-title":"Acta Neurobiol Exp (Wars)"},{"key":"zoi240651r46","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.yrtph.2019.03.005","article-title":"Sex differences in subacute manganese intoxication: oxidative parameters and metal deposition in peripheral organs of adult Wistar rats.","volume":"104","author":"Richter Schmitz","year":"2019","journal-title":"Regul Toxicol Pharmacol"},{"key":"zoi240651r47","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.tox.2016.05.012","article-title":"Gender influence on manganese induced depression-like behavior and Mn and Fe deposition in different regions of CNS and excretory organs in intraperitoneally exposed rats.","volume":"376","author":"Yamagata","year":"2017","journal-title":"Toxicology"},{"key":"zoi240651r48","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s12995-020-00268-x","article-title":"Chemical risk and safety awareness, perception, and practices among research laboratories workers in Italy.","volume":"15","author":"Papadopoli","year":"2020","journal-title":"J Occup Med Toxicol"},{"issue":"7906","key":"zoi240651r49","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/s41586-022-04554-y","article-title":"Brain charts for the human lifespan.","volume":"604","author":"Bethlehem","year":"2022","journal-title":"Nature"},{"issue":"7","key":"zoi240651r50","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1038\/s41591-023-02424-2","article-title":"The airway microbiome mediates the interaction between environmental exposure and respiratory health in humans.","volume":"29","author":"Lin","year":"2023","journal-title":"Nat Med"},{"key":"zoi240651r26","volume-title":"National Health and Nutrition Examination Survey: Analytic Guidelines, 2011\u20132014 and 2015\u20132016","author":"National Center for Health Statistics","year":"2018"},{"key":"zoi240651r3","unstructured":"World Health Organization. World misses most 2020 mental health targets; extension of WHO Mental Health Action Plan to 2030 provides new opportunity for progress. October 8, 2021. Accessed December 29, 2023. https:\/\/www.who.int\/news\/item\/08-10-2021-who-report-highlights-global-shortfall-in-investment-in-mental-health"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2820702\/guo_2024_oi_240651_1719419426.51945.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T15:07:15Z","timestamp":1720019235000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2820702"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,3]]},"references-count":50,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2024.20259","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,3]]}}}