Unraveling the connection between endocrine-disrupting chemicals and anxiety: An integrative epidemiological and bioinformatic perspective

Background: The evidence linking endocrine-disrupting chemicals (EDCs) to anxiety in adults is currently sparse, while the effects of various categories of EDCs on the risk of anxiety, along with the underlying mechanisms, remain poorly understood. Methods: Four EDCs—polycyclic aromatic hydrocarbons...

Full description

Saved in:
Bibliographic Details
Main Authors: Ziang Guo, Yuxuan Tan, Chuhang Lin, Haiying Li, Qianqian Xie, Zhengtian Lai, Xiao Liang, Lei Tan, Chunxia Jing
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Ecotoxicology and Environmental Safety
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S014765132500524X
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849713155007053824
author Ziang Guo
Yuxuan Tan
Chuhang Lin
Haiying Li
Qianqian Xie
Zhengtian Lai
Xiao Liang
Lei Tan
Chunxia Jing
author_facet Ziang Guo
Yuxuan Tan
Chuhang Lin
Haiying Li
Qianqian Xie
Zhengtian Lai
Xiao Liang
Lei Tan
Chunxia Jing
author_sort Ziang Guo
collection DOAJ
description Background: The evidence linking endocrine-disrupting chemicals (EDCs) to anxiety in adults is currently sparse, while the effects of various categories of EDCs on the risk of anxiety, along with the underlying mechanisms, remain poorly understood. Methods: Four EDCs—polycyclic aromatic hydrocarbons (PAHs), phenols, pesticides, and phthalates—were quantified in 3927 adults from the National Health and Nutrition Examination Survey (NHANES) (2007–2012). We employed five statistical models to assess the individual and joint impacts of EDCs on anxiety risk. Causal mediation analysis frameworks were constructed to explore the mediating role of oxidative stress (OS). We identified potential biological mechanisms linking analytes to outcomes using the Comparative Toxicogenomics Database (CTD), MalaCards, and Open Targets, followed by enrichment analyses with Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results: In individual chemical analyses, nine PAHs were significantly associated with increased anxiety risk (P < 0.05). Mixed-effects analyses showed that co-exposure to EDCs positively correlated with anxiety, primarily due to 2-hydroxyfluorene (2-FLU) and 3-hydroxyfluorene (3-FLU). Bilirubin mediated 5.42 % of the anxiety linked to the PAH mixture. The inflammatory genes TNF and IL-6 were identified as key biological stressors, with enrichment analysis indicating significant involvement in reactive oxygen species metabolic processes and the AGE-RAGE signaling pathway. Conclusion: This study highlights the association between EDCs and anxiety in a representative U.S. population, indicating that exposure to PAHs may elevate anxiety risk through OS, inflammation, and the AGE-RAGE signaling pathway. Further longitudinal study were merited to support our results.
format Article
id doaj-art-71f22604dff547e980c1d9d2f9969fb4
institution DOAJ
issn 0147-6513
language English
publishDate 2025-05-01
publisher Elsevier
record_format Article
series Ecotoxicology and Environmental Safety
spelling doaj-art-71f22604dff547e980c1d9d2f9969fb42025-08-20T03:14:02ZengElsevierEcotoxicology and Environmental Safety0147-65132025-05-0129611818810.1016/j.ecoenv.2025.118188Unraveling the connection between endocrine-disrupting chemicals and anxiety: An integrative epidemiological and bioinformatic perspectiveZiang Guo0Yuxuan Tan1Chuhang Lin2Haiying Li3Qianqian Xie4Zhengtian Lai5Xiao Liang6Lei Tan7Chunxia Jing8Guangdong Key Laboratory of Environmental Exposure and Health, Jinan University, Guangzhou, Guangdong 510632, China; Department of Epidemiology, School of Medicine, Jinan University , No.601 Huangpu Ave West, Guangzhou, Guangdong 510632, China; Guangzhou Center for Disease Control and Prevention, No.1 Qide Road, Guangzhou , Guangdong 510440, ChinaDepartment of Global Health, School of Public Health, Wuhan University, Wuhan, Hubei 430071, ChinaGuangdong Key Laboratory of Environmental Exposure and Health, Jinan University, Guangzhou, Guangdong 510632, China; Department of Epidemiology, School of Medicine, Jinan University , No.601 Huangpu Ave West, Guangzhou, Guangdong 510632, ChinaGuangdong Key Laboratory of Environmental Exposure and Health, Jinan University, Guangzhou, Guangdong 510632, China; Department of Epidemiology, School of Medicine, Jinan University , No.601 Huangpu Ave West, Guangzhou, Guangdong 510632, ChinaGuangdong Key Laboratory of Environmental Exposure and Health, Jinan University, Guangzhou, Guangdong 510632, China; Department of Epidemiology, School of Medicine, Jinan University , No.601 Huangpu Ave West, Guangzhou, Guangdong 510632, ChinaGuangdong Key Laboratory of Environmental Exposure and Health, Jinan University, Guangzhou, Guangdong 510632, China; Department of Epidemiology, School of Medicine, Jinan University , No.601 Huangpu Ave West, Guangzhou, Guangdong 510632, ChinaGuangdong Key Laboratory of Environmental Exposure and Health, Jinan University, Guangzhou, Guangdong 510632, China; Department of Epidemiology, School of Medicine, Jinan University , No.601 Huangpu Ave West, Guangzhou, Guangdong 510632, ChinaGuangzhou Center for Disease Control and Prevention, No.1 Qide Road, Guangzhou , Guangdong 510440, China; Corresponding author.Guangdong Key Laboratory of Environmental Exposure and Health, Jinan University, Guangzhou, Guangdong 510632, China; Department of Epidemiology, School of Medicine, Jinan University , No.601 Huangpu Ave West, Guangzhou, Guangdong 510632, China; Corresponding author at: Department of Epidemiology, School of Medicine, Jinan University, No.601 Huangpu Ave West, Guangzhou, Guangdong 510632, China.Background: The evidence linking endocrine-disrupting chemicals (EDCs) to anxiety in adults is currently sparse, while the effects of various categories of EDCs on the risk of anxiety, along with the underlying mechanisms, remain poorly understood. Methods: Four EDCs—polycyclic aromatic hydrocarbons (PAHs), phenols, pesticides, and phthalates—were quantified in 3927 adults from the National Health and Nutrition Examination Survey (NHANES) (2007–2012). We employed five statistical models to assess the individual and joint impacts of EDCs on anxiety risk. Causal mediation analysis frameworks were constructed to explore the mediating role of oxidative stress (OS). We identified potential biological mechanisms linking analytes to outcomes using the Comparative Toxicogenomics Database (CTD), MalaCards, and Open Targets, followed by enrichment analyses with Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results: In individual chemical analyses, nine PAHs were significantly associated with increased anxiety risk (P < 0.05). Mixed-effects analyses showed that co-exposure to EDCs positively correlated with anxiety, primarily due to 2-hydroxyfluorene (2-FLU) and 3-hydroxyfluorene (3-FLU). Bilirubin mediated 5.42 % of the anxiety linked to the PAH mixture. The inflammatory genes TNF and IL-6 were identified as key biological stressors, with enrichment analysis indicating significant involvement in reactive oxygen species metabolic processes and the AGE-RAGE signaling pathway. Conclusion: This study highlights the association between EDCs and anxiety in a representative U.S. population, indicating that exposure to PAHs may elevate anxiety risk through OS, inflammation, and the AGE-RAGE signaling pathway. Further longitudinal study were merited to support our results.http://www.sciencedirect.com/science/article/pii/S014765132500524XAnxietyEndocrine-disrupting ChemicalsPolycyclic aromatic hydrocarbonsOxidative stressInflammationAGE-RAGE signaling pathway
spellingShingle Ziang Guo
Yuxuan Tan
Chuhang Lin
Haiying Li
Qianqian Xie
Zhengtian Lai
Xiao Liang
Lei Tan
Chunxia Jing
Unraveling the connection between endocrine-disrupting chemicals and anxiety: An integrative epidemiological and bioinformatic perspective
Ecotoxicology and Environmental Safety
Anxiety
Endocrine-disrupting Chemicals
Polycyclic aromatic hydrocarbons
Oxidative stress
Inflammation
AGE-RAGE signaling pathway
title Unraveling the connection between endocrine-disrupting chemicals and anxiety: An integrative epidemiological and bioinformatic perspective
title_full Unraveling the connection between endocrine-disrupting chemicals and anxiety: An integrative epidemiological and bioinformatic perspective
title_fullStr Unraveling the connection between endocrine-disrupting chemicals and anxiety: An integrative epidemiological and bioinformatic perspective
title_full_unstemmed Unraveling the connection between endocrine-disrupting chemicals and anxiety: An integrative epidemiological and bioinformatic perspective
title_short Unraveling the connection between endocrine-disrupting chemicals and anxiety: An integrative epidemiological and bioinformatic perspective
title_sort unraveling the connection between endocrine disrupting chemicals and anxiety an integrative epidemiological and bioinformatic perspective
topic Anxiety
Endocrine-disrupting Chemicals
Polycyclic aromatic hydrocarbons
Oxidative stress
Inflammation
AGE-RAGE signaling pathway
url http://www.sciencedirect.com/science/article/pii/S014765132500524X
work_keys_str_mv AT ziangguo unravelingtheconnectionbetweenendocrinedisruptingchemicalsandanxietyanintegrativeepidemiologicalandbioinformaticperspective
AT yuxuantan unravelingtheconnectionbetweenendocrinedisruptingchemicalsandanxietyanintegrativeepidemiologicalandbioinformaticperspective
AT chuhanglin unravelingtheconnectionbetweenendocrinedisruptingchemicalsandanxietyanintegrativeepidemiologicalandbioinformaticperspective
AT haiyingli unravelingtheconnectionbetweenendocrinedisruptingchemicalsandanxietyanintegrativeepidemiologicalandbioinformaticperspective
AT qianqianxie unravelingtheconnectionbetweenendocrinedisruptingchemicalsandanxietyanintegrativeepidemiologicalandbioinformaticperspective
AT zhengtianlai unravelingtheconnectionbetweenendocrinedisruptingchemicalsandanxietyanintegrativeepidemiologicalandbioinformaticperspective
AT xiaoliang unravelingtheconnectionbetweenendocrinedisruptingchemicalsandanxietyanintegrativeepidemiologicalandbioinformaticperspective
AT leitan unravelingtheconnectionbetweenendocrinedisruptingchemicalsandanxietyanintegrativeepidemiologicalandbioinformaticperspective
AT chunxiajing unravelingtheconnectionbetweenendocrinedisruptingchemicalsandanxietyanintegrativeepidemiologicalandbioinformaticperspective