Association between chronic stress and the epigenome: Exploration of psychological and biological stress
Year: 2026
Type: article
Study design: Observational Study
Abstract: Chronic stress is a predictor of health outcomes. Epigenetic mechanisms such as DNA methylation (DNAm) have been proposed as mediators between stress and health trajectories, with evidence from animal models supporting a causal relationship between chronic stress and variation in the epigenome. However, when examining the impact of stress in humans, stress is often very broadly defined and includes both the perception of stress (psychological stress) and biological indices of stress such as variation in the stress hormone cortisol (biological stress). There has been limited exploration of the distinct epigenetic associations with psychological vs. biological stress or analysis of these relationships that consider genome-wide DNAm. The current study used a longitudinal design (9 weeks) with 69 healthy participants aged 18-35. Self-reported psychological stress was assessed several times a week and averaged over the 9-week period. Hair cortisol concentration (HCC) and salivary genome-wide DNAm were assessed at the end of the 9-week period. We identified epigenomic associations between chronic psychological stress (956 CpG sites) and HCC (10,335 CpG sites), with elevated chronic psychological stress generally associated with DNA hypomethylation and elevated HCC generally associated with DNA hypermethylation. Self-report stress and HCC were not correlated. DNAm at 16 CpG sites was significantly associated with both psychological stress and HCC, though in opposing directions which may suggest potential upregulation vs. downregulation of overlapping biological pathways identified in response to these stressors. Associations between stress (psychological and biological) and DNAm within stress-associated genes were observed, generally suggesting a positive association between stress and DNAm. Epigenetic age (PhenoAge) was negatively associated with psychological stress and HCC, though these relationships were sex-specific and varied based on ethnicity-race. Findings suggest unique associations between stress and the epigenome, highlighting the complex pathways through which the biological embedding of stress and subsequent stress-associated health outcomes may emerge.
Source: PLoS ONE
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Funders: U.S. Department of Agriculture, Doris Duke Charitable Foundation, Cystic Fibrosis Foundation, Pittsburgh Foundation, American Heart Association, Leakey Foundation, Rheumatology Research Foundation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, University of Michigan, Resnick Sustainability Institute for Science, Energy and Sustainability, California Institute of Technology, Rufford Foundation, Victorian Cancer Agency, University of Texas at Austin, Appalachian State University, International Society of Travel Medicine, Public Health Agency of Canada, Swedish Cancer Foundation, Crown Family Philanthropies, Carnegie Institution for Science, Chongqing Municipal Health Commission, Jiangsu Commission of Health, Universidad Científica del Sur, National Institute for Health and Care Research, Australian National University, Macquarie University, University of Tasmania, Victoria University of Wellington, Deutsche Forschungsgemeinschaft, University of the Sunshine Coast, Canada Research Chairs, National Natural Science Foundation of China, Svenska Forskningsrådet Formas, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Keimyung University, Cancerfonden, Carl Tryggers Stiftelse för Vetenskaplig Forskning, China Postdoctoral Science Foundation, Natural Science Foundation of Fujian Province, Ministry of Science, ICT and Future Planning, National Research Foundation of Korea, Svenska Sällskapet för Medicinsk Forskning, Iran National Science Foundation, Knut och Alice Wallenbergs Stiftelse, Helse Vest, Vetenskapsrådet, Chongqing Medical University, Fru Berta Kamprads Stiftelse, Stiftelsen Lars Hiertas Minne, Natural Science Foundation of Inner Mongolia, Hacettepe Üniversitesi, Universidade Federal de Goiás, National Taiwan University Hospital, Chengdu University of Technology, Natural Science Foundation of Henan Province, Southeast University, Mohamed bin Zayed Species Conservation Fund, Strålsäkerhetsmyndigheten, European Academy of Allergy and Clinical Immunology, Versus Arthritis, Nasjonalforeningen for Folkehelsen, Natural Science Foundation of Sichuan Province, Ege University Research Foundation, Science and Technology Bureau of Jiaxing City, South East Regional Health Authority, Kalinga Institute of Industrial Technology, Fonds de recherche du Québec, National Institutes of Health, Centers for Disease Control and Prevention, U.S. Fish and Wildlife Service, U.S. Bureau of Land Management, Novartis Pharma, Disney Conservation Fund, Canadian Institutes of Health Research, Economic and Social Research Council, Australian Research Council, National Health and Medical Research Council, Japan Society for the Promotion of Science, Consejo Superior de Investigaciones Científicas, Sahlgrenska Akademin, National Key Research and Development Program of China, Fundamental Research Funds for the Central Universities, Beijing Science and Technology Planning Project, Special Fund Project for Science and Technology Innovation Strategy of Guangdong Province, Birmingham Biomedical Research Centre, National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, NIH Office of the Director, National Institute of General Medical Sciences, Fogarty International Center, National Institute of Neurological Disorders and Stroke, National Institute of Child Health and Human Development, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Army Research Office
OpenAlex ID: W7151078629