Vangeel, Elise, Van Den Eede, Filip, Hompes, Titia et al. · Psychosomatic medicine · 2015 · DOI
This study looked at a chemical marker called DNA methylation on a gene (NR3C1) that controls how the body responds to stress. Researchers found that people with ME/CFS had lower levels of this methylation compared to healthy people, which may explain why their bodies don't handle stress hormones properly. Interestingly, childhood trauma did not appear to create additional changes in this marker among ME/CFS patients.
This study provides molecular evidence supporting the long-hypothesized HPA axis dysfunction in ME/CFS, offering a potential biological marker that could aid diagnosis and understanding of disease mechanisms. The findings suggest that altered gene regulation—not trauma exposure—may be the primary driver of HPA abnormalities in CFS, redirecting research focus toward genetic and epigenetic mechanisms rather than purely psychological pathways.
This study does not prove that NR3C1 hypomethylation causes ME/CFS; it only shows an association in a cross-sectional design. It cannot establish whether methylation changes are a primary driver of disease or a consequence of chronic illness. The study also does not demonstrate that childhood trauma has no role in CFS development—only that it does not appear to mediate its effects through NR3C1 methylation.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Vangeel, Elise, Van Den Eede, Filip, Hompes, Titia, Izzi, Benedetta, Del Favero, Jurgen, Moorkens, Greta, et al. (2015). Chronic Fatigue Syndrome and DNA Hypomethylation of the Glucocorticoid Receptor Gene Promoter 1F Region: Associations With HPA Axis Hypofunction and Childhood Trauma.. Psychosomatic medicine. https://doi.org/10.1097/PSY.0000000000000224
BibTeX
@article{mecfsatlas-vangeel-2015-chronic-fatigue,
author = {Vangeel, Elise and Van Den Eede, Filip and Hompes, Titia and Izzi, Benedetta and Del Favero, Jurgen and Moorkens, Greta and Lambrechts, Diether and Freson, Kathleen and Claes, Stephan},
title = {Chronic Fatigue Syndrome and DNA Hypomethylation of the Glucocorticoid Receptor Gene Promoter 1F Region: Associations With HPA Axis Hypofunction and Childhood Trauma.},
journal = {Psychosomatic medicine},
year = {2015},
doi = {10.1097/PSY.0000000000000224},
note = {PubMed: 26230484},
url = {https://www.mecfsatlas.com/evidence/vangeel-2015-chronic-fatigue},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/vangeel-2015-chronic-fatigue
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