Demitrack, M A, Crofford, L J · Annals of the New York Academy of Sciences · 1998 · DOI
This study found that people with ME/CFS have reduced activity in their stress-response system—a network in the brain called the HPA axis that normally helps the body cope with physical and emotional challenges. The researchers discovered that this underactive response pattern is different from what happens in depression, and it may explain why stress and exertion worsen ME/CFS symptoms. The findings suggest that problems with specific brain chemicals involved in stress regulation may contribute to the condition.
Understanding HPA axis dysfunction in ME/CFS is crucial because it provides a biological mechanism explaining why patients experience symptom exacerbation with stress and physical activity. This mechanistic insight could guide development of targeted treatments aimed at restoring normal stress-response function, moving beyond symptomatic management to address underlying pathophysiology.
This study does not prove that HPA dysregulation is the sole cause of ME/CFS or explain how this dysfunction initially develops. It does not establish whether observed HPA changes are primary drivers of illness or secondary consequences, nor does it directly test whether correcting HPA function would improve symptoms.
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
Demitrack, M A & Crofford, L J (1998). Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome.. Annals of the New York Academy of Sciences. https://doi.org/10.1111/j.1749-6632.1998.tb09607.x
BibTeX
@article{mecfsatlas-demitrack-1998-evidence-pathophysiologic,
author = {Demitrack, M A and Crofford, L J},
title = {Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome.},
journal = {Annals of the New York Academy of Sciences},
year = {1998},
doi = {10.1111/j.1749-6632.1998.tb09607.x},
note = {PubMed: 9629295},
url = {https://www.mecfsatlas.com/evidence/demitrack-1998-evidence-pathophysiologic},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-28. https://www.mecfsatlas.com/evidence/demitrack-1998-evidence-pathophysiologic
Contribute
Private, reviewed by a human. Not a public comment thread.