Cleare, A J, Bearn, J, Allain, T et al. · Journal of affective disorders · 1995 · DOI
This study compared hormone levels and brain chemistry in people with ME/CFS, people with depression, and healthy controls. The researchers found that people with ME/CFS had lower cortisol (a stress hormone) and higher responses to a serotonin-related chemical, which is the opposite pattern seen in depression. This suggests ME/CFS and depression are biologically different conditions despite sometimes sharing similar symptoms like fatigue.
This research provides biological evidence that ME/CFS and depression are distinct conditions with opposite neuroendocrine abnormalities, which helps validate ME/CFS as a separate disease and may guide future treatment approaches. Understanding these biological differences is important because ME/CFS and depression are sometimes conflated clinically, potentially leading to inappropriate treatment.
This study does not prove that low cortisol or altered serotonin function *cause* ME/CFS symptoms—it only shows an association. The cross-sectional design cannot establish causality or determine whether these hormonal changes are primary drivers of illness or secondary consequences. A single d-fenfluramine challenge does not fully characterize serotonergic function across different brain regions and time points.
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
Cleare, A J, Bearn, J, Allain, T, McGregor, A, Wessely, S, Murray, R M, et al. (1995). Contrasting neuroendocrine responses in depression and chronic fatigue syndrome.. Journal of affective disorders. https://doi.org/10.1016/0165-0327(95)00026-j
BibTeX
@article{mecfsatlas-cleare-1995-contrasting-neuroendocrine,
author = {Cleare, A J and Bearn, J and Allain, T and McGregor, A and Wessely, S and Murray, R M and O'Keane, V},
title = {Contrasting neuroendocrine responses in depression and chronic fatigue syndrome.},
journal = {Journal of affective disorders},
year = {1995},
doi = {10.1016/0165-0327(95)00026-j},
note = {PubMed: 8550954},
url = {https://www.mecfsatlas.com/evidence/cleare-1995-contrasting-neuroendocrine},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/cleare-1995-contrasting-neuroendocrine
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