Gold, P W, Licinio, J, Wong, M L et al. · Annals of the New York Academy of Sciences · 1995 · DOI
This research examines how the stress hormone system works differently in people with depression and chronic fatigue syndrome. The study found that while some people with depression have too much cortisol (a stress hormone), others—particularly those with fatigue-related conditions—may have too little activity in the part of the brain that normally triggers this hormone. This suggests that different types of depression and fatigue conditions might involve different problems with the body's stress response system.
This study is significant for ME/CFS because it proposes that chronic fatigue syndrome shares a common pathophysiological mechanism—reduced hypothalamic CRH function—with atypical depression, rather than simple stress-induced hypercortisolism. Understanding that ME/CFS may involve HPA axis hypofunction rather than hyperfunction could redirect research toward different diagnostic markers and therapeutic strategies, potentially improving diagnosis and treatment development for ME/CFS patients.
This mechanistic review does not prove causation or establish that CRH hypofunction is the primary driver of ME/CFS; it presents associations and theoretical mechanisms. The study cannot confirm that normalizing CRH function would alleviate ME/CFS symptoms, nor does it establish prevalence of HPA axis subtypes within ME/CFS populations. The findings are preliminary theoretical constructs requiring validation in controlled prospective studies.
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
Gold, P W, Licinio, J, Wong, M L, & Chrousos, G P (1995). Corticotropin releasing hormone in the pathophysiology of melancholic and atypical depression and in the mechanism of action of antidepressant drugs.. Annals of the New York Academy of Sciences. https://doi.org/10.1111/j.1749-6632.1995.tb44723.x
BibTeX
@article{mecfsatlas-gold-1995-corticotropin-releasing,
author = {Gold, P W and Licinio, J and Wong, M L and Chrousos, G P},
title = {Corticotropin releasing hormone in the pathophysiology of melancholic and atypical depression and in the mechanism of action of antidepressant drugs.},
journal = {Annals of the New York Academy of Sciences},
year = {1995},
doi = {10.1111/j.1749-6632.1995.tb44723.x},
note = {PubMed: 8597444},
url = {https://www.mecfsatlas.com/evidence/gold-1995-corticotropin-releasing},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-27. https://www.mecfsatlas.com/evidence/gold-1995-corticotropin-releasing
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