Shafran, S D · The American journal of medicine · 1991
ME/CFS is a serious condition causing extreme fatigue lasting at least 6 months that doctors cannot fully explain. While most patients report getting sick before their fatigue started, researchers have not found proof that any specific infection causes ME/CFS. The condition mainly affects people aged 20-50, with more women than men affected.
This foundational review helped establish ME/CFS as a recognized medical condition deserving systematic research. Identifying that no single infectious agent is definitively causative redirected research toward understanding complex pathophysiology rather than pursuing single-pathogen models. Understanding the high depression comorbidity remains clinically important for appropriate patient management.
This review does not prove that depression causes ME/CFS, only that it frequently co-occurs; the temporal relationship is variable. The absence of evidence for infectious etiology does not exclude the possibility that infections trigger ME/CFS through mechanisms not yet detected. The lack of proven effective treatments in 1991 does not mean effective treatments cannot be developed.
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
Shafran, S D (1991). The chronic fatigue syndrome.. The American journal of medicine. https://pubmed.ncbi.nlm.nih.gov/2042689/
BibTeX
@article{mecfsatlas-shafran-1991-chronic-fatigue,
author = {Shafran, S D},
title = {The chronic fatigue syndrome.},
journal = {The American journal of medicine},
year = {1991},
note = {PubMed: 2042689},
url = {https://www.mecfsatlas.com/evidence/shafran-1991-chronic-fatigue},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/shafran-1991-chronic-fatigue
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