O'Callaghan, James P, Miller, Diane B · Metabolism: clinical and experimental · 2019 · DOI
This review examines how inflammation in the brain and nervous system may be involved in ME/CFS and similar conditions. The authors suggest that various environmental stressors—like infections or other physical demands—can trigger or worsen this brain inflammation, leading to symptoms like fatigue, muscle pain, and brain fog. They propose that stress affects a key hormone system in the body (the HPA axis), which may play a role in how long these symptoms persist.
This study provides a unifying biological framework linking ME/CFS to documented neuroinflammatory mechanisms, potentially explaining why symptoms persist long after initial triggers resolve. Understanding the role of environmental stressors and HPA axis dysfunction may guide future therapeutic development and help validate ME/CFS as a neurobiological rather than purely psychiatric condition.
This review does not provide direct experimental evidence that neuroinflammation causes ME/CFS symptoms, nor does it establish which environmental stressors are most important in individual patients. The proposed HPA axis dysfunction remains a theoretical mechanism rather than a proven causative pathway in ME/CFS specifically.
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 →
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Primary citation
O'Callaghan, James P & Miller, Diane B (2019). Neuroinflammation disorders exacerbated by environmental stressors.. Metabolism: clinical and experimental. https://doi.org/10.1016/j.metabol.2019.153951
BibTeX
@article{mecfsatlas-ocallaghan-2019-neuroinflammation-disorders,
author = {O'Callaghan, James P and Miller, Diane B},
title = {Neuroinflammation disorders exacerbated by environmental stressors.},
journal = {Metabolism: clinical and experimental},
year = {2019},
doi = {10.1016/j.metabol.2019.153951},
note = {PubMed: 31610852},
url = {https://www.mecfsatlas.com/evidence/ocallaghan-2019-neuroinflammation-disorders},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/ocallaghan-2019-neuroinflammation-disorders
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