Morris, Gerwyn, Berk, Michael, Galecki, Piotr et al. · Molecular neurobiology · 2016 · DOI
This review examines why people with ME/CFS and similar immune-based illnesses experience severe, disabling fatigue. The authors identify multiple biological pathways that may contribute to this fatigue, including excessive inflammation, problems with how cells produce energy, and chemical imbalances in the brain and muscles. The fatigue appears to result from a complex interaction between the immune system, energy production, and brain function rather than a single cause.
This comprehensive review provides a unifying framework for understanding why ME/CFS fatigue is not simply 'deconditioning' or psychological, but rather involves measurable biological abnormalities across multiple systems. For patients, it validates that their fatigue has concrete physiological bases; for researchers, it identifies multiple interconnected pathways warranting targeted investigation and potential therapeutic intervention.
This narrative review does not establish which mechanisms are primary versus secondary in ME/CFS, nor does it prove that these pathways cause fatigue in all patients or that individual pathways are necessary and sufficient causes. The review synthesizes evidence across diverse disease states, so conclusions about ME/CFS-specific mechanisms require disease-focused 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 →
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Primary citation
Morris, Gerwyn, Berk, Michael, Galecki, Piotr, Walder, Ken, & Maes, Michael (2016). The Neuro-Immune Pathophysiology of Central and Peripheral Fatigue in Systemic Immune-Inflammatory and Neuro-Immune Diseases.. Molecular neurobiology. https://doi.org/10.1007/s12035-015-9090-9
BibTeX
@article{mecfsatlas-morris-2016-neuro-immune,
author = {Morris, Gerwyn and Berk, Michael and Galecki, Piotr and Walder, Ken and Maes, Michael},
title = {The Neuro-Immune Pathophysiology of Central and Peripheral Fatigue in Systemic Immune-Inflammatory and Neuro-Immune Diseases.},
journal = {Molecular neurobiology},
year = {2016},
doi = {10.1007/s12035-015-9090-9},
note = {PubMed: 25598355},
url = {https://www.mecfsatlas.com/evidence/morris-2016-neuro-immune},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-28. https://www.mecfsatlas.com/evidence/morris-2016-neuro-immune
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