Morris, Gerwyn, Berk, Michael, Walder, Ken et al. · BMC medicine · 2015 · DOI
This review proposes that ME/CFS fatigue may be caused by ongoing inflammation and immune system activation in the body, which then damages the brain's support cells (astrocytes) and energy-producing structures (mitochondria). The authors suggest that ME/CFS shares similar biological mechanisms with other inflammatory diseases like multiple sclerosis and lupus, and recommend that ME/CFS patients be tested for immune activation and receive specific brain imaging to look for evidence of inflammation.
This study provides a testable mechanistic framework linking ME/CFS to measurable biological markers of inflammation and immune activation, supporting the view that ME/CFS is a biological illness rather than psychological. It suggests concrete diagnostic approaches (immune testing, FLAIR MRI) and identifies specific cellular targets (astrocytes, mitochondria) that could guide future therapeutic development for ME/CFS patients.
This review does not establish causation—it identifies associations and proposes mechanisms without direct experimental evidence in ME/CFS populations. It does not prove that astrocyte dysfunction or mitochondrial damage in ME/CFS is primary rather than secondary, nor does it validate the proposed diagnostic tests as reliable biomarkers in ME/CFS specifically. The framework remains theoretical pending confirmation in ME/CFS-specific cohorts.
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
Morris, Gerwyn, Berk, Michael, Walder, Ken, & Maes, Michael (2015). Central pathways causing fatigue in neuro-inflammatory and autoimmune illnesses.. BMC medicine. https://doi.org/10.1186/s12916-014-0259-2
BibTeX
@article{mecfsatlas-morris-2015-central-pathways,
author = {Morris, Gerwyn and Berk, Michael and Walder, Ken and Maes, Michael},
title = {Central pathways causing fatigue in neuro-inflammatory and autoimmune illnesses.},
journal = {BMC medicine},
year = {2015},
doi = {10.1186/s12916-014-0259-2},
note = {PubMed: 25856766},
url = {https://www.mecfsatlas.com/evidence/morris-2015-central-pathways},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/morris-2015-central-pathways
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