Couch, Yvonne, Xie, Qin, Lundberg, Louise et al. · PloS one · 2015 · DOI
This study used mice to explore how infections might trigger the fatigue and depression-like symptoms seen in ME/CFS. After exposing mice to bacterial toxins (to mimic infection), researchers found that the animals showed signs of depression and fatigue even after obvious illness symptoms disappeared. The key finding was that certain brain receptors related to serotonin became more active, suggesting that changes in how the brain processes serotonin—rather than simply low serotonin levels—might explain fatigue after infection.
Understanding the biological mechanisms underlying ME/CFS fatigue is critical for developing targeted treatments. This research identifies altered serotonin receptor function—rather than serotonin deficiency—as a potential driver of post-infection fatigue, potentially explaining why standard antidepressants have limited efficacy in ME/CFS and suggesting new therapeutic targets.
This study does not prove that serotonin receptor changes cause ME/CFS in humans, as it uses an acute mouse model that may not fully replicate the chronic disease trajectory. It demonstrates association and mechanism in an experimental setting but cannot establish causation in the complex human condition. The relevance to chronic ME/CFS pathophysiology (versus acute post-infection states) remains unclear.
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
Couch, Yvonne, Xie, Qin, Lundberg, Louise, Sharp, Trevor, & Anthony, Daniel C (2015). A Model of Post-Infection Fatigue Is Associated with Increased TNF and 5-HT2A Receptor Expression in Mice.. PloS one. https://doi.org/10.1371/journal.pone.0130643
BibTeX
@article{mecfsatlas-couch-2015-model-post,
author = {Couch, Yvonne and Xie, Qin and Lundberg, Louise and Sharp, Trevor and Anthony, Daniel C},
title = {A Model of Post-Infection Fatigue Is Associated with Increased TNF and 5-HT2A Receptor Expression in Mice.},
journal = {PloS one},
year = {2015},
doi = {10.1371/journal.pone.0130643},
note = {PubMed: 26147001},
url = {https://www.mecfsatlas.com/evidence/couch-2015-model-post},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-27. https://www.mecfsatlas.com/evidence/couch-2015-model-post
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