Boruch, Alexander E, Lindheimer, Jacob B, Ninneman, Jacob V et al. · Brain, behavior, & immunity - health · 2023 · DOI
This study looked at whether post-exertional malaise (PEM)—the worsening of symptoms after physical activity—is caused by changes in gene activity in Gulf War illness patients. Veterans with Gulf War illness and healthy controls exercised on stationary bikes, and researchers measured gene expression in blood samples before and after exercise. While the study found that certain genes did change after exercise in Gulf War illness patients, these gene changes did not explain why their symptoms got worse.
Understanding PEM mechanisms is critical for developing targeted treatments in ME/CFS and related conditions. This study helps clarify that PEM cannot be simply explained by changes in a handful of well-studied genes related to immune and metabolic function, suggesting researchers need to investigate other biological pathways. Finding what actually causes PEM remains essential for validating patient experiences and developing effective interventions.
This study does not prove that gene expression plays no role in PEM—only that changes in these three specific genes (ACTB, COMT, TLR4) do not statistically mediate the symptom response. The gene expression changes observed may still be important or indicative of other underlying processes not captured by mediation analysis. The study also cannot rule out that PEM involves genes not measured or that different biological mechanisms operate in ME/CFS versus Gulf War illness.
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
Boruch, Alexander E, Lindheimer, Jacob B, Ninneman, Jacob V, Wylie, Glenn R, Alexander, Thomas, Klein-Adams, Jacquelyn C, et al. (2023). Exercise-induced changes in gene expression do not mediate post exertional malaise in Gulf War illness.. Brain, behavior, & immunity - health. https://doi.org/10.1016/j.bbih.2023.100612
BibTeX
@article{mecfsatlas-boruch-2023-exercise-induced,
author = {Boruch, Alexander E and Lindheimer, Jacob B and Ninneman, Jacob V and Wylie, Glenn R and Alexander, Thomas and Klein-Adams, Jacquelyn C and Stegner, Aaron J and Gretzon, Nicholas P and Samy, Bishoy and Falvo, Michael J and Cook, Dane B},
title = {Exercise-induced changes in gene expression do not mediate post exertional malaise in Gulf War illness.},
journal = {Brain, behavior, & immunity - health},
year = {2023},
doi = {10.1016/j.bbih.2023.100612},
note = {PubMed: 36950022},
url = {https://www.mecfsatlas.com/evidence/boruch-2023-exercise-induced},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-27. https://www.mecfsatlas.com/evidence/boruch-2023-exercise-induced
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