Aregawi, Lillian, Walitt, Brian, Sullivan, Patti et al. · Brain communications · 2026 · DOI
Researchers measured levels of norepinephrine (a brain chemical) in cerebrospinal fluid from people with ME/CFS, Long COVID, and Parkinson's disease, comparing them to healthy volunteers. They observed that norepinephrine pathway activity was lower in all three patient groups, and in Long COVID patients with post-exertional malaise, this reduction was particularly pronounced. This is one study in a small sample, and it remains unclear whether these findings fully explain fatigue and brain fog or apply directly to ME/CFS.
This study provides one of the first candidate biomarkers—a measurable brain chemistry difference—associated with post-exertional malaise and fatigue in post-infectious conditions by analogy to ME/CFS. By identifying noradrenergic deficiency as a potential mechanism distinct from dopamine dysfunction, the work may guide future research into symptom drivers and therapeutic targets, though relevance to ME/CFS beyond post-acute Long COVID remains to be established.
This cross-sectional design does not establish that noradrenergic deficiency causes fatigue or post-exertional malaise; it demonstrates association only. The study does not confirm a mechanism of ME/CFS, nor does it test any treatment. Sample sizes, case definition quality, and generalisability beyond the NIH cohort are not transparent in the abstract, and findings may not apply to all ME/CFS presentations.
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
Aregawi, Lillian, Walitt, Brian, Sullivan, Patti, Norato, Gina, Benjamin, Rohit Ninan, & Goldstein, David S (2026). Central noradrenergic deficiency in post-infectious chronic fatigue: neurobehavioral correlates.. Brain communications. https://doi.org/10.1093/braincomms/fcag173
BibTeX
@article{mecfsatlas-aregawi-2026-central-noradrenergic,
author = {Aregawi, Lillian and Walitt, Brian and Sullivan, Patti and Norato, Gina and Benjamin, Rohit Ninan and Goldstein, David S},
title = {Central noradrenergic deficiency in post-infectious chronic fatigue: neurobehavioral correlates.},
journal = {Brain communications},
year = {2026},
doi = {10.1093/braincomms/fcag173},
note = {PubMed: 42205163},
url = {https://www.mecfsatlas.com/evidence/aregawi-2026-central-noradrenergic},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/aregawi-2026-central-noradrenergic
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