E2 ModerateModerate confidencePEM ?Cross-SectionalPeer-reviewedMachine draft
Brain and muscle chemistry in myalgic encephalitis/chronic fatigue syndrome (ME/CFS) and long COVID: a 7T magnetic resonance spectroscopy study.
Godlewska, Beata R, Sylvester, Amy L, Emir, Uzay E et al. · Molecular psychiatry · 2025 · DOI
Quick Summary
Researchers used advanced brain scans to look at chemical differences in the brains and muscles of people with ME/CFS, long COVID, and healthy people. They found that people with ME/CFS had higher levels of lactate (a chemical related to energy use) in specific brain areas, suggesting their brains may be working harder to produce energy. People with long COVID showed different changes - lower levels of a chemical called choline in the brain. These findings suggest that ME/CFS and long COVID may have different underlying causes, even though they produce similar symptoms.
Why It Matters
This study provides objective biological evidence of brain chemistry abnormalities in ME/CFS, supporting the theory that the condition involves real metabolic dysfunction rather than psychological causes. The finding that ME/CFS and long COVID have different metabolic signatures is particularly important because it suggests they may need different treatment approaches, and that lumping them together in research studies may obscure important findings about each condition.
Observed Findings
- ME/CFS patients had elevated lactate levels in both the pregenual anterior cingulate cortex (pgACC) and dorsal anterior cingulate cortex (dACC) compared to healthy controls.
- Long COVID patients had reduced total choline levels specifically in the dorsal anterior cingulate cortex (dACC).
- No significant differences in skeletal muscle metabolites at rest were detected between ME/CFS, long COVID, and healthy control groups.
- The metabolic abnormalities differed between ME/CFS and long COVID despite both conditions presenting with similar clinical symptoms like fatigue and cognitive dysfunction.
- Cognitive assessment was performed but specific results relating to cognitive performance and metabolite levels were not detailed in the abstract.
Inferred Conclusions
- Elevated brain lactate in ME/CFS is consistent with mitochondrial dysfunction and energetic stress in the brain, supporting metabolic dysfunction as a pathophysiological mechanism.
- The distinct metabolic signatures between ME/CFS and long COVID suggest these conditions have different underlying neurobiological mechanisms despite overlapping clinical presentations.
- ME/CFS and long COVID should be studied as separate conditions rather than grouped together, at least until their underlying mechanisms are better understood.
- The reduction in choline in long COVID may relate to thromboembolic complications and cognitive dysfunction, suggesting a distinct pathophysiological pathway from ME/CFS.
What This Study Does Not Prove
This study does not prove that elevated lactate causes ME/CFS symptoms or that it is the only abnormality present. As a cross-sectional study, it cannot establish causation or whether these chemical changes develop before or after symptom onset. The findings are also limited to the specific brain regions examined and may not reflect whole-brain or systemic metabolic changes.
Tags
Symptom:Post-Exertional MalaiseCognitive DysfunctionFatigue
Biomarker:MetabolomicsNeuroimaging
Phenotype:Infection-TriggeredLong COVID Overlap
Method Flag:PEM Not DefinedSmall SampleExploratory Only