E3 PreliminaryPreliminaryPEM ?MechanisticPeer-reviewedMachine draft
Increased HDAC in association with decreased plasma cortisol in older adults with chronic fatigue syndrome.
Jason, Leonard, Sorenson, Matthew, Sebally, Kebba et al. · Brain, behavior, and immunity · 2011 · DOI
Quick Summary
This study examined stress hormone systems in older adults with ME/CFS. Researchers found that people with ME/CFS had lower levels of cortisol (a stress hormone) but higher levels of an enzyme called HDAC and lower antioxidant protection. These findings suggest that the body's stress response system isn't working properly in ME/CFS, possibly due to increased cellular stress.
Why It Matters
Understanding HPA axis dysregulation mechanisms in ME/CFS could explain why patients experience abnormal stress responses and fatigue. This work identifies potential molecular targets (HDAC, oxidative stress pathways) that might inform future therapeutic interventions.
Observed Findings
- Increased histone deacetylase (HDAC) activity in older adults with ME/CFS
- Decreased plasma cortisol levels
- Lower total antioxidant power
- Increased plasma dehydroepiandrosterone (DHEA)
- Decreased glucocorticoid receptor gene expression
Inferred Conclusions
- HPA axis dysregulation occurs in elderly ME/CFS patients
- Oxidative stress and altered HDAC activity may contribute to abnormal glucocorticoid signaling
- The combination of low cortisol with elevated DHEA and high HDAC represents a distinct hormonal pattern in ME/CFS
Remaining Questions
- Does HDAC elevation cause HPA axis dysfunction or result from it?
- How do these findings differ in younger ME/CFS patients compared to this elderly cohort?
- Can targeting HDAC activity or oxidative stress therapeutically restore normal HPA axis function?
- Do these molecular changes correlate with symptom severity or specific ME/CFS phenotypes?
What This Study Does Not Prove
This pilot study cannot establish causation or determine whether HDAC elevation causes cortisol reduction or vice versa. Results are limited to older adults with ME/CFS and cannot be generalized to younger patients or other age groups without further research.
Tags
Symptom:Fatigue
Biomarker:Gene ExpressionBlood Biomarker
Phenotype:Gradual Onset
Method Flag:PEM Not DefinedWeak Case DefinitionSmall SampleExploratory Only
Metadata
- DOI
- 10.1016/j.bbi.2011.04.007
- PMID
- 21549189
- Review status
- Machine draft
- Evidence level
- Early hypothesis, preprint, editorial, or weak support
- Last updated
- 8 April 2026