E2 ModerateModerate confidencePEM not requiredCase-ControlPeer-reviewedReviewed
Cortisol levels in chronic fatigue syndrome and atypical depression measured using hair and saliva specimens.
Herane-Vives, Andres, Papadopoulos, Andrew, de Angel, Valeria et al. · Journal of affective disorders · 2020 · DOI
Quick Summary
This study compared stress hormone (cortisol) levels in people with ME/CFS and people with a specific type of depression called atypical depression, both with and without fatigue. Researchers measured cortisol in two ways: through hair samples (showing levels over 3 months) and saliva samples (showing daily patterns). Both ME/CFS and atypical depression groups had lower daily cortisol output than healthy people, but normal cortisol levels when measured over longer periods, suggesting the low levels might be temporary or related to how the body's rhythm changes.
Why It Matters
Understanding cortisol patterns in ME/CFS helps clarify whether the condition shares biological mechanisms with depression and whether HPA axis dysfunction is a core or secondary feature. This research addresses the significant diagnostic confusion between ME/CFS and depression, potentially improving clinical recognition and tailoring treatment approaches specific to each condition's underlying biology.
Observed Findings
- Both CFS and A-MDE groups showed significantly lower salivary cortisol total daily output compared to healthy controls (CFS and A-MDE ~92-89 nmol/l.h vs controls ~125 nmol/l.h).
- Hair cortisol concentrations (3-month average) were normal and did not differ between patient groups and controls.
- CFS subjects reported fewer daily hassles and less severe psychic anxiety than A-MDE subjects, but showed similar somatic anxiety and overlapping symptoms like fatigue and concentration problems.
- No statistically significant differences in any cortisol measures between CFS and A-MDE groups.
Inferred Conclusions
- Low cortisol detected in short-term salivary measures may be transient rather than representing sustained HPA axis suppression, potentially explained by altered cortisol rhythm.
- CFS and atypical depression may share overlapping neuroendocrine features and could be manifestations of a broader somatic symptom disorder spectrum.
- Despite some distinct clinical features (daily hassles, psychic anxiety), the two conditions show similar patterns of cortisol secretion and overlapping somatic symptoms.
Remaining Questions
- What drives the apparent discrepancy between short-term (low) and long-term (normal) cortisol measures—is it truly a rhythm alteration, or another physiological mechanism?
- Do the transient low cortisol levels normalize over time, or do they persist cyclically in both conditions?
What This Study Does Not Prove
This study does not prove that low cortisol causes ME/CFS or atypical depression, nor does it establish that the conditions are identical. The cross-sectional design cannot determine causality or temporal relationships, and the normal hair cortisol levels suggest that acute low cortisol may be transient rather than a fundamental defining feature of either condition.
Tags
Symptom:Cognitive DysfunctionFatigue
Biomarker:Blood Biomarker
Method Flag:Weak Case DefinitionSmall SampleExploratory Only
Metadata
- DOI
- 10.1016/j.jad.2020.01.146
- PMID
- 32217231
- Review status
- Editor reviewed
- Evidence level
- Single-study or moderate support from human research
- Last updated
- 12 April 2026
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 →
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