Earlier this week, ME Research UK highlighted an article which, despite a small sample size, suggested that people with ME/CFS may have dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Notably, the HPA plays a critical role in regulating stress responses, immune function, and energy production and utilisation (metabolism) – all systems which have been linked to ME/CFS disease mechanisms.
A review by researcher Noé López-Amador, published in the journal “Exploration of Neuroprotective Therapy”, has explored the potential role HPA axis dysfunction may play in ME/CFS in more detail – specifically relating to the orexin system which coordinates the HPA axis, and plays a crucial role in regulating wakefulness, energy metabolism, and appetite.
The review, which considered the findings of 27 studies, concluded that “mounting evidence supports a unifying model wherein hypothalamic and orexinergic dysfunction contribute significantly to the core features of ME/CFS”.
Three key observations were made in the review:
- Imaging studies show abnormalities in the brain in people with ME/CFS which are associated with symptom severity – a finding also demonstrated by research carried out by Kiran Thapaliya and colleagues in Australia, funded by ME Research UK.
- Decreased activity of the HPA axis, and the associated hormonal imbalances, could perpetuate fatigue.
- Dysregulation of the orexin system might “further compromise wakefulness and energy regulation, potentially exacerbating inflammation and immune dysfunction”.
As in the review relating to biological abnormalities in ME/CFS and long COVID by Prof. Anthony Komaroff and Prof. Robert Dantzer, and an article by Jente Van Campenhout who is a PhD student working on research funded by ME Research UK, the author suggested that feedback loops – or vicious cycles – between these biological abnormalities may play a role in the persistence of symptoms in ME/CFS.
Limitations of the research included in the review, acknowledged by the author, include the predominance of studies which look at a single snapshot in time (cross sectional studies) rather than those which follow participants up over time (longitudinal studies). This means that it is impossible to tell whether HPA axis and orexin dysfunction could lead to the symptoms of ME/CFS, or whether ME/CFS disease mechanisms might cause dysfunction in these systems.
Interestingly, in his video series, Prof. Jarred Younger has also discussed orexin and ME/CFS, stating that hypothetically, problems with orexin could certainly lead to the symptoms of the disease. However, more high quality research is needed to enable any firm conclusions to be drawn.
