Study Finds HPA Axis Dysfunction in Chronic Fatigue Syndrome - Contradicts Childhood Trauma Findings


Founder of Health Rising and Phoenix Rising
Staff member
This study failed to find that childhood stress was associated with polymorphisms in the NR3C1 gene in ME/CFS. That was surely a suprise to them. This important gene helps to regulate the HPA axis - one of the two major stress response systems in the body. (Salivary cortisol is low in ME/CFS).

Several CDC studies, of course, have found evidence of increased childhood stress in ME/CFS patients. Several studies including the Light's and some CDC studies have found evidence of abnormalitiies in NR3c1 gene activity and makeup.

So it made sense that childhood trauma was associated with altered Nr3C1 expression in ME/CFS- but ME/CFS fooled them; it wasn't found more commonly in people with childhood trauma - but it was associated with reduced HPA axis activation in ME/CFS...

This suggests altered methylation processes in people with ME/CFS may result in reduced HPA axis activation - which, in turn, could be associated with increased inflammation. All in all a pretty darn good finding. :)
Psychosom Med. 2015 Jul 30. [Epub ahead of print] Chronic Fatigue Syndrome and DNA Hypomethylation of the Glucocorticoid Receptor Gene Promoter 1F Region: Associations With Hypothalamic-Pituitary-Adrenal Axis Hypofunction and Childhood Trauma. Vangeel E1, Van Den Eede F, Hompes T, Izzi B, Del Favero J, Moorkens G, Lambrechts D, Freson K, Claes S.

Chronic fatigue syndrome (CFS) has been associated with hypothalamic-pituitary-adrenal axis hypofunction and enhanced glucocorticoid receptor (GR) sensitivity. In addition, childhood trauma is considered a major risk factor for the syndrome. This study examines DNA methylation of the GR gene (NR3C1) in CFS and associations with childhood sexual and physical trauma.

Quantification of DNA methylation within the 1F promoter region of NR3C1 was performed in 76 female patients (46 with no/mild and 30 with moderate/severe childhood trauma) and 19 healthy controls using Sequenom EpiTYPER. Further, we examined the association of NR3C1-1F promoter methylation the low-dose (0.5 mg) dexamethasone/corticotropin-releasing factor test outcomes in a subset of the study population. Mann-Whitney U tests and Spearman correlations were used for statistical analyses.

Overall NR3C1-1F DNA methylation was lower in patients with CFS than in controls. After cytosine guanine dinucleotide (CpG)-specific analysis, CpG_1.5 remains significant after Bonferroni correction (adjusted p = .0014). Within the CFS group, overall methylation (? = 0.477, p = .016) and selective CpG units (CpG_1.5: ? = 0.538, p = .007; CpG_12.13: ? = 0.448, p = .025) were positively correlated with salivary cortisol after dexamethasone administration. There was no significant difference in NR3C1-1F methylation between traumatized and nontraumatized patients.

We found evidence of NR3C1 promoter hypomethylation in female patients with CFS and the functional relevance of these differences was consistent with the hypothalamic-pituitary-adrenalaxis hypofunction hypothesis (GR hypersuppression). However, we found no evidence of an additional effect of childhood trauma on CFS via alterations in NR3C1 methylation.
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Well-Known Member
Geez -us! How are you able to locate, understand and translate, then post these esoteric findings?...:eek:

IAE, I suppose most PWC's who have been around have at least surveyed the HPA theory, which makes
perfect sense (as such things go in explaining system stimulation followed by demise, sic PEM). However, correlating childhood trauma (CT) and specific receptor genes sure does crunch some gears in arriving at implications for PWC's, particularly when considering a time/affect framework.

Let's assume one suffered from CT AND is pumping cortisol or adrenaline a la hyper HEPA. Why would this be significant and/or different from the PWC w/o the CT but with a HPA dysfunction?

Consider a demonstrable parallel, e.g. the popular show 'Naked and Afraid'. Arrange for a contestant to win $100k by agreeing to occupy an empty dark house (all windows boarded and doors locked, in Africa, if you like) for a week beginning, say Monday. Condition to win the cash: no releases, no exceptions unless medical emergency, life or death.

With 3 days in and 4 more days to go advise him or her Wednesday that a Black Mamba was released into the house at the start of the event (whether or not it really was is likely irrelevant)... .

Assuming the contestant goes the distance (?) at the end of the week you would have one real world person demonstrating the effects of a hyper HEPA, ready for testing and affect predictions (e.g. IBS, to start). What significance would knowing if his/her background included CT at this point; would it make (or have made) a difference if it did?

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