Reduction of glucocorticoid receptor function in chronic fatigue syndrome

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Source: Mediators of Inflammation Preprint Date: April 20, 2018 URL: http://downloads.hindawi.com/journals/mi/aip/3972104.pdf

Reduction of glucocorticoid receptor function in chronic fatigue syndrome ----------------------------------------------------------
Megan Lynn(1), Laura Maclachlan(2), Andreas Finkelmeyer(1), James Clark(1), James Locke(5), Stephen Todryk(3,5), Wan-Fai Ng(4,5), Julia L Newton(4,5), Stuart Watson(1,6,*)

 1 Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK 2. Department of Public Health and Community Medicine, University of Gothenburg, Gothenburg, Sweden 3 Faculty of Health & Life Sciences, Northumbria University, Newcastle upon Tyne 4 Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK 5 Institute of Cellular Medicine & NIHR Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne, UK 6 Northumberland Tyne and Wear NHS Foundation Trust

* Corresponding author. Email: stuart.watson@newcastle.ac.uk

Abstract

Glucocorticoid receptor (GR) function may have aetiopathogenic significance in chronic fatigue syndrome (CFS), via its essential role in mediating inflammatory responses as well as in hypothalamic-pituitary-adrenal axis regulation. GR function can be estimated ex-vivo by measuring dexamethasone (dex) modulation of cytokine response to lipopolysaccharide (LPS), and in-vivo using the impact of dex on cortisol levels. This study aimed to compare GR function between CFS (n=48), Primary Sjogren's Syndrome (a disease group control) (n=27), and sedentary healthy controls (HCs) (n=20) and to investigate its relationship with clinical measures.

In the GR ex-vivo response assay whole blood was diluted and incubated with LPS (to stimulate cytokine production), with or without 10 or 100 nanomolar concentrations of dex. Cytometric bead array (CBA) and flow cytometry enabled quantification of cytokine levels (TNF-alpha interleukin (IL)- 6 and IL-10) in the supernatants. In the in-vivo response assay, five plasma samples were taken for determination of total cortisol concentration using ELISA at half hourly intervals on two consecutive mornings separated by ingestion of 0.5mg of dex at 11pm. The association of the data from the in-vivo and ex-vivo analyses with reported childhood adversity were also examined.

CFS patients had reduced LPS-induced IL-6 and TNF-alpha production compared to both control groups and reduced suppression of TNF-alpha by the higher dose of dex compared to HCs. Cortisol levels, before or after dex did not differ between CFS and HCs. Cortisol levels were more variable in CFS than HCs. In the combined group (CFS plus HC) cortisol concentrations positively, and ex-vivo GR function (determined by dex mediated suppression of Il-10) negatively, correlated with childhood adversity score. The results do not support the hypothesis that GR dysregulation is aetiopathogenic in CFS and suggest that current and future endocrine cross sectional studies in CFS may be vulnerable to the confounding influence of childhood trauma which is likely increased by co-morbid depression.

-------- (c) 2018 Hindawi

 

Could I please ask for an explanation of what this is saying? I can’t understand it.

 

Basically, the endocrine abnormalities (cortisol mainly, but others too), and presumably the so-called link to stress as a cause, are overstated. They're probably not causative.

The results in some studies, which focus on stress and psychosocial factors, appear to be confounded (confused, muddled) by patients with concurrent/co-morbid depression, perhaps caused by adverse childhood events (trauma).

If you remove patients with mood disorders, the supposed link to stress and trauma disappears.

 

This is also interesting because Klimas suggests GR receptors are involved in GWI. This suggests an obvious way in which they're different.

Klimas has said that she thinks stress hormones are more involved in GWI than ME, which makes sense (I think the GR receptor is over-active in GWI so has to be switched off by any successful treatment).

 

Thank you @adambeyoncelowe

 

The overall finding is the opposite to the predictions made in several other studies, but mostly the study shows that some patients have higher levels of cortisol (rather than low cortisol) and lower levels of GCr function as a result.

Overall the conclusion is spot on:

I had previously come to the same conclusion when looking at all of the neuroendocrine studies on CFS patients as a whole.

 

From what I've read, hormones are all over the place: too high, too low, normal, a mix. I think that means that they're not a key factor in the illness, and are just secondary problems caused by long-term neurological dysfunction.