Glucocorticoid receptor DNA methylation and childhood trauma in chronic fatigue syndrome patients

Abstract

In conclusion, we replicated findings of NR3C1-1F DNA hypomethylation in CFS patients versus controls. Our results support the hypothesis of HPA axis dysregulation and enhanced GR sensitivity in CFS.

Evidence for interaction between genetic liability and childhood trauma in the development of psychotic symptoms

“…A total of 138 subjects (18.5%) had at least one type of CT (Table 3). This was similar to or lower than other general population samples (Brazil 17% [35]; China, no total, subscales 11, 7, 2, 2, 5, respectively [36]) and far lower than various patient groups and a homeless control sample [36][37][38]. CT and genetic liability were associated (χ 2 = 8.2, df = 2, p = 0.016).…”

Epigenetic Components of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Uncover Potential Transposable Element Activation

“…Another 2 gene-focused methylation studies, performed by Vangeel et al, 35,36 explored the DNA methylation status of the glucocorticoid receptor (GR) NR3C1 gene by using mass spectrometry (Sequenom EpiTYPER; Agena Bioscience, San Diego, California) in 76 patients with CFS and 19 healthy subjects in one study, and in 80 patients with CFS and 91 healthy control subjects in the other study. In both cases, the authors found hypomethylation at this locus in CFS participants in relation to control subjects.…”

Myalgic encephalomyelitis or chronic fatigue syndrome: how could the illness develop?

“…There is also evidence of abnormalities in the epigenetic regulation of gene expression in CFS patients diagnosed via narrow criteria, most notably in gene promoter methylation patterns and elevation of microRNAs (miRNAs) involved in the regulation of the immune system (Brenu et al 2014a; de Vega et al 2014, 2017; Petty et al 2016; Vangeel et al 2015, 2018). The work of de Vega and others is of particular interest as these authors also selected patients according to criteria mandating the presence of post-exertional malaise and examined global patterns of gene methylation rather than a single gene as was the case for Vangeel and colleagues (de Vega et al 2014, 2017; Vangeel et al 2015, 2018).…”

“…The work of de Vega and others is of particular interest as these authors also selected patients according to criteria mandating the presence of post-exertional malaise and examined global patterns of gene methylation rather than a single gene as was the case for Vangeel and colleagues (de Vega et al 2014, 2017; Vangeel et al 2015, 2018). …”

“…Importantly, de Vega and others reported a global hypomethylation of cytosine residues in the promoter regions of immune system-related genes consistent with a chronically activated but dysregulated immune system, and abnormal patterns of DNA methylation in genes regulating metabolic pathways and various aspects of cellular homeostasis (de Vega et al 2014, 2017). The work of (Vangeel et al 2015, 2018) is also of interest as the pattern of hypomethylation of the glucocorticoid receptor gene NR3C1 1F region suggests an activated hypothalamic-pituitary-adrenal (HPA) axis in an attempt to counter peripheral inflammation rather than a blunted HPA response reported in people diagnosed with CFS according to wider criteria (reviewed (Morris et al 2017a)). The lack of association between childhood trauma and levels of methylation reported by these authors in studies where participants universally reported this phenomenon is also of interest as these patients were diagnosed according to the Fukuda criteria whereas studies which have reported a significant but slight association between childhood trauma and CFS involved participants recruited via alternative criteria (reviewed (Morris et al 2017a)).…”