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

Although the precise mechanisms are not yet understood, previous studies have suggested that chronic fatigue syndrome (CFS) is associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation and trauma in early childhood. Consistent with findings suggesting that early life stress-induced DNA methylation changes may underlie dysregulation of the HPA axis, we previously found evidence for the involvement of glucocorticoid receptor (GR) gene (NR3C1) methylation in whole blood of CFS patients. Methods In the current study, we assessed NR3C1-1F region DNA methylation status in peripheral blood from a new and independent sample of 80 female CFS patients and 91 female controls. In CFS patients, history of childhood trauma subtypes was evaluated using the Childhood Trauma Questionnaire short form (CTQ-SF). Results Although absolute methylation differences were small, the present study confirms our previous findings of NR3C1-1F DNA hypomethylation at several CpG sites in CFS patients as compared to controls. Following multiple testing correction, only CpG_8 remained significant (DNA methylation difference: 1.3% versus 1.5%, p < 0.001). In addition, we found associations between DNA methylation and severity of fatigue as well as with childhood emotional abuse in CFS patients, although these findings were not significant after correction for multiple testing. Conclusions 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

Comparison of bedtime rest classification from accelerometer placed on waist or wrist in the development and validation groups with classification obtained using whole- room indirect calorimeter.

a<p>– Area under the ROC curve calculated as sensitivity multiplied by specificity before data was rounded;</p>b<p>- defined as the probability of correctly classifying bedtime rest period;</p>c<p>- defined as a probability of correctly classifying activity period;</p>d<p>- Wilcoxon signed rank test;</p>e<p>- automated computer algorithm;</p>f<p>- cut points were 20 counts/min (bedtime) and 500 counts/min (activity);</p>g<p>- cut points were 250 counts/min (bedtime) and 3000 counts/min (activity).</p