The Relationship Between Methylation of the Glucocorticoid Receptor Gene (NR3C1) and Childhood Trauma and Alexithymia

Abstract

Background: Childhood traumas affect the hypothalamo-pituitary-adrenal (HPA) axis functions, and therefore emotional regulation response to stress. Glucocorticoid receptor (GR) gene NR3C1 plays a key role in HPA axis. The aim of the study was to investigate the relationship between methylation of NR3C1 gene with childhood trauma and alexithymia in somatic symptom disorder (SSD) and major depressive disorder (MDD). Methods: A total of 48 patients with SSD, 50 patients with MDD and 50 healthy controls were included in the study. Mongomery-Asberg Depression Rating Scale (MADRS), Toronto Alexithymia Scale (TAS-20), and the Childhood Trauma Questionnaire (CTQ) were applied to the participants. Methylation levels of the NR3C1 gene were determined quantitatively in DNA blood samples. Results: TAS-20 and CTQ total scores were found to be the highest in patients with SSD. CTQ scores were observed to be higher in SSD and MDD compared with the control group. NR3C1 gene methylation levels were found to be lowest in SSD and highest in MDD. There was no correlation between scores of TAS-20 and NR3C1 methylation. High alexithymia level was predictive for SSD (OR:1.237, 95% CI:1.018-1504). High methylation levels increase the risk of MDD (OP:7.449, 95% CI: 3.702-14.986), decrease the risk of SSD (OR: 0.00006 95% CI: 0.000-0.038). Conclusion: Our results show that emotion processing processes and GR methylation are different in both disorders. Childhood trauma may be related to epigenetic changes in the GR gene. The type of epigenetic changes may result in vulnerability to different psychiatric disorders.