Occupational stress and epigenetic regulation: methylation of the glucocorticoid receptor gene promoter in depressed workers

Epigenetic changes affecting genes in the glucocorticoid pathway have been studied as biomarkers for major depressive disorder (MDD). The aim of this cross-sectional study was to evaluate glucocorticoid receptor (GR) gene promoter methylation levels in depressed workers exposed to occupational stress. Nuclear receptor subfamily 3 group C member 1 (NR3C1) promoter methylation levels were measured by methylation-sensitive high-resolution melting (MS-HRM) in 70 patients with MDD and 40 healthy controls. Occupational stress was evaluated in patients and controls using the Job Content Questionnaire (JCQ). NR3C1 promoter methylation levels were found to be significantly higher in MDD patients than in controls (<i>p</i> = 0.0001). A multiple regression analysis revealed a significant positive association between NR3C1 methylation levels and MDD diagnosis (r = 0.507, <i>p</i> < 0.0001), and a negative association with occupational stress (r = -0.218, <i>p</i> = 0.03). No differences in NR3C1 methylation levels were found between depressed patients exposed and non-exposed to previous traumatic events and the history of trauma was not a significant independent predictor of NR3C1 methylation levels. Hypothalamic-pituitary-adrenal (HPA) axis dysregulation through GR gene hypermethylation could play a key role in the pathophysiology of occupational stress-related disorders. Occupational stress could independently contribute to the epigenetic mechanisms underlying vulnerability to psychopathology. Further research is needed focusing on biomarkers for stress-related disorders as a potential tool for the diagnosis and prevention of occupational diseases.