NR3C1 and major depressive disorder: The role of epigenetic mechanisms has been well investigated in relation to the ‘glucocorticoid resistance’ model, with several studies reporting the link between early life adversity/trauma, depression or stress-related conditions and the hypomethylation of the aforementioned FKBP5 gene or hypermethylation of the NR3C1 (GR) gene promoter, which leads to decreased GR activity or decreased GR mRNA and protein expression [24,10,43].