Methylation differences in NR3C1 have been reported in CpG islands located in its proximal promoter in response to trauma, PTSD, depression, and anxiety [24,29] Methylation levels in NR3C1 proximal promoter is negatively associated with transcript levels [30,31,32,33], which could be associated with sensitization of the HPA axis in cases of hypomethylation. This evidence concerns the gene NR3C1 and major depressive disorder.