NR3C1 and major depressive disorder: Epigenetic modulation of GR expression has also been described in humans as highlighted by Palma-Gudiel et al. (2015) and Smart et al. (2015) and although some studies point out the fact that stress (early-life adversities) lead to NR3C1 hypermethylation, it is still controversial the association of these epigenetic changes with psychopathologies such as depression in humans (McGowan et al., 2009; Alt et al., 2010; Na et al., 2014; Palma-Gudiel et al., 2015; Smart et al., 2015).