In MDD, but also in psychotic depression and bipolar disorder, preclinical and clinical studies were realized with the prototypical GR non-selective antagonist mifepristone (RU486) (Figure 2) and showed that this molecule seemed to be effective in inducing a rapid improvement of psychotic and depressive symptoms, while being well tolerated by patients (Belanoff et al., 2001, 2002b; Young et al., 2004; Oomen et al., 2007; Schatzberg and Lindley, 2008; Blasey et al., 2009; Wulsin et al., 2010; Howland, 2013; Block et al., 2017). The gene discussed is NR3C1; the disease is major depressive disorder.