NR3C1 and major depressive disorder: Hypersecretion of CRH may be due to impaired feedback mechanisms from reduced number or function of GRs, as demonstrated in post-mortem studies of patients with severe mood disorders and in mice with acquired forebrain-specific disruption of GR, which mimics major depressive disorder (MDD), and some of these abnormalities are normalized by chronic treatment with imipramine [18].