CRH and major depressive disorder: These reduced inhibitory function of CRH+ interneurons may initially increase activity of SST+ interneurons and increases activity-dependent gene expression, but chronic activation may cause endoplasmic reticulum stress due to excessive protein synthesis and compromised function of SST+ interneurons (62) and results in hyperactivity of pyramidal neurons, which may cause the increased metabolic activity of the sgACC that is observed in MDD patients (63).