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). This evidence concerns the gene SST and major depressive disorder.