Clinical and animal experiments proved that chronic stress-induced depression is attributed to the attenuation and disruption of the CORT negative feedback system, which induce the accumulation of CORT in the hippocampus that further damage the structure and function of neurons in the hippocampus by injuring the nutrition unit, lowering the energy metabolism level of neurons, and increasing the vulnerability of neurons to damage, and finally lead to alterations in physiological responsiveness and behavior22, 23. This evidence concerns the gene CORT and major depressive disorder.