GSR and major depressive disorder: Stress leads to hyperactivation of the HPA axis and disruption of the end product of HPA axis secretion, GC, which acts on glucocorticoid receptors (GR) in the hippocampus and hypothalamus, among other sites, after crossing the blood-brain barrier, causing disruption of the negative feedback regulation of the HPA axis, which in turn mediates the onset of depression (64–67).