Many studies have shown that enhanced activity of the hypothalamic–pituitary–adrenal (HPA) axis in depression can be evoked by a reduction in the expression of glucocorticoid receptors (GRs) in the hippocampus or frontal cortex and, as a consequence, a weakening of the inhibitory feedback mechanism [4,48,49]. This evidence concerns the gene NR3C1 and major depressive disorder.