Hyperactivity of the HPA axis in depression manifests as excessive secretion of corticoliberin (CRH), elevated cortisol levels, an increased cortisol response to adrenocorticotropic hormone (ACTH), impaired negative feedback mechanisms mediated by dexamethasone (DEX), and hypertrophy of the pituitary and adrenal glands [21]. This evidence concerns the gene CRH and major depressive disorder.