Individuals with major depression show hyperactivity of the HPA axis with elevated plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations under basal conditions and a blunted ACTH response in the corticotropin-releasing factor (CRF) stimulation test [39,40], the latter of which has been attributed to reduced CRFR1 expression in the anterior pituitary, secondary to chronic hypersecretion of CRF from the hypothalamus. Here, CRH is linked to major depressive disorder.