POMC and major depressive disorder: 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.