CRH and major depressive disorder: Severe depression with the overactive HPA axis in some patients is characterized by the hypersecretion of cortisol, the enlargement of pituitary and adrenal glands, and the increased levels of corticotropin-releasing factor (CRF) in the cerebrospinal fluid (CSF), which represent deficits in negative feedback systems and/or excessive central stimulation of the secretion of CRF and/or other substances that promote ACTH secretion [82,101,107].