Cortisol normally feeds back on glucocorticoid receptors in the anterior pituitary and hypothalamus to limit the further secretion of CRF and ACTH but these receptors become resistant to feedback regulation in depression possibly in response to the increased levels of pro-inflammatory cytokines found in this disorder such as IL-1, IL-2, IL-6 and TNF-α [61-63]. This evidence concerns the gene CRH and major depressive disorder.