Although the relationship of stress and depression has been considered to arise via the activation of corticosteroid receptors in brain (Holsboer, 2000), with polymorphisms in FKBP5 (a co-chaperone for the glucocorticoid receptor) being an important component of this relationship (Binder et al., 2004), the above described function of AC7 in control of CRF-mediated ACTH release (Antoni et al., 2003; Pronko et al., 2010) should also be considered in the etiology of depression. This evidence concerns the gene NR3C1 and major depressive disorder.