HPA axis functioning has been, accordingly, extensively studied using neuroendocrine challenge tests that attenuate or enhance CORT, ACTH, and CRH release (i.e., HPA axis suppression or stimulation) in terms of their potential predictive validity with respect to antidepressant response, as a subgroup of MDD patients with HPA axis alterations may be less likely to respond to treatment with antidepressants. This evidence concerns the gene CRH and major depressive disorder.