Behavioral and clinical studies implicate central CRF and 5-HT in the pathophysiology of drug relapse, anxiety disorders, trauma- and stressor-related disorders such as posttraumatic stress disorder (PTSD), depression, and other psychiatric disorders exacerbated by stress (Chalmers et al., 1996; Coplan et al., 1996; Deakin, 1998; Holsboer, 1999; Keck and Holsboer, 2001; Le et al., 2002; Waters et al., 2015). This evidence concerns the gene CRH and major depressive disorder.