CRH and major depressive disorder: Since corticotropin-releasing factor (CRF) was identified in 1981 (Vale et al., 1981), its role in stress responses in both humans and animals has been a focus of research (Bale and Vale, 2004; Binder and Nemeroff, 2010), linking CRF system dysregulation to depression and anxiety, especially via the CRFR1 receptor (Reul and Holsboer, 2002; Arborelius et al., 1999; Heinrichs et al., 1997).