Increased intracerebral corticotropin releasing factor (CRF; Strome et al., 2002; Kalin and Shelton, 2003; Shively et al., 2005) and lesions to the central nucleus of the amygdala or orbitofrontal cortex (Amaral, 2002; Kalin and Shelton, 2003; Kalin et al., 2007; Kenwood and Kalin, 2021) have also been applied to develop a depression- or anxiety-like phenotype. This evidence concerns the gene CRH and major depressive disorder.