CRH and major depressive disorder: A recent study in mice, incorporating a genetic deletion of pituitary adenylate cyclase-activating polypeptide (PACAP), maternal separation, and adult stress exposure as a three-hit model of depression, demonstrated increased CRF-positive neurons in the bed nucleus of the stria terminalis (Farkas et al., 2017), an additional limbic structure that plays a significant role in stress response.