Previously, we developed mice that lack the PACAP gene (PACAP−/−) and showed that these mice exhibited remarkable behavioral changes, including hyperactivity, novelty-seeking behavior, sensory-motor deficits, and depression-like behavior (Hashimoto et al. 2001, 2009; Tanaka et al. 2006), suggesting a role for altered PACAP-mediated signaling pathways in certain psychiatric conditions. Here, ADCYAP1 is linked to major depressive disorder.