ADCYAP1 and major depressive disorder: Estradiol (E2) interacts and modulates PACAP signalling in stress-related brain regions that are associated with depression and anxiety, such as the bed nucleus of the stria terminalis (BNST), amygdala, hippocampus, PVN, and medial prefrontal cortex (King, Toufexis, & Hammack, 2017).