Moreover, PACAP is directly involved in the regulation of monoamine synthesis and metabolism, brain-derived neurotrophic factor (BDNF) expression, and hypothalamic–pituitary–adrenal (HPA) axis activation [136], which, taken together with its distribution in anatomical areas that play a part in stress response and depression, allows the confirmation that this neuropeptide is closely related to the behavioral and endocrine responses to stress, as well as synaptic plasticity and neuroprotection [137]. This evidence concerns the gene BDNF and major depressive disorder.