CREB1 and depressive disorder: It has been demonstrated that BDNF phosphorylates and activates the protein CREB in the nucleus via the TrkB receptor, subsequently promoting the downstream MAPK/ERK and PI3K/AKT signaling cascades, which regulate the growth and survival of neuronal cells in the hippocampus, mediate depression (induced via stress), and exert antidepressant effects (Luo et al., 2015; Wu et al., 2018).