CREB1 and major depressive disorder: Then, given that cAMP is the key second messenger in the cAMP-PKA-CREB-BDNF pathway and the crucial role of BDNF in antidepressant response, it prompted the speculation that SCFs might exert its anti-depression effect by increasing the level of cAMP and hence the activation of the cAMP-CREB-PKA-BDNF pathway within the hippocampus.