cAMP can activate cAMP-dependent protein kinase (PKA), and subsequently PKA is able to activate CREB directly by phosphorylation of the transcription factor CREB [67] or indirectly [58, 68], thus further mediating multiple signaling molecules, like CREB and BDNF which play important roles in the signaling pathway of learning memory and depression [10]. This evidence concerns the gene CREB1 and major depressive disorder.