The pCREB is a known transcriptional regulator of numerous genes containing CREB binding sites [29, 57], including the circadian clock genes Per1 and Per2. Overexpression of CREB in hippocampal CA1 induces depression-like behaviors, while KD of CREB in this region leads to mania-like behavior, consistent with previous reports [26, 29, 58, 59]. This evidence concerns the gene CLOCK and major depressive disorder.