An imbalance between IL-1 receptor antagonist (IL-1ra) and IL-1β reduces the expression of the cAMP response element-binding protein (CREB)-brain-derived neurotrophic factor (BDNF) in the hippocampus and disrupts neurotransmission mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), resulting in depression-like behavior (21). Here, CREB1 is linked to major depressive disorder.