In rodent models of diabetes-associated depression, activation of indoleamine 2,3-dioxygenase (IDO)—a key enzyme in tryptophan metabolism—results in decreased hippocampal serotonin (5-HT) levels and elevated pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 [96]. This evidence concerns the gene TNF and major depressive disorder.