COX-2 overexpression leads to an increase in the pro-inflammatory cytokines IL-1β, IL-6 and TNF, which increases the activity of the 5-HT transporter protein SERT, increases the affinity of the 5-HT receptor 5-HT1A, and mediates depression through an IDO mechanism that alters tryptophan metabolism (57). This evidence concerns the gene TNF and major depressive disorder.