The induction of COX-2 in the CNS by stress and the increase in the PGE2 levels in the brain cortex are well documented phenomena [48,49] of significant importance in experimental models of depression and in depressive disorders [50], bearing in mind that PGE2, in turn, stimulates production of pro-inflammatory cytokines, expression of COX-2 and, as a co-factor, activity of indoleamine 2,3-dioxygenase (IDO), which reduces levels of 5-HT, a hallmark of depression. This evidence concerns the gene IDO2 and major depressive disorder.