Higher levels of proinflammatory cytokines, especially IL-6, have been shown to cause hypothalamic–pituitary–adrenal (HPA) hyperactivity, reduce 5-HT levels through activation of the tryptophan-metabolizing enzyme indoleamine-2,3-dioxygenase (IDO) and predict poorer clinical outcome in MDD patients treated with antidepressants (Lanquillon et al. 2000; Schiepers et al. 2005). This evidence concerns the gene IDO2 and major depressive disorder.