There is already evidence that direct activation of central cytokine signaling pathways by intracerebroventricular (ICV) administration of TNFα, LPS or the human immunodeficiency virus transactivator of transcription (Tat) can precipitate the development of depression-like behavior in rodents that is associated with upregulation of cytokines and IDO1[23-25]. Here, IDO1 is linked to major depressive disorder.