Cytokines lead to activation of IDO through multiple signaling pathways, including Nuclear Factor Kappa-light-chain-enhancer of activated B cells(NF-κB),Mitogen-Activated Protein Kinase (MAPK) and Signal Transducer and Activator of Transcription 5 (STAT5).53 IDO breaks down Tryptophan, the precursor of Serotonin, into Kynurenine (KYN), resulting in a reduction in the level of Serotonin.54 Reduction of Serotonin is associated with depression, as has long been known, but depression resulting from IDO activation and KYN production has additional Serotonin-independent effects as well. This evidence concerns the gene NFKB1 and depressive disorder.