Fig. 11.

Pathways connecting tryptophan (TRY) metabolism to behavioral outcomes. IDO in the periphery and the central nervous system is activated by proinflammatory cytokines (e.g., TNF-α, IL-6, IL-1β). IDO activation results in decreased 5-HT/TRY, which induces the decrease in the ratio of 5-HIAA/5-HT, triggering individual symptoms of depression and anxiety. IDO activation is followed by the increased KYN/TRY ratio, which induces the imbalance of KYN metabolism. Normally, KYN is metabolized to kynurenic acid (KA), an NMDA antagonist. When IDO is activated, KYN is more likely metabolized to quinolinic acid (QA), a potent N-methyl-d-aspartate (NMDA) receptor agonist and may be a key contributor to increased neurotoxicity and cognitive deficits