Chapter 6: Role of tryptophan metabolism in mood, behavior, and cognition

Abstract

During Th1-type immune response, tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) becomes activated and accelerates the breakdown of tryptophan, as expressed by a higher kynurenine to tryptophan ratio. Lowered tryptophan concentrations were detected in patients suffering from immunopathologies like virus infections, autoimmune syndromes, and certain types of cancer, and in some of these clinical conditions, an association between enhanced tryptophan breakdown and mood disturbances was observed. Tryptophan is required for the biosynthesis of 5-hydroxytryptamine (serotonin), and the availability of tryptophan in the blood is linked to its concentration in the brain, as tryptophan can cross the blood-brain barrier. In patients at risk for cardiovascular disease, higher concentrations of neopterin are associated with lower concentrations of vitamins C and E and other antioxidants. Data may indicate that chronic immune activation leads to an enhanced degradation of oxidation-sensitive biomolecules. Likewise, additional antioxidant vitamin supplementation might be able to counteract the infl ammation process. However, this concept is mainly derived from in vitro data, whereas in vivo fi ndings remain scarce. In vitro, it was also documented that several antioxidant compounds including vitamins C and E and stilbene resveratrol but also food preservatives and colorants are able to slow down Th1-type immune activation leading to a suppression of IDO activity. Similar effects were observed for extracts of beverages known to be rich in antioxidants like wine, beer, cacao, and coffee. Thesuppressive effects of antioxidant molecules and extracts on tryptophan breakdown could relate to their mood-enhancing properties.