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Role of Tryptophan Metabolism in Mood, Behavior, and Cognition

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Targeting the Broadly Pathogenic Kynurenine Pathway

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 inflammation process. However, this concept is mainly derived from in vitro data, whereas in vivo findings 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. The suppressive effects of antioxidant molecules and extracts on tryptophan breakdown could relate to their mood-enhancing properties.

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Abbreviations

GCH:

GTP cyclohydrolase I

IDO:

Indoleamine 2,3-dioxygenase

IFN-γ:

Interferon-γ

iNOS:

Inducible nitric oxide synthase

Kyn/Trp:

Kynurenine to tryptophan ratio

NAD:

Nicotinamide adenine dinucleotide

NF-κB:

Nuclear factor-κB

ROS:

Reactive oxygen species

TDO:

Tryptophan 2,3-dioxygenase

TNF:

Tumor necrosis factor

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Acknowledgments

There are no conflicts of interest and no financial interests.

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Authors and Affiliations

  1. Division of Medical Biochemistry, Biocenter, Medical University, Innrain 80, 6020, Innsbruck, Austria

    Johanna M. Gostner & Florian Überall

  2. Divisions of Biological Chemistry, Biocenter, Medical University, Innrain 80, 6020, Innsbruck, Austria

    Kathrin Becker, Dietmar Fuchs & Barbara Strasser

  3. Clinic for Biological Psychiatry, Department of Psychiatry and Psychotherapy, Medical University, Innsbruck, Austria

    Barbara Sperner-Unterweger

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  1. Johanna M. Gostner
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  2. Kathrin Becker
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Correspondence to Dietmar Fuchs .

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  1. Chairman, Department of Neurosurgery, Wayne State University, Detroit, Michigan, USA

    Sandeep Mittal

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Gostner, J.M., Becker, K., Sperner-Unterweger, B., Überall, F., Fuchs, D., Strasser, B. (2015). Role of Tryptophan Metabolism in Mood, Behavior, and Cognition. In: Mittal, S. (eds) Targeting the Broadly Pathogenic Kynurenine Pathway. Springer, Cham. https://doi.org/10.1007/978-3-319-11870-3_6

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