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Role of the Kynurenine Metabolism Pathway in Inflammation-Induced Depression: Preclinical Approaches

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Inflammation-Associated Depression: Evidence, Mechanisms and Implications

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 31))

Abstract

Physically ill patients with chronic inflammation often present with symptoms of depression. Our understanding of the pathophysiology of inflammation-associated depression has benefited from preclinical studies on the mechanisms of sickness and clinical studies on the symptoms of sickness and depression that develop in patients treated with immunotherapy. Sickness behavior develops when the immune system is activated by pathogen- or damage-associated molecular patterns. It is a normal biological response to infection and cell injury. It helps the organism to mobilize its immune and metabolic defenses to fight the danger. Depression emerges on the background of sickness when the inflammatory response is too intense and long lasting or the resolution process is deficient. The transition from sickness to depression is mediated by activation of the kynurenine metabolism pathway that leads to the formation of neurotoxic kynurenine metabolites including quinolinic acid, an agonist of N-methyl-d-aspartate receptors. The neuroimmune processes and molecular factors that have been identified in the studies of inflammation-associated depression represent potential new targets for the development of innovative therapies for the treatment of major depressive disorders.

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Acknowledgements

The research reported in this chapter has been supported by INRA, INSERM, CNRS, and the University of Bordeaux 2 for the work anterior to 2006. It has been supported by NIH since (current grant support: R01 NS073939, R01 NS074999, R21 CA183736, R21 MH104694, R01 CA193522). Additional support comes from the University of Texas MD Anderson Cancer Center and the National Institutes of Health MD Anderson Cancer Center Support Grant (CA016672). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding sources. In addition, I would like to thank Jeanie Woodruff for her assistance with text editing.

Conflict of Interest Statement

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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  1. Department of Symptom Research, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA

    Robert Dantzer

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  1. Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Robert Dantzer

  2. Nutrition and Integrative Neurobiology, INRA, University of Bordeaux, Bordeaux, France

    Lucile Capuron

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Dantzer, R. (2016). Role of the Kynurenine Metabolism Pathway in Inflammation-Induced Depression: Preclinical Approaches. In: Dantzer, R., Capuron, L. (eds) Inflammation-Associated Depression: Evidence, Mechanisms and Implications. Current Topics in Behavioral Neurosciences, vol 31. Springer, Cham. https://doi.org/10.1007/7854_2016_6

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