Inflammation-associated depression: From serotonin to kynurenine

Robert Dantzer, Jason C. O'Connor, Marcus A. Lawson, Keith W. Kelley

Research output: Contribution to journalReview articlepeer-review

465 Scopus citations

Abstract

In the field of depression, inflammation-associated depression stands up as an exception since its causal factors are obvious and it is easy to mimic in an animal model. In addition, quasi-experimental studies can be carried out in patients who are treated chronically with recombinant cytokines for a medical condition since these patients can be studied longitudinally before, during and after stimulation of the immune system. These clinical studies have revealed that depression is a late phenomenon that develops over a background of early appearing sickness. Incorporation of this feature in animal models of inflammation-associated depression has allowed the demonstration that alterations of brain serotoninergic neurotransmission do not play a major role in the pathogenesis. This is in contrast to the activation of the tryptotphan degrading enzyme indoleamine 2,3-dioxygenase that generates potentially neurotoxic kynurenine metabolites such as 3-hydroxy kynurenine and quinolinic acid. Although the relative importance of peripherally versus centrally produced kynurenine and the cellular source of production of this compound remain to be determined, these findings provide new targets for the treatment of inflammation-associated depression that could be extended to other psychiatric conditions mediated by activation of neuroimmune mechanisms.

Original languageEnglish (US)
Pages (from-to)426-436
Number of pages11
JournalPsychoneuroendocrinology
Volume36
Issue number3
DOIs
StatePublished - Apr 2011

Keywords

  • Depression
  • Indoleamine 2,3-dioxygenase
  • Inflammation
  • Interferon-alpha
  • Kynurenic acid
  • Kynurenine
  • Quinolinic acid
  • Tryptophane

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry

Fingerprint

Dive into the research topics of 'Inflammation-associated depression: From serotonin to kynurenine'. Together they form a unique fingerprint.

Cite this