Kynurenine pathway dysfunction in the pathophysiology and treatment of depression: Evidences from animal and human studies

Gislaine Z. Réus, Karen Jansen, Stephanie Titus, André F. Carvalho, Vilma Gabbay, João Quevedo

Research output: Contribution to journalReview articlepeer-review

91 Scopus citations

Abstract

Treatment-resistant depression affects up to 20% of individuals suffering from major depressive disorder (MDD). The medications currently available to treat depression, including serotonin re-uptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs), fail to produce adequate remission of depressive symptoms for a large number of patients. The monoamine hypothesis upon which these medications are predicated should be expanded and revised as research elucidates alternative mechanisms of depression and effective methods to treat the underlying pathologic consequences. Research into the role of tryptophan degradation and the kynurenine pathway in the setting of inflammation has brought new insight into potential etiologies of MDD. Further investigation into the connection between inflammatory mediators, tryptophan degradation, and MDD can provide many targets for novel antidepressant therapies. Thus, this review will highlight the role of the kynurenine pathway in the pathophysiology of depression, as well as a novel therapeutic target to classic and new modulators to treat depression based on findings from preclinical and clinical studies.

Original languageEnglish (US)
Pages (from-to)316-328
Number of pages13
JournalJournal of Psychiatric Research
Volume68
DOIs
StatePublished - Sep 1 2015

Keywords

  • Depression
  • Indoleamine 2,3-dioxygenase
  • Inflammation
  • Kynurenine pathway
  • Tryptophan

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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