Tryptophan and Kynurenine Metabolites: Are They Related to Depression?

Maurizio Pompili, Luana Lionetto, Martina Curto, Alberto Forte, Denise Erbuto, Franco Montebovi, Maria Elena Seretti, Isabella Berardelli, Gianluca Serafini, Marco Innamorati, Mario Amore, Ross J. Baldessarini, Paolo Girardi, Maurizio Simmaco

Research output: Contribution to journalArticlepeer-review


Background : Some previous studies found decreased concentrations of L-tryptophan (TRY) and increased L-kynurenine (KYN), or its metabolites, in the body fluids of subjects with major depressive disorder (MDD), sometimes in association with suicidal behavior. Such changes might indicate a shift of TRY away from serotonin production, possibly via the effects of inflammatory peptides which activate indoleamine-2,3-dioxygenase. However, these findings have been inconsistent and require replication. Methods: We used sensitive liquid-chromatography mass spectrometry methods to assay plasma concentrations of TRY, 5-hydroxyindoleacetic acid (5-HIAA), and KYN and its metabolites (anthranilic acid and xanthurenic acid). We compared 49 hospitalized, depressed subjects diagnosed with MDD (n = 37) or bipolar disorder (BD, n = 12), with (n = 22) or without (n = 27) previous suicide attempts, to 78 healthy, ambulatory controls of similar age and sex (total n = 127). Findings: Contrary to expectation, TRY plasma concentrations were higher, KYN plasma concentrations were lower, and their ratio much higher in depressed subjects, with no relationship to suicidal history. Concentrations of 5-HIAA and the kynurenine metabolites did not differ between depressed and healthy subjects. Conclusions: These findings are opposite to expectations and not consistent with a hypothesized increased conversion from TRY to KYN in depressed subjects. In addition, we found no evidence of altered production of serotonin as 5-HIAA concentration was unchanged. None of the observed changes was associated with a history of suicide attempt.

Original languageEnglish
Publication statusAccepted/In press - Jan 1 2018


  • Depression
  • Kynurenine
  • Serotonin
  • Suicide
  • Tryptophan

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Psychiatry and Mental health
  • Biological Psychiatry

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