The role of the kynurenine pathway in suicidality in adolescent major depressive disorder

Kailyn A.L. Bradley, Julia A.C. Case, Omar Khan, Thomas Ricart, Amira Hanna, Carmen M. Alonso, Vilma Gabbay

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

The neuroimmunological kynurenine pathway (KP) has been implicated in major depressive disorder (MDD) in adults and adolescents, most recently in suicidality in adults. The KP is initiated by the enzyme indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (TRP) into kynurenine (KYN) en route to neurotoxins. Here, we examined the KP in 20 suicidal depressed adolescents-composed of past attempters and those who expressed active suicidal intent-30 non-suicidal depressed youth, and 22 healthy controls (HC). Plasma levels of TRP, KYN, 3-hydroxyanthranilic acid (3-HAA), and KYN/TRP (index of IDO) were assessed. Suicidal adolescents showed decreased TRP and elevated KYN/TRP compared to both non-suicidal depressed adolescents and HC. Findings became more significantly pronounced when excluding medicated participants, wherein there was also a significant positive correlation between KYN/TRP and suicidality. Finally, although depressed adolescents with a history of suicide attempt differed from acutely suicidal adolescents with respect to disease severity, anhedonia, and suicidality, the groups did not differ in KP measures. Our findings suggest a possible specific role of the KP in suicidality in depressed adolescents, while illustrating the clinical phenomenon that depressed adolescents with a history of suicide attempt are similar to acutely suicidal youth and are at increased risk for completion of suicide.

Original languageEnglish (US)
Pages (from-to)206-212
Number of pages7
JournalPsychiatry Research
Volume227
Issue number2-3
DOIs
StatePublished - Jun 30 2015

Keywords

  • 3-dioxygenase
  • 3-hydroxyanthranilic acid
  • Adolescence
  • Depression
  • Indoleamine 2
  • Suicide
  • Tryptophan

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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