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. 2015 Jun 30;227(2-3):206-12.
doi: 10.1016/j.psychres.2015.03.031. Epub 2015 Apr 1.

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

Kailyn A L Bradley  1 , Julia A C Case  2 , Omar Khan  3 , Thomas Ricart  4 , Amira Hanna  5 , Carmen M Alonso  6 , Vilma Gabbay  7
Affiliations

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

Kailyn A L Bradley et al. Psychiatry Res. .

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.

Keywords: 3-dioxygenase; 3-hydroxyanthranilic acid; Adolescence; Depression; Indoleamine 2; Suicide; Tryptophan.

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Conflict of interest statement

CONFLICTS OF INTEREST

There are no conflicts of interest to report for any of the authors on this manuscript.

Figures

Fig. 1
Fig. 1
Depiction of the Kynurenine Pathway. Note, * indicates metabolites that cross the blood-brain barrier.
Fig. 2
Fig. 2
Group Differences in TRP and KYN/TRP (Index of IDO) Plasma Levels (in ng/ml). A) Differences between healthy controls, non-suicidal adolescents with MDD, and suicidal adolescents with MDD. B) Group differences when medicated participants were excluded. * indicates a significant difference between groups (p < 0.05).
Fig. 3
Fig. 3
Correlation Between BSSI Scores and KYN/TRP (Index of IDO) (in ng/ml). Only unmedicated adolescents with MDD that completed both sections of the BSSI (n=11) were included. The correlation between BSSI and KYN/TRP (index of IDO) was significant, [rs=0.63, p=0.038].
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