title: The role of the kynurenine pathway in suicidality in adolescent major depressive disorder.
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.
authors: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA. Electronic address: kailyn.bradley@mssm.edu.
authors: Kailyn A L
authors: KA
authors: Bradley
authors: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA. Electronic address: julia.case@mssm.edu.
authors: Julia A C
authors: JA
authors: Case
authors: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA. Electronic address: omar.khan@mssm.edu.
authors: Omar
authors: O
authors: Khan
authors: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA. Electronic address: thomas.ricart@mountsinai.org.
authors: Thomas
authors: T
authors: Ricart
authors: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA. Electronic address: amira.hanna@mssm.edu.
authors: Amira
authors: A
authors: Hanna
authors: NYU Child Study Center, Child and Adolescent Psychiatry, New York University School of Medicine, One Park Ave. 10th Floor, New York, NY 10016, USA. Electronic address: carmen.alonso@nyumc.org.
authors: Carmen M
authors: CM
authors: Alonso
authors: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA; Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd, Orangeburg, NY 10962, USA; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA. Electronic address: vilma.gabbay@mssm.edu.
authors: Vilma
authors: V
authors: Gabbay
mesh_terms: D000293:Adolescent; D059445:Anhedonia; D015415:Biomarkers / Q000097:blood; D003865:Major Depressive Disorder / Q000097:blood*; D005260:Female; D006801:Humans; D007737:Kynurenine / Q000097:blood*; D008297:Male; D013405:Suicide; D013406:Suicide, Attempted; D014364:Tryptophan / Q000097:blood
chemical_list: D015415:Biomarkers; D007737:Kynurenine; D014364:Tryptophan
keywords: 3-dioxygenase; 3-hydroxyanthranilic acid; Adolescence; Depression; Indoleamine 2; Suicide; Tryptophan