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The role of the kynurenine pathway in suicidality in adolescent major depressive disorder
Open accessAbstract
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.
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“Greater suicidal ideation severity is associated with higher CRP (197), IL-6, and IL-10 levels (215) and with activated microglia-related alterations of the tryptophan-kynurenine pathway (216).”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [216]
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The kynurenine pathway: a finger in every pie
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Feeding the microbiota–gut–brain axis: Diet, microbiome, and neuropsychiatry
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The kynurenine pathway and the brain: Challenges, controversies and promises
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Tryptophan in health and disease
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Biomarkers of Suicide Attempt Behavior: Towards a Biological Model of Risk
Sudol, K., & Mann, J. J. (2017) · Current Psychiatry Reports · doi:10.1007/s11920-017-0781-y · Cited by 225
Metadata
- Authors
- Bradley, K. A. L., Case, J. A. C., Khan, O., Ricart, T., Hanna, A., Alonso, C. M., & Gabbay, V.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- NYU Langone Health (US)
- Nathan Kline Institute for Psychiatric Research (US)
- Corresponding author
- Gabbay, Vilma
- Venue
- Psychiatry Research
- Publisher
- Elsevier BV
- Published
- 2015-06
- Volume
- 227
- Issue
- 2-3
- Pages
- 206-212
- ISSN
- 0165-1781 (ISSN-L)
- PMC
- PMC4430385
- OpenAlex
- W2055909204
- Cited by
- 115
- References
- 48
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 11 · 2023: 9 · 2022: 15 · 2021: 20 · 2020: 14 · 2019: 8 · 2018: 5 · 2017: 7 · 2016: 8 · 2015: 4
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychiatry Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (MH095807, MH101479)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- kynurenine pathway, suicidality, adolescent major depressive disorder, indoleamine 2,3-dioxygenase, tryptophan metabolism, kynurenine, 3-hydroxyanthranilic acid, suicide attempts, suicidal intent, neuroimmunology, plasma biomarkers
- MeSH terms
- Adolescent, Major Depressive Disorder, Female, Humans, Kynurenine, Male, Suicide, Suicide, Attempted, Tryptophan, Biomarkers, Anhedonia
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