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The correlation of inflammation, tryptophan-kynurenine pathway, and suicide risk in adolescent depression.

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Title: The correlation of inflammation, tryptophan-kynurenine pathway, and suicide risk in adolescent depression.
Authors: Yang, Shuran, Han, Jingjing, Ye, Zhihan, Zhou, Huizhi, Yan, Yangye, Han, Dong, Chen, Shi, Wang, Lu, Feng, Qiang, Zhao, Xudong, Kang, Chuanyuan
Source: European Child & Adolescent Psychiatry. May2025, Vol. 34 Issue 5, p1557-1567. 11p.
Subjects: Suicide risk factors, Amino acid metabolism, Tryptophan metabolism, Research funding, Metabolism, Amino acids, Inflammation, Tryptophan, Cytokines, Mental depression, Interleukins, Tumor necrosis factors, Adolescence
Abstract: Accumulating evidence suggests a role for the tryptophan-kynurenine pathway (TKP) in the psychopathology of major depressive disorder (MDD). Abnormal inflammatory profile and production of TKP neurotoxic metabolites appear more pronounced in MDD with suicidality. Progress in understanding the neurobiology of MDD in adolescents lags significantly behind that in adults due to limited empirical evidence. Aims of this study was to investigate the association between inflammation, TKP, and suicidality in adolescent depression. Seventy-three adolescents with MDD were assessed for serum levels of interleukin (IL)-1β, IL-6, IL-18, IL-10, tumor necrosis factor-α (TNF-α), tryptophan (TRP), kynurenine (KYN), 3-hydroxykynurenine (3-HK), and kynurenine acid (KA). Correlations between cytokines and TKP measures were examined. Patients were divided into high- (n = 42) and non-high-suicide-risk groups (n = 31), and serum levels of cytokines and TKP metabolites were compared. Significant negative correlations were found between TRP and IL-8 (r = – 0.27, P < 0.05) and IL-10 (r = – 0.23, P < 0.05), while a significant positive correlation was observed between 3-HK and IL-8 (r = 0.39, P < 0.01) in depressed adolescents. The KYN/TPR (index of indoleamine 2,3-dioxygenase, IDO) was positively correlated with IL-1β (r = 0.34), IL-6 (r = 0.32), IL-10 (r = 0.38) and TNF-α (r = 0.35) levels (P < 0.01); and 3-HK/KYN (index of kynurenine3-monooxidase, KMO) was positively correlated with IL-8 level (r = 0.31, P < 0.01). Depressed adolescents at high suicide risk exhibited significantly higher levels of IL-1β (Z = 2.726, P < 0.05), IL-10 (Z = 2.444, P < 0.05), and TNF-α (Z = 2.167, P < 0.05) and lower levels of 3-HK (Z = 2.126, P < 0.05) compared to their non-high suicide risk counterparts. Our findings indicated that serum inflammatory cytokines were robustly associated with IDO and KMO activity, along with significantly decreased serum level of TRP, increased level of 3-HK, and higher suicide risk in adolescent depression. [ABSTRACT FROM AUTHOR]
Copyright of European Child & Adolescent Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: The correlation of inflammation, tryptophan-kynurenine pathway, and suicide risk in adolescent depression.
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  Data: Accumulating evidence suggests a role for the tryptophan-kynurenine pathway (TKP) in the psychopathology of major depressive disorder (MDD). Abnormal inflammatory profile and production of TKP neurotoxic metabolites appear more pronounced in MDD with suicidality. Progress in understanding the neurobiology of MDD in adolescents lags significantly behind that in adults due to limited empirical evidence. Aims of this study was to investigate the association between inflammation, TKP, and suicidality in adolescent depression. Seventy-three adolescents with MDD were assessed for serum levels of interleukin (IL)-1β, IL-6, IL-18, IL-10, tumor necrosis factor-α (TNF-α), tryptophan (TRP), kynurenine (KYN), 3-hydroxykynurenine (3-HK), and kynurenine acid (KA). Correlations between cytokines and TKP measures were examined. Patients were divided into high- (n = 42) and non-high-suicide-risk groups (n = 31), and serum levels of cytokines and TKP metabolites were compared. Significant negative correlations were found between TRP and IL-8 (r = – 0.27, P &lt; 0.05) and IL-10 (r = – 0.23, P &lt; 0.05), while a significant positive correlation was observed between 3-HK and IL-8 (r = 0.39, P &lt; 0.01) in depressed adolescents. The KYN/TPR (index of indoleamine 2,3-dioxygenase, IDO) was positively correlated with IL-1β (r = 0.34), IL-6 (r = 0.32), IL-10 (r = 0.38) and TNF-α (r = 0.35) levels (P &lt; 0.01); and 3-HK/KYN (index of kynurenine3-monooxidase, KMO) was positively correlated with IL-8 level (r = 0.31, P &lt; 0.01). Depressed adolescents at high suicide risk exhibited significantly higher levels of IL-1β (Z = 2.726, P &lt; 0.05), IL-10 (Z = 2.444, P &lt; 0.05), and TNF-α (Z = 2.167, P &lt; 0.05) and lower levels of 3-HK (Z = 2.126, P &lt; 0.05) compared to their non-high suicide risk counterparts. Our findings indicated that serum inflammatory cytokines were robustly associated with IDO and KMO activity, along with significantly decreased serum level of TRP, increased level of 3-HK, and higher suicide risk in adolescent depression. [ABSTRACT FROM AUTHOR]
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  Data: &lt;i&gt;Copyright of European Child &amp; Adolescent Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder&#39;s express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.&lt;/i&gt; (Copyright applies to all Abstracts.)
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        Value: 10.1007/s00787-024-02579-4
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        Text: English
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        Type: general
      – SubjectFull: Amino acid metabolism
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      – SubjectFull: Tryptophan metabolism
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      – SubjectFull: Research funding
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      – SubjectFull: Metabolism
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              Text: May2025
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