ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Behavioral and Psychiatric Genetics
Association Between Interleukin-27 and Suicidal Ideation: A Mendelian Randomization Analysis and Peripheral Blood Experimental Study
Provisionally accepted
- 1Zhejiang University School of Medicine, Hangzhou, China
- 2Tongde Hospital of Zhejiang Province, Hangzhou, China
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Background: Suicide is a leading global cause of mortality, with major depressive disorder (MDD) contributing significantly. Neuroimmune mechanisms, particularly inflammation, are increasingly recognized in the pathophysiology of depression and suicidal ideation. This study investigated the relationship between inflammatory cytokines and suicidal ideation in patients with MDD. Methods: A two sample Mendelian randomization analysis using Genome-Wide Association Study data was performed to evaluate the associations between 16 inflammatory cytokines and suicidal ideation. Then the patients with MDD, stratified by suicidal ideation severity were assessed for peripheral cytokine levels (interleukin [IL])-2, IL-4, IL-6, IL-10, interferon-gamma [IFN-γ], IL-17, IL-12, IL-27, and tumor necrosis factor-α) using flow cytometry and enzyme-linked immunosorbent assay. Results: MR analysis revealed significant associations of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and IL-27 with negative and positive effects, respectively. Individuals with high suicide risk exhibited elevated IL-27, IL-12, IFN-γ and IL-4 compared with low suicide risk. Conclusion: There are genetic associations between IL-27 and suicidal ideation, which is biologically corroborated by elevated peripheral IL-27 levels in high-risk suicidal individuals, highlighting its potential as a clinically viable biomarker for assessing suicidal risk in depressive patients.
Keywords: Depression, Suicide, Cytokines, Suicidal Ideation, Mendelian randomization, il-27
Received: 03 Aug 2025; Accepted: 29 Oct 2025.
Copyright: © 2025 Hu, Yin, Wang, Zhu, Ju, Tan and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zhonglin Tan, zhonglint@hotmail.com
Lingna Lu, lulingnalab@163.com
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