Kouter Katarina, Šmon Julija, Videtič Paska Alja
Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia.
Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia.
World J Psychiatry. 2025 Sep 19;15(9):107726. doi: 10.5498/wjp.v15.i9.107726.
Suicidality is a complex phenomenon influenced by genetic, environmental, and epigenetic factors. Current tools to estimate suicide risk are insufficient, and there is an increasing need for reliable biomarkers to complement clinical approaches. Growing evidence suggests that immune system dysregulation contributes to the pathophysiology of psychiatric disorders and suicidal behavior. Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs, regulate gene expression and may act as a bridge between environmental stressors and (neuro)inflammatory responses. In this review, we examine the evidence of peripheral and central inflammation in suicide completers and individuals with suicidal behavior. Next, we review current knowledge from various studies on suicide-associated epigenetic alterations. Furthermore, we evaluate the mechanisms by which early life adversity and chronic stress contribute to suicide diathesis, focusing on their association with epigenetic modifications and inflammatory pathways. We also examine future prospects and limitations of immunology-related biomarkers and the possibilities of therapeutic interventions targeting the immune system and epigenetic regulation. While challenging, research on epigenetic and immune alterations in suicidality shows promise for identifying suicide risk subtypes and advancing personalized psychiatry.
自杀倾向是一种受遗传、环境和表观遗传因素影响的复杂现象。目前用于评估自杀风险的工具并不充分，因此越来越需要可靠的生物标志物来补充临床方法。越来越多的证据表明，免疫系统失调在精神疾病和自杀行为的病理生理学中起作用。表观遗传机制，包括DNA甲基化、组蛋白修饰和非编码RNA，调节基因表达，并可能在环境应激源和（神经）炎症反应之间起桥梁作用。在这篇综述中，我们研究了自杀完成者和有自杀行为个体的外周和中枢炎症证据。接下来，我们回顾了各种关于自杀相关表观遗传改变的研究的现有知识。此外，我们评估早期生活逆境和慢性应激导致自杀易感性的机制，重点关注它们与表观遗传修饰和炎症途径的关联。我们还研究了免疫相关生物标志物的未来前景和局限性，以及针对免疫系统和表观遗传调控的治疗干预的可能性。尽管具有挑战性，但对自杀倾向中表观遗传和免疫改变的研究有望识别自杀风险亚型并推动个性化精神病学的发展。
