Epigenetic Mechanisms of Suicidal Behavior Formation: A Review

Aruzhan Tussupova, Roza K. Tatayeva, Sholpan Koigeldinova, Zhannat Bazarbayeva, Zhibek Sembayeva, Aiman Mussina

2026

Full text Open access: Gold Metadata (CSL-JSON)
DOI 10.47176/mjiri.40.21
Data confidence 70 medium
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Abstract

Background: Suicidal behavior is a complex and multifactorial phenomenon rooted in both psychological and biological mechanisms. In recent years, there has been an increasing focus on epigenetic factors, which modulate the influence of environmental factors on the expression of genes associated with emotional and cognitive regulation. Review of the literature: This review aims to provide a comprehensive analysis of contemporary scientific data concerning the epigenetic mechanisms implicated in the pathogenesis of suicidal behavior. It synthesizes and systematizes findings published between 2013 and 2024, emphasizing DNA methylation, histone modifications, and non-coding RNA (microRNA and long non-coding RNA) regulation as key molecular pathways involved in impaired neuroplasticity, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, and dysfunction of neurotransmitter systems. Discussion: The review highlights the role of epigenetic regulation in genes associated with the serotonergic system (SLC6A4), neuroendocrine stress response (FKBP5), and HPA axis regulation (SKA2, NR3C1, NR3C2), as well as relatively novel candidate genes such as CACNA1C, SIRT1, and IMPA2. It underscores how stress-induced and trauma-related epigenetic modifications contribute to suicidal vulnerability and may underlie the biological heterogeneity observed among individuals exhibiting suicidal behavior. The potential reversibility of epigenetic changes positions them as attractive targets for therapeutic and preventive strategies. Conclusion: Epigenetic changes induced by environmental stressors, traumatic experiences, or mental disorders possess diagnostic and prognostic potential. The integration of epigenetic biomarkers into clinical research may enhance the early identification of individuals at risk, support the development of personalized interventions, and contribute to new approaches in suicide prevention. Overall, epigenetics offers a promising framework for bridging molecular biology with psychiatry and deepening our understanding of the biological mechanisms underlying suicidality.