Epigenetics and immunology: Under-recognized aspects of suicidality

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.