Suicidal behavior is a serious concern, especially for individuals facing psychiatric disorders or undergoing epigenetic modifications due to adversity. This article delves into the molecular changes associated with such conditions, shedding light on factors contributing to suicidal tendencies.

Psychiatric Disorders and Suicidal Behavior: People grappling with psychiatric disorders like Major Depressive Disorder (MDD), Bipolar Disorder (BP), or schizophrenia often face an increased risk of suicidal behavior. Studies reveal alterations in crucial systems, including the serotonergic system, HPA-axis, GABAergic/glutamatergic system, and a reduction in Brain-Derived Neurotrophic Factor (BDNF) in individuals with BP, MDD, and schizophrenia. Similarly, patients with Anxiety Disorders (AD) show heightened proinflammatory cytokines and changes in the HPA-axis. Borderline Personality Disorder (BPD) adds complexity, intertwining suicidal tendencies with comorbidities. Stressful situations can trigger impulsive suicides in those struggling to cope effectively.

Epigenetic Changes and Suicide: Even without a prior psychiatric diagnosis, suicide victims exhibit diverse molecular alterations. DNA methylation changes, documented in peripheral blood tissues, highlight the significance of epigenetic modifications. The methylation status of the NR3C1 gene, linked to cortisol signaling and stress responses, is altered in individuals exposed to childhood abuse or extreme stress, potentially contributing to Post-Traumatic Stress Disorder (PTSD). Genetic alterations in the serotonergic system are also observed in suicide victims.

Exploring Other Systems: Recent emphasis on the Endocannabinoid System (ECS) has uncovered significant findings. Postmortem studies indicate lower gene expression of CB2r and GPR55 in the DLPCx of suicide victims, alongside higher CB2r protein expression. Additionally, alterations in the GABAergic and glutamatergic balance, increased inflammatory interleukins (IL-1, IL-6, TNF-alpha), and decreased BDNF are found in the Prefrontal Cortex (PFC) of suicide victims.

A Multifaceted Approach to Suicide Prevention: Understanding suicidal behavior requires acknowledging the intricate interplay of various factors. Comprehensive suicide prevention strategies must recognize the global and preventable nature of this issue. By addressing molecular changes associated with psychiatric disorders, epigenetic influences, and alterations in crucial systems, we can move toward developing more effective prevention and intervention measures.

Reference

Daniela Navarro, Marta Marín-Mayor, Ani Gasparyan, María Salud García-Gutiérre, Gabriel Rubio, Jorge Manzanares. Molecular Changes Associated with Suicide. Int. J. Mol. Sci. 2023, 24(23), 16726