Comprehensive Notes on the Neurobiology of Suicidal Behavior

Psychoneuroimmunoendocrinological and Neuroanatomical Basis of Suicidal Behavior

Introduction

• Suicidal behavior is influenced by psychological, environmental, and biological factors.
• Globally, over 720,000 deaths occur annually due to suicide, with millions experiencing suicidal ideation.
• Only a fraction of those who attempt suicide die, highlighting the importance of understanding individual vulnerabilities.
• Survivors of suicide attempts often experience profound psychological distress, linked to critical life events like bereavement, financial hardship, or relationship dissolution.
• Perceived social rejection and inner emptiness are common themes among suicide attempt survivors.
• Albert Camus viewed suicide as an escape from the “absurd,” the conflict between humanity’s search for meaning and a meaningless universe.
• Suicide is categorized into: suicide (fatal self-injury with intent to die), suicide attempt (non-lethal self-injury with suicidal intent), and suicidal ideation (contemplation of ending one’s life).
• Suicidal planning involves detailed preparation for a suicide attempt.
• In 2021, suicide was the third leading cause of death among individuals aged 15–29 and the second leading cause among those aged 25–34.
• Approximately 73% of suicides worldwide occur in low- and middle-income countries.
• In the United States, over 49,000 suicide deaths were reported in 2022, equating to one suicide every 11 minutes.
• In the US, 13.2 million individuals seriously contemplated suicide, and 3.8 million formulated a suicide plan in 2022, according to the CDC.
• For every completed suicide, about 20 attempts occur, translating to an estimated 16 million annual suicide attempts globally and 160 million individuals experiencing suicidal ideation.
• Self-harm, including suicide attempts and non-suicidal self-injury, is more prevalent among females and younger individuals.
• Among suicide attempters, 1.6% die by suicide within a year, and 3.9% within five years.
• Suicide rates in low- and middle-income regions (7.3–10.1 per 100,000) are comparable to high-income countries (10.9 per 100,000).

Biological and Environmental Contributions to Suicide Risk

• Suicide results from a combination of biological predisposition and environmental influences.
• Genetic susceptibility, epigenetic modifications, and a family history of psychiatric disorders are critical individual-level factors.
• Mental health conditions like depression, bipolar disorder, schizophrenia-spectrum disorders, substance use disorders, epilepsy, and traumatic brain injury significantly increase suicide risk.
• Adolescence is often marked by the onset of severe psychiatric disorders, including mood and personality disorders.
• In adulthood and later life, substance use and chronic medical conditions further exacerbate risk.
• Environmental factors include financial stress, social isolation, exposure to suicidal behavior in media, and access to lethal means.
• Social and environmental stressors peak during adolescence and adulthood.
• Approximately 80% of individuals who attempt suicide have a preexisting psychiatric disorder.
• One in eight people globally (970 million individuals) lives with a mental health condition (WHO, 2022).

Neurobiological Mechanisms and Therapeutic Perspectives

• While many individuals endure profound distress, only a subset proceeds to suicidal actions, highlighting the importance of individual vulnerability.
• This vulnerability, influenced by genetic, epigenetic, and neurobiological mechanisms, is mediated by specific neural circuits.
• From a neuroanatomical perspective, alterations in the prefrontal cortex, limbic system, and serotonergic pathways have been implicated in suicidal behavior.
• Functional and structural abnormalities in these regions disrupt emotional regulation, impulse control, and cognitive flexibility—key factors in suicidal crises.
• These findings hold significant potential for developing predictive tools to assess high-risk individuals and inform therapeutic strategies.
• Neuromodulation techniques, such as transcranial magnetic stimulation (TMS), offer promising avenues for targeted intervention, particularly in individuals with treatment-resistant psychiatric conditions.
• TMS modulates neural circuits implicated in suicidality and represents a potential adjunct to pharmacological and psychotherapeutic interventions.
• This review examines the neuroanatomical basis of suicidal behavior and explores emerging therapeutic approaches, particularly the role of TMS, in modulating suicide-related neural circuitry.
• Understanding these mechanisms may facilitate the development of more effective prevention and intervention strategies, ultimately reducing suicide-related mortality.

Materials and Methods: Systematic Search Process

• A multi-stage literature search was conducted using electronic databases, including Google Scholar, Scopus, and PubMed, to identify scientific publications suitable for analysis.
• The analysis process is flowcharted in Fig. 1, detailing article selection and compilation.

Neuronatomical Basis of Suicide

• Separate review sessions were conducted using keywords for suicide anatomical basis:
  • Pubmed: (