Psychoneuroimmunoendocrinological and neuroanatomical basis of suicidal behavior: potential therapeutic strategies with a focus on transcranial magnetic stimulation (TMS)

Suicidal behavior is a complex phenomenon influenced by psychological, environmental, and biological factors. It affects a significant portion of the global population, with more than 720,000 deaths annually and millions of individuals experiencing suicidal ideation. Among those who attempt suicide, only a fraction progresses to a fatal outcome, emphasizing the importance of understanding individual vulnerabilities. This review explores the neuroanatomical basis of suicidal behavior, focusing on key brain regions and potential pathways for neuromodulation therapies, particularly Transcranial Magnetic Stimulation (TMS). The dorsolateral prefrontal cortex (DLPFC) plays a central role in cognitive control and emotional regulation, with extensive connections to the anterior cingulate cortex, amygdala, orbitofrontal cortex, hippocampus, and thalamus. Dysfunctions in these circuits contribute to heightened impulsivity, impaired decision-making, and emotional dysregulation in individuals with suicidal behavior. Structural and functional abnormalities in the DLPFC, coupled with altered neurotransmitter systems and inflammatory markers, have been consistently linked to suicidality. TMS, targeting the left DLPFC, has shown promise in reducing suicidal ideation by modulating frontostriatal connectivity, enhancing neuroplasticity, and improving cortical excitability. High-frequency TMS and accelerated theta-burst stimulation protocols demonstrate rapid therapeutic effects, though further research is needed to establish standardized treatment guidelines. Understanding the anatomical circuits implicated in suicidal behavior provides valuable insights for early risk assessment and the development of targeted neuromodulation interventions aimed at reducing the burden of suicide across diverse psychiatric populations.