Biological Risk Factors for Suicidal Behavior in Children and Adolescents: A Narrative Review

Suicidal behavior in children and adolescents is a major global public health issue and one of the leading causes of death in this age group. While psychosocial determinants of suicidality are well established, understanding its biological risk factors is crucial for targeted prevention and treatment. This narrative review summarizes current evidence on the biological mechanisms that contribute to youth suicidality. Genetic liability plays a substantial role, often interacting with environmental stressors. Key neurobiological factors include dysfunction of the serotonin system and impaired neuroplasticity, characterized by a glutamate–gamma-aminobutyric acid imbalance and reduced brain-derived neurotrophic factor. Psychosocial stress appears linked to these changes through several pathways, including dysregulation of the hypothalamic-pituitary-adrenal axis, chronic low-grade inflammation, oxidative stress, and activation of the kynurenine pathway. Neurodevelopmental conditions like autism spectrum disorders and attention deficit hyperactivity disorder, as well as sleep disturbances, may further increase risk. While therapeutic agents such as ketamine and lithium target these neurobiological systems, robust evidence for their anti-suicidal efficacy in youth is limited. Biological research offers valuable insights, but the use of varied study methods and a lack of longitudinal data complicate its translation into clinical practice. Future studies should employ integrative, developmentally informed models to elucidate causal mechanisms and inform more effective interventions.