Abstract

Suicidal thoughts and actions occur due to a dynamic interaction of biological vulnerability, exposure to stress, psychological processes, and social context. This paper reviews neurobiological domains linked to suicidal thoughts and behavior, with a focus on monoaminergic signaling, HPA-axis dysregulation, neuroinflammation, neurotrophic and synaptic-plasticity pathways, large-scale brain networks, and geneticepigenetic vulnerability. A range of post mortem and neuroimaging findings, as well as molecular, genetic and clinical findings have shown that serotonergic functioning is altered, prefrontal limbic connectivity is disrupted, there is atypical cortisol responsivity, inflammatory activation and reduced neurotrophic signaling. Nevertheless, these findings are heterogeneous and not specific to suicidal phenotypes; many also occur in the context of major depressive disorder, trauma-related disorders, chronic stress and other psychiatric disorders. Changes related to a crisis may be measured during a situation, but “what is most important is the timing, context, situation”. According to current evidence, multidimensional risk assessment should integrate biological findings with clinical, psychological, and social information, and isolated biomarkers should not be used clinically. It is essential to carry out prospective, longitudinal, multimodal studies that feature well-matched psychiatric comparison groups. Doing so will help researchers make the distinction between trait vulnerability and state-dependent crisis markers. Furthermore, scientists must begin to determine whether biomarker combinations can contribute to precision prevention in an ethical and dependable manner.

Keywords

Suicidal ideation, suicide, neurobiology, serotonin, HPA axis, neuroinflammation, BDNF, brain networks, epigenetics, biomarkers