In order to reveal biological correlates of suicidal behavior, we have to study three major fronto-limbic circuits: 1) orbitomedial prefrontal-limbic (OM PFC-L), 2) precingulate prefrontal-limbic (PC PFC-L), and 3) dorsomedial-dorsoanterolateral (DL PFC-L) limbic circuit. Limbic structures form the limbic lobe, which includes the limbic cortex (cingulate cortex and hippocampal formation) and subcortical structures (amygdala, nucleus accumbens septi, septal nuclei, hypothalamus and limbic midbrain area). The nuclei with identified neurotransmitter systems in the limbic midbrain area (LMA) project directly on three frontal cortical circuits and serve as major modulatory systems: serotoninergic (5-HT), noradrenergic (NA), and dopaminergic (DA) system.

The neural pathways (structural wiring) of fronto-limbic (FC-L) cortical systems connect amygdala - orbitofrontal cortex, dorsomedial thalamic nucleus - dorsolateral prefrontal cortex, prefrontal cortex - nucleus accumbens, precingulate cortex - subcortical limbic nuclei, and numerous cortico-cortical pathways, which interconnect OM, PC and DL prefrontal cortices and establish bilateral connections with limbic cingulate and hippocampal formation cortices.

For each of the fronto-limbic circuits, certain prominent functions have been proposed; OM PFC-L is essential for decision-making and impulse control. Consecutively, fine abnormalities of function of this system are one of the neural substrates for suicidal “diathesis.” These abnormalities were documented in neuroimaging studies in individuals who attempted suicide and in postmortem studies in people who committed suicide. The abnormalities may involve different levels of circuitry: principal neurons, interneurons, afferent pathways, synapses, and receptors. It is generally accepted that a decrease in serotonin transporter binding is one of the most prominent and most constant findings in people who have committed suicide. However, the principal abnormality lies in the frontolimbic circuit, which is under the influence of the 5-HT system. The abnormalities of DL PFC-L are less well documented, but we believe that this circuit plays a role in suicidal behavior because it is necessary for conscious representation of suicidal ideation. For proper diagnostic assessment of underlying psychiatric disorders and suicidal behavior, it is necessary to obtain the following “neurobiologically”-relevant data: imaging on a high-resolution device with 3D morphometry and volumetry, tractography, MR spectroscopy, SPECT, and, in advanced clinical centers, functional MRI and pharmacogenomic screening. The plasticity of frontolimbic circuits is present throughout life. The structural plasticity of pathways is present only during prenatal and early postnatal life; the plasticity of synapses lasts at least until the third decade of life, while plasticity of the receptors lasts throughout life. The MR imaging and pharmacogenomic parameters may serve as useful indicators for detection of vulnerable individuals who have an increased risk of suicide in addition to principal mental disorder.

Using this neurobiologically-based approach we hope to succeed in lowering suicide risk.