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Nature Reviews Neuroscience 4, 819 -828 (2003); doi:10.1038/nrn1220


NEUROBIOLOGY OF SUICIDAL BEHAVIOUR

J. John Mann

Preface
About one million suicides and ten million suicide attempts occur worldwide each year. Suicide is not simply a response to stress, but generally a complication of a psychiatric disorder. A proposed stress–diathesis model is described in clinical and neurobiological terms. Neurobiological correlates of the diathesis for suicidal acts point to the involvement of the serotonergic and noradrenergic systems, and the ventromedial prefrontal cortex. Some treatments seem to reduce suicide risk independently of an effect on the primary psychiatric disorder, perhaps by reducing the diathesis.

Summary

Suicidal behaviour refers to the occurrence of self-directed injurious acts with intent to end one's own life. Suicide is not simply a response to stress, but is a complication of an existing psychiatric disorder.
Many models of suicidal behaviour have been put forward. This article presents a stress–diathesis model in which a stressor leads to the acute worsening of a psychiatric disorder, leading to suicidal behaviour. Many factors are components of the diathesis for suicidal behaviour. They include pessimism, aggression, impulsivity, familial/genetic factors and childhood experiences.
Most of the neurochemical evidence, particularly evidence obtained from the brains of suicide victims, points to the involvement of the serotonergic system in suicidal behaviour. The noradrenergic and dopaminergic systems have also been implicated, but the evidence is more fragmentary.
As a result of the neurochemical observations, the genetic study of suicidal behaviour has centred on the study of genes that govern the function of the serotonergic system. Although different polymorphisms in the genes that encode tryptophan hydroxylase, the serotonin transporter, the different serotonin receptors and monoamine oxidase have been found, their relationship to suicidal behaviour remains unclear.
Neuroanatomically, people who display suicidal behaviour tend to show abnormalities in the ventromedial prefrontal cortex. These abnormalities largely correlate with the neurochemical deficits that have been reported in this population.
The diathesis of suicidal behaviour offers new therapeutic possibilities. However, these are still early days in the study of suicide, and it will be important to identify additional markers (genetic, anatomical and neuropsychological) for identifying people at risk of showing suicidal behaviour.