[Neurobiological correlates of suicidal behavior]

Studies in postmortem brain tissue from suicide victims show a presynaptic serotonergic deficit resulting in compensatory upregulation of postsynaptic 5-HT2 receptors in the prefrontal cortex. Reduced levels of cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid, the major serotonin metabolite, are associated with violent suicide attempts independent of psychiatric diagnosis and predict future suicide attempts and suicide completion, consistent with the notion of a biochemical trait. Neuroendocrine challenge tests, platelet studies and a polymorphism in the gene for tryptophan hydroxylase, the rate-limiting enzyme in the biosynthesis of serotonin, suggest that serotonergic activity may be reduced. This serotonergic abnormality might be related to the vulnerability or diathesis for suicidal behaviour by predisposing individuals to impulsive and autoaggressive behaviour. The hypothesis of hyperactivity of the hypothalamic pituitary adrenal axis (HPA) is supported by the postmortem findings of increased CSF corticotropin releasing hormone (CRH) concentrations and reduced CRH receptor binding sites in the frontal cortex of suicide victims (interpreted as downregulation following CRH hypersecretion) and dexamethasone nonsuppression in suicide attempters. Animal studies and in vitro experiments indicate that the HPA system modulates serotonergic activity. It is hypothesized that the serotonergic alterations potentially result from dysregulation of the HPA system. Data from epidemiological and clinical studies demonstrate that low levels of cholesterol are associated with increased suicide risk. In neuronal membranes cholesterol modulates presynaptic and postsynaptic serotonergic neurotransmission. In monkeys dietary cholesterol lowering inhibits central serotonergic activity and predisposes the animals to impulsive and aggressive behaviour. It is speculated that dysregulation of the HPA system and disordered cholesterol metabolism could enhance the serotonergic deficit, thus contributing to a neurobiological vulnerability or diathesis for impulsive and autoaggressive behaviour.