title: [The neuroscience of suicide].
abstract: Various postmortem brain studies have provided evidence that reduced serotonin (5-HT) transmission in the ventrolateral prefrontal cortex (vlPFC) is associated with depression-related suicide. Suicide victims have fewer 5-HT transporter sites and a large number of postsynaptic 5-HT1A and 5-HT receptors in the vlPFC, which are implicated in behavioral inhibition and impulsivity. These could be compensatory changes in response to 5-HT hypofunction in depression and suicide. Selective serotonin reuptake inhibitors (SSRIs) are commonly used for the treatment of depression and suicidal ideation. 5-HT innervation of the PFC arises predominantly from 5-HT neurons in the brainstem dorsal raphe nucleus (DRN). In the DRN of suicide cases, 5-HT1A autoreceptors are increased and the levels of 5-HT biosynthetic enzyme, tryptophan hydroxylase (TPH), are reduced. Reduced 5-HT1A feedback inhibition and increased TPH may reflect compensatory changes in response to 5-HT hypofunction in depression-related suicide. Genetic polymorphisms in TPH, 5-HT transporter (5-HTTLPR allele), and 5-HT2A receptor were examined for their association with depression-related suicide, but no consistent associations were found. Stress is a risk factor for depression and is linked to hyperactivity of the hypothalamo-pituitary-adrenal axis and suicide. Corticotropin-releasing factor (CRF)-immunoreactive varicose fibers were detected in the DRN of suicide victims, suggesting that CRF neurons in the paraventricular nucleus of the hypothalamus and 5-HT neurons in the DRN may form a circuit in stress-induced depression. Alcoholics are at a significantly greater risk of suicide than the general population. Alcoholism is associated with alterations in the 5-HT system.
authors.affiliation: Department of Physiology, Toho University School of Medicine, Japan.
authors.forename: Hideho
authors.initials: H
authors.lastname: Arita
mesh_terms: D003866:Depressive Disorder / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D011903:Raphe Nuclei / Q000378:metabolism / Q000503:physiopathology; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D013405:Suicide
chemical_list: D011985:Receptors, Serotonin; D012701:Serotonin