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BRAIN and NERVE Volume 64, Issue 8 （August 2012）

BRAIN and NERVE 64巻8号（2012年8月発行）

Japanese English

総説

自殺の神経科学 The Neuroscience of Suicide 有田秀穂 ¹ Hideho Arita ¹ ¹東邦大学医学部統合生理学 ¹Department of Physiology, Toho University School of Medicine キーワード： suicide , postmortem , serotonin , dorsal raphe nucleus , prefrontal cortex Keyword: suicide , postmortem , serotonin , dorsal raphe nucleus , prefrontal cortex pp.929-935

発行日 2012年8月1日 Published Date 2012/8/1

DOI https://doi.org/10.11477/mf.1416101270

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はじめに

　うつ病で自殺したヒトの脳を調べることによって，自殺の脳内機構を解析する研究が地道に続けられてきている。1980年代になって選択的セロトニン再取り込み阻害薬（selective serotonin reuptake inhibitors：SSRI）がうつ病治療で脚光を浴びるようになってからは，自殺脳でのセロトニン（5-HT）神経の数や密度，投射領域での5-HT受容体，5-HTトランスポーターの計測など，多方面からの検討がなされてきている。特に，ニューヨークのArangoとMannらのグループの研究¹⁾は自殺脳を多方面から検討していて注目に値する。うつ病における自殺企図と関係するのは，背側縫線核の5-HT神経が前頭前野腹外側部に投射する経路であり，その回路の5-HT伝達機能低下が主要な役割を果たすという知見が蓄積されつつある。いまだ十分な解明には至っていないが，現時点での情報を整理した。

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-HT_1A and 5-HT_2A 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-HT_1A autoreceptors are increased and the levels of 5-HT biosynthetic enzyme, tryptophan hydroxylase (TPH), are reduced. Reduced 5-HT_1A 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-HT_2A 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.