Studies on serotonergic dysfunction in suicide

自杀中血清素功能障碍的研究

• 批准号: 14570923
• 负责人: SHIRAKAWA Osamu
• 金额: $ 2.24万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570923/
• 关键词: suicide; serononin; gene polymorphism

We investigated the association of suicide with serotonin transporter promoter region (5HTT-LPR), dopamine receptor promoter region (DRD4), monoamine oxydase A promoter region (MAOA-uVNTR ) and catechol-O-methyltransferase (COMT) which could affect monoamine neurotransmission and might be related to temperament. Gene variants were determined using PCR-based techniques in 163 completed suicides and 169 controls. There were no statistical differences between completed suicides and controls in the genotypes and allelic distribution of 5HTT-LPR, MAOA-uVNTR and DRD4. We found that the genotype distribution of COMT between male suicide completers and malecontrols was significantly different. In addition, the G allele, high-activity allele showed a tendency to occur less frequently in male suicide completers. These results indicate that in male the high COMT activity could play an inhibitory role in suicide. We also investigated possible genetic interactions among these four polymorphisims. Significant interactions were observed in 5HTT-LPR x MAOA-uVNTR and 5HTT-LPR x COMT between male suicide completers and male controls. Further studies are needed to clarify the epistatic effects of these genes.

我们研究了自杀与5-羟色胺转运体启动子区（5 HTT-LPR）、多巴胺受体启动子区（DRD 4）、单胺氧化酶A启动子区（MAOA-uVNTR）和儿茶酚-O-甲基转移酶（COMT）的关系，这些基因可能影响单胺神经传递，并可能与气质有关。使用基于PCR的技术在163名自杀者和169名对照中确定了基因变异。自杀既遂组与对照组的5 HTT-LPR、MAOA-uVNTR和DRD 4基因型和等位基因分布差异无统计学意义。结果发现，COMT基因型在男性自杀完成者和男性对照组中的分布有显著性差异。此外，G等位基因、高活性等位基因在男性自杀完成者中出现频率较低。这些结果表明，在男性中，高COMT活性可能在自杀中起抑制作用。我们还研究了这四种多态性之间可能的遗传相互作用。在男性自杀完成者和男性对照之间观察到5 HTT-LPR x MAOA-uVNTR和5 HTT-LPR x COMT的显著相互作用。需要进一步的研究来阐明这些基因的上位效应。

项目成果

Ono, H.: "Association between Catechol-O-Methyltransferase Functional Polymorphism and Male Suicide Completers"Neuropsychopharmacology. (In press.). (2004)

Ono, H.：“儿茶酚-O-甲基转移酶功能多态性与男性自杀完成者之间的关联”神经精神药理学。

Ono, H.: "自殺と気質規定遺伝子との相関研究"精神薬療研究年報. 35. 88-92 (2003)

Ono, H.：“自杀与气质定义基因之间的相关性研究”精神药理学治疗年度报告 35. 88-92 (2003)。

白川治: "自殺者におけるセロトニン神経伝達系遺伝子多型"精神薬療研究年報. 34. 242-247 (2002)

Osamu Shirakawa：“自杀患者的血清素神经递质基因多态性”精神药理学治疗年度报告。34. 242-247 (2002)

白川 治: "自殺の予防 今日の治療指針(山口徹, 北原光夫編)"医学書院. 1169 (2004)

白川修：“预防自杀：当今的治疗指南（山口彻和北原光男编辑）” Igaku Shoin 1169 (2004)。

小野 久江: "自殺企図 その病理と予防・管理(樋口輝彦編)"永井書店. 10 (2003)

小野久惠：“自杀未遂：其病理学、预防和管理（樋口照彦编辑）”永井书店 10 (2003)。