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单核苷酸多态性、串联重复可变数和等位基因对 5-羟色胺酶调节剂在攻击和自杀行为中的影响:综述。

Single nucleotide polymorphisms, variable number tandem repeats and allele influence on serotonergic enzyme modulators for aggressive and suicidal behaviors: A review.

机构信息

PTSD Laboratory, Department of Histology and Embryology, Basic Medical University, China Medical University, Shenyang 110122, China; Department of Neurology, Shengjing Hospital of China Medical University, Shenyang 110004, China.

PTSD Laboratory, Department of Histology and Embryology, Basic Medical University, China Medical University, Shenyang 110122, China; Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China.

出版信息

Pharmacol Biochem Behav. 2019 May;180:74-82. doi: 10.1016/j.pbb.2019.03.008. Epub 2019 Mar 27.

Abstract

The serotonergic system plays key regulatory roles in cognition and emotion. Several lines of evidence suggest that genetic variation is associated with aggressive and suicidal behaviors. Genetic studies have largely focused on three types of variations: single nucleotide polymorphisms (SNPs), variable number tandem repeats (VNTRs), and alleles. 95 published papers (49 papers for aggression and 46 for suicide) were reviewed to summarize the impact of SNPs, VNTRs, and alleles of tryptophan hydroxylase (TPH, the rate-limiting enzyme in serotonin [5-HT] synthesis), 5-HT transporter (5-HTT), serotonergic receptors, monoamine oxidase (an enzyme that catalyzes 5-HT degradation) on aggression and suicidal behaviors. These study samples include healthy controls, psychiatric disease patients, and animal models. This article mainly reviews studies on the relationship between 5-HT transmissions and genetic variations involved in aggression (particularly impulsive aggression) or suicide in people with different ethnicities and psychiatric disorders. We found that most SNPs, VNTRs, and alleles exerted influences on aggression or suicide. Only A128C in TPH1, A138G in 5-HT2A, and L type in the VNTR of monoamine oxidase A (MAOA) affected both aggression and suicide. The associations between some genetic variations and aggression/suicide may be influenced by gender, age, ethnicity, psychiatric disease, and even parenting or prenatal stress. These findings may help clarify how genetic and environmental factors influence the development of aggressive and suicidal behaviors.

摘要

血清素能系统在认知和情绪中发挥关键的调节作用。有几条证据表明,遗传变异与攻击和自杀行为有关。遗传研究主要集中在三种类型的变异上:单核苷酸多态性(SNPs)、可变数串联重复(VNTRs)和等位基因。综述了 95 篇已发表的论文(49 篇关于攻击行为,46 篇关于自杀),总结色氨酸羟化酶(TPH,5-羟色胺[5-HT]合成的限速酶)、5-羟色胺转运体(5-HTT)、血清素受体、单胺氧化酶(一种催化 5-HT 降解的酶)的 SNP、VNTR 和等位基因对攻击和自杀行为的影响。这些研究样本包括健康对照、精神疾病患者和动物模型。本文主要综述了不同种族和精神障碍人群中 5-HT 传递与遗传变异之间关系的研究,这些遗传变异与攻击(特别是冲动性攻击)或自杀有关。我们发现,大多数 SNP、VNTR 和等位基因对攻击或自杀有影响。只有 TPH1 的 A128C、5-HT2A 的 A138G 和 MAOA 的 VNTR 的 L 型同时影响攻击和自杀。一些遗传变异与攻击/自杀之间的关联可能受到性别、年龄、种族、精神疾病甚至育儿或产前压力的影响。这些发现可能有助于阐明遗传和环境因素如何影响攻击和自杀行为的发展。

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