NEUROGENETICS, SEROTONIN, AND HUMAN AGGRESSION

神经遗传学、血清素和人类攻击性

• 批准号: 6654890
• 负责人: Stephen B Manuck
• 金额: $ 34.4万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6654890
• 关键词: African American; aggression; amine oxidase (flavin); behavioral /social science research tag; caucasian American; clinical research; gene expression; genetic polymorphism; human middle age (35-64); human subject; neurogenetics; neuropsychological tests; racial /ethnic difference; serotonin; tryptophan 5 monooxygenase; young adult human (21-34)

Aggression is a prominent feature of many clinical conditions (such as antisocial personality disorder), a common cause of criminal incarceration, and a frequent concomitant of alcohol and other substance abuse. The social costs associated with aggressive behavior also rank among the primary concerns of contemporary society. In addition to environmental determinants, genetic factors contribute to the etiology of aggressive temperament. Reduced central nervous system (CNS) serotonergic activity is also correlated with human aggression, as seen in clinical, forensic and non patient samples. We have previously found that among unrelated individuals in a non patient population, life history of aggression and anger-related personality traits, as well as CNS serotonergic responsivity, are associated with polymorphisms of two genes regulating elements of the serotonergic system: tryptophan hydroxylase and monoamine oxidase A. The purpose of the proposed research is to confirm and extend these observations by more definitive methodology, utilizing family-based controls in conjunction with transmission-disequilibrium (TDT) analysis of adult, community volunteers and their parents. The primary study sample will include 800 individuals comprising relative ends (quartiles) of the population distribution of aggressive phenotype, as assessed by standardized clinical interview. Additional polymorphisms in the serotonergic system will also be evaluated, and if alleles of non-functional polymorphisms are found to differentiate high and low aggressive subjects, detailed molecular analyses will be conducted to identify functional variation that may account for these associations. Psychiatric characterization of study participants will be made by structured diagnostic evaluation and group differences in aggressive behavior will be confirmed by additional interview, questionnaire and observational measures of antagonistic disposition and impulsivity. The findings of this project will advance understanding of the genetic correlates of an important dimension of human temperament germane to antisocial behavior, violence, interpersonal distress, and personality-related psychopathology. This application is the resubmission of a prior proposal of the same title.

攻击性是许多临床病症（例如反社会人格障碍）的显着特征，是刑事监禁的常见原因，并且经常伴随酒精和其他药物滥用。与攻击性行为相关的社会成本也是当代社会关注的主要问题之一。除了环境决定因素之外，遗传因素也是攻击性气质的病因之一。正如临床、法医和非患者样本中所见，中枢神经系统 (CNS) 血清素能活性的降低也与人类攻击性相关。我们之前发现，在非患者群体中的无关个体中，攻击性生活史和愤怒相关的人格特征以及中枢神经系统血清素反应性与调节血清素系统元件的两个基因的多态性相关：色氨酸羟化酶和单胺氧化酶 A。拟议研究的目的是通过更明确的方法来确认和扩展这些观察结果，利用基于家族的控制与传递不平衡相结合(TDT) 对成人、社区志愿者及其父母的分析。主要研究样本将包括 800 名个体，包括通过标准化临床访谈评估的攻击性表型群体分布的相对末端（四分位数）。还将评估血清素能系统中的其他多态性，如果发现非功能性多态性等位基因可以区分高攻击性和低攻击性受试者，则将进行详细的分子分析，以确定可能解释这些关联的功能变异。研究参与者的精神特征将通过结构化的诊断评估来确定，攻击行为的群体差异将通过额外的访谈、问卷调查以及对抗性倾向和冲动的观察措施来确认。该项目的研究结果将促进对人类气质的一个重要维度的遗传关联的理解，该维度与反社会行为、暴力、人际困扰和与人格相关的精神病理学密切相关。本申请是对先前同标题提案的重新提交。