NEUROGENETICS, SEROTONIN, AND HUMAN AGGRESSION

攻击性是许多临床病症（如反社会人格障碍）的突出特征，是刑事监禁的常见原因，也是酒精和其他药物滥用的常见伴随症状。与攻击行为相关的社会成本也是当代社会关注的主要问题之一。除了环境因素外，遗传因素对攻击性性情的病因也有影响。中枢神经系统（CNS）血清素活性的降低也与人类的攻击性有关，这在临床、法医和非患者样本中都可以看到。我们之前已经发现，在非患者人群中的非亲属个体中，攻击性和愤怒相关人格特征的生活史以及CNS 5 -羟色胺能反应性与两种调节5 -羟色胺能系统元件的基因多态性有关：该研究的目的是通过更明确的方法来证实和扩展这些观察结果，利用基于家庭的控制，结合对成人、社区志愿者及其父母的传播不平衡（TDT）分析。主要研究样本将包括800个个体，包括侵略性表型种群分布的相对末端（四分位数），通过标准化临床访谈进行评估。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的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。研究对象的精神病学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、问卷调查和敌对倾向和冲动的观察测量来证实。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相关性的理解，该维度与反社会行为、暴力、人际关系困扰和人格相关的精神病理学密切相关。本申请是对先前同名提案的重新提交。

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.