The genetic basis of impulsive behavior in humans

人类冲动行为的遗传基础

基本信息

批准号：
8182033
负责人：
HARRIET DE WIT
金额：
$ 47.36万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-15 至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8182033
关键词：
Address Affect Behavior Behavior Control Behavioral Behavioral Genetics Behavioral inhibition Candidate Disease Gene Categories Clinical Complex Decision Making Diagnosis Dopamine Drug abuse Drug usage Enzymes Exhibits Factor Analysis Genes Genetic Genetic Polymorphism Genetic Predisposition to Disease Genetic Variation Genome Genotype Human Human Volunteers Impairment Impulsive Behavior Impulsivity Individual Individual Differences Literature Measures Mediating Mental disorders Neurotransmitters Participant Pathway interactions Performance Pharmaceutical Preparations Phenotype Prevention Prevention strategy Probability Process Publishing RTN4 gene Research Personnel Risk Risk Factors Sampling Self-control as a personality trait Source Specificity Structure Substance abuse problem Surveys Symptoms Systems Biology Task Performances Testing Time Variant analog base behavior measurement design discounting dopamine system dopamine transporter genetic analysis genetic association healthy volunteer indexing innovation insight interest neuromechanism receptor receptor expression research study response treatment strategy young adult

项目摘要

DESCRIPTION (provided by applicant): This project will examine the underlying factor structure of impulsive behaviors, and investigate the genetic basis of impulsive behaviors in healthy human volunteers. Impulsive behaviors are strongly implicated in risk for drug abuse, and are thought to be determined in part by genetic factors. Here, the investigators will examine the two main components of impulsive behavior: Impulsive Choice (maladaptive decision-making) and Impulsive Action (i.e., behavioral inhibition) using standardized behavioral tasks. They will empirically derive constructs based on subjects' performance on the tasks, and then examine polymorphisms in genes thought to contribute to variations in the constructs. The investigators will focus on genes that affect function of the dopamine system. The project addresses an urgent need to define behaviorally the underlying components of impulsivity, and to identify genetic factors that influence variability. The findings will help us understand impulsive behaviors, which are key risk factors, or intermediate phenotypes, for drug use. First, we will phenotype healthy unrelated young adults (N=1,000) on carefully selected behavioral measures of Impulsive Choice and Impulsive Action, and identify the factors comprising these heterogeneous behaviors. Participants will be tested twice for maximum reliability, and we will use factor analysis to identify the underlying latent factors. Second, we will examine associations between the derived factors and genetic variation in dopamine and other selected genotypes, in three levels of analysis. Using a candidate gene approach, we will focus on polymorphisms in selected genes related specifically to dopamine function. We hypothesize that genotypes resulting in low dopamine function will be associated with higher impulsive behaviors. Using a pathway-based approach, we will investigate polymorphisms in a larger set of genes of interest based on the published literature. Finally, using a hypothesis-free approach, we will examine ~1 million polymorphisms that will survey all the genes in the genome. Thus, we will include both hypothesis testing and exploratory approaches to comprehensively examine the genetic basis of impulsivity. The project is significant because it will advance understanding of impulsive behavior and its genetic underpinnings, which has direct relevance to risk for substance abuse. The study is innovative because it combines rigorous behavioral analysis with multi-level genetic analysis. PUBLIC HEALTH RELEVANCE: One of the primary risk factors for developing problems related to drug use and abuse is impulsivity. Individuals who have difficulty either exerting self-control in decision-making situations, or inhibiting inappropriate behaviors, are more likely to experiment with drugs and progress to excessive use. In this project we will investigate the genetic basis of these impulsive behaviors. Healthy volunteers will complete validated tasks measuring different forms of impulsive behaviors, and their performance will then be examined in relation to selected genes thought to control these behaviors. This study will help us to understand the underlying factor structure of impulsive behavior, and the degree to which genetic factors contribute to these behaviors.

描述（由申请人提供）：该项目将研究冲动行为的潜在因素结构，并调查健康人类志愿者冲动行为的遗传基础。冲动行为与药物滥用风险密切相关，并且被认为部分是由遗传因素决定的。在这里，研究人员将使用标准化的行为任务来检查冲动行为的两个主要组成部分：冲动选择（适应不良决策）和冲动行动（即行为抑制）。他们将根据受试者在任务中的表现凭经验推导出结构，然后检查被认为有助于结构变化的基因多态性。研究人员将重点关注影响多巴胺系统功能的基因。该项目迫切需要从行为上定义冲动的潜在组成部分，并确定影响变异性的遗传因素。这些发现将帮助我们了解冲动行为，这是吸毒的关键危险因素或中间表型。首先，我们将根据仔细选择的冲动选择和冲动行动行为测量对健康的无关年轻人（N = 1,000）进行表型分析，并确定构成这些异质行为的因素。参与者将接受两次测试以获得最大可靠性，我们将使用因素分析来识别潜在的潜在因素。其次，我们将在三个分析水平上检查派生因素与多巴胺和其他选定基因型的遗传变异之间的关联。使用候选基因方法，我们将重点关注与多巴胺功能具体相关的选定基因的多态性。我们假设导致多巴胺功能低下的基因型与较高的冲动行为有关。使用基于途径的方法，我们将根据已发表的文献研究更多感兴趣基因的多态性。最后，使用无假设的方法，我们将检查约 100 万个多态性，这些多态性将调查基因组中的所有基因。因此，我们将采用假设检验和探索性方法来全面检查冲动的遗传基础。该项目意义重大，因为它将促进对冲动行为及其遗传基础的理解，这与药物滥用风险直接相关。这项研究具有创新性，因为它结合了严格的行为分析和多层次的遗传分析。公共卫生相关性：出现与吸毒和滥用相关问题的主要危险因素之一是冲动。在决策情况下难以自我控制或抑制不当行为的人更有可能尝试药物并发展到过度使用。在这个项目中，我们将研究这些冲动行为的遗传基础。健康的志愿者将完成测量不同形式的冲动行为的经过验证的任务，然后将根据被认为控制这些行为的选定基因来检查他们的表现。这项研究将帮助我们了解冲动行为的潜在因素结构，以及遗传因素对这些行为的影响程度。