A Twin-Family Study of Drug Use, Abuse, and Dependence

描述(由申请人提供)：已有确凿证据表明，精神活性物质使用(PSU)和精神活性物质使用障碍(PSUD)存在显著的遗传影响。广泛的研究还表明，环境对PSU和PSUD的风险有一系列影响。当前研究人员面临的挑战是澄清这些遗传和环境风险因素之间的相互作用，随着时间的推移，这些因素可能导致精神活性物质的启动和随后的滥用/依赖。 这一竞争性续签要求为一组独特的孪生数据集的一系列详细分析提供4年的支持，这些数据集的收集现已接近完成。这个样本将包括大约750对完整的成年男性-男性对，他们的大量数据已经在前两次采访中收集到。本次访谈采用生活史访谈的形式，在5个发育阶段(8-11岁、12-14岁、15-17岁、18-21岁和22-25岁)获得了多发性硬化症和多发性硬化症的关键风险和保护因素。此外，在这个样本中，基本上已经完成了PSU和PSUD的风险年龄，我们第二次获得了对PSU和PSUD寿命的详细评估，以及记录关键寿命转变和PSU的开始、偏移量和频率的寿命日历。 我们试图利用这一丰富而有价值的数据集来加深我们对PSU和PSUD风险发展的理解。我们明确了四个主要目标：1.PSUD的发展。我们将确定PSUD及其相关危险因素在青春期和青春期的轨迹的性质和模式，并通过探索基因、环境和PSUD之间的关系，建立一个全面的PSUD发展框架。2.背景因素--我们将澄清多发性硬化症和多发性多发性硬化症的遗传和环境风险因素在多大程度上受到关键发展经验的影响，包括同伴偏差和获得非法物质。3.异质性--PSUD可能存在多种亚型。使用青少年有限的和终生的持续反社会行为作为范式，我们希望为PSUD开发有意义的类型学，这将以一种有用的方式映射到可用的病因范围。4.Sequella-给出PSU的第一集，我们将探索PSUD的进一步使用和发展的预测。鉴于PSUD的发展，我们将阐明预测后续成人结局的因素。 我们的研究团队由临床医生、统计学家和遗传学家组成，对人类遗传流行病学中的复杂问题，如PSU和PSUD的开发，有着创新和严格的数据分析方法的长期记录。

DESCRIPTION (provided by applicant): Significant genetic influences on psychoactive substance use (PSU) and psychoactive substance use disorders (PSUD) have been conclusively demonstrated. An extensive body of research has also implicated a range of environmental influences on risk for PSU and PSUD. The challenge facing current researchers is to clarify the interplay between these genetic and environmental risk factors which over time can lead to the initiation and subsequent abuse/dependence of psychoactive substances. This competitive renewal requests 4 years of support for a series of detailed analyses of a unique twin data set, collection of which is now nearing completion. This sample will consist ofapproximately 750 complete adult male-male pairs, on whom extensive data has been collected in two previous interview waves. The current interview obtains, using a life-history format interview, key risk and protective factors for PSU and PSUD over 5 developmental periods (ages 8-11, 12-14, 15-17, 18-21, and 22-25). In addition, in this sample, which has essentially completed its age at risk for PSU and PSUD, we have obtained, for a second time, detailed assessments of lifetime PSU and PSUD and a lifetime calender recording key life transitions and onsets, offsets and frequency of PSU. We seek to use this rich and valuable data set to further our understanding of the development of risk for PSU and PSUD. We articulate 4 primary aims: 1. The Development of PSUD. We will identify the nature and pattern of trajectories of PSUD and related risk factors across adolescence and young adulthood, and develop a comprehensive developmental framework for PSUD by exploring the associations between genes, environment, and PSUD. 2. Contextual Factors - We will clarify the extent to which genetic and environmental risk factors for PSU and PSUD are moderated by key developmental experiences including, peer deviance and access to illicit substances. 3. Heterogeneity - Multiple subtypes of PSUD probably exist. Using the adolescent limited versus life-course persistent antisocial behavior as a paradigm, we hope to develop meaningful typologies for PSUD that will map in a useful way on the range of available etiologic factors. 4. Sequella - Given an initial episode of PSU, we will explore what predicts further use and the development of PSUD. Given the development of PSUD, we will clarify the factors that predict subsequent adult outcomes. Our research team, a combination of clinicians, statisticians and geneticists, has a long track-record of innovative and rigorous data analytic approaches to complex problems in human genetic epidemiology such as the development of PSU and PSUD.