Genetic, Social, and Developmental Epidemiology of Drug Use Disorders

项目摘要 这一竞争性更新的修订旨在继续我们的创新和高生产率的研究 旨在了解药物失效的原因、后果和原因的计划 使用瑞典所有人口数据的使用障碍(DUD)，具有无与伦比的完整性 和深度。我们有八个具体目标，重点关注哑巴的病因、过程和后果。 这些目标是：i)开发一种基于结构方程(SEM)的方法来进行相关性分析，然后 将其应用于瑞典现有的DUD的关键风险因素，允许进行比 到目前为止，风险因素与哑巴的关联在多大程度上是由于家庭混杂与 因果关系；ii)检验智商和个性在18岁时对哑巴的预测能力 约97%的瑞典男性1951年至1975年出生，并澄清这些关联的程度 可能是因果关系；iii)探索1.2%以上人群中哑巴和吸烟风险因素的相似性和差异性 作为护士-助产士报告的一部分，提供吸烟状况的100万育龄妇女；四)探讨如何 与移民有关的因素，重点放在宏观层面的背景特征(即住宅 隔离)，对移居瑞典的第一代和第二代移民中哑巴的影响风险 地理信息系统(地理信息系统)方法；v)阐明DUD的风险因素如何按性别变化 不和谐的异性亲属对以及这些风险因素在多大程度上是哑巴与 与酒精使用障碍和犯罪的其他关键外化症状共享；vi)发展 对被领养人、双胞胎、兄弟姐妹、同父异母兄弟姐妹以及典型的非同居和同父异母的儿童进行全面的扫描电子显微镜检查 将允许联合估计家庭环境影响的四个来源的父母，以检查 青春期至中期痴呆遗传和环境危险因素的发育动态 使用纵向孪生兄弟姐妹设计并阐明从远端到更远端的关键中介机制 通过构建DUD的表型-发育扫描电子显微镜模型来研究近端危险因素 一系列遗传和环境风险因素；vii)开发纵向模型，以澄清社会、 DUD的精神病学和医学后果使用相关设计控制家庭混杂和 八)探讨在潜在和特定风险因素水平上的DUD停滞的预测因素 通过相关设计阐明这些关联的因果性质。我们将使用来自 瑞典全国范围内的多个数据来源对1180万名男性和女性实现这些目标进行了调查。 运用我们在弗吉尼亚联邦和隆德大学的研究小组在药物方面的深厚专业知识 从虐待研究、社会和遗传流行病学以及因果模型到一个独特的强大样本，我们 预计这项研究将对哑巴研究、预防和政策产生重要影响。

Project Summary This revision of a competitive renewal seeks to continue our innovative and highly productive research program which has the goal of understanding the etiology, consequences and causes of desistance of drug use disorders (DUD) utilizing data available on the entire population of Sweden of unparalleled completeness and depth. We have eight specific aims which focus on the etiology and course and consequences of DUD. These aims are: i) to develop a structural equation (SEM) based approach to co-relative analyses and then apply it to critical risk factors for DUD available in Sweden, permitting a more rigorous assessment than hitherto possible of the degree to which risk factor-DUD associations are due to familial confounding versus causal effects; ii) to examine how strongly DUD is predicted by measures of IQ and personality at age 18 available on ~ 97% of all Swedish males born 1951-1975 and to clarify the degree to which these associations are likely causal; iii) to explore the similarity and differences in risk factors for DUD and smoking in over 1.2 million fertile women for whom smoking status is available as part of nurse-midwife's reports; iv) to explore how factors related to immigration, with a focus on macro-level contextual characteristics (i.e., residential segregation), impact risk for DUD among first and second generation immigrants to Sweden using analytical Geographic Information Systems (GIS) methods; v) to clarify how risk factors for DUD vary by gender using discordant opposite-sex relative pairs and the degree to which these risk factors are specific to DUD versus shared with other key externalizing syndromes of alcohol use disorders and crime; vi) to develop a comprehensive SEM for DUD in adoptees, twins, siblings, half-siblings, and typical, not-lived-with and step- parents that will permit joint estimation of four sources of familial-environmental effects, to examine developmental dynamics in the genetic and environmental risk factors for DUD from adolescence to middle age utilizing a longitudinal twin-sibling design and to clarify key mediating mechanisms from distal to more proximal risk factors by constructing a phenotypic-developmental SEM model for DUD that incorporates a wide array of genetic and environmental risk factors; vii) to develop longitudinal models to clarify the social, psychiatric and medical consequences of DUD using co-relative designs to control for familial confounding and viii) to explore the predictors of desistance from DUD on both the latent and specified risk factor level and clarify the causal nature of these associations via co-relative designs. We will use comprehensive data from multiple nationwide data sources in Sweden on 11.8 million men and women to accomplish these goals. Applying the deep expertise of our research groups at Virginia Commonwealth and Lund University in drug abuse research, social and genetic epidemiology and causal modeling to a uniquely powerful sample, we expect this study to have important implications for DUD research, prevention and policy.