Family Study of Risk for Alcoholism Over the Life Course

描述（申请人提供）：这项前瞻性高风险家庭研究，密歇根纵向研究（MLS）开始于27年前，以描述儿童酒精使用障碍（AUD）风险的发展（第二代或G2）在入学前开始，目的是检测后期障碍的风险标志物是否可以很早就被识别出来，描述已确定的风险因素在儿童期和成年早期的演变情况，并确定风险发展的中介和调节因素，以指导预防或早期干预方案的制定。父母（G1）的目标是确定预测复发，缓解和社会适应的因素。该项目是目前正在进行的最早开始（3岁）的AUD高风险研究，涉及酒精/其他药物使用的前瞻性评估跨度最长的项目之一。它的数据矩阵涉及对行为、认知和心理功能、社会环境、物质使用/滥用和精神症状的可变网络的重复测量。它还与其他5个项目相互交叉，这些项目将MLS用作其招聘，数据管理和概念核心，并共享所有数据。该更新申请建议继续将G2描述为研究中科学上最独特的部分，将G1评估限制为对G2社会化环境特征至关重要的措施。从学龄前开始评估G2，从发病时开始评估饮酒/其他药物使用。这些数据的持续收集将允许评估与早期物质使用相互作用的成瘾风险对以后行为的预期影响。我们打算充分描述G2中的两个关键问题：1）识别导致AUD结果的发展风险途径，而不是精神病合并症，与涉及合并症外部化或内部化诊断的发展风险途径形成对比;（目标1）和2）识别预测成年期出现弹性（非酒精滥用）结果的因素，尽管过度暴露于逆境（目标2）。此外，我们打算利用核心研究及其分支合作伙伴项目提供的全面的多领域数据矩阵，为问题酒精使用和AUD的关键风险和弹性表型建立跨基因水平的机制结构的跨层次发展模型，神经网络，社会环境和发展（目标3）。为了充分利用这项研究的成熟性，我们还将使用广泛的多波数据库来描述G1中的一个关键问题：评估酒精消费负担对成年中后期认知功能的长期影响（目标4）。有了一代以上的真实的时间信息，该项目将能够前瞻性地评估27年来的这些影响。最后，我们打算提供现在非常长期的纵向数据库作为该领域的资源。因此，我们的最终目标是 建立一个项目开发计划，包括与RSA和CPDD相关的会议，以便调查人员共享数据和问题，目的是建立一个合作网络（目标5）。

DESCRIPTION (provided by applicant): This prospective high-risk family study, the Michigan Longitudinal Study (MLS) began 27 years ago to characterize the development of risk for alcohol use disorder (AUD) among children (2nd generation or G2s) beginning prior to school entry, with the aims to detect whether risk markers of later disorder could be identified very early, to characterize the evolution of identified risk factors over the course of childhood and early adulthood, and to identify mediators and moderators of risk development that could guide prevention or early intervention programming. Aims for the parents (G1s) were to identify factors that predict relapse, remission, and social adaptation. The project is the earliest beginning (age 3) high risk for AUD study currently active, and involves one of the longest spans of prospective assessment of alcohol/other drug use. Its data matrix involves repeated measurement of a variable network of behavioral, cognitive, and psychological functioning, social environment, substance use/abuse, and psychiatric symptoms. It is also interdigitated with 5 other projects which utilize the MLS as their recruitment, data management, and conceptual core, and share all data. This renewal application proposes continued characterization of G2s as the scientifically most unique segment of the study, limiting G1 assessments to measures critical to characterizing the socialization environment of G2s. G2s have been assessed since preschool and drinking/other drug use is assessed from time of onset. Continued collection of these data will allow evaluation of the prospective effects of precursive risk, in interaction with early substance use, upon later behavior. We intend to fully characterize two critical issues in G2s: 1) Identification of the developmental risk pathways that lead to an AUD outcome without psychiatric comorbidity as contrasted with one involving a comorbid externalizing or internalizing diagnosis; (Aim 1); and 2) Identification of the factors that predict a resilient (non-alcohol abusing) outcome in emerging adulthood, despite precursive exposure to adversity (Aim 2). Furthermore, we intend to take advantage of the comprehensive multi-domain matrix of data available from the core study and its offshoot partner-projects to build cross-level, developmental models of mechanistic structure for critical risk and resilience phenotypes for problem alcohol use and AUD across levels of genes, neural networks, social environment, and development (Aim 3). In order to fully capitalize on the maturity of the study, we will also use th extensive multi-wave database to characterize a critical issue in the G1s: evaluating the long term effects of alcohol consumption burden upon cognitive function in middle to later adulthood (Aim 4). With more than a generation of real time information the project will be able to prospectively evaluate these effects over the course of 27 years. Finally, we intend to provide the now very long-term longitudinal database as a resource for the field. Thus, our final aim is to establish a project development program involving meetings adjunctive to RSA and CPDD for investigators to share data and issues, with the goal of developing a collaborative network (Aim 5).