Family Study of Risk for Alcoholism Over the Life Course

描述(由申请人提供)：这项名为密歇根纵向研究(MLS)的前瞻性高危家庭研究始于27年前，旨在研究从入学前开始的儿童(第二代或G2代)酒精使用障碍(AUD)风险的发展，目的是检测是否可以很早就发现晚发障碍的风险标记物，描述已确定的风险因素在儿童期和成年期早期的演变，并确定可指导预防或早期干预规划的风险发展的中介和调节因素。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AUD研究中最早开始的(3岁)高风险研究，并涉及对酒精/其他药物使用的前瞻性评估的最长跨度之一。它的数据矩阵包括重复测量行为、认知和心理功能、社会环境、药物使用/滥用和精神症状的可变网络。它还与其他5个项目交织在一起，这些项目将最低限度作为其招聘、数据管理和概念核心，并共享所有数据。这一续订申请建议继续将G2作为研究中科学上最独特的部分，将G1评估限制为对表征G2社会化环境至关重要的措施。从学龄前就开始评估G2S，从发病时开始评估饮酒/其他药物使用情况。继续收集这些数据将能够评估先兆风险的预期影响，并与早期药物使用相互作用，对后来的行为产生影响。我们打算充分描述G2S中的两个关键问题：1)识别导致AUD结局的发育风险途径，而不是涉及外化或内在化诊断的共病的AUD结局；(目标1)以及2)尽管有先兆暴露在逆境中，但识别预测初成年(非酗酒)结果的因素(目标2)。此外，我们打算利用核心研究及其分支伙伴项目提供的全面的多领域数据矩阵，在基因、神经网络、社会环境和发展水平(目标3)上建立跨水平的机制结构的跨水平发展模型，以应对问题酒精使用和AUD的严重风险和弹性表型(目标3)。为了充分利用这项研究的成熟度，我们还将使用这个广泛的多波数据库来描述G1S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)。有了超过一代的实时信息，该项目将能够在27年的过程中前瞻性地评估这些影响。最后，我们打算提供现在非常长期的纵向数据库，作为外地的资源。因此，我们的最终目标是 建立一个项目发展方案，包括召开RSA和CPDD的附属会议，供调查人员分享数据和问题，目的是发展一个协作网络(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).