Alcohol Use Disorders Across the Lifespan: Subtypes, Course, Comorbidity

描述（由申请人提供）：这是针对NIAAA项目公告（05-088）现有酒精流行病学数据的二次分析而撰写的修订申请（1 R01 AA016392-01A1）的修订，并由BGES IRG在其2006年10月会议上审查。在这次修订中，我们试图解决最初提交的审稿人提出的问题，同时保持我们最初的主要目标，即通过利用国家酒精及相关疾病流行病学调查（NESARC）研究的独特方面，将酒精使用障碍（AUDs）的结构和过程描述为青少年晚期和成人发展的功能，该研究包括对精神病理学（包括第一轴和第二轴疾病）的广泛评估。以人群为基础的抽样，样本量大（约43,000人），覆盖成人年龄跨度，并进行了三年的纵向随访。我们的主要重点是AUDs的心理测量结构和过程（例如，发病、进展、消退和缓解/持续）作为发展（实足年龄）的函数。尽管酒精研究人员越来越多地将AUDs视为发育障碍，但对于依赖综合征的结构（在维度上或分类上进行评估）是否随着发育而变化，以及各种协变量在决定生命周期不同阶段的病程中所起的作用，人们知之甚少。除了将年龄作为从测量和预后角度理解AUDs的关键框架外，我们还计划研究其他主要的人口统计学（即性别和种族/民族）和临床变量（即轴I和轴II病理）如何与年龄相互作用以影响AUDs的结构和病程。我们特别感兴趣的是通过使用NESARC对人格病理学的评估来扩展以前的工作，这是该数据集的一个独特方面。我们认为人格病理学在AUD的病因和病程中发挥着重要但未被充分认识的作用，并计划进行广泛和系统的分析，以描绘AUD/人格障碍（轴二）共病的本质。由于I轴“临床综合征”与II轴疾病之间的高共病性，目前尚不清楚AUD与I轴疾病共病的现有文献在多大程度上代表了病理学的伪产物。只有同时对I轴和II轴病理进行全面建模，我们才能确定各种共病综合征与aud在统计学上的独特关系。除了研究项目的实质性目标外，我们还建议发展和完善表征酒精相关综合征的方法，并研究其随时间的稳定性。我们相信这些心理测量调查可以告知临床分类学和对新表型感兴趣的研究人员，这可能对遗传调查有用。

DESCRIPTION (provided by applicant): This is a revision of an amended application (1 R01 AA016392-01A1) written in response to NIAAA Program Announcement (05-088) Secondary Analysis of Existing Alcohol Epidemiology Data and reviewed by the BGES IRG at its October, 2006, meeting. In this revision, we have attempted to address concerns raised by the reviewers of the initial submission while maintaining our original primary goals which involve characterizing the structure and course of alcohol use disorders (AUDs) as a function of late adolescent and adult development by exploiting the unique aspects of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) study which include extensive assessment of psychopathology (including both Axis I and Axis II disorders), population-based sampling, large (~43,000 individuals) sample size, coverage of the adult age span, and three-year longitudinal follow-up. Our main focus is on the psychometric structure and course (e.g., onset, progression, regression, and remission/desistence) of AUDs as a function of development (chronological age). Although alcohol researchers increasingly view AUDs as developmental disorders, little is known about whether the structure of the dependence syndrome (assessed either dimensionally or categorically) varies as a function of development and the role that various covariates play in determining course at different points along the lifespan. In addition to focusing on age as critical scaffolding for understanding AUDs from both a measurement and prognostic perspective, we plan to examine how other major demographic (i.e., sex and race/ethnicity) and clinical variables (i.e., Axis I and Axis II pathology) interact with age to affect the structure and course of AUDs. We are particularly interested in extending previous work by using the NESARC's assessment of personality pathology, a unique aspect of this data set. We believe personality pathology plays an important but under-recognized role in the etiology and course of AUDs, and plan extensive and systematic analyses to portray the nature of AUD/personality disorder (Axis II) comorbidity. Because of the high comorbidity between Axis I "clinical syndromes" and Axis II disorders, it is unclear to what extent the existing literature on AUD comorbidity with Axis I disorders represents an artifact of pathology. Only by comprehensively and simultaneously modeling both Axis I and Axis II pathology can we resolve the extent that various comorbid syndromes have a statistically unique relation with AUDs. In addition to the substantive goals of the research project, we also propose to develop and refine methodologies for characterizing alcohol-related syndromes and studying their stabilities over time. We believe these psychometric investigations can inform both clinical nosology and researchers interested in novel phenotypes that may be useful in genetic investigations. Relevance to public health: Alcohol use disorders (AUDs) are among the most prevalent psychological disorders in the Nation and produce substantial burden to affected individuals, their friends and families, and society at large. Although primarily a disorder of adolescence and early adulthood, AUDs represent significant health challenges throughout the course of adulthood. The proposed study seeks to characterize factors important in the development and course of AUDs as a function of stage of adult development in order to better understand the causes and consequences of AUDs in a developmental context.