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.
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