GENETIC AND ENVIRONMENTAL CONTRIBUTIONS TO THE COURSE OF ALCOHOL USE IN WOMEN

PI是华盛顿大学医学院精神病学系的临床心理学家，在精神病学研究方面处于国际领先地位，在成瘾和遗传学方面有着完善的研究项目。PI正在制定一项研究方案，以发展精神病理学框架为基础，研究遗传和环境对酒精使用和依赖的影响。她的研究重点是问题饮酒行为和相关的精神疾病，从青少年到青年，重点是在使用的各个阶段的进展和这些转变发生的速度。童年性创伤在形成酒精使用障碍过程中的作用在她在这一领域的工作中占据突出地位，并将成为拟议的k奖项目的主要焦点，该项目将她对创伤暴露人群的丰富经验（临床和研究经验）与行为遗传学方法相结合，以研究与物质相关的行为。K08将有助于她实现建立一个由r01资助的独立研究项目的目标，该项目旨在在遗传信息框架内描述酒精使用和酒精使用障碍的过程。该研究计划将解决三个核心问题：1)遗传和环境影响在不同使用阶段酒精相关结果的可变性程度，以及作为这些阶段过渡速度的贡献者；2)使用和滥用其他物质、创伤暴露和同时发生的精神疾病对酒精相关问题的影响程度随时间而变化；3)短期饮酒行为模式与当前和未来酒精相关问题之间关系的本质，包括这种关系在整个发育时期的一致性。PI长期职业规划的第二个关键组成部分是加强与进行治疗结果研究和预防项目开发的研究人员的合作，以促进这方面研究的转化工作。拟议的职业发展计划将在导师Andrew Heath博士、联合导师Kenneth Sher博士、顾问James Anthony博士和Phillip Wood博士的指导下进行，旨在通过教程、对现有数据以及拟议的新数据收集的数据进行统计分析的实践经验和正式课程，为PI向独立研究者身份的过渡做好准备。该培训计划的四个主要目标是：获得描述酒精使用过程的遗传信息方法方面的专门知识，提高纵向数据分析技能，奠定遗传学和基因组学基本原则的基础，并熟练掌握基于网络的酒精相关行为数据收集。

The PI is a clinical psychologist in the Department of Psychiatry at Washington University School of Medicine, an international leader in psychiatric research with well-established research programs in addictions and genetics. The PI is developing a program of research on genetic and environmental contributions to alcohol use and dependence rooted in a developmental psychopathology framework. Her research focuses on problem drinking behaviors and associated psychiatric disorders from the adolescent to young adult years, with an emphasis on the progression through stages of use and the rate at which those transitions occur. The role of childhood assaultive trauma in shaping the course of alcohol use disorders has figured prominently in her work in this area and will be a major focus of the proposed K-award project, which integrates her extensive experience with trauma-exposed populations (clinical as well as research experience) with behavioral genetic approaches to studying substance-related behaviors. The K08 will be instrumental in moving her toward her goal of establishing an independent R01-funded research program aimed at characterizing the course of alcohol use and alcohol use disorders in genetically-informative frameworks. This program of research will address three core issues: 1) the degree of variability in heritable and environmental influences on alcohol- related outcomes across stages of use and as contributors to the rate of transitions through these stages; 2) the extent to which the contributions of use and misuse of other substances, trauma exposure, and co-occurring psychiatric disorders to alcohol-related problems vary over time; and 3) the nature of the association between short-term patterns of drinking behaviors and current as well as future alcohol-related problems, including the consistency of this relationship across developmental periods. A second critical component of the PI's long-term career plans is to increase collaborations with researchers conducting treatment outcome studies and prevention program development to promote translational efforts of this line of research. The proposed career development plan, which will be undertaken under the guidance of mentor Dr. Andrew Heath, co-mentor Dr. Kenneth Sher, and consultants Dr. James Anthony and Dr. Phillip Wood, is designed to prepare the PI for the transition to independent investigator status through tutorials, hands-on experience conducting statistical analyses with existing data as well as data from the proposed new data collection, and formal coursework. The four major goals of the training plan are to gain expertise in genetically-informative approaches to characterizing the course of alcohol use, advance skills in longitudinal data analysis, establish a foundation in the basic principles of genetics and genomics, and develop proficiency in web-based data collection on alcohol-related behaviors. The proposed research project will address genetic and environmental contributions to two dimensions of the course of alcohol use: the rate of progression between drinking milestones, and day to day patterns in alcohol use. Their underrepresentation in alcohol-related studies makes identifying distinct vulnerabilities or patterns of use in women a challenging task. The current project focuses exclusively on female samples in an effort to address this issue. Progression through drinking milestones, specifically, the potential mediating and moderating effects of psychiatric and psychosocial risk factors (e.g., conduct disorder, depression, childhood assaultive trauma) on genetic contributions to transitions in alcohol use and dependence, will be examined in secondary analyses with retrospective reports of drinking history in two existing datasets. The first is a sample comprised of 4,417 female twins from the Missouri Adolescent Female Twin Study (MOAFTS) and 535 female participants from the Missouri Family Study, a high risk alcoholism family study oversampled for African-American ethnicity (50%); and b) 2,632 female twins from an Australian twin cohort. Day to day patterns of alcohol use will be investigated in a new web-based data collection with a subset of twin pairs (n=100), selected by childhood sexual abuse (CSA) status from MOAFTS. Brief telephone diagnostic interviews will be followed up with weekly web-based surveys of alcohol consumption and other substance use (as well as exposure to substance-using environments) administered in a daily diary format over a period of 12 weeks. An additional measure assessing trauma exposure in the previous 12 weeks will be included in the week 12 assessment. One year after completion of the web-based component of the study, participants will be re-contacted for a follow-up telephone interview covering the same domains of psychiatric and psychosocial functioning covered in the baseline interview. The 12 month follow-up will also involve recall of substance use and related behaviors reported over the 12 week assessment period in an effort to test consistency in reporting between prospective reports and retrospective summaries. Analyses will be aimed at quantifying familial liability and environmental contributions to patterns of problem alcohol use and determining whether women with CSA histories exhibit unique patterns of use. The project will provide feasibility data for an R01 application to conduct a longitudinal genetic association study of short-term patterns of alcohol and other substance use in adolescents using web-based data collection methods. By enhancing understanding of genetic and environmental contributions to the course of alcohol use and the development of problem drinking behaviors in women, the proposed K-award project will facilitate development of interventions targeting high-risk patterns of use and transition points in drinking course distinguished by elevated liability to problem alcohol use.