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

遗传和环境对女性饮酒过程的影响

• 批准号: 8536074
• 负责人: CAROLYN E SARTOR
• 金额: $ 13.76万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-10 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8536074
• 关键词: Accounting; Address; Adolescent; Adult; African American; Age; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohol or Other Drugs use; Alcoholism; Alcohols; Anxiety Disorders; Area; Award; Behavior; Behavioral Genetics; Characteristics; Child Sexual Abuse; Childhood; Clinical; Collaborations; Conduct Disorder; Consumption; Data; Data Analyses; Data Collection; Data Set; Dependence; Development; Development Plans; Diagnostic; Dimensions; Disease remission; Environment; Ethnic Origin; Event; Exhibits; Exposure to; Family Study; Female; Female Adolescents; Foundations; Funding; Future; Genetic; Genomics; Goals; Household; International; Interview; Investigation; K-Series Research Career Programs; Measures; Mediating; Mediator of activation protein; Mental Depression; Mental disorders; Mentors; Methodology; Methods; Missouri; Modeling; Nature; Online Systems; Outcome; Outcome Study; Parental Leave; Participant; Pattern; Plant Roots; Population; Prevention program; Program Development; Psychiatry; Psychologist; Psychopathology; Recording of previous events; Recruitment Activity; Relative (related person); Reporting; Research; Research Personnel; Research Project Grants; Resources; Risk; Risk Factors; Role; Sampling; Shapes; Staging; Subgroup; Surveys; Telephone; Telephone Interviews; Testing; Time; Training; Trauma; Treatment outcome; Twin Multiple Birth; Twin Studies; Universities; Variant; Washington; Woman; Wood material; Work; addiction; alcohol behavior; alcohol related problem; alcohol use disorder; base; career; career development; cohort; design; diaries; disorder prevention; drinking; drinking behavior; experience; follow-up; genetic association; high risk; medical schools; programs; prospective; psychosocial; skills; social; therapy development; young adult; young woman

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.

PI是华盛顿大学医学院精神病学系的临床心理学家，是精神病学研究的国际领导者，在成瘾和遗传学方面有着完善的研究计划。PI正在制定一项研究计划，研究遗传和环境对酒精使用和依赖的影响，该计划植根于发展精神病理学框架。她的研究重点是从青少年到年轻人的问题饮酒行为和相关的精神疾病，重点是通过使用阶段的进展和这些转变发生的速度。儿童期攻击性创伤在塑造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了突出地位，并将成为拟议的K奖项目的主要焦点，该项目将她与创伤暴露人群（临床和研究经验）的广泛经验与行为遗传学方法结合起来，以研究物质相关行为。K 08将有助于推动她实现建立一个独立的R 01资助的研究计划的目标，该计划旨在描述遗传信息框架中酒精使用和酒精使用障碍的过程。这项研究计划将解决三个核心问题：1）遗传和环境对酒精相关结果的影响在使用阶段的可变程度，以及对这些阶段过渡率的贡献; 2）使用和滥用其他物质，创伤暴露和并发精神障碍对酒精相关问题的贡献随时间变化的程度; 3）短期饮酒行为模式与当前和未来酒精相关问题之间的关联性质，包括这种关系在各个发育阶段的一致性。PI长期职业计划的第二个关键组成部分是增加与进行治疗结果研究和预防方案开发的研究人员的合作，以促进这一研究领域的转化工作。拟定的职业发展计划将在导师Andrew Heath博士、共同导师Kenneth Sher博士以及顾问James Anthony博士和菲利普伍德博士的指导下进行，旨在通过指导、使用现有数据以及拟定的新数据收集数据进行统计分析的实践经验，和正式的课程培训计划的四个主要目标是获得遗传信息方法的专业知识，以描述酒精使用的过程，提高纵向数据分析的技能，建立遗传学和基因组学基本原理的基础，并熟练掌握基于网络的酒精相关行为数据收集。 拟议的研究项目将解决遗传和环境对酒精用途：饮酒里程碑之间的进展速度和酒精使用的日常模式的两个方面的贡献。她们在酒精相关研究中的代表性不足，使得识别女性的明显脆弱性或使用模式成为一项具有挑战性的任务。目前的项目专门侧重于女性样本，以努力解决这一问题。通过饮酒里程碑的进展，特别是精神和心理社会风险因素的潜在中介和调节作用（例如，行为障碍，抑郁症，儿童期攻击性创伤）对酒精使用和依赖转变的遗传贡献，将在二次分析中进行检查，并在两个现有数据集中回顾性报告饮酒史。第一个样本包括来自密苏里州青少年女性双胞胎研究（MOAFTS）的4,417名女性双胞胎和来自密苏里州家庭研究的535名女性参与者，这是一项针对非洲裔美国人种族（50%）进行过抽样的高风险酒精中毒家庭研究;以及B）来自澳大利亚双胞胎队列的2,632名女性双胞胎。将在新的基于网络的数据收集中调查日常饮酒模式，其中包括根据MOAFTS的儿童性虐待（CSA）状态选择的双胞胎子集（n=100）。在简短的电话诊断访谈之后，将在12周内以每日日记的形式对酒精消费和其他物质使用（以及暴露于使用物质的环境）进行每周网络调查。在第12周评估中将纳入评估前12周创伤暴露的额外指标。在完成基于网络的研究部分一年后，将再次联系参与者进行后续电话访谈，涵盖与基线访谈中相同的精神和心理社会功能领域。12个月的随访还将涉及12周评估期内报告的物质使用和相关行为的回忆，以测试前瞻性报告和回顾性总结之间报告的一致性。分析的目的是量化家庭责任和环境因素对问题酒精使用模式的影响，并确定有CSA病史的妇女是否表现出独特的使用模式。该项目将为R 01应用程序提供可行性数据，以便使用基于网络的数据收集方法对青少年使用酒精和其他物质的短期模式进行纵向遗传关联研究。通过加强对遗传和环境对酒精使用过程和妇女问题饮酒行为发展的贡献的理解，拟议的K奖项目将促进制定针对高风险使用模式和饮酒过程中的过渡点的干预措施，这些模式和过渡点的特点是对问题酒精使用的责任增加。