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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

基本信息

批准号：
8721262
负责人：
CAROLYN E SARTOR
金额：
$ 14.49万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-10 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8721262
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 child depression 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

项目摘要

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先者，拥有成熟的成瘾和遗传学研究项目。该协会正在制定一项研究计划，研究遗传和环境因素对酒精使用和依赖的影响，该计划植根于发展的精神病理学框架。她的研究重点是从青春期到青壮年的问题饮酒行为和相关的精神障碍，重点是饮酒过程中各个阶段的进展以及这些转变发生的速度。童年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有突出地位，并将成为拟议的K奖项目的主要重点，该项目将她与创伤暴露人群的丰富经验(临床和研究经验)与行为遗传学方法结合起来，研究与物质相关的行为。K08将有助于推动她实现建立一个由R01资助的独立研究项目的目标，该项目旨在基因信息框架下描述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)不同使用阶段的遗传和环境影响对酒精相关结果的可变性程度，以及这些阶段的过渡率的贡献者；2)其他物质的使用和误用、创伤暴露和共生精神障碍对酒精相关问题的贡献随时间的不同而不同的程度；3)短期饮酒行为模式与当前和未来与酒精相关的问题之间关联的性质，包括这种关系在不同发育阶段的一致性。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计划开发的研究人员的合作，以促进这一研究领域的转化努力。拟议的职业发展计划将在导师安德鲁·希思博士、共同导师肯尼思·谢尔博士以及顾问詹姆斯·安东尼博士和菲利普·伍德博士的指导下进行，旨在通过教程、对现有数据以及拟议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向独立调查员地位的过渡做好准备。培训计划的四个主要目标是获得以遗传信息方法描述饮酒过程的专门知识，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。拟议的研究项目将探讨遗传和环境对酒精使用过程的两个方面的影响：饮酒里程碑之间的进展率，以及酒精使用的日常模式。在与酒精相关的研究中，她们的代表性不足，这使得识别女性独特的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(例如品行障碍、抑郁、童年攻击创伤)对酒精使用和依赖转变的遗传贡献的潜在中介和缓和作用，将在二次分析中进行审查，并在现有的两个数据集中回顾饮酒史报告。第一个样本是来自密苏里州青少年女性双胞胎研究(MOAFTS)的4417名女性双胞胎和来自密苏里州家庭研究(MisSouri Family Study)的女性参与者，密苏里州家庭研究是一项针对非裔美国人种族的高风险酒精中毒家庭研究(50%)；以及b)来自澳大利亚双胞胎队列的2632名女性双胞胎。一项新的基于网络的数据收集将调查日常饮酒模式，其中包括一组双胞胎(n=100)，他们是根据MOAFTS的儿童期性虐待(CSA)状况挑选出来的。在简短的电话诊断性访谈之后，将对酒精消费和其他物质使用(以及暴露在物质使用环境中)进行每周基于网络的调查，以每日日记的形式进行，为期12周。评估前12周创伤暴露的额外措施将包括在第12周评估中。在这项研究的网络部分完成一年后，将再次与参与者联系，进行后续电话访谈，内容与基线访谈所涵盖的精神和心理社会功能领域相同。12个月的随访还将包括回忆在12周评估期内报告的药物使用和相关行为，以努力测试前瞻性报告和回溯性摘要之间报告的一致性。分析的目的将是量化家庭责任和环境对问题酒精使用模式的贡献，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R01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短期酒精和其他物质使用模式进行纵向遗传关联研究。通过加强对遗传和环境因素对女性饮酒过程和问题饮酒行为发展的影响的了解，拟议的K奖项目将促进针对高风险饮酒模式和饮酒过程中的转折点的干预措施的开发，这些转折点以问题饮酒的风险增加为特征。