Genetics, Brain Activity, and Relapse to Alcoholism

遗传学、大脑活动和酗酒复发

• 批准号: 7319080
• 负责人: KIRK J BROWER
• 金额: $ 21.25万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-20 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7319080
• 关键词: Age-Years; Alcohol dependence; Alcoholism; Alcohols; American; Applications Grants; Area; Arts; Back; Biological Markers; Brain; Butyric Acid; Butyric Acids; Collaborations; Collection; DNA; Data; Data Collection; Depressed mood; Development; Device or Instrument Development; Doctor of Medicine; Doctor of Philosophy; Drug abuse; Electroencephalography; Frequencies; Funding; Future; Genetic; Genetic Markers; Genotype; Human Resources; Impulsivity; Individual; Institutes; Intake; International; Learning; Measurement; Measures; Medical; Michigan; Mission; Neurotransmitters; Outcome Study; Patients; Phenotype; Poland; Polishes; Protocols documentation; Psychiatry; Purpose; Questionnaires; Relapse; Research; Research Ethics Committees; Research Personnel; Research Training; Review Literature; Risk; Serotonin; Structure; Substance abuse problem; Suicide; System; Techniques; Testing; Training; Training Programs; Translating; Travel; United States National Institutes of Health; Universities; Visit; Woman; Work; Writing; addiction; base; behavior measurement; computerized; design; drinking; drug of abuse; endophenotype; international center; men; problem drinker; professor; programs; prospective; size; statistics

DESCRIPTION (provided by applicant): This is an R21 developmental application and collaborative international project, designed to strengthen existing cooperative relationships between alcohol researchers in the U.S. and Poland. Its broad, long-term objective is to identify subtypes of alcoholic patients predisposed to relapse, because of genetically determined abnormalities in brain functioning. Thus, it is directly related to NIAAA's mission to conduct research in the areas of genetics and treatment, and to collaborate with international programs engaged in alcohol-related work. It will accomplish its objective by investigating relationships among genetic markers, quantitative EEG activity, impulsivity, and relapse in alcohol-dependent individuals from the U.S. and Poland. Hypothesized relationships among variables, based on literature review and preliminary data, will be tested with an aim to demonstrate feasibility and calculate effect sizes for a larger NIH grant proposal, which would also include larger scale genotyping. The specific aims are to (1) investigate relationships between impulsivity and relapse in alcohol-dependent subjects; (2) investigate relationships between biological markers of two neurotransmitter systems (serotonin and GABA) and impulsivity in alcohol-dependent subjects; and (3) investigate relationships between genetic and electrophysiological markers of the serotonin and GABA systems and relapse risk in alcohol-dependent subjects. Included in this prospective, naturalistic outcome study are 300 men and women, 18 years of age and over, who meet study criteria for alcohol dependence, and are entering treatment in either Warsaw or Ann Arbor. Visits for structured data collection will occur at intake (baseline) and after 3 and 6 months. The major dependent variable is relapse to alcoholic drinking. Relapse to other drugs of abuse is also considered. The major independent variables are genetic variability in serotonin and GABA neurotransmitter systems (genotypes), fast beta frequency brain activity (endophenotype) as measured by quantitative electroencephalograpy (QEEG), and depressed mood, suicidality, and impulsivity (phenotypes) as measured by validated questionnaires and a computerized stopping task.

描述（由申请人提供）：这是R21的发展应用和协作国际项目，旨在加强美国与波兰酒精研究人员之间的现有合作关系。它广泛的长期目标是确定易于复发的酒精患者的亚型，这是由于脑功能的遗传确定异常。因此，它与NIAAA在遗传学和治疗领域进行研究，并与从事与酒精有关的工作的国际计划合作进行研究直接相关。它将通过研究遗传标志物之间的关系，定量的脑电图活性，冲动性以及来自美国和波兰的酒精依赖人的复发来实现其目标。基于文献综述和初步数据的变量之间的假设关系将进行测试，目的是证明可行性并计算较大的NIH赠款提案的效应大小，这还将包括较大规模的基因分型。 具体的目的是（1）研究抗酒精依赖性受试者冲动性与复发之间的关系； （2）研究两个神经递质系统（5-羟色胺和GABA）的生物学标记与酒精依赖性受试者的冲动性之间的关系； （3）研究5-羟色胺和GABA系统的遗传学和电生理标记与酒精依赖受试者的复发风险之间的关系。这项前瞻性自然主义结果研究中包括300名男性和女性，18岁及以上，符合酒精依赖的学习标准，并正在华沙或安阿伯（Ann Arbor）进行治疗。访问结构化数据收集将在摄入量（基线）和3个月后发生。主要因变量是酗酒的复发。还考虑了其​​他滥用药物的复发。主要的自变量是通过定量脑电图（QEEG）（QEEG）测量的血清素和GABA神经递质系统（基因型），快速β频率脑活动（内型型）的遗传变异性，以及通过有效的问题和一定的任务来衡量的情绪，自杀性和脉冲性（脉冲）（现场型）。