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.

这是一个R21开发应用和国际合作项目，旨在加强美国和波兰酒精研究人员之间的现有合作关系。其广泛、长期的目标是识别由于基因决定的大脑功能异常而容易复发的酒精患者的亚型。因此，它与NIAAA的使命直接相关，即在遗传学和治疗领域进行研究，并与从事酒精相关工作的国际方案合作。它将通过调查来自美国和波兰的酒精依赖个体的遗传标记、定量EEG活动、冲动性和复发之间的关系来实现其目标。基于文献综述和初步数据，将对变量之间的假设关系进行测试，旨在证明可行性并计算更大NIH拨款提案的效应量，其中还包括更大规模的基因分型。 具体目标是：（1）研究酒精依赖受试者冲动性和复发之间的关系;（2）研究两种神经递质系统（5-羟色胺和GABA）的生物标志物与酒精依赖受试者冲动性之间的关系;（3）研究5-羟色胺和GABA系统的遗传和电生理标志物与酒精依赖受试者复发风险之间的关系。这项前瞻性自然结局研究包括300名18岁及以上的男性和女性，他们符合酒精依赖的研究标准，正在华沙或安阿伯接受治疗。结构化数据收集访视将在入组时（基线）以及3个月和6个月后进行。主要的因变量是酒精饮料的复发。还考虑了对其他滥用药物的复吸。主要的自变量是5-羟色胺和GABA神经递质系统的遗传变异性（基因型），通过定量脑电图（QEEG）测量的快速β频率脑活动（内表型），以及通过验证问卷和计算机化停止任务测量的抑郁情绪，自杀倾向和冲动（表型）。