BRAIN ALCOHOL MRS AND FAMILY HISTORY OF ALCOHOLISM

脑酒精女士和酗酒家族史

• 批准号: 2842000
• 负责人: JACK H MENDELSON
• 金额: $ 31.73万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2842000
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; bioimaging /biomedical imaging; brain metabolism; clinical research; ethanol; family genetics; female; gender difference; human subject; male; neuropsychological tests; nuclear magnetic resonance spectroscopy; putamen; young adult human (21-34)

This project is designed to examine the covariance between family history of alcoholism and in vivo detection of brain alcohol with proton magnetic resonance spectroscopic imaging (MRSI). There is an abundant literature which suggests that one effect of alcohol is to increase brain cell membrane rigidity and reduce partitioning of alcohol into the bilipid neuronal membrane layer. Recently we discovered that magnetic resonance spectroscopy (MRS) detection of brain alcohol is about two fold higher in heavy drinkers than in occasional drinkers after administration of an identical dose of alcohol. One implication of our finding is that MRS detection of alcohol in brain may be a biological correlate of chronic alcohol exposure. Although the precise mechanism(s) underlying greater MRS alcohol detectability in heavy drinkers are unknown, we postulate that this difference may result from reduced ethanol partitioning into the hydrophobic core of the neuronal membranes and reduced hydration of phospholipid headgroups with ethanol on the extensive axonal membrane surface. We have refined the analytic procedures for MRSI detection of brain alcohol by suitable manipulation of the times (echo times TE=20 ms and 270 ms) at which the alcohol signals are collected. In vivo proton MRSI enables amplified signals from nuclei in specific molecular entities (e.g., the methyl group in ethanol) to be detected from a chosen voxel of interest (VOI) in the human brain in vivo. Moreover, our preliminary data show that acutely- induced alcohol tolerance can be detected in men after two consecutive drinks. We propose to determine brain alcohol levels with MRSI detection techniques in men and women who differ in current alcohol consumption and family history of alcoholism. Women and men will be selected with objective criteria for family history of alcoholism and current drinking patterns (occasional versus heavy drinkers). Inclusion criteria will be based in part on the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). Retrospective reports of alcohol use will be validated by daily monitoring of alcohol intake, health and mental status with an Interactive Telephone Voice response program. MRSI measurements of alcohol detection in brain will be complemented by well validated psychomotor, cognitive and perceptual test assessments. Subjects will be studied under controlled research ward conditions. Alcohol (2.2 ml, 2.75 ml and 3.3 ml of 40 percent ethanol per kg of body weight) or placebo will be administered in a counter-balanced order. Women will be studied during the mid-follicular phase of the menstrual cycle (days 6-8) and cycle phase will be verified with hormonal measures. Results of the proposed study will show whether increased detection of brain alcohol is associated with a family history of alcoholism, current alcohol intake or an interaction of both in women and men. Data obtained will show if there are significant gender differences in MRSI- detected brain alcohol levels. In vivo MRSI detection or brain alcohol may prove to be a useful tool to ascertain risk for development of alcohol problems in women and men with a positive family history of alcoholism. To the best of our knowledge there have been no previous investigations of the concordance of neurobiological, genetic and alcohol consumption variables which may influence occurrence of alcohol dependence in men and women.

该项目旨在检查家庭之间的协方差 酗酒史及质子体内脑酒精检测 磁共振波谱成像（MRSI）。 有丰富的 文献表明酒精的作用之一是增加 脑细胞膜刚性并减少酒精进入 双脂神经元膜层。最近我们发现磁性 磁共振波谱（MRS）检测脑酒精大约有两种 重度饮酒者比偶尔饮酒者的倍数更高 给予相同剂量的酒精。 我们的含义之一 研究发现，MRS 检测大脑中的酒精可能是一种生物 慢性酒精暴露的相关性。 虽然精确 MRS 酒精检测能力更强的机制 饮酒者未知，我们假设这种差异可能是由于 减少乙醇分配到神经元疏水核心 膜和减少磷脂头基与乙醇的水合作用 广泛的轴突膜表面。 我们完善了分析 通过适当的操作进行 MRSI 检测脑酒精的程序 酒精释放的时间（回波时间 TE=20 ms 和 270 ms） 收集信号。体内质子 MRSI 可放大信号 来自特定分子实体中的原子核（例如， 乙醇）从选定的感兴趣体素（VOI）中检测 人脑在体内。 此外，我们的初步数据表明， 男性连续两次饮酒后可检测到诱导的酒精耐受性 饮料。 我们建议通过 MRSI 检测来确定大脑酒精水平 目前饮酒量不同的男性和女性的技术 以及酗酒家族史。 女性和男性将被选择 酗酒家族史和当前饮酒的客观标准 模式（偶尔饮酒者与大量饮酒者）。 纳入标准将 部分基于半结构化遗传学评估 酗酒（SSAGA）。酒精使用情况的回顾性报告将 通过每日监测酒精摄入量、健康状况和心理状况进行验证 交互式电话语音应答程序的状态。 磁共振成像 大脑中酒精检测的测量将得到很好的补充 经过验证的精神运动、认知和知觉测试评估。 受试者将在受控研究病房条件下进行研究。 酒精（每公斤体重 2.2 毫升、2.75 毫升和 3.3 毫升 40% 乙醇） 体重）或安慰剂将以平衡的顺序施用。 女性将在月经中期卵泡期接受研究 周期（第 6-8 天）和周期阶段将通过荷尔蒙进行验证 措施。 拟议研究的结果将表明是否增加了 脑酒精与酗酒家族史有关，目前 酒精摄入量或女性和男性的相互作用。 数据 获得的结果将显示 MRSI 是否存在显着的性别差异 检测到大脑酒精浓度。 体内 MRSI 检测或脑酒精 可能被证明是确定发展风险的有用工具 有阳性家族史的女性和男性的酒精问题 酗酒。 据我们所知，之前没有 研究神经生物学、遗传学和 可能影响酒精发生的饮酒变量 男性和女性的依赖性。