BRAIN ALCOHOL MRS AND FAMILY HISTORY OF ALCOHOLISM

脑酒精女士和酗酒家族史

• 批准号: 6168385
• 负责人: JACK H MENDELSON
• 金额: $ 33.68万
• 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/6168385
• 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.

这个项目的目的是检查家庭之间的协方差 酒精中毒史与质子活体检测脑内酒精含量 磁共振波谱成像（MRSI）。 有一个丰富的 有文献表明，酒精的一个作用是增加 脑细胞膜的硬度和减少分配到酒精 双脂神经元膜层。最近我们发现， 核磁共振波谱（MRS）检测大脑酒精含量约为2 重度饮酒者比偶尔饮酒者高出一倍， 服用相同剂量的酒精。 我们的一个含义是， 研究发现，大脑中酒精的MRS检测可能是一种生物学方法， 与慢性酒精暴露有关 虽然精确的 重度患者更高的MRS酒精检测能力的潜在机制 饮酒者是未知的，我们假设这种差异可能是由于 减少乙醇分配到神经元的疏水核心 膜和减少磷脂头部基团与乙醇的水合作用 在广泛的轴突膜表面。 我们已经完善了分析 通过适当操作进行脑部酒精MRSI检测的程序 的时间（回波时间TE=20 ms和270 ms），其中酒精 信号被收集。体内质子MRSI能够放大信号 从特定分子实体中的核（例如，甲基在 乙醇）从所选的感兴趣体素（VOI）中检测到。 人体大脑 另外，我们的初步数据显示- 在连续两次饮酒后，可以在男性中检测到诱导的酒精耐受性。 的饮品 我们建议用MRSI检测来确定大脑中的酒精水平 目前饮酒量不同的男性和女性的技术 还有家族酗酒史 男女将被挑选出来， 酒精中毒家族史和当前饮酒的客观标准 模式（偶尔与重度饮酒者）。 入选标准将 部分基于遗传学的半结构化评估， 酗酒（SSAGA）。酒精使用的回顾性报告将 通过每日监测酒精摄入量、健康和心理状况来验证 状态与交互式电话语音响应程序。 MRSI 大脑中酒精检测的测量将得到补充， 经验证的心理、认知和知觉测试评估。 受试者将在受控研究病房条件下接受研究。 酒精（2.2 ml、2.75 ml和3.3 ml 40%乙醇/kg体重 体重）或安慰剂将以平衡顺序施用。 女性将在月经的中期卵泡阶段进行研究 周期（第6-8天）和周期阶段将用激素进行验证 措施 拟议研究的结果将显示， 大脑酒精与酗酒家族史有关，目前 酒精摄入或男女之间的相互作用。 数据 将显示MRSI是否存在显著的性别差异- 检测大脑酒精含量 体内MRSI检测或脑酒精 可能被证明是一个有用的工具，以确定风险的发展， 酒精问题的女性和男性有积极的家族史， 酒精中毒 据我们所知，此前没有 研究神经生物学、遗传学和 可能影响饮酒发生的饮酒变量 男人和女人的依赖。