BRAIN ALCOHOL MRS AND FAMILY HISTORY OF ALCOHOLISM

该项目旨在检验家庭之间的协方差 酒精中毒史与脑组织酒精质子活体检测 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 脑细胞膜的刚性和减少酒精进入脑细胞的分配 胆脂神经元膜层。最近我们发现，磁力 脑部酒精的共振光谱(MRS)检测约为两个 大量饮酒的人比偶尔饮酒的人折叠得更高 注射相同剂量的酒精。我们的一个含义是 研究发现，MRS在大脑中检测到酒精可能是一种生物 与慢性酒精暴露的相关性。尽管准确地说 重型患者MRS酒精检测率提高的机制(S) 饮酒者是未知的，我们推测这种差异可能是 还原乙醇进入神经元疏水核心的研究 膜与乙醇对磷脂头基的还原水合作用 在广泛的轴索膜面上。我们已经提炼了分析 脑内酒精磁共振成像检测方法的研究 酒精的回声时间(回声时间TE=20ms和270ms) 信号被收集起来。体内质子磁共振成像使放大的信号成为可能 从特定分子实体的核(例如，中的甲基 乙醇)将从选定的感兴趣体素(VOI)中检测 活体中的人脑。此外，我们的初步数据显示，尖锐地- 男性在连续两次饮酒后可检测到诱导的酒精耐受 饮料。 我们建议通过核磁共振成像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 和酗酒家族史。女性和男性将被选为 酒精中毒家族史和当前饮酒的客观标准 模式(偶尔饮酒与大量饮酒)。纳入标准将 在一定程度上基于对儿童遗传学的半结构化评估 酒精中毒(SSAGA)。酒精使用的回顾报告将是 通过每日监测酒精摄入量、健康和精神状况进行验证 交互式电话语音应答程序的状态。MRSI 大脑酒精检测的测量将得到WELL的补充 经过验证的精神运动、认知和知觉测试评估。 受试者将在受控的研究病房条件下进行研究。 酒精(每公斤身体含2.2毫升、2.75毫升和3.3毫升40%乙醇 体重)或安慰剂将以平衡顺序给予。 女性将在月经的卵泡中期进行研究。 周期(6-8天)和周期阶段将通过激素进行验证 措施。 拟议研究的结果将表明，增加对 脑部酒精与酗酒家族史有关，目前 女性和男性的酒精摄入量或两者的互动。数据 获得的结果将显示MRSI是否存在显著的性别差异- 检测到脑部酒精含量。体内MRSI检测或脑内酒精 可能被证明是确定开发风险的有用工具 有阳性家族史的男性和女性的酒精问题 酗酒。据我们所知，以前没有过 神经生物学、遗传学和生物学的一致性研究 可能影响酒精发生的酒精消费变量 对男人和女人的依赖。

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.