NEUROPHYSIOLOGY IN CHILDREN AT HIGH RISK FOR ALCOHOLISM

在过去的20年里，人们反复观察到事件相关电位（ERP）的P3（00）成分并不 只有在酗酒者中显着降低，而且在酗酒者的年轻后代中也有高风险（HR）发展为酗酒。 观察结果表明，HR个体P3成分振幅的降低可能是酒精发展的先兆 依赖有一些证据表明，HR个体在儿童期和青春期的P3电压降低与以下因素有关： 外化障碍（行为障碍、注意缺陷多动、对立违抗性障碍和成人反社会行为） 和增加物质使用，并可能预测以后的物质和酒精滥用。对所有人力资源研究的荟萃分析得出结论， HR个体的低振幅P3提供了一个可靠的酒精中毒表型标记，它被认为是指示 增加中枢神经系统（CNS）去抑制。因此，P3作为一个潜在的脆弱性标记可以提供一些洞察力， 参与酒精依赖发展的致病病理生理过程。 这里假设P3振幅可以指示一些CNS脆弱性（例如去抑制），其可以导致任何 许多不良状况之一，如酒精依赖、药物滥用、反社会人格、注意力缺陷多动等 障碍，品行障碍，对立障碍等。迄今为止使用的研究策略是基于家族性高风险模型 因为众所周知，酗酒者的子女很容易对酒精产生依赖。在目前的更新中， 基于"神经生理高风险"模型提出了一种互补策略。在这个模型中，假设个人 仅基于他们在神经生理学特征（例如视觉P3振幅）上的极端分数， 相关的wuh一些临床条件，如酒精依赖，药物滥用等，一些科学问题将 使用这种新的方法进行检查，使用创新的神经生理学测定和方法。 关于Adole^rnKCmyi7!在随机确定的大样本中记录eCt ^Phpyl <$10 gif ^sasuKSf2 <$d其他测量值<*）<$" 15 - 17岁的青少年P3b振幅提供了一个定量变量，通常在一般情况下产生正态分布 人民。stnbuhon将被分为下，上和中三分之一。基于P3b振幅的这三组将 为后续的因变量提供基础，如其他EEG/ERP实验，收集临床数据 （外化症状、其他精神症状、饮酒、吸毒、精神疾病家族史等） 假设那些处于P3振幅分布低端的个体将表现出更多的电生理学证据， dismh. bition，externalizing traits，and substance use.此外，有人提出，具有低P3b振幅的个体将表现出 与P3b振幅高的受试者相比，外化特征、酒精和药物滥用的患病率显著更高， 四年后（19 - 21岁）重新测试。重新测试将在本申请的最后一年开始开始，并将在未来继续进行。 识别具有神经电缺陷的个体将在预防措施中具有很大的效用

For the past twenty years it has been repeatedly observed that the P3(00) component of the event-related potential (ERP) is not only sigmficantly lower in alcoholics, but also in young offspring of alcoholics at high risk (HR) for developing alcoholism These observations suggested that reduced amplitudes of the P3 component in HR individuals might antecede the development of alcohol dependence. There is some evidence that reduced P3 voltage in childhood and adolescence in HR individuals is associated with externalizing disorders (conduct disorder, attention deficit hyperactivity, oppositional defiant disorder and adult antisocial behavior) and increased substance use, and may predict later substance and alcohol abuse. A meta-analysis of all HR studies concluded that the low amplitude P3 in HR individuals provides a reliable phenotypic marker of alcoholism, and it has been postulated to be indicative of increased Central Nervous System (CNS) disinhibition. Thus P3 as a potential vulnerability marker may provide insight into some causative pathophysiology process involved in the development of alcohol dependence. Here it is hypothesized that the P3 amplitude may index some CNS vulnerability (e.g. disinhibition) which may result in any one of a number of adverse conditions, such as alcohol dependence, drug abuse, antisocial personality, attention deficit hyperactivity disorder, conduct disorder, oppositional disorder, etc. The research strategy used to date has been based on a familial high-risk model because it is well known that children of alcoholics are at high risk to develop alcohol dependence. In the present renewal a complementary strategy is proposed based on a "neurophysiological high-risk" model. In this model, individuals are hypothesized to be at h.gh-nsk based solely on their extreme scores on neurophysiological features (e.g.visual P3 amplitude), well established to be associated wuh a number of clinical conditions such as alcohol dependence, substance abuse, etc. Several scientific issues will be examined with the use of this novel approach, usinginnovativeneurophysiological assays and methods. of adole^rnKCmyi7!eCt^Phpyl¿10gif ^sasuKSf2 ¿d other measur<*) ¿" be recorded in a large randomly ascertained sample ot adolescents (15-17) The P3b amplitude provides a quantitativevariable that typically yields a normal distributionin the general populauon. Th,sd.stnbuhon will be divided into the lower, upper and middle third. These three groups based on P3b amplitudewill provide the basis for subsequent dependent variables, such as other EEG/ERP experiments, the clinical data to be collected (externalizing symptoms, other psychiatric symptoms, alcohol use,drug use, family history of psychiatric disorders etc) It is hypothesized that those individualsat the low end of the P3 amplitude distribution will manifest more evidence of electrophysiological dismh.bition, externalizing traits, and substance use. Moreover, it is proposed that individuals with low P3b amplitude will manifest significantly greater prevalence of externalizing traits, alcohol and drug abuse compared to subjects with high P3b amplitude when retested four years later (ages 19-21). Retesting will begin in the last year of this application, and will continuein the future The identification of individuals with neuroelectric deficits will have great utility in prevention initiatives