NEUROPHYSIOLOGY IN CHILDREN AT HIGH RISK FOR ALCOHOLISM

描述（由申请人提供）：在过去的二十年里， 反复观察到事件相关电位的P3（00）成分， (ERP)不仅在酗酒者中显著降低， 酗酒者的后代有酗酒的高风险（HR）。这些 观察结果表明，HR中P3分量的振幅降低 个人可能会提前酒精依赖的发展。有一些 证据表明HR个体在儿童期和青春期的P3电压降低 与外化障碍（行为障碍、注意力缺陷）有关 多动、对立违抗性障碍和成人反社会行为）， 增加物质使用，并可能预测以后的物质和酒精滥用。一 所有HR研究的荟萃分析得出结论，HR中的低振幅P3 个体提供了一个可靠的酗酒表型标记，它具有 被认为是中枢神经系统（CNS）增加的指标 去抑制因此，P3作为一个潜在的脆弱性标记， 一些致病的病理生理学过程， 酒精依赖 这里假设P3振幅可能指示某些CNS脆弱性 (e.g.这可能会导致许多不利因素中的任何一个 条件，如酒精依赖，药物滥用，反社会人格， 注意缺陷多动障碍，品行障碍，对立 迄今为止使用的研究策略是基于一个家族性的 高风险模型，因为众所周知，酗酒者的孩子 酒精依赖风险高。在当前的更新中， 基于"神经生理学高风险"模型提出了一种策略。在这 模型，个人被假设为处于高风险，仅仅基于他们的 神经生理学特征（例如视觉P3振幅）的极端分数，以及 已确定与许多临床病症相关，例如 酒精依赖，药物滥用等。一些科学问题将 使用这种新颖的方法进行检查，使用创新的 神经生理学测定和方法。 具体地，将电生理测量（P3和其他测量） 记录在一个大的随机确定的样本的青少年（15 - 17）。P3B 振幅提供了一个定量变量， 在一般人群中的分布。该分布将分为 下、上、中三分之一。这三组基于P3b振幅 将为随后的因变量提供基础，如其他 EEG/ERP实验，要收集的临床数据（外化症状， 其他精神症状，酒精使用，药物使用，家族史 精神疾病等）。据推测，这些人在 P3振幅分布的低端将显示更多的证据， 电生理去抑制、外化特征和物质使用。 此外，有人提出，具有低P3b振幅的个体将表现出 外化特征、酒精和药物的患病率显著增加 四年后重新测试时，与P3 b振幅较高的受试者相比，滥用行为 （19 - 21岁）。重新测试将在本申请的最后一年开始， 并将在未来继续。识别个人与 神经电缺陷将在预防措施中具有很大的效用。

DESCRIPTION (provided by applicant): For the past twenty years it has been repeatedly observed that the P3(00) component of the event-related potential (ERP) is not only significantly 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 high-risk based solely on their extreme scores on neurophysiological features (e.g. visual P3 amplitude), well established to be associated with 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, using innovative neurophysiological assays and methods. Specifically, electrophysiological measures (P3 and other measures) will be recorded in a large randomly ascertained sample of adolescents (15-17). The P3b amplitude provides a quantitative variable that typically yields a normal distribution in the general population. This distribution will be divided into the lower, upper and middle third. These three groups based on P3b amplitude will 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 individuals at the low end of the P3 amplitude distribution will manifest more evidence of electrophysiological disinhibition, 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 continue in the future. The identification of individuals with neuroelectric deficits will have great utility in prevention initiatives.