NEUROPHYSIOLOGY IN CHILDREN AT HIGH RISK FOR ALCOHOLISM

描述(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，而且在年轻人中也显著降低 酗酒者的后代有发展成酒精中毒的高风险(HR)。这些 观察表明，HR中P3成分的波幅降低 个体可能先于酒精依赖的发展。有一些 HR个体在童年和青春期P3电压降低的证据 与外化障碍(品行障碍、注意力缺陷)有关 多动症、对立违抗障碍和成人反社会行为)和 更多的物质使用，并可能预示着以后物质和酒精的滥用。一个 对所有HR研究的Meta分析得出结论：HR的低波幅P3 个体提供了一个可靠的酒精中毒的表型标记，而且它已经 被认为是中枢神经系统(CNS)增强的迹象 解除抑制。因此，P3作为潜在的脆弱性标记可以提供洞察力 探讨了一些致病的病理生理学过程中涉及的发展 酒精依赖。 这里假设P3波幅可能指示某些CNS易损性 (例如解除抑制)，这可能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 到目前为止使用的研究策略是基于一个家庭成员 高风险模式，因为众所周知，酗酒者的孩子 患上酒精依赖的风险很高。在本次更新中，有一项补充 提出了基于“神经生理学高危”模型的治疗策略。在这 模型中，假设个人处于高危状态，仅基于其 神经生理特征(例如视觉P3波幅)的极端分数，很好 被证实与一系列临床情况有关，例如 酒精依赖、药物滥用等。几个科学问题将是 使用这一新方法进行了检查，使用创新的 神经生理学分析和方法。 具体地说，电生理措施(P3和其他措施)将是 记录在随机确定的大样本青少年(15-17岁)中。P3b 幅值提供了一个量化变量，该变量通常会产生正常 在普通人群中的分布。此分发将分为 下、上、中三分音符。基于P3b波幅的这三组 将为后续的因变量提供基础，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 精神障碍等)。据推测，这些人在 P3波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，P3b波幅低的个体将表现出 外化特征、酗酒和吸毒的患病率显著增加 与P3b波幅较高的受试者相比，四年后重新测试 以后(19-21岁)。重新测试将在本申请的最后一年开始， 并将在未来继续下去。对具有以下特征的个人的识别 神经电缺陷将在预防措施中发挥巨大作用。

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.