NEUROPHYSIOLOGICAL ENDOPHENOTYPE OF ALCOHOL DEPENDENCE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。酒精依赖个体的临床症状的数量和种类反映了很大的异质性。因此，在酒精中毒的遗传研究中，诊断可能不是最理想的表型描述。我们建议发展量化与酒精中毒相关的神经生物学和神经行为特征的基本内表型。基于神经去抑制是酒精中毒发展的核心生物学特征的假设，我们建议使用一套新的神经电特征，专门设计来评估酒精中毒家庭中兄弟姐妹对的去抑制。这个程序;应用仅涵盖了复杂的、正在进行的合作研究的基线神经生理学数据收集部分，这些研究涉及更广泛的酒精中毒风险的遗传决定因素。这些研究包括酒精中毒遗传学合作研究（COGA），该研究已经开展了13年，重点是对至少5年前已经测试过的受试者进行随访，以及最近资助的衍生项目：互动研究计划拨款的印第安纳部分。由这些赠款资助的其他研究涉及收集和分析接触酒精前后收集的神经生理学数据：这些活动已经获得GCRC批准（GCRC# 903A）。然而，其他部分涉及DNA的血液采样，DNA分析，整个数据库的遗传分析，以及根本不需要与GCRC交互的实质性诊断面谈过程，并且不属于本应用程序的一部分。本申请中引用的招聘标准是最新的，包括自审查原始资金申请（并大幅减少）以来所做的更改，并反映了COGA指导委员会同意的后续更改。该应用程序包括对收集的数据进行统计分析，这些数据将由纽约布鲁克林州立大学的研究人员与德克萨斯州奥斯汀的基因分析人员合作完成。对全美9个神经生理学实验室提供的数据进行分析，所有这些实验室的设备都相同，包括位于印第安纳波利斯GCRC的神经系统实验室（包括VAMC的C-6130）。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The number and variety of clinical symptoms noted in alcohol dependent individuals reflect a great deal of heterogeneity. Therefore, the use of diagnosis may not be optimal as a phenotypic descriptor in genetic studies of alcoholism. We propose to develop fundamental endophenotypes quantifying neruobiological and neurobehavioral characteristics associated with alcoholism. Based on the hypothesis that neural disinhibition is a central biologic feature in the development of alcoholism, we propose to use a novel set of neuroelectric features specifically designed to assess disinhibition in sib-pairs from families with a high density of alcoholism. This app;ication covers only the baseline neurophysiology data collection portion of complex, ongoing collaborative studies that involve a much broader range of the genetic determinants of the risk for alcoholism. Those studies include the Collaboration on the Genetics of Alcoholism (COGA), now in its 13th year of work and concentrating on the follow-up of subjects already tested at least five years ago, and the recently funded spin-off: the Indiana portion of a Interactive Research Program Grant. Other studies funded by these grants involve the collection and analysis of neurophysiological data collected before and after exposure to alcohol: those activities already have GCRC approval (GCRC# 903A). Yet other portions involve blood sampling for DNA, DNA analysis, genetic analysis of the entire database, and a substantial diagnostic interview process that require no interaction with the GCRC at all, and are not a part of this application. The recruiting cited criteria in this application are current, and include changes made since the original applications for funding were reviewed (and substantially reduced), and reflect subsequent changes agreed to by the Steering Committee of COGA. This application involves statistical analyses of the collection data to be performed by investigators at SUNY Downstate, Brooklyn, New York, in collaboration with genetic analysts in Austin, Texas. Analyses are performed on data contributed by nine Neurophysiology Laboratories throughout the USA, all identically equipped, including the Neural System Labs located at the GCRC (including C-6130 at the VAMC) in Indianapolis.