Integration of Five Large-Scale Neuropsychiatric Genetic Datasets under the RDoC Framework

 描述(由申请人提供)：NIMH研究领域标准(RDoC)倡议代表了一种定义精神障碍的新方法，基于可能跨越多个诊断类别的行为和神经生物学测量的可量化维度。利用RDoC框架，拟议的项目将利用来自美国、荷兰和拉丁美洲的五个现有的大型、广泛表型的基于家庭和以人口为基础的队列，以建立一个多维数据的综合数据库。所有这些研究都收集了广泛的遗传、基因组、维度症状和神经认知数据，以及神经成像测量。跨项目数据包括利用多个RDoC域的广泛结构，包括正价和负价系统、认知系统、工作记忆以及唤醒和调节系统。整合数据库后，该项目将测试RDoC项目的核心动机之一；与分类诊断相比，跨诊断类别的症状维度可能与神经系统联系更紧密的假设。然后，我们将使用通过研究获得的广泛的结构脑成像数据来确定与RDoC结构和维度症状表达最相关的神经回路，从而为后续的遗传学研究提供最有希望的生物学途径。

 DESCRIPTION (provided by applicant): The NIMH Research Domains Criteria (RDoC) initiative represents a novel approach to defining mental disorders, based on quantifiable dimensions of behavior and neurobiological measures that may span multiple diagnostic categories. Using the RDoC framework, the proposed project will leverage five existing large, extensively phenotyped family-based and population-based cohorts from the US, the Netherlands, and Latin America in order to build an integrated database of multi-dimensional data. All of these studies collected extensive genetic, genomic, dimensional symptom and neurocognitive data, as well as neuroimaging measures. Cross-project data includes a broad range of constructs tapping multiple RDoC domains including positive and negative valence systems, cognitive systems, working memory, and arousal and regulatory systems. After assembling the integrated database, the project will test one of the central motivations of the RDoC project; the hypothesis that symptom dimensions that cut across diagnostic categories may be more closely linked to neural systems, as compared to categorical diagnoses. We will then use the extensive structural brain imaging data acquired across studies to identify neural circuits most relevant to both RDoC constructs and dimensional symptom expression, and thus represent the most promising biological pathways for subsequent genetic investigations.