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）倡议代表了一种新的方法来定义精神障碍，基于行为和神经生物学测量的可量化维度，可以跨越多个诊断类别。使用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基于人群的队列，以建立多维数据的综合数据库。所有这些研究收集了广泛的遗传、基因组、维度症状和神经认知数据，以及神经影像学测量。跨项目数据包括利用多个RDoC域的广泛结构，包括正和负效价系统、认知系统、工作记忆以及唤醒和调节系统。在整合数据库后，该项目将测试RDoC项目的核心动机之一;与分类诊断相比，跨越诊断类别的症状维度可能与神经系统更密切相关的假设。然后，我们将使用跨研究获得的广泛的结构脑成像数据来识别与RDoC构建和维度症状表达最相关的神经回路，从而代表随后遗传研究最有前途的生物学途径。

 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.