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

University Of California Los Angeles, Los Angeles CA

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Abstract

? 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.