Longitudinal Family/Molecular Genetic Study to Validate Research Domain Criteria

纵向家族/分子遗传学研究以验证研究领域标准

• 批准号: 9251066
• 负责人: STEPHEN V FARAONE
• 金额: $ 15.84万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-25 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9251066
• 关键词: Adopted; Adult; Age; Behavior; Behavioral; Candidate Disease Gene; Catchment Area; Categories; Characteristics; Child; Child Psychiatry; Childhood; Clinic; Communities; Databases; Development; Diagnostic; Dimensions; Disease; Enrollment; Ensure; Exhibits; Family; Family member; Funding; Future; Genes; Genetic; Genetic study; Goals; Gold; Health; Impairment; Individual; Longitudinal Studies; Measures; Mental disorders; Methods; Molecular Genetics; National Institute of Mental Health; Neurobiology; Neurosciences; Parents; Pathway interactions; Patient Self-Report; Patients; Positive Valence; Psychopathology; Request for Applications; Research; Research Domain Criteria; Research Infrastructure; Robin bird; Running; Sampling; Siblings; Single Nucleotide Polymorphism; Staging; System; Target Populations; Testing; Time; Update; Validation; Validity of Self Report; Work; base; clinically significant; disease classification; disorder risk; follow-up; genome wide association study; genome-wide; member; psychiatric symptom; psychobiology; symptom cluster; tool; trait; transmission process; working group

DESCRIPTION (provided by applicant): The NIMH Research Domain Criteria (RDoC) project is intended to further a long-range goal of contributing to diagnostic systems as informed by research on genetics, neuroscience, and behavior. The Request for Applications to which we are responding encourages applications to study RDoC Constructs that cut across traditional diagnostic categories. Because RDoC Constructs are theoretical entities instantiated by behavioral and neurobiologic assessments, their validation (in the absence of a known gold standard) requires an empirical framework. This proposal seeks to apply such a framework to RDoC Constructs of the Positive Valence Systems. We will apply an updated version of the validation system proposed by Robins and Guze, which has been used for many decades as a tool for validating psychiatric constructs. We will focus on four of the five questions asked by ths method: Is the Construct coherent? Is it familial? Is it associated with neurobiologic measures? Is it stable over time? Our work will answer the first three questions and will set the stage for a longitudinal study to answer the fourth. In the RDoC spirit, we will take an agnostic approach regarding nosology by ascertaining families having a child with any psychiatric disorder through referrals to our general child psychiatry clinic. We will also sample non-psychiatric comparison subjects from the community to assure that we have a wide range of scores on the RDoC Constructs represented in our study and to assess the clinical significance of Construct measures. We are adopting a clinic-based approach with appropriately matched community controls because, although the RDoC Domains are not intended to define particular disorders, any study of these domains should be more powerful when studying a sample enriched for individuals with extreme values on these traits (i.e., those with or without psychiatric disorders)2 As a consequence, we can simultaneously evaluate RDoC constructs and the predominant traditionally defined childhood psychiatric disorders in one study. Our approach is also clearly relevant to the target population of NIMH and the RDoC initiative; i.e., children and adults exhibiting impairing psychiatric symptoms. Using this sample, we will accomplish the following Specific Aims: 1) Determine if Constructs in the Positive Valence System Domains proposed by the NIMH Working Groups are homogenous theoretical Constructs; 2) Determine if Positive Valence System Constructs are familial; 3) Determine if Positive Valence System Constructs predict psychopathology and impairment; 4) Determine if Positive Valence System Constructs are associated with Construct candidate genes, with recently identified genome-wide significant cross-disorder candidate genes, and with cross-disorder polygenic scores; and 5) Establish a database of enrolled families and maintain annual contact with them to ensure the viability of longitudinal follow-up analyses.

描述（由申请人提供）：NIMH研究领域标准（RDOC）项目旨在进一步促进对遗传学，神经科学和行为的研究所告知的诊断系统的长期目标。我们响应的申请请求鼓励应用程序研究跨传统诊断类别的RDOC结构。由于RDOC结构是由行为和神经生物学评估实例化的理论实体，因此其验证（在没有已知黄金标准的情况下）需要经验框架。该建议旨在将这种框架应用于正价系统的RDOC构建体。 我们将应用Robins和Guze提出的验证系统的更新版本，该系统已数十年来用作验证精神病结构的工具。我们将专注于THS方法提出的五个问题中的四个：构造是否相干？是家族吗？它与神经生物学措施有关吗？随着时间的流逝稳定吗？我们的工作将回答前三个问题，并为 纵向研究回答第四。本着RDOC的精神，我们将通过确定患有任何精神疾病的家庭通过转介给我们的普通儿童精神病学诊所来采取不可知的方法。我们还将采样来自社区的非精神比较主题，以确保我们在研究中代表的RDOC构建体上的得分很广，并评估构建体测量的临床意义。 We are adopting a clinic-based approach with appropriately matched community controls because, although the RDoC Domains are not intended to define particular disorders, any study of these domains should be more powerful when studying a sample enriched for individuals with extreme values on these traits (i.e., those with or without psychiatric disorders)2 As a consequence, we can simultaneously evaluate RDoC constructs and the predominant traditionally defined childhood一项研究中的精神疾病。我们的方法也显然与NIMH的目标人群和RDOC倡议有关。即，表现出损害精神症状的儿童和成人。使用此样本，我们将完成以下特定目的：1）确定NIMH工作组提出的正价系统域中的构建体是否是同质的理论构造； 2）确定正价系统构建体是否是家族性的； 3）确定正价系统是否可以预测精神病理学和障碍； 4）确定正价系统构建体是否与构造候选基因相关联，最近鉴定出全基因组显着的跨diSorder候选基因以及跨disorder多基因分数； 5）建立一个注册家庭的数据库，并保持与他们的年度联系，以确保纵向后续分析的生存能力。