Pathway(s) From Genes to Functional Deficits of Schizophrenia Patients

精神分裂症患者从基因到功能缺陷的途径

基本信息

批准号：
7644345
负责人：
GREGORY A LIGHT
金额：
$ 34.76万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-25 至 2011-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7644345
关键词：
Accounting Activities of Daily Living Address Architecture Area Behavior Behavioral Behavioral Genetics Biological Biological Markers Candidate Disease Gene Characteristics Clinical Code Complex DNA Sequence Data Data Set Developmental reading disorder Diagnostic Discrimination Disease Education Equation Exhibits Family Family member Functional disorder Funding Future Gender Genes Genetic Genetic Determinism Genetic Research Genetic Risk Genetic Variation Goals Grant Healthcare Systems Independent Living Indium Individual Intermediate Variables Intervention Investigation Laboratories Lead Life Link Measures Mediating Mediator of activation protein Mental disorders Methods Modeling Multivariate Analysis National Institute of Mental Health Neurobiology Neurocognition Neurocognitive Outcome Pathway interactions Patient Self-Report Patients Performance Phenotype Policy Maker Positioning Attribute Principal Component Analysis Process Proteins Regression Analysis Research Research Design Research Infrastructure Research Personnel Research Support Resources Role Sampling Schizophrenia Scientist Sensory Process Short-Term Memory Single Nucleotide Polymorphism Social Functioning Staging Statistical Methods Symptoms Testing To specify Transportation United States Department of Veterans Affairs Variant Work base cohort daily functioning design endophenotype functional disability functional outcomes functional status gene function genetic association genetic linkage analysis genome wide association study indexing instrument neurophysiology neuropsychological novel programs psychogenetics response skills social tool trait

项目摘要

DESCRIPTION (provided by applicant): This RFA supports studies designed to find genes that relate to functional "behavioral phenotypes of relevance to patients, their families, and policymakers." In response to this RFA, this application will extend the existing body of information regarding the genetics of schizophrenia with a unique focus on understanding the genetic basis for functional deficits in schizophrenia patients. The PI has assembled a team of experts in the areas of schizophrenia research, functional assessment, neurophysiological and neurocognitive assessment, statistical genetics and structural equation modeling. The research team will have access to substantial existing infrastructure and patient resources via two mature and highly productive schizophrenia research programs. Cohorts of 400 schizophrenia patients and 100 nonpsychiatric comparison subjects (NCS) will be characterized by clinical, neurocognitive, neurophysiological, and multi- dimensional functional assessments. From these functional assessments, core and dissociable functional deficits in schizophrenia patients will then be identified via principal components analysis (PCA). PCA will capture the core features of the deficits that are responsible for the difficulties faced by schizophrenia patients as they "navigate" through a maze of functional challenges in real-world day-to-day living. These features will be used as a means of understanding the complex genetic architecture underlying functional impairment in this disorder. The pathways from gene to function, including possible mediating and moderating neurobiological and neuropsychological processes, will then be identified via structural equation modeling. Thus, one key final product of this work will be the identification of core functional deficits in schizophrenia patients and the specification of genes that substantially contribute to those core deficits so that both gene-function and the possible biological pathways by which genes impact behavior and thereby regulate real world functioning will be explicated.

描述（由申请人提供）：该RFA支持旨在找到与功能性“与患者，家人和决策者相关的行为表型的基因”的研究。为了响应这种RFA，该应用将扩展有关精神分裂症遗传学的现有信息体系，并独特地关注精神分裂症患者功能缺陷的遗传基础。 PI已组建了一个精神分裂症研究，功能评估，神经生理学和神经认知评估，统计遗传学和结构方程建模领域的专家团队。研究团队将通过两个成熟且高效的精神分裂症研究计划获得大量现有的基础设施和患者资源。 400名精神分裂症患者和100名非精神比较受试者（NCS）的队列将以临床，神经认知，神经生理学和多维功能评估为特征。从这些功能评估中，将通过主成分分析（PCA）确定精神分裂症患者的核心和可分离功能缺陷。 PCA将捕获缺陷的核心特征，这些缺陷是由于精神分裂症患者在现实世界中日常生活中的功能挑战中“导航”时所面临的困难。这些特征将被用作理解该疾病中功能障碍的复杂遗传结构的一种手段。从基因到功能的途径，包括可能介导和调节神经生物学和神经心理学过程，然后通过结构方程建模来识别。因此，这项工作的一个关键最终产物将是鉴定精神分裂症患者中核心功能缺陷以及基因的规范，这些基因实质上有助于这些核心缺陷，从而阐明基因功能和基因影响行为并因此调节现实世界功能的可能生物学途径。