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

• 批准号: 7845512
• 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
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-25 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7845512
• 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

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 支持旨在寻找与功能性“与患者、其家人和政策制定者相关的行为表型”相关的基因的研究。作为对该 RFA 的回应，该应用程序将扩展有关精神分裂症遗传学的现有信息，特别侧重于了解精神分裂症患者功能缺陷的遗传基础。 PI 组建了一支精神分裂症研究、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项目获得大量现有基础设施和患者资源。 400 名精神分裂症患者和 100 名非精神科对照受试者 (NCS) 组成的队列将通过临床、神经认知、神经生理学和多维功能评估进行表征。根据这些功能评估，精神分裂症患者的核心和可分离功能缺陷将通过主成分分析（PCA）来识别。 PCA 将捕捉导致精神分裂症患者在现实日常生活中“导航”通过迷宫般的功能挑战时所面临困难的缺陷的核心特征。这些特征将被用作理解这种疾病功能障碍背后的复杂遗传结构的一种手段。然后，将通过结构方程模型确定从基因到功能的途径，包括可能的介导和调节神经生物学和神经心理学过程。因此，这项工作的一个关键最终成果将是鉴定精神分裂症患者的核心功能缺陷，并明确导致这些核心缺陷的基因，以便阐明基因功能和基因影响行为并从而调节现实世界功能的可能生物学途径。

项目成果

Relationship between effortful motivation and neurocognition in schizophrenia.

• DOI: 10.1016/j.schres.2017.06.042
• 发表时间: 2018-03
• 期刊: Schizophrenia research
• 影响因子: 4.5
• 作者: Bismark AW;Thomas ML;Tarasenko M;Shiluk AL;Rackelmann SY;Young JW;Light GA
• 通讯作者: Light GA

γ oscillations in schizophrenia: mechanisms and clinical significance.

精神分裂症中的γ振荡：机制和临床意义。

• DOI: 10.1016/j.brainres.2011.06.065
• 发表时间: 2011
• 期刊: Brain research
• 影响因子: 2.9
• 作者: Sun,Yinming;Farzan,Faranak;Barr,MeraS;Kirihara,Kenji;Fitzgerald,PaulB;Light,GregoryA;Daskalakis,ZafirisJ
• 通讯作者: Daskalakis,ZafirisJ

Neurophysiological measures of sensory registration, stimulus discrimination, and selection in schizophrenia patients.

精神分裂症患者的感觉登记、刺激辨别和选择的神经生理学测量。

• DOI: 10.1007/7854_2010_59
• 发表时间: 2010
• 期刊: Current topics in behavioral neurosciences
• 作者: Rissling,AnthonyJ;Light,GregoryA
• 通讯作者: Light,GregoryA