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: 7233011
• 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 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7233011
• 关键词: Accounting; Activities of Daily Living; Address; Appendix; Architecture; Area; Behavior; Behavioral; Biological; Biological Markers; Candidate Disease Gene; Characteristics; Clinical; Code; Complex; DNA; DNA Sequence; Data; Data Set; Developmental reading disorder; Diagnostic; Discrimination; Disease; Disease regression; 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; Numbers; Outcome; Pathway interactions; Patient Self-Report; Patients; Performance; Phenotype; Policy Maker; Positioning Attribute; Principal Component Analysis; Process; Proteins; Purpose; Rate; Regression Analysis; Research; Research Design; Research Infrastructure; Research Personnel; Resources; Role; Sampling; Schizophrenia; Scientist; Screening procedure; Sensory Process; Short-Term Memory; Single Nucleotide Polymorphism; Social Functioning; Staging; Statistical Methods; Support of Research; Symptoms; Testing; To specify; Transportation; United States Department of Veterans Affairs; Variant; Work; base; cohort; daily functioning; day; 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; size; 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.

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.