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Combined brain and gene network approaches to the developmental hypothesis of schizophrenia

大脑和基因网络相结合的精神分裂症发育假说

基本信息

批准号：
9806046
负责人：
Aaron Felix Alexander-Bloch
金额：
$ 2.7万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2019-09-08
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9806046
关键词：
Address Adolescence Adolescent Adult Affect Age Anatomy Area Autopsy Base of the Brain Big Data Bioinformatics Biological Biological Markers Brain Brain imaging Brain region Candidate Disease Gene Chronic Clinical Communities Community Networks Complex Data Data Analyses Data Analytics Data Set Development Disease Environmental Risk Factor Epidemiology Faculty Freedom Functional Magnetic Resonance Imaging Gene Expression Gene Proteins Genes Genetic Genomic approach Genomics Goals Heritability Human Image Investigation Leukocytes Link Magnetic Resonance Imaging Mediating Mental disorders Mentors Mentorship Molecular National Institute of Mental Health Nature Network-based Pathogenesis Pathogenicity Pathology Pathway Analysis Pattern Personality Phenotype Process Proteins Psychiatry Psychotic Disorders Public Domains Questionnaires Research Research Methodology Research Personnel Risk Sampling Schizophrenia Schizotypal Personality Disorder Science Signal Transduction Source Structure Symptoms Synapses Techniques Testing Thick Training Translating Variant Work age effect brain tissue career clinical phenotype clinical risk computerized tools data integration developmental disease experience functional disability genetic variant genome wide association study genome-wide analysis in vivo insight member neurodevelopment neuroimaging novel peripheral blood phenomics risk variant segregation synaptic pruning theories tool transcriptomics

项目摘要

PROJECT SUMMARY/ABSTRACT As a computational psychiatry faculty candidate with a strong background in neuroimaging and quantitative data analysis, I seek mentored-support to incorporate genetic and transcriptomic data into my work during my path towards independence as an investigator. I propose a project at the intersection of human neuroimaging, genomics and transcriptomics, using computational tools from network theory to investigate risk for schizophrenia and other forms of chronic psychosis. Prior work suggests that synaptic over-pruning in adolescence disrupts functional and structural connectivity within brain networks, giving rise to symptoms and functional impairments associated with schizophrenia. This process is a product of the interplay of genetic and environmental factors in development, and it is reflected in alterations observed in structural and functional neuroimaging. Network-based analytic approaches allow one to extract deeper insights into the nature of the disturbances in network function, in contrast to simpler attempts to link complex diseases to single brain regions, genes or proteins. The project uses an imaging-genomics approach to test whether networks of genes that are implicated in schizophrenia risk by genome-wide studies of common genetic variants – and have been shown in many cases to be related to synaptic integrity – affect the development of cortical thickness and the functional connections within and between brain networks in typical adolescence. The project also proposes to directly test whether these genetic factors jointly influence these imaging phenotypes and psychosis risk in clinical samples. To meet the research goals of the project, I require formal training in genomics and transcriptomics approaches (and especially their intersection with neuroimaging research). The primary mentorship team (Drs Pearlson and Glahn) has specific expertise in imaging-genomics in clinical datasets, as well as extensive experience as successful research mentors. Other key contributors and consultants provide expertise in imaging-transcriptomics (Dr Holmes), developmental neuroimaging (Dr Satterthwaite), data and network science (Dr Bassett), developmental transcriptomics (Dr Geschwind) and statistical genetics (Dr Blangero). This proposal will provide me with the direct training in research methodology and career support that is required for me to become a fully independent investigator, using tools from neuroimaging, genomics and transcriptomics to investigate psychosis pathogenesis.

项目总结/文摘