Precision brain charts for imaging-genomics of schizophrenia and the psychosis spectrum

用于精神分裂症和精神病谱系成像基因组学的精确脑图

基本信息

批准号：
10717605
负责人：
Aaron Felix Alexander-Bloch
金额：
$ 84.47万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-01 至 2028-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10717605
关键词：
Acceleration Adolescence Adult Age Anatomy Area Benchmarking Brain Brain imaging Brain region Brain scan Caring Case/Control Studies Childhood Clinical Communities Data Data Set Development Developmental Gene Diagnosis Disease Early identification Evolution Follow-Up Studies Foundations Future Genetic Genetic study Genome Genomics Genotype Goals Growth Height Heritability Image Individual Individual Differences Investigation Link Longevity MRI Scans Magnetic Resonance Imaging Maps Measures Modeling Nature Neuroanatomy Neurobiology Noise Participant Pattern Pediatrics Pennsylvania Phenotype Philadelphia Psychiatry Psychoses Publishing Quality Control Reference Standards Reporting Reproducibility Research Research Personnel Resolution Resources Risk Sample Size Sampling Scanning Schizophrenia Scientist Sensory Shapes Side Signal Transduction Site Surface Symptoms Synapses Techniques Testing Thick Twin Multiple Birth Universities Weight Work Youth age effect association cortex biobank brain magnetic resonance imaging brain morphology case control cohort follow-up functional genomics genetic variant genome wide association study genome-wide analysis gray matter heritability pattern high risk population image processing imaging genetics imaging study innovation longitudinal analysis neurodevelopment neuroimaging neuroinformatics novel online resource psychosis risk rate of change research clinical testing risk variant spectrograph transcriptome translational study treatment stratification trend

项目摘要

ABSTRACT An unmet need for psychiatric neuroimaging is a standard developmental frame of reference to benchmark studies of neurodevelopmental conditions such as schizophrenia the psychosis spectrum (PS). Using a modelling approach that has proven successful for non-imaging growth charts in clinical pediatrics, and in our preliminary work that was focused on a limited set of global brain MRI features, we propose to leverage data from our multi-site Brain Chart Consortium to produce computational charts of brain maturation for a far richer set of brain morphological features across anatomical scales. Our Consortium aims to be the largest and most inclusive possible, with preliminary data covering the entire lifespan, over 130,000 MRI scans, over 100,000 individuals and over 300 MR scanners. Using advanced, fully-reproducible pipelines for quality control, image processing and harmonization, multi-scale brain charts will define normative trends and milestones of growth which can be used to benchmark a new individual brain scan, or group of scans, while controlling for study- specific technical confounds. We will create and maintain an open resource to disseminate these charts for use by other researchers. We will use brain charts to identify clusters of developmental imaging phenotypes – brain profiles benchmarked by growth chart norms – with similarly-shaped maturational trajectories. Longitudinal analysis of twin datasets will specifically delineate heritable brain profiles, which we hypothesize will show genotype-by-age effects organized along the sensory-to-association (SA) axis of cortical maturation, in developmental epochs where risk for PS is hypothesized to emerge (Aim 1). We will perform genome- and transcriptome-wide association studies to identify brain profiles that are influenced by functionally active genetic variants associated with risk for PS (Aim 2). We will perform brain profile subtyping of individuals with PS diagnoses in our Consortium case-control studies (over 2000 MRIs), to characterize a PS subtype where deviations are most prominent along the SA axis in association cortices that undergo prolonged maturation through adolescence. Any individual’s chart-benchmarked brain profile, in a new study, can thus be characterized with a loading score that quantifies similarity to this PS subtype, and we will evaluate the association of the PS subtype loading score with the evolution of PS symptoms across multiple longitudinal follow-up studies of PS conducted at the University of Pennsylvania (over 2200 longitudinal MRIs, 800 participants, 450 with PS, age 8-35) that will be pooled and harmonized for this proposal (Aim 3). This proposal’s overarching goal is to create a practically useful brain chart resource and to demonstrate its transformative potential for studies of brain development in PS. This work capitalizes on the PI and assembled team’s expertise in psychiatric and developmental brain imaging, imaging-genetics and neuroinformatics. Cumulatively, the proposed research will provide a substantial advance in our understanding of typical brain development and altered neurodevelopment in PS.

抽象的对精神神经影像学的未满足需要是标准的基准发展框架精神分裂症等神经发育状况的研究（PS）。使用在临床儿科的非成像增长图中已证明成功的建模方法，在我们的初步工作集中在有限的全球大脑MRI功能上，我们建议利用数据从我们多站点的大脑图表联盟中产生大脑成熟的计算图表，以更丰富跨解剖量表的脑形态特征集。我们的财团旨在成为最大，最大的包括包含的最初数据涵盖了整个寿命，超过130,000次MRI扫描，超过100,000 个人和300多名MR扫描仪。使用高级，完全可复制的管道进行质量控制，图像处理和协调，多尺度的大脑图表将定义正常趋势和增长里程碑可以用来基准进行新的个体脑扫描或一组扫描，同时控制研究 - 具体的技术混杂。我们将创建并维护开放资源以传播这些图表以供使用由其他研究人员。我们将使用大脑图表来识别开发成像表型的簇 - 大脑由生长图规范基准测试的轮廓 - 具有类似形状的材料轨迹。纵向双胞胎数据集的分析将专门描述可遗传的脑轮廓，我们假设这将显示沿着感觉与关联（SA）轴的基因型效应在皮质成熟的轴上，在假设出现PS风险的发展时期（AIM 1）。我们将执行基因组和整个转录组的关联研究以识别受功能活性影响的大脑特征与PS风险相关的遗传变异（AIM 2）。我们将执行个人的大脑概况。 PS在我们的财团病例对照研究（超过2000 MRI）中的PS诊断，以表征PS亚型出发是沿SA轴的最突出的，在结合长期成熟的皮层中通过青少年。因此，在一项新研究中，任何个人的图表基准的大脑概况都可以是以量化与此PS亚型相似的加载评分表征，我们将评估 PS亚型加载评分与PS符号在多个纵向上的演变的关联在宾夕法尼亚大学进行的PS的后续研究（超过2200个纵向MRI，800 参与者，450名PS，8-35岁）将在此提案中汇总和统一（AIM 3）。提案的总体目标是创建实际有用的大脑图表资源，并证明其在PS中研究脑发育的变革潜力。这项工作大写在PI上并组装团队在精神病和发展性脑成像，成像生成学和神经信息学方面的专业知识。累积地，拟议的研究将为我们对典型大脑的理解提供重大的进步 PS中的开发和改变神经发育。