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.

抽象的精神科神经影像学未满足的需求是基准的标准发展参考框架使用精神病谱 (PS) 来研究精神分裂症等神经发育状况。建模方法已被证明在临床儿科和我们的非成像生长图方面是成功的初步工作侧重于一组有限的全球大脑 MRI 特征，我们建议利用数据来自我们的多站点脑图联盟，为更富有的人制作大脑成熟的计算图表我们的联盟旨在成为最大、最全面的大脑形态特征集。包容性可能，初步数据覆盖整个生命周期，超过 130,000 次 MRI 扫描，超过 100,000 个人和超过 300 台 MR 扫描仪使用先进的、完全可重复的管道进行质量控制、图像。处理和协调，多尺度脑图将定义规范趋势和成长里程碑它可以用来对新的个体脑部扫描或一组扫描进行基准测试，同时控制研究- 我们将创建并维护一个开放资源来传播这些图表以供使用。我们将使用脑图来识别发育成像表型的集群——大脑以生长图表规范为基准的概况——具有相似形状的成熟轨迹。对双胞胎数据集的分析将具体描述可遗传的大脑轮廓，我们将展示这一点基因型与年龄的影响沿着皮质成熟的感觉-联想（SA）轴组织起来， PS 风险再次出现的发育时期（目标 1）。全转录组关联研究，以确定受功能活动影响的大脑特征与 PS 风险相关的遗传变异（目标 2）我们将对患有 PS 的个体进行大脑概况亚型分析。我们的联盟病例对照研究（超过 2000 个 MRI）中的 PS 诊断，用于表征 PS 亚型，其中在经历长期成熟的联合皮层中，沿 SA 轴的偏差最为明显一项新的研究表明，任何人在青春期的大脑图谱都可以通过图表来衡量。以量化与此 PS 亚型相似性的加载分数为特征，我们将评估 PS 亚型负荷评分与多个纵向 PS 症状演变的关联宾夕法尼亚大学进行的 PS 后续研究（超过 2200 个纵向 MRI、800 参与者（450 名具有 PS，年龄 8-35 岁）将针对本提案（目标 3）进行汇集和协调。该提案的总体目标是创建一个实用的脑图资源并展示其 PS 中大脑发育研究的变革潜力这项工作利用了 PI 和组装。团队在精神病学和发育性脑成像、成像遗传学和神经信息学方面的专业知识。总而言之，拟议的研究将为我们对典型大脑的理解提供实质性的进展。 PS 中的发育和神经发育改变。