A Longitudinal MRI Study of Brain Development in Fragile X Syndrome

描述（由申请人提供）：本申请“脆性X综合征脑发育的纵向MRI研究”是一项对脆性X综合征（FXS）婴儿在6、12和24个月时的极早期脑和行为发育进行纵向MRI研究的提案。本研究将研究患有FXS的婴儿的大脑发育轨迹和生长如何与后来患上自闭症谱系障碍的婴儿（自闭症高危）和具有典型大脑发育的婴儿的早期大脑发育进行比较。由于许多患有FXS的儿童也患有自闭症谱系障碍（ASD），这项研究的设计将使我们能够对比没有FXS的ASD儿童的大脑发育概况，以及那些可能患有ASD的FXS儿童。高风险自闭症受试者和典型对照组正在收集作为自闭症卓越中心（ACE）网络的一部分，该网络名为“自闭症风险婴儿的纵向MRI研究”，目前处于第2年。ACE网络的三个研究中心将参与本项目（两个临床数据收集中心：蒙特利尔大学和华盛顿大学，以及蒙特利尔神经学研究所的一个数据协调中心）。该网络中的资源以及该提案可用的资源包括婴儿大脑成像方法的专业知识和检测自闭症早期（新兴）迹象的行为工具。本研究中FXS的最终样本将包括37名患有FXS的婴儿（每个婴儿进行2或3次纵向扫描）。对于当前提案中的数据分析，将FXS婴儿与68名ASD婴儿（无FXS），163名有ASD风险但被认为ASD（-）的婴儿和66名TYP对照的ACE数据集进行比较。分析将检查这些儿童在6、12和24个月时的纵向MRI和行为数据。我们小组的初步数据表明，FXS和自闭症儿童的脑容量在2岁时有显着差异。患有FXS的个体在2岁时显示出与典型的和发育延迟（非FXS）的2岁奥尔兹不同的大脑异常模式（具有显著的颞叶白色物质增大和~40%的尾状核增大），患有FXS的自闭症的2岁奥尔兹与自闭症的非FXS的2岁奥尔兹显著不同。通过对比婴儿与FXS的早期大脑发育，我们将能够解决关于FXS中早期纳塔尔后大脑过度生长（区域、组织、结构和纤维束）的轨迹的几个重要假设，如在MRI和DTI上测量的，以及其与临床特征的潜在关系，特别是ASD的特征和与ASD相关的那些特征。这项研究有可能区分特定的行为，遗传和神经生物学特征，这些特征与FXS婴儿相比，没有FXS的自闭症风险婴儿和具有典型发育的婴儿。该提案是对RFA PA-07-284的回应，该提案要求提交审查自闭症和脆性X综合征的界面。公共卫生相关性：“脆性X综合征大脑发育的纵向MRI研究”是一项利用磁共振成像（MRI）和扩散张量成像（DTI）研究脆性X综合征（FXS）婴儿在6、12和24个月时的早期大脑和行为发育的建议。我们将研究FXS婴儿大脑发育的轨迹和生长如何与自闭症高危婴儿（后来发展为自闭症谱系障碍）以及典型发育婴儿的早期大脑发育进行比较。我们将讨论几个重要的假设的轨迹出生后早期大脑过度生长（区域，组织，结构和纤维束）在FXS，测量MRI和DTI，其潜在的关系，临床特征，特别是ASD的特征。这项研究有可能区分特定的行为，遗传和神经生物学特征，与自闭症高危婴儿和典型发育的婴儿相比，这些特征是FXS婴儿的特征。

DESCRIPTION (provided by applicant): This application "A Longitudinal MRI Study of Brain Development in Fragile X Syndrome," is a proposal to conduct a longitudinal MRI study of very early brain and behavior development at 6, 12 and 24 months in infants with Fragile X Syndrome (FXS). This study will examine how the trajectory and growth of brain development in infants with FXS compares to early brain development in infants (at high-risk for autism) who later develop an autism spectrum disorder and in infants with typical brain development. Since many children with FXS also have an autism spectrum disorder (ASD), the design of this study will allow us to contrast brain development profiles in ASD children without FXS, as well as those FXS children who may also have an ASD. The high-risk autism subjects and typical controls are being collected as part of a funded Autism Centers of Excellence (ACE) Network entitled, "A Longitudinal MRI Study of Infants at Risk for Autism", currently in year 2. Three of the ACE Network sites will be participating in this project (two clinical data collection sites: UNC and Washington University, and a data coordinating site at Montreal Neurological Institute). Resources in this network, and available to this proposal, include expertise in imaging methods for infant brain and behavioral tools for detecting early (emerging) signs of autism. The final sample of FXS in this study will include 37 infants with FXS (with either 2 or 3 longitudinal scans each). For data analysis in this current proposal, the infants with FXS will be compared to the ACE dataset of 68 infants with ASD (without FXS), 163 infants at risk for ASD but considered ASD(-), and 66 TYP controls. Analysis will examine longitudinal MRI and behavioral data at 6, 12 and 24 months for these children. Preliminary data from our group suggests that the brain volume profiles of FXS and autistic children are significantly different at age 2. Individuals with FXS show a pattern of brain abnormalities at age 2 that differs from typical and developmentally-delayed (non-FXS) two year olds (with marked temporal lobe white matter enlargement, and ~40% caudate enlargement), and autistic two year olds with FXS differ strikingly from autistic non-FXS two year olds. By contrasting the early brain development of infants with FXS, we will be able to address several important hypotheses about the trajectory of early post- natal brain overgrowth (regions, tissues, structures and fiber tracts) in FXS, as measured on MRI and DTI, and its potential relationship to clinical features, particularly those features characteristic of and associated with ASD. This study has the potential to distinguish specific behavioral, genetic, and neurobiological features that characterize infants with FXS in comparison to infants at risk for autism without FXS and those with typical development. This proposal is a response to RFA PA-07-284 that requests submissions examining the interface of autism and Fragile X Syndrome. PUBLIC HEALTH RELEVANCE: "A Longitudinal MRI Study of Brain Development in Fragile X Syndrome," is a proposal to study very early brain and behavior development at 6, 12 and 24 months in infants with Fragile X Syndrome (FXS) using Magnetic Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI). We will examine how the trajectory and growth of brain development in infants with FXS compares to early brain development in infants at high-risk for autism (who later develop an autism spectrum disorder), as well as typical developing infants. We will address several important hypotheses about the trajectory of early post-natal brain overgrowth (regions, tissues, structures and fiber tracts) in FXS, as measured on MRI and DTI, and its potential relationship to clinical features, particularly those features characteristic of ASD. This study has the potential to distinguish specific behavioral, genetic, and neurobiological features that characterize infants with FXS in comparison with infants at high-risk for autism and those with typical development.