A Longitudinal MRI Study of Brain Development in Fragile X Syndrome

描述（由申请人提供）：本申请“A Longitudinal MRI Study of Brain Development in Fragile X Syndrome”，是对脆性X综合征（FXS）婴儿在6、12和24个月的早期大脑和行为发育进行纵向MRI研究的建议。本研究将研究FXS婴儿的大脑发育轨迹和生长情况，与后来发展为自闭症谱系障碍的婴儿（自闭症高危人群）和典型大脑发育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），因此本研究的设计将使我们能够对比没有FXS的ASD儿童以及可能患有ASD的FXS儿童的大脑发育概况。高风险自闭症受试者和典型对照者正在被收集，作为资助的自闭症卓越中心（ACE）网络的一部分，题为“自闭症风险婴儿的纵向MRI研究”，目前已进入第2年。ACE网络的三个站点将参与该项目（两个临床数据收集站点：北卡罗来纳大学和华盛顿大学，以及蒙特利尔神经学研究所的数据协调站点）。这个网络中的资源，以及对这个提议可用的资源，包括婴儿大脑成像方法的专业知识和用于检测早期（新出现的）自闭症迹象的行为工具。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）。在本研究的数据分析中，FXS患儿将与ACE数据集进行比较，ACE数据集包括68名ASD患儿（无FXS）、163名有ASD风险但被认为是ASD的患儿（-）和66名TYP对照。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和自闭症儿童在2岁时的脑容量谱有显著差异。患有FXS的个体在2岁时表现出与典型和发育迟缓（非FXS）两岁儿童（颞叶白质明显增大，尾状核增大约40%）不同的大脑异常模式，患有FXS的两岁自闭症儿童与患有非FXS的两岁自闭症儿童有着显著差异。通过对比FXS婴儿的早期大脑发育，我们将能够通过MRI和DTI测量FXS早期产后大脑过度生长（区域、组织、结构和纤维束）的轨迹，以及其与临床特征，特别是与ASD相关的特征的潜在关系，提出几个重要的假设。本研究有可能区分患有FXS的婴儿的特定行为、遗传和神经生物学特征，并将其与有自闭症风险的无FXS婴儿和发育正常的婴儿进行比较。该提案是对RFA PA-07-284的回应，RFA PA-07-284要求提交审查自闭症和脆性X综合征的界面。

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.