A Longitudinal MRI Study of Brain Development in Fragile X Syndrome

描述(申请人提供)：本申请名为“脆性X综合征(FXS)婴儿大脑发育的纵向MRI研究”，旨在对脆性X综合征(FXS)婴儿在6个月、12个月和24个月时的大脑和行为发育进行纵向MRI研究。这项研究将研究患有FXS的婴儿的大脑发育轨迹和发育情况，与后来发展为自闭症谱系障碍的婴儿(自闭症的高危人群)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儿童以及那些可能也有ASD的FXS儿童的大脑发育情况。高危自闭症受试者和典型对照正在作为一个由自闭症卓越中心(ACE)资助的网络的一部分进行收集，该网络名为“孤独症风险婴儿的纵向核磁共振研究”，目前处于第二年。ACE网络的三个站点将参与这一项目(两个临床数据收集站点：北卡罗来纳大学和华盛顿大学，以及蒙特利尔神经研究所的一个数据协调站点)。这个网络中的资源，以及这项提案的可用资源，包括婴儿大脑成像方法方面的专业知识，以及检测自闭症早期(出现)迹象的行为工具。这项研究的最终FXS样本将包括37名患有FXS的婴儿(每名婴儿进行2次或3次纵向扫描)。为了在目前的提案中进行数据分析，我们将把患有FXS的婴儿与ACE的数据集进行比较，包括68名患有ASD的婴儿(没有FXS)、163名有ASD风险但被认为ASD(-)的婴儿和66名TYP对照婴儿。分析将检查这些儿童6个月、12个月和24个月的纵向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岁时的脑体积特征有显著不同。FXS患者在2岁时表现出不同于典型的和发育迟缓(Non-FXS)两岁儿童的脑异常模式(有明显的颞叶白质增大，约40%的尾状核增大)，而患有FXS的自闭症两岁儿童与非FXS自闭症儿童有显著差异。通过对比FXS和FXS的早期脑发育，我们将能够解决几个重要的假说，即FXS出生后早期脑过度生长的轨迹(区域、组织、结构和纤维束)，如MRI和DTI所测量的，及其与临床特征的潜在关系，特别是ASD的特征和相关特征。这项研究有可能将FXS婴儿的特定行为、遗传和神经生物学特征与没有FXS的自闭症风险婴儿和那些具有典型发育的婴儿区分开来。这项提案是对RFA PA-07-284的回应，RFA PA-07-284要求提交研究自闭症和脆性X综合征之间的接口的文件。公共卫生相关性：“脆性X综合征脑发育的纵向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。我们将研究患有FXS的婴儿的大脑发育轨迹和发育情况，与自闭症高危婴儿(他们后来患上自闭症谱系障碍)以及典型发育中的婴儿的早期大脑发育进行比较。我们将讨论几个重要的假说，如MRI和DTI所测量的，FXS中出生后早期脑过度生长的轨迹(区域、组织、结构和纤维束)，以及它与临床特征的潜在关系，特别是ASD的特征。这项研究有可能将FXS婴儿的特定行为、遗传和神经生物学特征与自闭症高危婴儿和具有典型发育的婴儿区分开来。

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.