Evaluating the Impact of Restrictive Eating Disorders on White Matter Development

项目摘要 在斯蒂芬一世的申请中。卡茨早期研究者研究项目赠款，首席研究员，博士。 阿曼达E. Lyall提出了一个项目，该项目将支持她职业生涯的一个新的研究方向： 使用神经影像学来研究精神障碍，以调查限制性饮食障碍。过度- 本申请的主要目的是全面描述限制性饮食障碍对 白色物质发育。这项研究将利用现有的神经影像学，临床，血液， 在4个NIMH资助机制下收集的膳食摄入数据（R 01 MH 103402; R 01 MH 108595; R 01 MH 116205; K23 MH 125143）在马萨诸塞州综合医院的进食障碍临床研究项目中 医院，哈佛医学院。我们将使用我们经过充分验证的扩散磁共振成像（dMRI） 将这些数据与健康对照的2个公开可用的dMRI数据集相结合的协调框架： 费城神经发育队列和人类连接组项目-年轻成人，产生队列 从9岁到40岁的白色发育期的协调成像数据。与 这些数据，我们将研究全球和区域特定的白色物质发展的轨迹，使用 在健康对照组和限制性饮食障碍患者之间使用先进的dMRI分析工具（目标1）。 接下来，我们将确定年龄或青春期阶段在多大程度上改变了潜在的 限制性进食障碍个体的白色改变和饮食限制的持续时间（目的 2）。最后，我们将评估总热量和/或特定营养缺乏的程度， 因为严重的饮食限制影响了白色物质的发育（目的3）。我们认为， 本提案中产生的信息将为建立有关影响的知识库迈出关键的第一步， 严重的饮食限制对大脑发育的影响该提案将提供一个机会， 治疗干预可能是必要的或具有最大影响的时期。此外，结果 这项研究也可能为未来的工作提供基础，以测试新的有效性和耐受性。 以改善白色物质健康为中心的无创个体化治疗的应用。

Project Summary In this application for a Stephen I. Katz Early Investigator Research Project Grant, the principal investigator, Dr. Amanda E. Lyall, proposes a project that will support a new research direction for her career: the transition from the use of neuroimaging to study psychotic disorders to the investigation of restrictive eating disorders. The over- arching goal of this application is to comprehensively characterize the impact of restrictive eating disorders on white matter development. This study will leverage unique access to extant neuroimaging, clinical, blood, and dietary intake data collected under 4 parent NIMH grant mechanisms (R01MH103402; R01MH108595; R01MH116205; K23MH125143) at the Eating Disorders Clinical Research Program at Massachusetts General Hospital, Harvard Medical School. We will use our well-validated diffusion magnetic resonance imaging (dMRI) harmonization framework to combine these data with 2 publicly available dMRI datasets of healthy controls: The Philadelphia Neurodevelopmental Cohort and The Human Connectome Project – Young Adult, yielding a cohort of harmonized imaging data spanning the period of white matter development from ages 9 to 40 years. With these data, we will examine the trajectories of global and region-specific white matter development using advanced dMRI analysis tools between healthy controls and individuals with restrictive eating disorders (Aim 1). Next, we will determine the extent to which age or pubertal stage modifies the relationship between potential white matter alterations in individuals with restrictive eating disorders and the duration of dietary restriction (Aim 2). Finally, we will evaluate the extent to which total caloric and/or specific nutritional deficiencies that arise because of severe dietary restriction impact white matter development (Aim 3). We believe that the information generated within this proposal will provide a critical first step in developing a knowledge base about the impact of severe dietary restriction on brain development. This proposal will provide an opportunity to identify vulnerable periods where therapeutic interventions may be necessary or have the most impact. Additionally, the results of this study may also provide a foundation for future work to test the effectiveness and tolerability of novel applications of non-invasive individualized therapies centering on improving white matter health.