Neurophenotypic Trajectories and Behavioral Outcomes in Autism Spectrum Disorder

自闭症谱系障碍的神经表型轨迹和行为结果

基本信息

批准号：
8888079
负责人：
David G Amaral
金额：
$ 77.06万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2020-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8888079
关键词：
11 year old 6 year old Address Adult Age-Years Amygdaloid structure Anxiety Atlases Autistic Disorder Back Behavior Therapy Behavior assessment Behavioral Biological Body Size Brain Child Childhood Clinical Cognitive DNA Sequence Alteration Data Data Collection Development Developmental Delay Disorders Diagnosis Diagnostic Diffusion Magnetic Resonance Imaging Emotional Enrollment Epilepsy Fright Funding Goals Growth Heterogeneity Image Impaired cognition Impairment Individual Institutes Intervention Literature Longevity MRI Scans Machine Learning Magnetic Resonance Imaging Medical Multivariate Analysis Mutation National Institute of Mental Health Outcome Pattern Phenotype Procedures Quality of life Recruitment Activity Relative (related person)Research Rest Risk Factors Scanning Severities Strategic Planning Structure Subgroup Symptoms Testing Time Visit autism spectrum disorder base behavioral impairment behavioral outcome biobehavior brain size cognitive function disability disorder risk early childhood functional outcomes gastrointestinal infancy interest phenome programs public health relevance relating to nervous system social social communication

项目摘要

DESCRIPTION (provided by applicant): Autism spectrum disorder (ASD) has a common set of diagnostic features that nonetheless vary substantially in severity in different individuals. There are also many co-morbid features ranging from developmental delay to epilepsy to gastrointestinal disturbances that further complicate the phenotypes of ASD. To discover and integrate multilevel phenotypic information that would allow definition of biological subtypes and potentially predict and facilitate optimal outcomes, the MIND Institute initiated the Autism Phenome Project (APP) in 2006. To date, behavioral, medical, immunological and magnetic resonance imaging (MRI) data have been acquired on 279 children (189 ASD, 90 typically developing controls - TD) at 2-3.5 years of age. Of these, 210 (134 ASD, 76 TD) have received a second MRI scan one year later and thus far 142 (83 ASD, 59 TD) have received a third scan at 5-6.5 years of age. This program of research has identified a number of neurophenotypes of ASD related to abnormal amygdala growth and abnormal brain enlargement. But, do these brain differences really matter? An overarching goal of the proposed research is to determine whether identified neural phenotypes persist into middle childhood and are associated with the quality and severity of core and co-morbid behavioral impairments. A unifying hypothesis is that different morphometric patterns will be associated with clinical features and with the quality of behavioral outcome. We are particularly interested in whether there are different patterns of brain organization that may predict optimal behavioral outcomes in ASD. Using recently developed behavioral modification procedures that yield high quality MRI images from children at all severity levels of ASD, we propose to obtain an additional MRI time point and conduct extensive behavioral assessment of children enrolled in the APP when they reach 9-11 years of age. Based on previous return rates, we estimate that 195 children will participate. We will also recruit 100 new subjects into the APP program. This research would allow an unprecedented exploration of the relationship between brain development, behavioral abnormalities, and cognitive and functional outcome in children transitioning from early to middle childhood. We propose: 1. To evaluate brain and behavioral consequences of three patterns of early amygdala growth; 2. To evaluate brain and behavioral consequences of abnormal brain enlargement in early childhood; and 3. To identify a pattern of brain organization that is associated with optimal behavioral outcome. These projects are consistent with Objectives 1 and 2 of the NIMH Strategic plan and address the 2009 IACC Strategic Plan crosscutting themes of Heterogeneity and Lifespan Perspective. They also contribute to the still unmet research opportunity for "Multi-disciplinary, longitudinal, biobehavioral studies of children, youths, and adults beginning during infancy that characterize neurodevelopmental and medical developmental trajectories across the multiple axes of ASD phenotype...". An important goal is to identify children who will need additional or specialized help to achieve the highest quality of life.

描述（由申请人提供）：自闭症谱系障碍（ASD）具有一组共同的诊断特征，但不同个体的严重程度差异很大。还有许多共病特征，从发育迟缓到癫痫再到胃肠道紊乱，这些特征使情况进一步复杂化。为了发现和整合多层次的表型信息，从而定义生物亚型并有可能预测和促进最佳结果，MIND 研究所启动了自闭症表型项目。 (APP) 于 2006 年进行。迄今为止，已获取了 279 名 2-3.5 岁儿童（189 名 ASD，90 名典型发育对照 - TD）的行为、医学、免疫学和磁共振成像 (MRI) 数据。一年后，210 名患者（134 名 ASD，76 名 TD）接受了第二次 MRI 扫描，迄今为止，142 名患者（83 名 ASD，59 名 TD）接受了第三次扫描该研究项目已经确定了许多与杏仁核异常生长和大脑异常增大相关的自闭症神经表型，但是，该研究的首要目标是确定这些大脑差异是否真的重要？已确定的神经表型持续到童年中期，并且与核心和共病行为障碍的质量和严重程度相关。一个统一的假设是，不同的形态测量模式将与临床特征和行为结果的质量相关。我们特别感兴趣的是，是否存在可以预测自闭症谱系障碍最佳行为结果的不同脑组织模式，我们建议使用最近开发的行为矫正程序，为所有自闭症谱系障碍严重程度的儿童提供高质量的 MRI 图像。根据之前的回报率，我们还将在 APP 项目中招募 100 名新受试者。允许前所未有的探索我们建议： 1. 评估早期杏仁核生长的三种模式的大脑和行为后果； 2. 评估大脑和行为。儿童早期大脑异常增大的后果；以及 3. 确定与最佳状态相关的大脑组织模式这些项目与 NIMH 战略计划的目标 1 和 2 一致，并解决了 2009 年 IACC 战略计划的异质性和寿命视角的跨领域主题。从婴儿期开始对儿童、青少年和成人进行的研究，描述了自闭症谱系障碍表型多个轴上的神经发育和医学发育轨迹……”。重要的目标是确定需要额外或专门帮助才能实现最高生活质量的儿童。