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

• 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
• 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

 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，但在不同个体中严重程度差异很大。还有许多共病特征，从发育迟缓到癫痫到胃肠道紊乱，这些特征进一步使ASD的表型复杂化。为了发现和整合多层次的表型信息，以定义生物亚型并可能预测和促进最佳结果，MIND研究所于2006年启动了自闭症表型组项目（APP）。到目前为止，行为，医学，免疫学和磁共振成像（MRI）数据已获得279名儿童（189 ASD，90典型发展对照-TD）在2 - 3.5岁。其中，210例（134例ASD，76例TD）在一年后接受了第二次MRI扫描，迄今为止，142例（83例ASD，59例TD）在5 - 6.5岁时接受了第三次扫描。这项研究计划已经确定了一些与杏仁核异常生长和大脑异常增大相关的ASD神经表型。但是，这些大脑差异真的重要吗？拟议研究的首要目标是确定已鉴定的神经表型是否持续到儿童中期，并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，不同的形态学模式将与临床特征和行为结果的质量。我们特别感兴趣的是，是否有不同的大脑组织模式可以预测ASD的最佳行为结果。使用最近开发的行为矫正程序，从ASD的所有严重程度的儿童中产生高质量的MRI图像，我们建议获得额外的MRI时间点，并在9 - 11岁时对入组APP的儿童进行广泛的行为评估。根据以往的回报率，我们估计将有195名儿童参加。我们还将招募100名新受试者加入APP计划。这项研究将允许前所未有的探索大脑发育之间的关系，行为异常，以及儿童从早期过渡到中期的认知和功能结果。我们建议：1.评估杏仁核早期生长的三种模式对大脑和行为的影响; 2.评估幼儿期异常脑增大的脑和行为后果; 3.为了确定一种大脑组织模式， 行为结果这些项目符合国家精神卫生战略计划的目标1和2，并涉及2009年机构间咨询委员会战略计划的跨领域主题，即异质性和寿命前景。他们还为“儿童，青少年和成人的多学科，纵向，生物行为研究”提供了尚未满足的研究机会，这些研究从婴儿期开始，在ASD表型的多个轴上表征神经发育和医学发育轨迹。".一个重要的目标是确定需要额外或专门帮助的儿童，以实现最高的生活质量。