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（由适用提供）：自闭症谱系障碍（ASD）具有一组共同的诊断特征，但在不同个体的严重程度方面差异很大。从发育延迟到癫痫再到胃肠道灾害，也有许多合并的特征，使ASD的表型更加复杂。 To discover and integrate multilevel phenotypic information that would allow definition of biologic 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.其中，一年后，有210（134 ASD，76 TD）已进行了第二次MRI扫描，到目前为止，有142（83 ASD，59 TD）在5-6.5岁时接受了第三次扫描。该研究计划已经确定了许多与异常杏仁核生长和脑增强异常的ASD神经表述。但是，这些大脑差异真的重要吗？拟议的研究的总体目标是确定确定的神经形式是否持续到中年童年，并与核心和莫里伯利行为障碍的质量和严重程度相关。一个统一的假设是，不同的形态计量学模式将与临床特征和行为结果的质量有关。我们对大脑组织是否可以预测ASD中最佳行为结果的不同模式特别感兴趣。使用最近开发的行为修改程序，该程序在ASD的所有严重性水平下产生了来自儿童的高质量MRI图像，我们建议获得额外的MRI时间点，并对在9-11岁大的孩子达到9-11岁时对入学的儿童进行广泛的行为评估。根据先前的回报率，我们估计将有195名儿童参加。我们还将招募100个新主题进入应用程序。这项研究将使从童年早期到中期过渡的儿童中脑发育，行为异常以及认知和功能结果之间的关系前所未有。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。评估儿童早期脑扩张异常的大脑和行为后果； 3。确定与最佳相关的大脑组织模式 行为结果。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，跨越了异质性和寿命观点的主题。它们还为“跨婴儿期”开始的儿童，青年和成年人的“多学科，纵向，生物行为研究”的研究机会做出了贡献。一个重要的目标是确定需要其他或专业帮助以实现最高质量生活的孩子。