Neurophenotypic Trajectories and Behavioral Outcomes in Autism Spectrum Disorder

 描述(由申请人提供)：自闭症谱系障碍(ASD)有一套共同的诊断特征，但不同的人在严重程度上存在很大差异。还有许多共病特征，从发育迟缓到癫痫，再到胃肠功能障碍，使ASD的表型进一步复杂化。为了发现和整合多层次表型信息，从而能够定义生物学亚型，并潜在地预测和促进最佳结果，思维研究所于2006年发起了自闭症表型组项目(APP)。到目前为止，已经获得了279名2-3.5岁儿童的行为、医学、免疫学和磁共振成像(MRI)数据(189名ASD，90名典型的发育正常儿童-TD)。其中，210名(134名房间隔缺乏症，76名TD)在一年后接受了第二次MRI扫描，到目前为止，142名(83名ASD，59名TD)在5-6.5岁时接受了第三次扫描。这项研究已经确定了一些与杏仁核异常生长和异常脑增大有关的ASD神经表型。但是，这些大脑差异真的重要吗？这项拟议研究的首要目标是确定已识别的神经表型是否持续到童年中期，并与核心和共病行为损害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修改程序，从所有严重程度的ASD儿童中生成高质量的MRI图像，我们建议获得额外的MRI时间点，并在9-11岁时对注册在APP中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名儿童参与。我们还将在APP计划中招募100名新科目。这项研究将对从儿童早期过渡到中期的儿童的大脑发育、行为异常以及认知和功能结果之间的关系进行前所未有的探索。我们建议：1.评估杏仁核早期生长的三种模式的大脑和行为后果；2.评估儿童早期大脑异常增大的大脑和行为后果；3.确定与最佳大脑组织模式相关的大脑组织模式 行为结果。这些项目符合NIMH战略计划的目标1和目标2，并涉及2009年机构间协调委员会战略计划的异质性和寿命视角的横向主题。他们还为“从婴儿期开始对儿童、青少年和成人进行多学科、纵向的生物行为研究，表征ASD表型多个轴的神经发育和医学发展轨迹……”的研究机会做出了贡献。一个重要的目标是确定将需要额外或专门帮助以实现最高生活质量的儿童。

 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.