Determinants of Social, Communicative, and Other Core Deficits in Autism

描述(由申请人提供)：本申请中概述的研究致力于一种独特的多学科方法来确定自闭症社交沟通缺陷的基础、后果和易变性。项目I(Sigman)建议对300多名有自闭症风险的婴儿进行纵向研究，根据他们有被诊断为自闭症综合征的哥哥姐姐的家族史。我们将描述儿童亚群的发展轨迹，这些儿童表现出不同的症状模式，从完全自闭症到更广泛的自闭症表型，再到未受影响的兄弟姐妹，从而开发出早期诊断和更好地确定预后的工具，这对家庭至关重要。这项研究的一个独特特点是，项目II(GeschWind)将使用相同的样本来调查儿童语言习得中的差异在多大程度上可归因于遗传因素，这些因素以前被认为与自闭症儿童的语言技能获得有关。项目二改进了先前的遗传学研究，因为可以首次调查遗传对语言习得轨迹的贡献，因为可以获得儿童早期生活过程中广泛的语言技能表型衡量标准。项目III(Dapretto)研究了自闭症患者的社会沟通障碍在多大程度上是由于大脑系统中特定的神经生理模式，特别是镜像神经元和大脑奖励系统的紊乱所致。项目III将在参加治疗干预(Kasari)的儿童样本中检查镜像神经系统的可塑性，该治疗干预成功地改善了他们的沟通能力，这是一项将大脑回路激活与治疗结果联系起来的开创性研究。项目IV(Kasari)将大大扩展我们以前的工作，展示成功干预自闭症儿童的社会沟通缺陷的显着后果。项目四调查是否可以由父母而不是训练有素的干预者对患有自闭症的幼儿进行治疗，从而使这种治疗更容易获得。项目V(McCracken)研究利培酮对儿童重复行为的影响，以及这些影响的媒介，通过使用功能磁共振成像来识别区分治疗和未治疗的自闭症儿童的功能模式。总而言之，这些项目代表了一套精心交织的设计，通过研究重叠的受试者群体和识别自闭症核心缺陷的性质和决定因素的互补方法来提供协同作用。来自这些研究的信息将有助于更好地了解自闭症的这些缺陷与其特定的遗传风险因素和大脑回路之间的关系，以及改进自闭症的早期诊断和治疗。

DESCRIPTION (provided by applicant): The research outlined in this application is devoted to a uniquely multi-disciplinary approach toward determining the bases, consequences, and mutability of social communication deficits in autism. Project I (Sigman) proposes a longitudinal study of over 300 infants at risk for autism based on their family history of having older siblings who are diagnosed with the autism syndrome. We will describe the developmental trajectories of subgroups of children who manifest varying patterns of symptoms ranging from full autism to the broader autism phenotype to non-affected siblings, thus developing the tools for earlier diagnosis and better determination of prognosis, an issue of critical importance to families. A unique feature of this research is that Project II (Geschwind) will use the same sample to investigate the extent to which the variability in the children's language gains is attributable to genetic factors that have previously been tied to the acquisition of language skills in children with autism. Project II improves upon earlier genetic studies in that genetic contributions to the trajectory of language acquisition can be investigated for the first time due to the availability of a broad range of phenotypic measures of language skills over the course of the children's early lives. Project III (Dapretto) examines the extent to which the social communication deficits in autism are due to specific neurophysiological patterns in brain systems, particularly to disorders of the mirror neuron and brain reward systems. Project III will examine the plasticity of the mirror neuron system in a sample of children who participated in a therapeutic intervention (Kasari) that succeeded in improving their communicative abilities, a path-breaking study to connect brain circuit activation with treatment outcome. Project IV (Kasari) will significantly extend our previous work demonstrating the remarkable consequences of successfully intervening with social communicative deficits of children with autism. Project IV investigates whether the treatment of very young children with autism can be carried out by parents rather than trained interventionists, thereby making such treatment more accessible. Project V (McCracken) researches the effects of risperidone on repetitive behaviors in children as well as the mediators of these effects by using fMRI to identify functional patterns that differentiate treated and non-treated children with autism. In summary, these projects represent a set of carefully interwoven designs, providing synergy by studying overlapping subject populations with complimentary methods that identify the nature and determinants of core deficits in autism. Information from these studies will lead to a better understanding of the relationships between these deficits in autism and their specific genetic risk factors and brain circuitry, as well as improved early diagnosis and treatment of autism.