NEUROPSYCHOLOGICAL BASIS OF THE BROAD AUTISM PHENOTYPE

广泛自闭症表型的神经心理学基础

• 批准号: 6560402
• 负责人: Joseph Piven
• 金额: $ 21.5万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6560402
• 关键词: Downs syndrome; amygdala; autism; behavioral /social science research tag; behavioral genetics; brain injury; clinical research; cognition; family genetics; frontal lobe /cortex; human subject; neuropsychological tests; neuropsychology; phenotype; social behavior; somesthetic sensory cortex

DESCRIPTION (provided by applicant): For over 15 years our research team and others have taken Kanner?s original observations about personality features characteristic of some parents of autistic individuals and developed definitions of, and standardized measures for, a broader autism phenotype. The broad autism phenotype (BAP) is thought to represent the phenotypic expression of the genetic liability to autism in non-autistic relatives of autistic probands, and is defined by characteristics that are milder but qualitatively similar to the defining features of autism. This work has potential importance for 1) teasing apart the gene-behavior relationships in autism, 2) understanding brain-behavior relationships in autism and, 3) providing additional qualitative and quantitative information on the range and nature of the phenotypic expression of autism genes, which may augment our ability to find those genes. While autism and the BAP are defined by particular behavioral characteristics, they are clinically and etiologically heterogeneous, and are the end result of a range of underlying neuropsychological, neural and genetic mechanisms. In this project we propose to examine the relatives of autistic and Down syndrome probands on selected neuropsychological measures of social cognition, central coherence and executive function, three principal cognitive frameworks proposed as theories to explain the neuropsychological basis of autism. These neuropsychological characteristics will be examined in relationship to our clinically-based measures of the BAP, in order to both elucidate the neuropsychological basis of the BAP and to provide efficient, valid and reliable measures for future studies of the BAP. Autism and OS relatives will be compared in these three neuropsychological domains, to a unique sample of individuals with focal brain lesions in the amygdala, orbital-frontal cortex and right somatosensory cortex, drawn from a brain injury registry at the University of Iowa, to provide insights into the neural basis of the behavioral and neuropsychological characteristics of autism and the BAP. Finally, patterns of co-occurrence of these characteristics will be examined in individuals and families. This study will complement ongoing studies of the same neuropsychological characteristics in autistic probands. This project brings together a unique group of experienced researchers with complementary expertise in family-genetic (Piven) and neuropsychological studies of autism (Happe), and in the neural basis of social cognition (Adolphs), to study the neuropsychological basis of the broad autism phenotype.

描述（由申请人提供）：超过 15 年以来，我们的研究团队和其他人一直采用坎纳对一些自闭症患者父母的人格特征特征的原始观察，并制定了更广泛的自闭症表型的定义和标准化措施。 广泛的自闭症表型（BAP）被认为代表了自闭症先证者的非自闭症亲属中自闭症遗传倾向的表型表达，并且由较温和但在质量上与自闭症的定义特征相似的特征来定义。这项工作具有潜在的重要性：1）梳理自闭症的基因-行为关系，2）理解自闭症的大脑-行为关系，3）提供关于自闭症基因表型表达的范围和性质的额外定性和定量信息，这可能会增强我们寻找这些基因的能力。虽然自闭症和 BAP 是由特定的行为特征定义的，但它们在临床和病因学上是异质的，并且是一系列潜在的神经心理学、 神经和遗传机制。在这个项目中，我们建议检查自闭症和唐氏综合症先证者亲属的社会认知、中枢一致性和执行功能的选定神经心理学测量，这三个主要认知框架被提出作为解释自闭症神经心理学基础的理论。这些神经心理学特征将与我们基于临床的 BAP 测量相关联进行检查，以便阐明 BAP 的神经心理学基础，并为 BAP 的未来研究提供高效、有效和可靠的测量。自闭症和 OS 亲属将在这三个神经心理学领域与来自爱荷华大学脑损伤登记处的杏仁核、眶额皮质和右侧体感皮质有局灶性脑损伤的个体的独特样本进行比较，以提供深入了解自闭症和 BAP 的行为和神经心理学特征的神经基础。最后，将在个人和家庭中检查这些特征的共现模式。这项研究将补充正在进行的自闭症先证者相同神经心理学特征的研究。该项目汇集了一组独特的经验丰富的研究人员，他们在自闭症的家庭遗传（Piven）和神经心理学研究（Happe）以及社会认知的神经基础（Adolphs）方面具有互补的专业知识，以研究神经心理学 广泛的自闭症表型的基础。