Gene-Brain-Behavior Relationships in Autism

描述（由申请人提供）：15年来，我们的研究团队和其他人已经采用了Kanner对一些自闭症患者父母的性格特征的原始观察，并开发了更广泛的自闭症表型的定义和标准化措施。广义自闭症表型（BAP）被认为代表了自闭症先证者的非自闭症亲属对自闭症的遗传倾向性的表型表达，并由一些更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)提供自闭症基因表型表达范围和性质的额外定性和定量信息，这可能会增强我们发现这些基因的能力。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、神经和遗传机制的最终结果。在这个项目中，我们将研究自闭症和唐氏综合症先证者的亲属在社会认知、中央连贯和执行功能等方面的神经心理学测量，这三个主要的认知框架被认为是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，以阐明BAP的神经心理学基础，并为未来的BAP研究提供有效、有效和可靠的测量方法。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、眶额皮层和右侧体感皮层局灶性脑病变个体的独特样本进行比较，以深入了解自闭症和BAP的行为和神经心理学特征的神经基础。最后，这些特征共同出现的模式将在个人和家庭中进行检查。这项研究将补充正在进行的自闭症先证者相同神经心理特征的研究。该项目汇集了一群独特的经验丰富的研究人员，他们在自闭症的家庭遗传学（Piven）和神经心理学研究（Happ¿）以及社会认知的神经基础（Adolphs）方面具有互补的专业知识，以研究广泛的自闭症表型的神经心理学基础。

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 (Happ¿), and in the neural basis of social cognition (Adolphs), to study the neuropsychological basis of the broad autism phenotype.