Gene-Brain-Behavior Relationships in Autism

自闭症的基因-大脑-行为关系

• 批准号: 7125014
• 负责人: Joseph Piven
• 金额: $ 110.89万
• 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: 2002-09-15 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7125014
• 关键词: autism; behavior; clinical research; genetics

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.

描述(由申请人提供)：15年来，我们的研究团队和其他人采用了Kanner对一些自闭症患者父母的个性特征的原始观察，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中自闭症遗传易感性的表型表达，其定义是由较温和但定性上类似于自闭症的定义特征的特征定义的。这项工作对于1)梳理自闭症中的基因-行为关系，2)理解自闭症中的大脑-行为关系，以及3)提供关于自闭症基因表型表达的范围和性质的额外的定性和定量信息，可能会增强我们发现这些基因的能力，具有潜在的重要性。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上是不同的，是一系列潜在的神经心理、神经和遗传机制的最终结果。在这个项目中，我们建议对自闭症和唐氏综合症先证者的亲属进行社会认知、中央一致性和执行功能的神经心理学测量，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测量相联系，以阐明BAP的神经心理学基础，并为未来BAP的研究提供有效、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领域与杏仁核、眼眶-额叶皮质和右侧躯体感觉皮质局限性脑损伤的独特样本进行比较，这些样本来自爱荷华大学的脑损伤登记处，以提供对自闭症和BAP行为和神经心理特征的神经基础的洞察。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关于自闭症先证者相同神经心理学特征的研究。该项目汇集了一群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。

项目成果

Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism.

• DOI: 10.1001/archgenpsychiatry.2009.30
• 发表时间: 2009-06
• 期刊: ARCHIVES OF GENERAL PSYCHIATRY
• 作者: King, Bryan H.;Hollander, Eric;Sikich, Linmarie;McCracken, James T.;Scahill, Lawrence;Bregman, Joel D.;Donnelly, Craig L.;Anagnostou, Evdokia;Dukes, Kimberly;Sullivan, Lisa;Hirtz, Deborah;Wagner, Ann;Ritz, Louise
• 通讯作者: Ritz, Louise

Baseline factors predicting placebo response to treatment in children and adolescents with autism spectrum disorders: a multisite randomized clinical trial.

• DOI: 10.1001/jamapediatrics.2013.2698
• 发表时间: 2013-11
• 期刊: JAMA pediatrics
• 影响因子: 26.1
• 作者: King BH;Dukes K;Donnelly CL;Sikich L;McCracken JT;Scahill L;Hollander E;Bregman JD;Anagnostou E;Robinson F;Sullivan L;Hirtz D
• 通讯作者: Hirtz D

Design and subject characteristics in the federally-funded citalopram trial in children with pervasive developmental disorders.

联邦政府资助的针对患有广泛性发育障碍的儿童的西酞普兰试验的设计和受试者特征。

• DOI: 10.1007/s10803-011-1251-8
• 发表时间: 2012
• 期刊: Journal of autism and developmental disorders
• 影响因子: 3.9
• 作者: Scahill,Lawrence;McCracken,JamesT;Bearss,Karen;Robinson,Fay;Hollander,Eric;King,Bryan;Bregman,Joel;Sikich,Lin;Dukes,Kimberly;Sullivan,Lisa;Anagnostou,Evdokia;Donnelly,Craig;Kim,Young-Shin;Ritz,Louise;Hirtz,Deborah;Wagner,An
• 通讯作者: Wagner,An

Distinct face-processing strategies in parents of autistic children.

• DOI: 10.1016/j.cub.2008.06.073
• 发表时间: 2008-07-22
• 期刊: CURRENT BIOLOGY
• 影响因子: 9.2
• 作者: Adolphs, Ralph;Spezio, Michael L.;Parlier, Morgan;Piven, Joseph
• 通讯作者: Piven, Joseph

Neuropsychological profile of autism and the broad autism phenotype.

• DOI: 10.1001/archgenpsychiatry.2009.34
• 发表时间: 2009-05
• 期刊: ARCHIVES OF GENERAL PSYCHIATRY
• 作者: Losh, Molly;Adolphs, Ralph;Poe, Michele D.;Couture, Shannon;Penn, David;Baranek, Grace T.;Piven, Joseph
• 通讯作者: Piven, Joseph