NEUROIMAGING & SYMPTOM DOMAINS IN AUTISM

神经影像学

• 批准号: 8171024
• 负责人: JENNIFER G. LEVITT
• 金额: $ 0.61万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171024
• 关键词: Affect; Autistic Disorder; Behavior; Behavioral; Biological; Biology; Brain; Candidate Disease Gene; Child; Communication; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Diagnostic; Dimensions; Disease; Early Diagnosis; Etiology; Family; First Degree Relative; Foundations; Funding; Future; General Population; Genes; Genetic; Genotype; Goals; Grant; Individual; Institution; Intervention; Investigation; Measures; Nature; Outcome; Pathway interactions; Phenotype; Population Study; Prevalence; Radioactive; Research; Research Personnel; Resources; Sampling; Scientist; Siblings; Social Functioning; Source; Stereotyped Behavior; Subgroup; Symptoms; Techniques; United States National Institutes of Health; Variant; Work; base; communication behavior; endophenotype; family genetics; genetic resource; genome-wide linkage; improved; language onset; neurochemistry; neuroimaging; social reciprocity; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Autism represents one of the most severe disorders of development, yet its biological underpinnings remain unknown. Although the prevalence of autism in the general population is estimated at 0.05 -- 0.1 percent, a variety of studies indicate that deficits in social functioning and communication affect 15 percent of first-degree relatives of autistic individuals. The poor long-term outcomes seen in such children underscores the need for a better understanding of the biological mechanisms involved in autism. Three intersecting domains of behavior: communication, social reciprocity and restricted/repetitive behaviors, taken together are diagnostic of the illness, but appear partially independent. This fact, in concert with evidence from genome-wide linkage investigations and candidate gene studies, provides evidence that a single etiology of autism is unlikely. Given the heterogeneous nature of autism, identification of homogeneous subgroups is essential to furthering our understanding o f the biology underlying the behaviors associated with this disorder. The availability of noninvasive, non-radioactive neuroimaging techniques and sophisticated data analytic approaches used in combination with family genetic data holds the promise of greatly improving our ability to identify these subgroups. The principal goal of the work proposed in this project is to use these tools to identify neuromorphometric and neurochemical measures that define meaningful endophenotypes in autism. In addition, the extent to which these measures are shared among siblings and therefore are familial will be explored as a means of identifying these endophenotypes. Using these tools, Affected Sibling Pairs selected from the Autism Genetic Resource Exchange multiplex families, and a sample of non-autistic control children selected from an ongoing study of normal children at UCLA will be examined. The CAN/AGRE study population is a large group of multiplex families with phenotypic and genotype data a vailable for access by research scientists. We propose that key behavioral phenotypic dimensions of autism including: delay of language onset, repetitive/stereotyped behaviors and social reciprocity, are associated with specific brain neuromorphometric and neurochemical measures. Furthermore, we will examine the extent to which the neurobiologic findings underlying these phenotypic variations will be correlated among siblings, suggesting that they may be useful phenotypes for future investigations. Taken together, these studies will provide the basis for genetic studies to delineate specific gene brain behavioral pathways and lay the foundation for early detection and better intervention in autism.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 自闭症是最严重的发育障碍之一，但其生物学基础仍然未知。尽管自闭症在一般人群中的患病率估计为 0.05% 至 0.1%，但多项研究表明，社会功能和沟通缺陷影响了自闭症患者 15% 的一级亲属。这些儿童的长期不良结局凸显出需要更好地了解自闭症的生物学机制。三个交叉的行为领域：沟通、社会互惠和限制/重复行为，合在一起可以诊断疾病，但似乎部分独立。这一事实，与全基因组连锁调查和候选基因研究的证据相结合，提供了自闭症不可能有单一病因的证据。鉴于自闭症的异质性，识别同质亚组对于进一步了解与这种疾病相关的行为背后的生物学至关重要。非侵入性、非放射性神经影像技术以及与家族遗传数据结合使用的复杂数据分析方法有望大大提高我们识别这些亚群的能力。该项目提出的工作的主要目标是使用这些工具来识别定义自闭症有意义的内表型的神经形态测量和神经化学测量。此外，将探讨这些措施在兄弟姐妹之间共享并因此具有家族性的程度，作为识别这些内表型的一种手段。使用这些工具，将从自闭症遗传资源交换多重家庭中选出的受影响兄弟姐妹，以及从加州大学洛杉矶分校正在进行的正常儿童研究中选出的非自闭症对照儿童样本进行检查。 CAN/AGRE 研究群体是一大群多重家族，其表型和基因型数据可供研究科学家访问。我们认为自闭症的关键行为表型维度包括：语言开始延迟、重复/刻板行为和社会互惠，与特定的大脑神经形态测量和神经化学测量相关。此外，我们将检查这些表型变异背后的神经生物学发现在兄弟姐妹之间的相关程度，表明它们可能是未来研究有用的表型。总而言之，这些研究将为遗传学研究提供基础，以描绘特定基因的大脑行为途径，并为自闭症的早期发现和更好的干预奠定基础。