Development of Behavioral and Neural Biomarkers for Autism Spectrum Disorder Using a Genetically Defined Subtype

使用基因定义的亚型开发自闭症谱系障碍的行为和神经生物标志物

• 批准号: 9264590
• 负责人: Joseph D. Buxbaum
• 金额: $ 21.19万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-19 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9264590
• 关键词: Accounting; Affect; Animal Model; Auditory; Auditory Evoked Potentials; Behavior; Behavioral; Behavioral Mechanisms; Biological Markers; Centers for Disease Control and Prevention (U.S.); Child; Clinical; Clinical Research; DSM-V; Data; Databases; Deletion Mutation; Development; Diagnostic and Statistical Manual of Mental Disorders; Electroencephalography; Electrophysiology (science); Esthesia; Family; Funding; Genes; Genetic; Glutamates; Goals; Grant; Individual; Intellectual functioning disability; Intervention; Knowledge; Measures; Methods; Modality; Modeling; National Institute of Neurological Disorders and Stroke; Neurophysiology - biologic function; Outcome Measure; Outcomes Research; Parents; Pathway interactions; Phenotype; Pilot Projects; Point Mutation; Population; Questionnaires; Rare Diseases; Reporting; Research; Research Infrastructure; Scaffolding Protein; Sensory; Standardization; Symptoms; Synapses; Syndrome; Translating; Treatment outcome; Vision; Visual; Visual Pathways; Visual evoked cortical potential; Visual system structure; Yang; autism spectrum disorder; base; behavior measurement; cohort; experience; glutamatergic signaling; interest; neural patterning; neuromechanism; novel; novel diagnostics; patient population; public health relevance; relating to nervous system; response; sensory system; tool; transmission process; visual processing; visual stimulus

 DESCRIPTION (provided by applicant): Autism spectrum disorder (ASD) affects 1 in 68 children (CDC, 2014) with known genetic causes accounting for 10-15% of cases (Devlin & Scherer, 2012; Gaugler et al., 2014). Approximately 2% of severely affected children with ASD have deletions or point mutations in the SHANK3 gene, which results in Phelan- McDermid syndrome (PMS) (Betancur & Buxbaum, 2013; Leblond et al, 2014). SHANK3 is a scaffolding protein in glutamate synapses (Bodzdagi et al., 2013; Yang et al., 2012). Over 80% of children with PMS meet Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for ASD and intellectual disability and are minimally verbal (Soorya et al., 2013). Sensory reactivity abnormalities such as hypo- and hyper-reactivity represent a new DSM-5 criterion for ASD. While sensory reactivity issues have been shown in idiopathic forms of ASD (Tomcheck & Dunn, 1997; Tavassoli et al., 2012, 2013), no studies have investigated sensory reactivity abnormalities in severely affected children, including those with PMS. Identifying sensory reactivity abnormalities is especially important in such children as they cannot verbally describe their sensory experiences. In idiopathic forms of ASD, vision is the most researched sensory modality (Simmons et al., 2009; Tavassoli et al., 2011; Weinger et al., 2014). Moreover our pilot studies suggest that hyporeactivity in the visual domain is common in children with PMS. Preliminary data also show that behavioral and electrophysiological measures of sensory reactivity may have the capacity to objectively differentiate between children with (1) PMS, (2) idiopathic ASD, and (3) typically developing controls. The aim of the proposed project is to develop behavioral and neural biomarkers of sensory reactivity in ASD, which are feasible in severely affected individuals (including PMS) and can be translated to other genetically defined subtypes and across sensory modalities. This project aims to develop reliable measures of behavioral and neural sensory reactivity within the visual system of children with PMS and ASD more broadly. The knowledge gained will provide an enhanced understanding of how one sensory system is affected in PMS and ASD, while assessing the relationship with neural functioning. This study is important because it seeks to develop biomarkers that can be applied to other clinical populations of severely affected individuals.

 描述（由适用提供）：自闭症谱系障碍（ASD）影响68名儿童（CDC，2014年），其中已知的遗传原因占10-15％的病例（Devlin＆Scherer，2012; Gaugler等，2014）。大约2％的ASD严重影响儿童在Shank3基因中具有缺失或点突变，这导致了菲兰 - 麦克德米德综合征（PMS）（Betancur＆Buxbaum，2013; Leblond et al，2014）。 Shank3是谷氨酸突触中的脚手架蛋白（Bodzdagi等，2013; Yang等，2012）。超过80％的PMS儿童符合ASD和智力障碍的精神障碍诊断和统计手册（DSM）标准，并且言语最少（Soorya等，2013）。感觉反应性异常（例如低反应性和高反应性）代表了ASD的新DSM-5标准。尽管已经以ASD的特发性形式显示了感官反应性问题（Tomcheck＆Dunn，1997; Tavassoli等，2012，2013），但没有研究研究受影响的严重受影响儿童（包括PMS）的感觉反应性异常。在这样的儿童中，识别感觉反应性异常尤为重要，因为他们无法口头描述他们的感觉经历。 ASD，视觉的特发性形式是最受研究的感觉方式（Simmons等，2009； Tavassoli等，2011； Weinger等，2014）。此外，我们的试点研究表明，在PMS儿童中，视觉结构域中的低作用性很常见。初步数据还表明，感觉反应性的行为和电生理测量方法可能具有客观地区分（1）PMS，（2）特发性ASD的儿童，以及（3）通常会发展控制。拟议项目的目的是开发ASD中感觉反应性的行为和神经生物标志物，在严重影响的个体（包括PM）中是可行的，可以转化为其他遗传定义的亚型以及跨感觉方式。该项目旨在在患有PMS和ASD的儿童视觉系统内开发可靠的行为和神经感觉反应性衡量标准。获得的知识将对PMS和ASD中一种感觉系统的影响提供增强的理解，同时评估与神经功能的关系。这项研究很重要，因为它试图开发可用于严重影响个体的其他临床人群的生物标志物。

项目成果

Objective frequency analysis of transient visual evoked potentials in autistic children.

自闭症儿童瞬态视觉诱发电位的客观频率分析。

• DOI: 10.1002/aur.2654
• 发表时间: 2022
• 期刊: Autism research : official journal of the International Society for Autism Research
• 作者: Brittenham,Chloe;Gordon,James;Zemon,VanceM;Siper,PaigeM
• 通讯作者: Siper,PaigeM

Rapid and Objective Assessment of Neural Function in Autism Spectrum Disorder Using Transient Visual Evoked Potentials.

使用瞬态视觉诱发电位快速客观地评估自闭症谱系障碍的神经功能。

• DOI: 10.1371/journal.pone.0164422
• 发表时间: 2016
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Siper,PaigeM;Zemon,Vance;Gordon,James;George-Jones,Julia;Lurie,Stacey;Zweifach,Jessica;Tavassoli,Teresa;Wang,ATing;Jamison,Jesslyn;Buxbaum,JosephD;Kolevzon,Alexander
• 通讯作者: Kolevzon,Alexander