Augmenting language interventions for ASD: A translational approach

加强自闭症谱系障碍的语言干预：一种转化方法

基本信息

批准号：
8426260
负责人：
JAMES T. MCCRACKEN
金额：
$ 28.11万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-04 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8426260
关键词：
Address Adolescence Adult Aftercare Age Autistic Disorder Awareness Behavioral Biological Biological Assay Biological Markers Blinking Brain Child Clinical Clinical Trials Design Cognition Communication Controlled Study Data Development Diagnosis Dopamine Early Diagnosis Early treatment Electrophysiology (science)Eye Functional disorder Future Genetic Glutamates Glutamine Goals Individual Instruction Intervention Intervention Studies Joints Language Language Development Learning Magnetic Resonance Spectroscopy Measures Mediator of activation protein Medical Motivation Outcome Pharmaceutical Preparations Placebos Randomized Rewards Sampling School-Age Population Signal Transduction Speech Stimulus Testing Time age related aripiprazole autism spectrum disorder base biobehavior emotional stimulus indexing innovation memory process middle childhood novel phrases psychosocial response social social communication translational approach translational study treatment response visual process visual processing

项目摘要

This proposal reflects the overarching goal of enhancing interventions that address core communication deficits common in children with autism spectrum disorders (ASD). Despite earlier diagnosis and increased awareness of the importance of early intervention, language and communication outcomes remain highly variable in ASD, with some longitudinal samples showing as many as 50% of children diagnosed with autism at age 2 still non-verbal, or lacking phrase speech by age 9 (Anderson et al., 2007). Despite the importance of such an unmet treatment need, few studies have empirically tested the possible additive effects of combined interventions, especially combined psychosocial and medical interventions, as we propose to do. This innovative project tests the hypothesized benefits of the addition of the dopamine-stabilizing drug, aripiprazole (ARI) versus placebo, on short-term social communication and language outcomes in 6-11 year old children with ASD lacking phrase speech receiving an intensive, developmentally informed language intervention. Drawing from converging lines of evidence suggesting abnormalities in social motivation and reward responsivity in ASD, and behavioral moderators of treatment response in ASD, we propose a translational study to test for a hypothesized positive effect of ARI administration, based on effects on social motivation, in combination with a state-of-the-art communication intervention in children with ASD and low language ability. Data from the proposed study can inform an empirically based approach to choices of intervention for school-age children with ASD and low language ability. The proposed study should represent a trial design that could serve as a platform for future studies of future targeted treatments for ASD, identified by anticipated new understandings of the core pathophysiology. If our proof-of-concept trial suggests that ARI facilitates language acquisition in ASD, such a result could have clinical implications once replicated in a larger controlled study. The project directly addresses goals of the lACC to increase controlled intervention studies addressing key needs of individuals with ASD.

该提案反映了加强干预措施的总体目标，以解决自闭症谱系障碍 (ASD) 儿童常见的核心沟通缺陷问题。尽管诊断较早并且人们对早期干预重要性的认识有所提高，但 ASD 患者的语言和沟通结果仍然存在很大差异，一些纵向样本显示，多达 50% 的 2 岁时被诊断为自闭症的儿童仍然不会说话，或缺乏短语言语9 岁时（Anderson 等，2007）。尽管这种未满足的治疗需求很重要，但很少有研究像我们建议的那样，对联合干预措施，特别是联合心理社会和医疗干预措施可能产生的累加效应进行实证检验。该创新项目测试了添加多巴胺稳定药物阿立哌唑 (ARI) 与安慰剂相比，对患有缺乏短语言语的 6-11 岁自闭症谱系障碍 (ASD) 儿童接受强化、发展性发育训练的短期社交沟通和语言结果的假设益处。知情的语言干预。根据表明自闭症谱系障碍中社交动机和奖励反应异常以及自闭症谱系障碍治疗反应的行为调节因素的汇聚证据，我们提出了一项转化研究，以测试基于对社交动机的影响的 ARI 管理的假设积极作用，结合针对自闭症谱系障碍和语言能力低下儿童的最先进的沟通干预。拟议研究的数据可以为患有自闭症谱系障碍和语言能力低下的学龄儿童选择干预措施提供基于经验的方法。拟议的研究应该代表一种试验设计，可以作为未来自闭症谱系障碍靶向治疗研究的平台，通过对核心病理生理学的预期新理解来确定。如果我们的概念验证试验表明 ARI 有助于 ASD 患者的语言习得，那么一旦在更大的对照研究中重复，这样的结果可能会产生临床意义。该项目直接解决了 lACC 的目标，即增加受控干预研究，满足自闭症患者的关键需求。