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

• 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
• 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

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.

该建议反映了加强干预措施的总体目标，这些干预措施解决了自闭症谱系障碍儿童（ASD）常见的核心沟通缺陷。尽管较早的诊断并提高了对早期干预的重要性的认识，但ASD的语言和沟通结果仍然很大，其中一些纵向样本显示出多达50％的在2岁时被诊断出患有自闭症的儿童仍然是非语言的，或者是9岁以下的言语（Anderson等人，2007年）。尽管这种未满足的治疗需求很重要，但很少有研究在经验上测试了合并干预措施的可能添加效应，尤其是联合心理社会和医疗干预措施，就像我们建议的那样。这个创新的项目测试了增加多巴胺稳定药物Aripiprazole（ARI）与安慰剂的假设好处，该药物在短期的社交交流和6-11岁的ASD儿童中缺乏位词言语的短期社会交流和语言结果，该词会接受强烈的语言，从而获得了一种大量的语言。我们从ASD中的社会动机和奖励反应性异常以及ASD中治疗反应的行为主持人中的反应性异常的融合线中得出，我们提出了一项转化研究，以测试ARI给药的假设积极影响，基于对社交动机的影响，并结合ASD和低语能力的儿童的最新交流干预。拟议研究的数据可以为基于经验的方法提供基于经验的方法来选择ASD和低语言能力的学龄儿童的干预措施。拟议的研究应代表试验设计，该设计可以作为对ASD未来目标治疗的未来研究的平台，并通过对核心病理生理学的新理解确定。如果我们的概念验证试验表明ARI促进了ASD中的语言获取，那么一旦在更大的对照研究中复制，这种结果就会具有临床意义。该项目直接解决了LACC的目标，以增加受控干预研究，以满足ASD个人的关键需求。