Augmenting language interventions for ASD: A translational approach

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。尽管早期诊断和对早期干预重要性的认识提高，但ASD的语言和交流结果仍然高度可变，一些纵向样本显示，在2岁时诊断为自闭症的儿童中，多达50%的儿童到9岁时仍然不说话，或缺乏短语语言（安德森等人，2007年）。尽管这样一个未满足的治疗需求的重要性，很少有研究经验性地测试了可能的叠加效应的综合干预措施，特别是结合心理和医疗干预措施，我们建议这样做。这个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，对缺乏短语言语的6-11岁ASD儿童接受强化的，发育知情的语言干预的短期社会沟通和语言结果的假设益处。从证据表明ASD的社会动机和奖励反应性异常以及ASD治疗反应的行为调节剂的会聚线中，我们提出了一项翻译研究，以测试ARI管理的假设积极作用，基于对社会动机的影响，结合最先进的沟通干预，ASD和低语言能力儿童。这项研究的数据可以为自闭症和语言能力低下的学龄儿童提供基于经验的干预选择方法。拟议的研究应代表一种试验设计，可作为未来ASD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促进ASD的语言习得，那么一旦在更大规模的对照研究中复制，这样的结果可能具有临床意义。该项目直接解决了lACC的目标，以增加控制干预研究，解决ASD患者的关键需求。

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.