Augmenting language interventions for ASD: A translational approach

这项建议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)儿童中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有所提高，但在自闭症患者中，语言和沟通结果仍然存在很大的变数，一些纵向样本显示，在2岁时被诊断为自闭症的儿童中，多达50%的儿童到9岁时仍然不会说话，或者缺乏短语语言(Anderson等人，2007年)。尽管这种未得到满足的治疗需求很重要，但很少有研究经验性地测试联合干预，特别是心理社会和医学联合干预的可能的相加效应，正如我们所建议的那样。这一创新项目测试了添加多巴胺稳定剂阿立哌唑(ARI)与安慰剂对6-11岁自闭症儿童短期社交和语言结果的假设益处，这些儿童缺乏短语言语，接受了密集的、发育知情的语言干预。根据ASD在社会动机和奖励反应方面的异常证据，以及ASD治疗反应的行为调节因素，我们提出了一项转化性研究，以测试ARI管理对社会动机的影响，并结合最先进的沟通干预对ASD和语言能力低下的儿童的积极影响。这项拟议研究的数据可以为患有自闭症和语言能力低下的学龄儿童选择干预措施提供经验依据。拟议的研究应该代表一种试验设计，可以作为未来研究ASD靶向治疗的平台，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患者的语言习得，一旦在更大规模的对照研究中复制，这样的结果可能会有临床意义。该项目直接解决了LACC的目标，即增加针对ASD患者关键需求的受控干预研究。

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.