Augmenting language interventions for ASD: A translational approach

这一建议反映了加强干预措施以解决自闭症谱系障碍（ASD）儿童常见的核心沟通缺陷的总体目标。尽管早期诊断和对早期干预重要性的认识有所提高，但ASD的语言和交流结果仍然存在很大的差异，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在9岁时仍然无法言语，或缺乏短语语言（Anderson et al, 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，从经验上测试联合干预措施，特别是心理社会和医疗干预措施的可能叠加效应。这个创新的项目测试了添加多巴胺稳定药物阿立哌唑（ARI）与安慰剂对6-11岁缺乏短语语言的ASD儿童的短期社会沟通和语言结果的假设益处，这些儿童接受了密集的发育信息语言干预。基于ASD社会动机和奖励反应异常以及ASD治疗反应的行为调节因子的证据，我们提出了一项转化研究，以测试基于社会动机影响的ARI管理的假设积极效果，并结合最先进的ASD和低语言能力儿童的沟通干预。该研究的数据可以为ASD和低语言能力学龄儿童的干预选择提供基于经验的方法。拟议的研究应该代表一种试验设计，可以作为未来研究ASD未来靶向治疗的平台，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促进了ASD的语言习得，那么一旦在更大的对照研究中重复，这样的结果可能具有临床意义。该项目直接解决了lACC的目标，即增加针对ASD患者关键需求的控制干预研究。

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.