Cognitive Enhancement Therapy for Adult Autism Spectrum Disorder

 描述(由申请人提供)：自闭症谱系障碍(ASD)的特征是社会和非社会认知能力明显受损，一直持续到成年，并导致严重的功能残疾。自闭症的治疗几乎完全集中在儿童身上，几乎没有经验支持的干预措施来解决自闭症患者在过渡到成年时面临的核心认知和功能挑战。认知康复已经成为一套系统的治疗认知障碍的方法，为自闭症认知障碍的治疗带来了巨大的希望，但这些干预措施还没有在这一人群中进行足够有力和严格控制的研究。认知增强疗法(CET)是成人ASD最有前途的认知康复方法之一，因为它针对神经认知和社会认知障碍的全面和发展的方法，以及它对精神分裂症的既定疗效，精神分裂症的特征是类似的认知缺陷。在NIMH的支持下，我们最近已经证明了将CET适应于患有ASD的成年人的可行性，并且从我们最初在这一人群中进行的CET的小规模随机试验中出现了证据，表明目标参与不同的认知领域，对功能结果具有实质性的下游好处。令人兴奋的是，这些与CET相关的认知改善似乎也得到了额颞脑功能和连接的潜在神经可塑性变化的支持。这些证据表明，CET作为成人ASD的循证认知康复干预具有相当大的前景，关键是这些早期发现与足够强大的疗效试验相结合。针对PA-13-216《自闭症谱系障碍研究》的心理社会干预重点，本项目建议对100名患有自闭症的成年人进行CET的随机对照疗效试验。参与者将被随机分配到CET或强化支持疗法(EST)对照条件下，并接受为期18个月的治疗。该项目的具体目标是(1)评估CET和EST在不同认知和行为结果上的比较有效性，以评估目标参与和功能影响；(2)检查CET对额内侧颞脑功能和连接性的影响，以阐明这一人群认知增强的神经机制；(3)使用个人和神经生物学指标来探索治疗反应的异质性，并确定最有可能从CET中受益的个体的调节因素。拟议的项目将导致成人ASD中最大的心理社会干预研究，以及第一个对这一人群有前景的认知康复方法的充足动力的研究。如果成功，这个项目将在为成人自闭症患者提供干预方面向前迈出重要的一步，并将展示成人自闭症大脑的可塑性及其对认知康复的反应，为自闭症的新一代治疗铺平道路。

 DESCRIPTION (provided by applicant): Autism spectrum disorder (ASD) is characterized by marked impairments in social and non-social cognitive ability that persist well into adulthood and contribute to significant functional disability. The treatment of ASD has focused almost exclusively on children, and few empirically supported interventions are available to address the core cognitive and functional challenges individuals with ASD face as they transition to adulthood. Cognitive rehabilitation has emerged as a set of systematic approaches to the remediation of cognitive impairments that hold considerable promise for the treatment of cognitive deficits in autism, yet adequately-powered and rigorously controlled studies of these interventions have not been conducted in this population. Cognitive Enhancement Therapy (CET) represents one of the most promising cognitive rehabilitation approaches for adult ASD due to its comprehensive and developmental approach to targeting neurocognitive and social-cognitive impairments as well as its established efficacy in schizophrenia, a disorder characterized by similar cognitive deficits. With support from NIMH, we have recently demonstrated the feasibility of adapting CET to adults with ASD, and evidence is emerging from our initial, small-scale randomized trial of CET in this population indicating target engagement on diverse areas of cognition with substantial downstream benefits to functional outcomes. Excitingly, these improvements in cognition associated with CET also appear to be supported by underlying neuroplastic changes in fronto-temporal brain function and connectivity. Such evidence suggests that CET has considerable promise as an evidence-based cognitive rehabilitation intervention for adult ASD, and it is critical that these early findings are followe-up with an adequately-powered efficacy trial. In response to the psychosocial intervention focus of PA-13-216, "Research on Autism Spectrum Disorders", this project proposes to conduct a randomized-controlled efficacy trial of CET in 100 verbal adults with ASD. Participants will be randomized to CET or an Enriched Supportive Therapy (EST) control condition and treated for 18 months. Specific aims of the project are to (1) evaluate the comparative effectiveness of CET versus EST on diverse cognitive and behavioral outcomes to assess target engagement and functional impact, (2) examine the effects of CET on fronto-medial temporal brain function and connectivity to elucidate the neural mechanisms of cognitive enhancement in this population, and (3) use personal and neurobiological indicators to explore heterogeneity in treatment response and identify moderators indicative of individuals most likely to benefit from CET. The proposed project will result in the largest psychosocial intervention study in adult ASD, and the first adequately-powered study of a promising cognitive rehabilitation approach for this population. If successful, this project will provide a major step forward in making interventions available for adults with ASD, and will demonstrate the plasticity of the adult ASD brain and its responsiveness to cognitive rehabilitation, paving the way for a new generation of treatments in autism.