Proof of Mechanism Study for the Treatment of Social Anhedonia in ASD

项目摘要 理解社会“想要”的变化的生物学基础，或缺乏，在个人 ASD可以开辟重要的干预领域。尽管有可靠的基于证据的方法来改善 ASD的社会功能，大多数高功能ASD成人仍然孤立，结果 研究一致指出，很少或根本没有动机实现关系。然而，与坎纳最初的观点相反， 假设自闭症是一种普遍存在的“情感接触缺陷”，当代研究发现， ASD中社会行为的变化，保留了典型的依恋行为，社会认知， 社会知识在很多方面。社会神经科学揭示了中枢神经系统的重要性 多巴胺与其他系统的相互作用，如正常社会功能中的神经肽信号，但 多巴胺在自闭症患者中的作用尚未得到仔细研究。该项目提出了一个证明， 一项机制研究，以检验多巴胺能紧张度的个体差异有助于揭示 社会动机的差异，以及多巴胺能紧张度的改变将影响社会“想要”， 社会奖励反应性我们计划招募一个高功能青少年和年轻人的样本， ASD将接受为期16周的社交技能培训计划。我们将研究指数的差异， 多层次的社会动机和社会奖励，从：1）神经奖励回路激活; 2）生理 反应; 3）对社会互动的情感反应;和4）社会兴趣和享受，在治疗前， 以及在安慰剂对照的多巴胺激动剂给药期间。该项目是协同与其他 中心组件，在项目3中获得奖励响应度的共同措施，应用共享 诊断和表型分析核心措施，以及收集生物标本， 分析，从而能够更广泛地调查不同年龄和性别的异质性。项目成果将产生 明确“是”或“否”确认多巴胺作为ASD社交功能障碍的可能治疗靶点。 !

PROJECT SUMMARY Understanding the biological underpinnings of variation in social “wanting”, or lack thereof, in individuals with ASD could open important areas for intervention. Despite solid evidence-based approaches for improving social functioning in ASD, the majority of high-functioning adults with ASD remain isolated, with outcome studies consistently noting little or no motivation to achieve relationships. Yet contrary to Kanner's original hypothesis that autism is a ubiquitous “deficit in affective contact”, contemporary studies find extraordinary variation in social behavior in ASD, with preservation of typical attachment behaviors, social cognition, and social knowledge in many. Social neuroscience has revealed the importance of central nervous system dopamine interactions with other systems such as neuropeptide signaling in normal social function, but dopamine's role has not been carefully probed in people with ASD. This project proposes a proof of mechanism study to test the hypothesis that individual differences in dopaminergic tone will help reveal differences in social motivation, and that modification of dopaminergic tone will impact social “wanting” and social reward responsivity. We plan to enroll a sample of high-functioning adolescents and young adults with ASD who will be receiving a 16-week social skills training program. We will examine differences in indices at multiple levels of social motivation and social reward, from: 1) neural reward circuit activation; 2) physiologic responses; 3) affective responses to social interaction; and 4) social interest and enjoyment, at pre-treatment, and during the placebo-controlled administration of a dopamine agonist. This project is synergistic with other Center components, obtaining common measures of reward responsivity in Project 3, applying shared Diagnostic and Phenotyping Core measures, and collecting biospecimens for combined genetic and other analyses, enabling broader investigations of heterogeneity across age and gender. Project results will yield a definitive “Yes” or “No” confirmation of dopamine as a possible treatment target for social dysfunction in ASD. !