Neural Effects of Sustained Oxytocin Treatment in Children with Autism

项目摘要 社会交往的显著缺陷是自闭症谱系障碍（ASD）的标志性特征。催产素扮演着 在动物和人类的社会行为中起着重要作用，最近已经成为一种有前途的 候选人针对ASD的社会障碍。然而，很少有人知道的神经机制， 催产素一般影响人类的社会行为，特别是ASD。该项目旨在 研究催产素治疗对儿童社会功能障碍的神经系统的影响 关于ASD我们正在参与NIH ACE网络拨款，以进行一项明确的随机，双盲， 持续鼻内催产素治疗对儿童互惠社会行为的安慰剂对照临床试验 ASD儿童这提供了一个利用现有基础设施的独特机会， 使我们能够提供有关催产素治疗反应的神经机制的重要信息 孤独症。这个项目的具体目标是研究：1）催产素如何影响神经回路 社会信息处理的基本方面，即“镜像神经元”系统， 社会奖励，以及2）这些回路中的活动预测或与治疗相关的程度 反应中心假设是催产素治疗会增强这些“社会脑”的活动 系统，并增加在关键的大脑区域（例如，腹侧额下回盖部 纹状体、杏仁核和内侧前额叶皮质）将与社会行为的临床改善相关。我们 将使用先前验证的功能磁共振成像范例来检查治疗前后大脑活动的差异 催产素和安慰剂在ASD儿童中的作用。建议的理由 研究表明，更好地了解催产素影响的神经系统将为 开发针对这些网络的新药理学策略，无论它们是“社会大脑”还是 补偿电路这种方法在使用功能磁共振成像任务方面是创新的， 自闭症的功能障碍，与社会症状的严重程度相关，并与假设的 催产素的作用机制拟议的项目是重要的，因为它将产生重要的信息， 探讨缩宫素治疗ASD的作用机制，为临床治疗ASD提供科学依据。 制定个性化的治疗方法。增加对神经结构的了解 ASD样本中催产素的作用有望有助于刺激新策略的发展， 在受影响的网络中激活。这项研究也有望帮助确定神经预测因子和相关性， 治疗反应，这可能会支持生物标志物的发展，因此，个性化 治疗-一个被广泛认为对该领域至关重要的目标。

PROJECT SUMMARY Striking deficits in social interaction are hallmark features of autism spectrum disorders (ASD). Oxytocin plays an important role in social behavior in animals and humans and has recently emerged as a promising candidate for targeting social impairment in ASD. However, little is known about the neural mechanisms by which oxytocin influences social behavior in humans in general and ASD in particular. This project aims to investigate the impact of oxytocin treatment on the neural systems underlying social impairments in children with ASD. We are participating in an NIH ACE network grant to conduct a definitive randomized, double-blind, placebo-controlled clinical trial of sustained intranasal oxytocin treatment on reciprocal social behaviors in children with ASD. This presents a unique opportunity to take advantage of existing infrastructure that will enable us to provide important information on the neural mechanisms underlying oxytocin treatment response in autism. The specific aims of this project are to examine: 1) how oxytocin impacts the neural circuitry underlying fundamental aspects of social information processing-namely, the 'mirror neuron' system and social reward, and 2) the extent to which activity in these circuits predicts or correlates with treatment response. The central hypothesis is that treatment with oxytocin will enhance activity in these 'social brain' systems and that increases in key brain areas (e.g., pars opercularis of the inferior frontal gyrus, ventral striatum, amygdala, and medial prefrontal cortex) will correlate with clinical improvement in social behavior. We will use previously validated fMRI paradigms to examine differences in brain activity before and after treatment with oxytocin and placebo in children with ASD participating in the network trial. The rationale for the proposed research is that a better understanding of the neural systems impacted by oxytocin will pave the road for developing new pharmacological strategies for targeting these networks, whether they are "social brain" or compensatory circuits. The approach is innovative in its use of fMRI tasks that tap circuitry known to be dysfunctional in autism, correlate with severity of social symptoms, and have a direct link to a hypothesized mechanism of oxytocin. The proposed project is significant because it will yield important information on the therapeutic mechanism of oxytocin in children with ASD, and offer a scientific basis on which to ultimately develop individualized approaches to treatment. Increasing knowledge about the neural architecture impacted by oxytocin in an ASD sample is expected to help stimulate the development of novel strategies for increasing activation in affected networks. This study is also expected to help identify neural predictors and correlates of treatment response, which will likely support the development of biomarkers, and thus, personalization of treatments-a target widely acknowledged as critically important for the field.