Neural Effects of Sustained Oxytocin Treatment in Children with Autism

持续催产素治疗自闭症儿童的神经效应

• 批准号: 8913245
• 负责人: A. Ting Wang
• 金额: $ 19.83万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8913245
• 关键词: Adult; Affect; Aftercare; American; Amygdaloid structure; Animals; Architecture; Area; Association Learning; Autistic Disorder; Basal Ganglia; Behavioral; Biological Markers; Brain; Brain region; Child; Clinical; Controlled Clinical Trials; Development; Dose; Double-Blind Method; Emotions; Employee Strikes; Enrollment; Facial Expression; Functional Magnetic Resonance Imaging; Functional disorder; Fusiform gyrus; Goals; Grant; Health; Human; Impairment; Individual; Individual Differences; Inferior frontal gyrus; Intervention; Knowledge; Learning; Life; Link; Medial; Mediator of activation protein; Nucleus Accumbens; Oxytocin; Pattern; Pilot Projects; Placebo Control; Placebos; Play; Prefrontal Cortex; Randomized; Relative (related person); Research; Research Infrastructure; Rewards; Role; Sampling; Severities; Social Behavior; Social Functioning; Social Interaction; Support System; Symptoms; System; Therapeutic; United States National Institutes of Health; Ventral Striatum; autism spectrum disorder; base; cost; improved; information processing; innovation; interest; mirror neuron; mirror neuron system; neural circuit; neuromechanism; novel strategies; relating to nervous system; response; reward circuitry; social; social cognition; social communication; treatment response

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：社交互动的显着缺陷是自闭症谱系障碍（ASD）的标志性特征。催产素在动物和人类的社会行为中发挥着重要作用，最近已成为治疗自闭症谱系障碍社交障碍的有希望的候选药物。然而，人们对催产素影响人类社会行为（尤其是自闭症谱系障碍）的神经机制知之甚少。该项目旨在调查催产素治疗对自闭症儿童社交障碍的神经系统的影响。我们正在参与 NIH ACE 网络拨款，以开展一项明确的随机、双盲、安慰剂对照临床试验，研究持续鼻内催产素治疗对自闭症谱系障碍 (ASD) 儿童交互社会行为的影响。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自闭症催产素治疗反应背后的神经机制的重要信息。该项目的具体目标是研究：1）催产素如何影响社会信息处理基本方面的神经回路，即“镜像神经元”系统和社会奖励，以及 2）这些回路中的活动预测或预测的程度 与治疗反应相关。中心假设是，催产素治疗将增强这些“社交大脑”系统的活动，并且增加关键大脑区域（例如，额下回的盖部、腹侧纹状体、杏仁核和内侧前额叶皮层）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式来检查催产素治疗前后大脑活动的差异 参与网络试验的自闭症谱系障碍儿童使用催产素和安慰剂。拟议研究的基本原理是，更好地了解受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铺平道路，无论它们是“社交大脑”还是补偿回路。该方法的创新在于使用功能磁共振成像任务，该任务利用已知在自闭症中功能失调的电路，与 社会症状的严重程度， 并与催产素的假设机制有直接联系。该项目意义重大，因为它将产生有关自闭症儿童催产素治疗机制的重要信息，并为最终开发个体化治疗方法提供科学依据。增加对 ASD 样本中受催产素影响的神经结构的了解预计将有助于刺激新策略的开发，以增加受影响网络的激活。这项研究还有望帮助识别治疗反应的神经预测因素和相关因素，这可能会支持生物标志物的开发，从而支持个性化治疗——这一目标被广泛认为对该领域至关重要。