AN FMRI STUDY OF EFFECTS OF OXYTOCIN VS PLACEBO IN AUTISM

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。自闭症是一种神经发育障碍，包括所有形式的障碍在内，每10000人中就有60人受到影响。它影响社会交往、语言能力，并与重复性行为和有限的兴趣有关。然而，FDA仍然没有批准治疗自闭症的药物。越来越多的证据表明，使用5 -羟色胺再摄取抑制剂治疗自闭症患者的重复行为，一些证据表明，非典型抗精神病药物和抗惊厥药物治疗共病攻击。然而，没有任何药物被证明可以提高社交能力或语言能力。一些成像数据表明自闭症患者的面部处理激活模式异常；对社会赤字的一种可能解释。额纹状体回路的异常与重复行为的产生有关。关于催产素的基础科学和有限的临床研究将其缺乏与重复行为和社交缺陷联系起来。目前，除了静脉注射外，没有其他可行的配方来为人类受试者提供催产素。这项研究的目的是检验静脉注射催产素是否会通过改善面部处理或面部处理相关区域的激活模式来提高社交能力。此外，我们将尝试评估静脉注射催产素是否能改善额纹状体回路的激活模式，这可能对自闭症患者重复行为的治疗有影响。方法：招募30名符合DSM-IV、ADI-R和/或ADOS自闭症标准的成年人。有重大医学疾病的患者将被排除在外，这些患者可能会增加催产素副作用的风险。所有入组患者都将进行fMRI基线扫描，观察面部处理和反应抑制。然后，他们将在4小时内接受催产素/安慰剂的注射。在最后一小时内，将重复fMRI扫描。此外，两项社会认知测试将在基线和输液结束时进行。将对接受催产素组和接受安慰剂组在社会认知测试中的激活模式和表现进行分析比较。假设1。接受催产素治疗的受试者与接受安慰剂治疗的受试者相比，在治疗后梭状回面部区域的激活会增加。接受催产素和安慰剂治疗的受试者在眶额外侧皮质、背外侧皮质和尾状核次级1的激活上存在差异。接受催产素的受试者在社会归因测试（SAT）和埃克曼面孔测试（Ekman Faces）中的表现比接受安慰剂的受试者有更大的提高。在催产素输注期间，重复fMRI显示梭状回激活增加与SAT和Ekman面部表现的改善有关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Autism is a neurodevelopmental disorder affecting 60/10,000 individuals, when all forms of the disorder are included. It affects social interactions, language abilities and is associated with repetitive behaviors and restricted interests. However, there are still no medications approved by FDA for the treatment of autism. There is accumulating evidence for the use of serotonin reuptake inhibitors in treating the repetitive behaviors in autism and some evidence for atypical antipsychotics and anticonvulsants for the treatment of comorbid aggression. However, no medications have been shown to improve social abilities or language. Some imaging data points to abnormalities in activation patterns in face processing in autism; a possible explanation for the social deficits. Abnormalities in the frontostriatal circuitry have been implicated in the generation of repetitive behaviors. Basic science and limited clinical research with oxytocin has linked its deficiency to both repetitive behaviors and social deficits. At this time there is no available formulation other than IV to provide oxytocin to human subjects. The goal of this study is to examine whether an IV challenge with oxytocin will improve social abilities by means of improving face processing or activation patterns in areas involved in face processing. In addition we will try to assess whether IV challenge with oxytocin improves activation patterns in the frontostriatal circuitry, which may have implications for the treatment of repetitive behaviors in autism. Methods: Thirty adults meeting criteria for autism by DSM-IV, ADI-R and/or ADOS will be recruited. Patients with significant medical disease that may be at increased risk for side effects from oxytocin will be excluded. All enrolled patients will have a baseline fMRI scan looking at face processing and response inhibition. They will then receive an oxytocin/placebo infusion over 4 hours. During the last hour, the fMRI scan will be repeated. In addition, two social cognition tests will be administered at baseline and at the end of the infusion. Analysis will be done to compare activation patterns and performance on social cognition tests between the group that received oxytocin vs. the group that received placebo. Hypotheses Primary 1. Subjects receiving oxytocin will show increased activation of the fusiform face area post treatment vs. subjects receiving placebo 2. Subjects receiving oxytocin vs. placebo will differentially activate the lateral orbitofrontal cortex, dorsolateral cortex and caudate nucleus Secondary 1. Subjects receiving oxytocin will show greater improvements in their performance of the social attribution test (SAT) and Ekman Faces than subjects who receive the placebo 2. Improvements in the performance on the SAT and Ekman Faces will correlate with increased fusiform gyrus activation on repeat fMRI during oxytocin infusion.