AN FMRI STUDY OF EFFECTS OF OXYTOCIN VS PLACEBO IN AUTISM

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。自闭症是一种神经发育障碍，影响60/10，000的个体，包括所有形式的障碍。它影响社会交往，语言能力，并与重复行为和有限的兴趣有关。然而，仍然没有FDA批准用于治疗自闭症的药物。有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的重复行为，以及一些非典型抗精神病药和抗惊厥药治疗共病攻击的证据。然而，没有药物被证明可以改善社交能力或语言。一些成像数据指出自闭症患者面部处理的激活模式异常;这可能是社交缺陷的一种解释。额纹状体回路的异常与重复行为的产生有关。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。此时，除了IV外，没有可用的制剂向人类受试者提供催产素。本研究的目的是检查是否与催产素的IV挑战将提高社会能力，通过改善面部处理或激活模式，在涉及面部处理的领域。此外，我们将尝试评估是否IV挑战催产素改善激活模式的额纹状体电路，这可能对自闭症的重复行为的治疗有影响。方法：将招募30名符合DSM-IV、ADI-R和/或ADOS自闭症标准的成年人。将排除患有可能会增加催产素副作用风险的重大医学疾病的患者。所有入组的患者将接受基线fMRI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/安慰剂输注。在最后一个小时，功能磁共振成像扫描将重复进行。此外，将在基线和输注结束时进行两项社会认知测试。将进行分析以比较接受催产素的组与接受安慰剂的组之间的激活模式和社会认知测试的表现。 假设主要1。与接受安慰剂2的受试者相比，接受催产素的受试者在治疗后将显示梭形面部区域的激活增加。接受催产素与安慰剂的受试者将差异地激活外侧眶额皮质、背外侧皮质和尾状核次级1。接受催产素的受试者在社交归因测试（SAT）和埃克曼面孔方面的表现比接受安慰剂2的受试者有更大的改善。在SAT和Ekman面孔上的表现的改善将与催产素输注期间重复fMRI上梭状回激活的增加相关。

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.