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.
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