• Takamitsu Watanabe, Osamu Abe, Hitoshi Kuwabara, Noriaki Yahata, Yosuke Takano, Norichika Iwashiro, Tatsunobu Natsubori, Yuta Aoki, Hidemasa Takao, Yuki Kawakubo, Yoko Kamio, Nobumasa Kato, Yasushi Miyashita, Kiyoto Kasai, and Hidenori Yamasue.
• Department of Neuropsychiatry, School of Medicine, University of Tokyo, Tokyo, Japan2Department of Physiology, School of Medicine, University of Tokyo, Tokyo, Japan.
• JAMA Psychiatry. 2014 Feb 1;71(2):166-75.

ImportanceSociocommunicational deficits make it difficult for individuals with autism spectrum disorders (ASD) to understand communication content with conflicting verbal and nonverbal information. Despite growing prospects for oxytocin as a therapeutic agent for ASD, no direct neurobiological evidence exists for oxytocin's beneficial effects on this core symptom of ASD. This is slowing clinical application of the neuropeptide.ObjectiveTo directly examine whether oxytocin has beneficial effects on the sociocommunicational deficits of ASD using both behavioral and neural measures.Design, Setting, And ParticipantsAt the University of Tokyo Hospital, we conducted a randomized, double-blind, placebo-controlled, within-subject-crossover, single-site experimental trial in which intranasal oxytocin and placebo were administered. A total of 40 highly functioning men with ASD participated and were randomized in the trial.InterventionsSingle-dose intranasal administration of oxytocin (24 IU) and placebo.Main Outcomes And MeasuresUsing functional magnetic resonance imaging, we examined effects of oxytocin on behavioral neural responses of the participants to a social psychological task. In our previous case-control study using the same psychological task, when making decisions about social information with conflicting verbal and nonverbal contents, participants with ASD made judgments based on nonverbal contents less frequently with longer time and could not induce enough activation in the medial prefrontal cortex. Therefore, our main outcomes and measures were the frequency of the nonverbal information-based judgments (NVJs), the response time for NVJs, and brain activity of the medial prefrontal cortex during NVJs.ResultsIntranasal oxytocin enabled the participants to make NVJs more frequently (P = .03) with shorter response time (P = .02). During the mitigated behavior, oxytocin increased the originally diminished brain activity in the medial prefrontal cortex (P < .001). Moreover, oxytocin enhanced functional coordination in the area (P < .001), and the magnitude of these neural effects was predictive of the behavioral effects (P ≤ .01).Conclusions And RelevanceThese findings provide the first neurobiological evidence for oxytocin's beneficial effects on sociocommunicational deficits of ASD and give us the initial account for neurobiological mechanisms underlying any beneficial effects of the neuropeptide.Trial Registrationumin.ac.jp/ctr Identifier: UMIN000002241 and UMIN000004393.

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