title: Mitigation of sociocommunicational deficits of autism through oxytocin-induced recovery of medial prefrontal activity: a randomized trial.
abstract: OBJECTIVE
  Sociocommunicational 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.
  
  
  OBJECTIVE
  To directly examine whether oxytocin has beneficial effects on the sociocommunicational deficits of ASD using both behavioral and neural measures.
  
  
  METHODS
  At 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.
  
  
  METHODS
  Single-dose intranasal administration of oxytocin (24 IU) and placebo.
  
  
  METHODS
  Using 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.
  
  
  RESULTS
  Intranasal 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
  These 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.
  
  
  BACKGROUND
  umin.ac.jp/ctr Identifier: UMIN000002241 and UMIN000004393.
authors.affiliation: Department of Neuropsychiatry, School of Medicine, University of Tokyo, Tokyo, Japan2Department of Physiology, School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Radiology, School of Medicine, Nihon University, Tokyo, Japan4Department of Radiology, School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Abe
authors.affiliation: Department of Child Neuropsychiatry, School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kuwabara
authors.affiliation: Department of Neuropsychiatry, School of Medicine, University of Tokyo, Tokyo, Japan6Global Center of Excellence Program, University of Tokyo, Tokyo, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Yahata
authors.affiliation: Department of Neuropsychiatry, School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Takano
authors.affiliation: Department of Neuropsychiatry, School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Norichika
authors.initials: N
authors.lastname: Iwashiro
authors.affiliation: Department of Neuropsychiatry, School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Tatsunobu
authors.initials: T
authors.lastname: Natsubori
authors.affiliation: Department of Neuropsychiatry, School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Aoki
authors.affiliation: Department of Radiology, School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Takao
authors.affiliation: Department of Child Neuropsychiatry, School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kawakubo
authors.affiliation: Department of Child and Adolescent Mental Health, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kamio
authors.affiliation: Department of Neuropsychiatry, School of Medicine, Showa University, Tokyo, Japan.
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Kato
authors.affiliation: Department of Physiology, School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miyashita
authors.affiliation: Department of Neuropsychiatry, School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Kasai
authors.affiliation: Department of Neuropsychiatry, School of Medicine, University of Tokyo, Tokyo, Japan8Department of Neuropsychiatry, School of Medicine, Showa University, Tokyo, Japan9Japan Science and Technology Agency, Tokyo, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Yamasue
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D002659:Child Development Disorders, Pervasive / Q000188:drug therapy*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D008297:Male; D010121:Oxytocin / Q000008:administration & dosage / Q000494:pharmacology*; D015990:Placebo Effect; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology*; D012919:Social Behavior; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D010121:Oxytocin