eprintid: 1476935 rev_number: 23 eprint_status: archive userid: 608 dir: disk0/01/47/69/35 datestamp: 2016-03-23 13:12:29 lastmod: 2021-09-20 00:23:13 status_changed: 2016-03-23 13:12:29 type: article metadata_visibility: show creators_name: Watanabe, T creators_name: Kuroda, M creators_name: Kuwabara, H creators_name: Aoki, Y creators_name: Iwashiro, N creators_name: Tatsunobu, N creators_name: Takao, H creators_name: Nippashi, Y creators_name: Kawakubo, Y creators_name: Kunimatsu, A creators_name: Kasai, K creators_name: Yamasue, H title: Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism ispublished: pub divisions: UCL divisions: B02 divisions: C07 keywords: clinical trial, functional MRI, neuropeptide, pervasive developmental disorder, resting-state functional connectivity, Administration, Intranasal, Adult, Autism Spectrum Disorder, Autistic Disorder, Brain, Cross-Over Studies, Double-Blind Method, Functional Neuroimaging, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Neural Pathways, Oxytocics, Oxytocin, Prefrontal Cortex, Social Behavior, Treatment Outcome, Young Adult note: This is a pre-copyedited, author-produced PDF of an article accepted for publication in Brain following peer review. The version of record, Watanabe, T; Kuroda, M; Kuwabara, H; Aoki, Y; Iwashiro, N; Tatsunobu, N; Takao, H; (2015) Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism. Brain, 138 (11) pp. 3400-3412, is available online at: http://dx.doi.org/10.1093/brain/awv249. abstract: Autism spectrum disorder is a prevalent neurodevelopmental disorder with no established pharmacological treatment for its core symptoms. Although previous literature has shown that single-dose administration of oxytocin temporally mitigates autistic social behaviours in experimental settings, it remains in dispute whether such potentially beneficial responses in laboratories can result in clinically positive effects in daily life situations, which are measurable only in long-term observations of individuals with the developmental disorder undergoing continual oxytocin administration. Here, to address this issue, we performed an exploratory, randomized, double-blind, placebo-controlled, crossover trial including 20 high-functional adult males with autism spectrum disorder. Data obtained from 18 participants who completed the trial showed that 6-week intranasal administration of oxytocin significantly reduced autism core symptoms specific to social reciprocity, which was clinically evaluated by Autism Diagnostic Observation Scale (P = 0.034, PFDR < 0.05, Cohen's d = 0.78). Critically, the improvement of this clinical score was accompanied by oxytocin-induced enhancement of task-independent resting-state functional connectivity between anterior cingulate cortex and dorso-medial prefrontal cortex (rho = -0.60, P = 0.011), which was measured by functional magnetic resonance imaging. Moreover, using the same social-judgement task as used in our previous single-dose oxytocin trial, we confirmed that the current continual administration also significantly mitigated behavioural and neural responses during the task, both of which were originally impaired in autistic individuals (judgement tendency: P = 0.019, d = 0.62; eye-gaze effect: P = 0.03, d = 0.56; anterior cingulate activity: P = 0.00069, d = 0.97; dorso-medial prefrontal activity: P = 0.0014, d = 0.92; all, PFDR < 0.05). Furthermore, despite its longer administration, these effect sizes of the 6-week intervention were not larger than those seen in our previous single-dose intervention. These findings not only provide the evidence for clinically beneficial effects of continual oxytocin administration on the core social symptoms of autism spectrum disorder with suggesting its underlying biological mechanisms, but also highlight the necessity to seek optimal regimens of continual oxytocin treatment in future studies. date: 2015-11-01 date_type: published official_url: http://dx.doi.org/10.1093/brain/awv249 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1051693 doi: 10.1093/brain/awv249 pii: awv249 lyricists_name: Watanabe, Takamitsu lyricists_id: TWATA89 actors_name: Watanabe, Takamitsu actors_id: TWATA89 actors_role: owner full_text_status: public publication: Brain volume: 138 number: 11 pagerange: 3400-3412 event_location: England issn: 1460-2156 citation: Watanabe, T; Kuroda, M; Kuwabara, H; Aoki, Y; Iwashiro, N; Tatsunobu, N; Takao, H; ... Yamasue, H; + view all <#> Watanabe, T; Kuroda, M; Kuwabara, H; Aoki, Y; Iwashiro, N; Tatsunobu, N; Takao, H; Nippashi, Y; Kawakubo, Y; Kunimatsu, A; Kasai, K; Yamasue, H; - view fewer <#> (2015) Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism. Brain , 138 (11) pp. 3400-3412. 10.1093/brain/awv249 <https://doi.org/10.1093/brain%2Fawv249>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1476935/1/TWatanabe_etal_2015_Brain.pdf