Evidence map›Paper›PMID 33622389›Full record

Trial reportMolecular autism2021

Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms.

Yasuhiko Kato, Hitoshi Kuwabara, Takashi Okada, Toshio Munesue, Seico Benner, Miho Kuroda, Masaki Kojima, Walid Yassin, Yosuke Eriguchi, Yosuke Kameno and 7 more

Open access · goldAbstract readMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in Molecular autism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
2.0field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 5 institutions in 1 country.

Yasuhiko KatoDepartment of Psychiatry, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashiku, Hamamatsu City, 431-3192, Japan.
Hitoshi KuwabaraDepartment of Psychiatry, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashiku, Hamamatsu City, 431-3192, Japan.
Takashi OkadaDepartment of Psychiatry, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
Toshio MunesueResearch Center for Child Mental Development, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8640, Japan.
Seico BennerDepartment of Psychiatry, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashiku, Hamamatsu City, 431-3192, Japan.
Miho KurodaDepartment of Child Neuropsychiatry, School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Masaki KojimaDepartment of Child Neuropsychiatry, School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Walid YassinDepartment of Child Neuropsychiatry, School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Yosuke EriguchiDepartment of Child Neuropsychiatry, School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Yosuke KamenoDepartment of Psychiatry, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashiku, Hamamatsu City, 431-3192, Japan.
Chihiro MurayamaDepartment of Psychiatry, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashiku, Hamamatsu City, 431-3192, Japan.
Tomoko NishimuraUnited Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Osaka/Kanazawa/Hamamatsu/Chiba/Fukui, Japan.
Kenji TsuchiyaUnited Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Osaka/Kanazawa/Hamamatsu/Chiba/Fukui, Japan.
Kiyoto KasaiDepartment of Neuropsychiatry, School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Norio OzakiDepartment of Psychiatry, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
Hirotaka KosakaDepartment of Neuropsychiatry, Faculty of Medical Sciences, University of Fukui, Eiheiji, Fukui, 910-1193, Japan.
Hidenori YamasueDepartment of Psychiatry, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashiku, Hamamatsu City, 431-3192, Japan. yamasue@hama-med.ac.jp.ORCID 0000-0002-2748-6317
Hamamatsu University School of Medicine · JPThe University of Tokyo · JPKanazawa University · JPNagoya University · JPUniversity of Fukui · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efficacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efficacy of the neuropeptide underlying the controversial effects of repeated administration; however, the underlying mechanisms remained unknown.

methodsThe current study explored metabolites representing the molecular mechanisms of oxytocin's efficacy using high-throughput metabolomics analysis on plasma collected before and after 6-week repeated intranasal administration of oxytocin (48 IU/day) or placebo in adult males with ASD (N = 106) who participated in a multi-center, parallel-group, double-blind, placebo-controlled, randomized controlled trial.

resultsAmong the 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in the subjects administered oxytocin compared with those given placebo at a medium effect size (false discovery rate (FDR) corrected P = 0.043, d = 0.74, N = 83). Furthermore, subgroup analyses of the participants displaying a prominent time-course change in oxytocin efficacy revealed a significant effect of oxytocin on N,N-dimethylglycine levels with a large effect size (P LIMITATIONS: The metabolites changes caused by oxytocin administration were quantified using peripheral blood and therefore may not directly reflect central nervous system changes.

conclusionOur findings demonstrate an association of N,N-dimethylglycine upregulation with the time-course change in the efficacy of oxytocin on autistic social deficits. Furthermore, the current findings support the involvement of the N-methyl-D-aspartate receptor and neural plasticity to the time-course change in oxytocin's efficacy.

trial registrationA multi-center, parallel-group, placebo-controlled, double-blind, confirmatory trial of intranasal oxytocin in participants with autism spectrum disorders (the date registered: 30 October 2014; UMIN Clinical Trials Registry: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017703 ) (UMIN000015264).

Indexed as

Administration, IntranasalAdolescentAdultAutistic DisorderDouble-Blind MethodFacial ExpressionHumansMaleMetabolomicsMiddle AgedOxytocinSarcosineSocial BehaviorTreatment OutcomeYoung AdultdimethylglycineOxytocinSarcosineAspergerAutismClinical trialDevelopmental disordersFacial expressionMetabolomicsNeuropeptideN,N-DimethylglycineOxytocinPlasticity

Identifiers

PMID33622389
PMCPMC7903697
OpenAlexW3120467646

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.