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Study · Randomized controlled trial · n = 83 · 2021

4 results

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

Kato Y, Kuwabara H, Okada T, Munesue T, Benner S, Kuroda M, Kojima M, Yassin W, Eriguchi Y, Kameno Y, Murayama C, Nishimura T and 5 more

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Tsuchiya K, Kasai K, Ozaki N, Kosaka H, Yamasue H

Molecular autism23 Feb 2021Cited by 8 (Europe PMC)

PMID33622389 (opens in a new tab)PMCIDPMC7903697 (opens in a new tab)DOI10.1186/s13229-021-00423-z (opens in a new tab)PepBankPUB-33622389
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Summary

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 (PFDR = 0.004, d = 1.13, N = 60). The increase in N,N-dimethylglycine was significantly correlated with oxytocin-induced clinical changes, assessed as changes in quantifiable characteristics of autistic facial expression, including both of improvements between baseline and 2 weeks (PFDR = 0.006, r = - 0.485, N = 43) and deteriorations between 2 and 4 weeks (PFDR = 0.032, r = 0.415, N = 37).LimitationsThe 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).
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

4 results from studies that gave the peptide. 4 results from people.

  1. 01HumanRandomized controlled trialMechanism

    In adult men with autism spectrum disorder, repeated intranasal oxytocin increased plasma N,N-dimethylglycine versus placebo, among 35 metabolites measured.

    In plain wordsIn men with autism, six weeks of nasal oxytocin raised blood levels of the metabolite N,N-dimethylglycine compared with placebo.

    Peptide
    Oxytocin
    Outcome
    IncreasePlasma N,N-dimethylglycine change
    Study

    n = 83

    Comparator
    Placebo
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    48 IU/day · intranasal · 6 weeksAs given in this study (human).

    Measurements

    Cohen's d
    0.74
    oxytocin vs placebo

    Source sentences

    Summary
    Among 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).
    1 context sentence
    Summary · context
    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.
  2. 02HumanRandomized controlled trialMechanism

    In adult men with autism whose oxytocin efficacy changed prominently over time, oxytocin significantly increased N,N-dimethylglycine with a large effect size.

    In plain wordsIn men with autism who showed a clear change in oxytocin response over time, oxytocin raised N,N-dimethylglycine levels strongly.

    Peptide
    Oxytocin
    Outcome
    IncreasePlasma N,N-dimethylglycine change in participants with prominent time-course change in efficacy
    Study

    n = 60

    Comparator
    Placebo
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    48 IU/day · intranasal · 6 weeksAs given in this study (human).

    Measurements

    Cohen's d
    1.13
    subgroup

    Source sentences

    Summary
    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 (PFDR = 0.004, d = 1.13, N = 60).
    1 context sentence
    Summary · context
    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.
  3. 03HumanRandomized controlled trialMechanism

    In adult men with autism given oxytocin, the increase in N,N-dimethylglycine correlated with improvements in autistic facial expression between baseline and 2 weeks.

    In plain wordsIn men with autism given oxytocin, a rise in N,N-dimethylglycine was linked to early improvements in facial expression.

    Peptide
    Oxytocin
    Outcome
    Not applicableCorrelation of N,N-dimethylglycine increase with improvements in autistic facial expression (baseline to 2 weeks)
    Study

    n = 43

    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    48 IU/day · intranasal · 6 weeksAs given in this study (human).

    Measurements

    correlation r
    −0.485
    baseline to 2 weeks

    Source sentences

    Summary
    The increase in N,N-dimethylglycine was significantly correlated with oxytocin-induced clinical changes, assessed as changes in quantifiable characteristics of autistic facial expression, including both of improvements between baseline and 2 weeks (PFDR = 0.006, r = - 0.485, N = 43)
    1 context sentence
    Summary · context
    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.
  4. 04HumanRandomized controlled trialMechanism

    In adult men with autism given oxytocin, the increase in N,N-dimethylglycine correlated with deteriorations in autistic facial expression between 2 and 4 weeks.

    In plain wordsIn men with autism given oxytocin, a rise in N,N-dimethylglycine was linked to later worsening of facial expression.

    Peptide
    Oxytocin
    Outcome
    Not applicableCorrelation of N,N-dimethylglycine increase with deteriorations in autistic facial expression (2 to 4 weeks)
    Study

    n = 37

    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    48 IU/day · intranasal · 6 weeksAs given in this study (human).

    Measurements

    correlation r
    0.415
    2 to 4 weeks

    Source sentences

    Summary
    The increase in N,N-dimethylglycine was significantly correlated with oxytocin-induced clinical changes, assessed as changes in quantifiable characteristics of autistic facial expression, including both of improvements between baseline and 2 weeks (PFDR = 0.006, r = - 0.485, N = 43) and deteriorations between 2 and 4 weeks (PFDR = 0.032, r = 0.415, N = 37)
    1 context sentence
    Summary · context
    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.

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Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    11 Oct 2026, 00:50 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 02:48 UTC

    First added · source update from Europe PMC

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Terms as the source lists them.

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