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Cited by 102Neuroendocrine regulation and behaviorAutism Spectrum Disorder ResearchGenetics and Neurodevelopmental Disorders

Behavioral effects of multiple-dose oxytocin treatment in autism: a randomized, placebo-controlled trial with long-term follow-up

Open access
Bernaerts, Sylvie, Boets, Bart, Bosmans, Guy, Steyaert, Jean, Alaerts, Kaat·2020·Molecular Autism
DOI 10.1186/s13229-020-0313-1PMC PMC6964112

Published version of a preprint

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Abstract

Background: Intranasal administration of the “prosocial” neuropeptide oxytocin is increasingly explored as a potential treatment for targeting the core characteristics of autism spectrum disorder (ASD). However, long-term follow-up studies, evaluating the possibility of long-lasting retention effects, are currently lacking. Methods: Using a double-blind, randomized, placebo-controlled, parallel design, this pilot clinical trial explored the possibility of long-lasting behavioral effects of 4 weeks of intranasal oxytocin treatment (24 International Units once daily in the morning) in 40 adult men with ASD. To do so, self-report and informant-based questionnaires assessing core autism symptoms and characterizations of attachment were administered at baseline, immediately after 4 weeks of treatment (approximately 24 h after the last nasal spray administration), and at two follow-up sessions, 4 weeks and 1 year post-treatment. Results: No treatment-specific effects were identified in the primary outcome assessing social symptoms (Social Responsiveness Scale, self- and informant-rated). In particular, with respect to self-reported social responsiveness, improvements were evident both in the oxytocin and in the placebo group, yielding no significant between-group difference ( p = .37). Also informant-rated improvements in social responsiveness were not significantly larger in the oxytocin, compared to the placebo group (between-group difference: p = .19). Among the secondary outcome measures, treatment-specific improvements were identified in the Repetitive Behavior Scale and State Adult Attachment Measure, indicating reductions in self-reported repetitive behaviors ( p = .04) and reduced feelings of avoidance toward others ( p = .03) in the oxytocin group compared to the placebo group, up to 1 month and even 1 year post-treatment. Treatment-specific effects were also revealed in screenings of mood states (Profile of Mood States), indicating higher reports of “vigor” (feeling energetic, active, lively) in the oxytocin, compared to the placebo group ( p = .03). Conclusions: While no treatment-specific improvements were evident in terms of core social symptoms, the current observations of long-term beneficial effects on repetitive behaviors and feelings of avoidance are promising and suggestive of a therapeutic potential of oxytocin treatment for ASD. However, given the exploratory nature of this pilot study, future studies are warranted to evaluate the long-term effects of OT administration further. Trial registration: The trial was registered with the European Clinical Trial Registry (Eudract 2014-000586-45) on January 22, 2014 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-000586-45/BE ).

AI snapshot

Written from the paper’s full text.

TL;DR

In a 4-week randomized, placebo-controlled pilot trial of intranasal oxytocin (24 IU once daily) in 40 adult men with ASD, no treatment-specific effect was found on the primary social responsiveness outcome. Exploratory secondary analyses found oxytocin-specific improvements in repetitive behaviors and attachment avoidance that persisted up to 1 month and 1 year post-treatment.

Key findings

  • No significant between-group difference in the primary outcome, Social Responsiveness Scale (SRS-A): self-rated p = .37; informant-rated p = .19.
  • Oxytocin-specific improvements were found for repetitive behaviors on the Repetitive Behavior Scale-Revised (RBS-R; p = .04), with between-group Cohen’s d of −0.63 at T1, −0.50 at T2, and −0.98 at T3.
  • Oxytocin-specific reductions in attachment avoidance on the State Adult Attachment Measure (SAAM avoidance; p = .03) persisted to 1 month and 1 year post-treatment, with between-group Cohen’s d of −0.61 at T1, −0.53 at T2, and −0.80 at T3.
  • A treatment-specific effect was also found for the mood state “vigor” on the Profile of Mood States (p = .03), with higher reports in the oxytocin group.

Methods

  • Double-blind, randomized, placebo-controlled, parallel pilot trial in 40 high-functioning adult men with ASD recruited at Leuven University Hospital; participants were randomized to oxytocin (n = 22) or placebo (n = 18).
  • Participants self-administered intranasal oxytocin 24 IU once daily in the morning for 4 consecutive weeks (28 doses total); questionnaires were completed at baseline, immediately post-treatment, 4 weeks post-treatment, and 1 year post-treatment.
  • Pre-to-post difference scores were analyzed with linear mixed-effects models (one-tailed) including treatment, session, and treatment × session, using intention-to-treat with last-observation-carried-forward; significance was set at p < .05 without correction for multiple comparisons.

Limitations

  • The paper states that the sample was small and comparable to prior similar trials, that findings from this exploratory pilot without correction for multiple comparisons should be interpreted with caution, and that larger studies are warranted.
  • The paper states that oxytocin was administered once daily rather than twice daily as in most prior multiple-dose studies, that self-report questionnaires may introduce subjective bias, and that results cannot be extended to women or children with ASD.
  • Evident from the text: no primary time point was pre-specified, several reported benefits come from secondary/exploratory outcomes, and placebo response is discussed as a possible explanation for unspecific improvements in social symptoms.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1186/s13229-020-0313-1

Cites

Statistics

24 tests recomputed · 0 with the reported and recomputed p on opposite sides of .05

Claims the paper makes

0 of 68 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Higher baseline SRS-A scores were significantly associated with lower perceived secure attachment (IPPA) toward mother.

    “Higher self-reported SRS-A scores (at baseline) (more impairment in social responsiveness) were significantly associated with lower perceived secure attachment (IPPA) towards peers (r = − .55, p < .001), mother (r = − .51, p = .001) and father (r = − .34, p = .034)”
    Quote in the paperNot a substantial claim
  • Findingown data

    Only minimal, non-treatment-specific side effects were reported in this trial.

    “As listed in detail in Additional file 1: Table S2, only minimal, non-treatment specific side effects were reported.”
    Quote in the paperNot a substantial claim
  • Findingown data

    In this trial, oxytocin treatment did not produce a treatment-specific improvement in attachment security across assessment sessions.

    “Between-group analyses identified no main effect of treatment F(1,76) = .88, p = .18, ŋ2 = .02), nor a treatment × session interaction effect (F(2,76) = 1.08, p = .17, ŋ2 = .03), indicating no treatment-specific improvement in attachment security across assessment sessions”
    • Also stated in: § Secondary outcome—State Adult Attachment Measure · plain
      “Also no significant within-group pre-to-post changes were identified in the OT or PL group separately”
    Quote in the paperNot a substantial claim
  • Findingown data

    Treatment-specific effects were revealed in screenings of mood states (Profile of Mood States), indicating higher reports of vigor in the oxytocin compared to the placebo group (p = .03).

    “Treatment-specific effects were also revealed in screenings of mood states (Profile of Mood States), indicating higher reports of “vigor” (feeling energetic, active, lively) in the oxytocin, compared to the placebo group (p = .03).”
    Quote in the paperNot a substantial claim
  • Findingown data

    In this trial, oxytocin treatment did not produce a treatment-specific improvement in attachment anxiety across assessment sessions.

    “Between-group analyses identified no main effect of treatment (F(1,76) = .25, p = .31, ŋ2 = .01), nor a treatment × session interaction effect (F(2,76) = 1.566, p = .10, ŋ2 = .04), indicating no treatment-specific improvement in attachment anxiety across assessment sessions”
    • Also stated in: § Secondary outcome—State Adult Attachment Measure · plain
      “Also no significant within-group pre-to-post changes were identified in the OT or PL group separately”
    Quote in the paperSubstantial claim
  • May combine two claims. 35
  • Classified as probably not a substantial claim. 29

  • May combine two claims.

    Findingown data

    Within-group analyses showed that self-reported SRS-A scores were significantly reduced compared to baseline in the oxytocin group at T1 (p = .033) and T2 (p = .048), and at trend-level at T3 (p = .07).

    “Within-group analyses showed that Social Responsiveness Scale (SRS-A) scores were significantly reduced (compared to baseline) in the OT group at session T1 (immediately after treatment: p = .033), T2 (1 month post-treatment; p = .048), and at trend-level at session T3 (1 year post-treatment: p = .07).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Between-group analyses of informant-rated SRS-A scores revealed no significant main effect of treatment (F(1,60) = .78, p = .19), nor a treatment × session interaction (F(2,60) = .83, p = .22), indicating that pre-to-post changes in informant-rated social responsiveness were not significantly larger in the oxytocin compared to the placebo group.

    “Between-group analyses of the informant-rated SRS-A scores revealed no significant main effect of treatment (F(1, 60) = .78, p = .19, ŋ2 = .03), nor a treatment x session interaction effect (F(2, 60) = .83, p = .22, ŋ2 = .03), indicating that pre-to-post changes in informant-rated social responsiveness were not significantly larger in the OT compared to the PL group”
    • Also stated in: § Results · plain
      “Also informant-rated improvements in social responsiveness were not significantly larger in the oxytocin, compared to the placebo group (between-group difference: p = .19).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Self-reported social responsiveness improvements were evident in both the oxytocin and placebo groups, yielding no significant between-group difference (p = .37).

    “In particular, with respect to self-reported social responsiveness, improvements were evident both in the oxytocin and in the placebo group, yielding no significant between-group difference (p = .37).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Between-group analyses revealed no significant main effect of treatment on self-reported social responsiveness (F(1,76) = .12, p = .37, ŋ2 = .00), nor a treatment × session interaction (F(2,76) = 1.17, p = .16, ŋ2 = .03), indicating that pre-to-post changes in self-reported social responsiveness were not significantly larger in the oxytocin compared to the placebo group.

    “Between-group analyses revealed no significant main effect of treatment (F(1,76) = .12, p = .37, ŋ2 = .00), nor a treatment × session interaction effect (F(2,76) = 1.17, p = .16, ŋ2 = .03), indicating that pre-to-post changes in self-reported social responsiveness were not significantly larger in the OT compared to the PL group”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Between-group analyses identified a significant main effect of treatment on attachment avoidance (F(1,76) = 3.70, p = .03, ŋ2 = .09) but no treatment × session interaction (F(2,76) = .27, p = .38, ŋ2 = .01), indicating that across assessment sessions pre-to-post improvements in attachment avoidance were significantly larger in the oxytocin compared to the placebo group.

    “In terms of attachment avoidance, between-group analyses identified a significant main effect of treatment (F(1,76) = 3.70, p = .03, ŋ2 = .09) (but no treatment x session interaction: F(2,76) = .27, p = .38, ŋ2 = .01), indicating that across assessment sessions, pre-to-post improvements in attachment avoidance were significantly larger in the OT compared to the PL group”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Within-group analyses confirmed that RBS-R scores were significantly reduced compared to baseline in the oxytocin group at T1 (p = .002), T2 (p = .002), and T3 (p = .02), but not consistently in the placebo group (T1 p = .15; T2 p = .012; T3 p = .70).

    “Within-group analyses confirmed that Repetitive Behavior Scale-Revised (RBS-R) scores were significantly reduced (compared to baseline) in the OT group at session T1 (immediately after treatment: p = .002), T2 (1 month post-treatment; p = .002), and session T3 (1 year post-treatment: p = .02), but not consistently in the PL group (T1: p = .15; T2: p = .012; T3: p = .70)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    At T2 (1 month post-treatment), informant-rated SRS-A scores were significantly reduced in the oxytocin group (p = .002) but not in the placebo group (p = .67).

    “Note however that at session T2 (1 month post-treatment), informant-rated SRS-A scores were significantly reduced in the OT group (compared to baseline) (p = .002), but not in the PL group (p = .67)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The placebo group showed a significant reduction in self-reported vigor at session T1 compared to baseline, while the oxytocin group showed no significant pre-to-post changes.

    “While no significant pre-to-post changes were evident within the OT group, the PL group showed a significant reduction (compared to baseline) in self-reported vigor at session T1 (p = .002)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Within-group analyses confirmed that attachment avoidance scores were significantly reduced compared to baseline in the oxytocin group at T1 (p = .016), T2 (p = .018), and T3 (p = .05), but not in the placebo group (T1 p = .81; T2 p = .73; T3 p = 1.00).

    “Within-group analyses confirmed that attachment avoidance scores were significantly reduced (compared to baseline) in the OT group at session T1 (immediately after treatment: p = .016), T2 (1-month post-treatment; p = .018), and session T3 (1-year post-treatment: p = .05), but not in the PL group (T1: p = .81; T2: p = .73; T3: p = 1.00)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Between-group analyses identified a significant main effect of treatment on repetitive behaviors (F(1,74) = 3.20, p = .04, ŋ2 = .08) but no treatment × session interaction (F(2,74) = 1.04, p = .18, ŋ2 = .03), indicating that across assessment sessions pre-to-post improvements in repetitive behaviors were significantly larger in the oxytocin compared to the placebo group.

    “In terms of repetitive behaviors, between-group analyses identified a significant main effect of treatment (F(1, 74) = 3.20, p = .04, ŋ2 = .08) (but no treatment x session interaction: F(2, 74) = 1.04, p = .18, ŋ2 = .03), indicating that across assessment sessions, pre-to-post improvements in repetitive behaviors were significantly larger in the OT compared to the PL group”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    A similar reduction in self-reported SRS-A scores compared to baseline was evident in the placebo group at T2 (p = .015), indicating no specific benefit of oxytocin over placebo treatment.

    “However, a similar reduction (compared to baseline) was evident in the PL group at session T2 (p = .015), indicating no specific benefit of OT over the PL treatment”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In this study, impairments in social responsiveness and more frequent and/or severe repetitive behaviors were associated with a more avoidant attachment style and with less secure attachment toward significant others, especially the mother.

    “In terms of associations between core autism characteristics and attachment characteristics, our study showed that impairments in social responsiveness and more frequent and/or severe repetitive behaviors were associated with a more avoidant attachment style and with less secure attachment toward significant others (especially the mother).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    No overall treatment-specific improvements were observed in informant-based reports of social responsiveness (SRS-A), despite a reduction in informant-rated symptom severity in the OT group but not the PL group at session T2.

    “Also with respect to the effect of multiple-dose OT treatment on informant-based reports of social responsiveness (SRS-A), no overall treatment-specific improvements were observed (despite the identification of a reduction in informant-rated symptom severity in the OT group, but not in the PL group at session T2)”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Autism spectrum disorder (ASD) is characterized by lifelong impairments in social and communicative functioning and by the presence of stereotyped behaviors and interests.

    “Autism spectrum disorder (ASD) is characterized by lifelong impairments in social and communicative functioning, and the presence of stereotyped behaviors and interests [1].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-5®) [Internet]. 5th ed. Arlington, editor. American Psychiatric Association; 2013 [cited 2016 Feb 4]. 50–59. Available from: https://books.google.com/books?hl=nl&lr=&id=-JivBAAAQBAJ&pgis=1

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In typically developing individuals, oxytocin has been linked to interpersonal bonding, parental care, and the ability to establish trust and form social attachments.

    “In typically developing individuals, OT has been linked to interpersonal bonding, parental care, and the ability to establish trust and form social attachments [2, 3].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [2] Bakermans-Kranenburg MJ, van I Jzendoorn MH. Sniffing around oxytocin: review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy. Transl Psychiatry [Internet]. 2013 [cited 2015 Sep 7];3:e258. Available from: https://doi.org/10.1038/tp.2013.34 source

      Not checked in the free run.

    • cites [3] Bartz JA, Zaki J, Bolger N, Ochsner KN. Social effects of oxytocin in humans: context and person matter. Trends Cogn Sci [Internet]. 2011;15(7):301–9 Available from: http://linkinghub.elsevier.com/retrieve/pii/S1364661311000830.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A recent meta-analysis concluded that more severe autism characteristics are associated with less secure attachment in children with ASD.

    “In addition, a recent meta-analysis concluded that more severe autism characteristics are associated with less secure attachment in children with ASD [22].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Teague SJ, Gray KM, Tonge BJ, Newman LK. Attachment in children with autism spectrum disorder: a systematic review. Res Autism Spectr Disord [Internet]. 2017;35:35–50 Available from: https://doi.org/10.1016/j.rasd.2016.12.002. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    To date, potential long-term effects of oxytocin treatment that outlast the period of actual administration have not yet been addressed in adults with ASD.

    “To date, however, potential long-term effects of OT treatment that outlast the period of actual administration have not yet been addressed in adults with ASD.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    A prior study from the authors' lab showed that 2 weeks of oxytocin treatment in typically developing young-adult men reduced self-reported feelings of attachment avoidance and increased self-reported feelings of secure attachment toward peers.

    “While prior multiple-dose trials mainly explored the effects of treatment on these core autism symptom domains, a recent study from our lab [17] showed that 2 weeks of OT treatment in typically developing young-adult men reduced self-reported feelings of attachment avoidance and increased self-reported feelings of secure attachment toward peers.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Bernaerts S, Prinsen J, Berra E, Bosmans G, Steyaert J, Alaerts K. Long-term oxytocin administration enhances the experience of attachment. Psychoneuroendocrinology. 2017;78:1–9. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Parker et al. showed an increase in parent-reported social responsiveness after 4-week intranasal oxytocin treatment in 32 children with ASD.

    “Similarly, Parker et al. [14] investigated whether a 4-week intranasal OT treatment could improve core autism characteristics in 32 children (6–12 years old) with ASD and showed an increase in parent-reported social responsiveness.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Parker KJ, Oztan O, Libove RA, Sumiyoshi RD, Jackson LP, Karhson DS, et al. Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism. Proc Natl Acad Sci [Internet]. 2017;114(30):201705521 Available from: http://www.pnas.org/lookup/doi/10.1073/pnas.1705521114.

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The study used a two-arm, double-blind, randomized, placebo-controlled parallel design.

    “This two-arm, double-blind, randomized, placebo-controlled parallel study was performed at the Leuven University Hospital (Leuven, Belgium) to assess multiple-dose effects of intranasal oxytocin (OT) administration on core autism characteristics and experience of attachment in adult men with ASD.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Anagnostou et al. showed improved emotion recognition, quality of life, and tentative improvements in repetitive behaviors after 6 weeks of intranasal oxytocin treatment in 19 adults with ASD.

    “Anagnostou et al. [8] assessed the safety and efficacy of 6 weeks of intranasal OT treatment on core autism symptom domains (social cognition/function and repetitive behaviors) in 19 adults with ASD (16 men, three women), and showed improved emotion recognition, quality of life, and tentative improvements in repetitive behaviors after OT treatment.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] Anagnostou E, Soorya L, Chaplin W, Bartz J, Halpern D, Wasserman S, et al. Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial. Mol Autism [Internet]. 2012;3(1):16 Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3539865&tool=pmcentrez&rendertype=abstract. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Watanabe et al. showed significant improvements in social reciprocity and social functioning after 6 weeks of intranasal oxytocin treatment in 20 adult men with ASD.

    “In another study with 20 adult men with ASD, Watanabe et al. [9] studied the effects of 6 weeks of intranasal OT administration on core autism characteristics and showed significant improvements in social reciprocity and social functioning (social-judgment task).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [9] Watanabe T, Kuroda M, Kuwabara H, Aoki Y, Iwashiro N, Tatsunobu N, et al. Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism. Brain [Internet]. 2015 [cited 2016 Jan 6];138(Pt 11):3400–3412. Available from: http://brain.oxfordjournals.org/content/138/11/3400 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Early-life impairments in social attention/orienting may deprive patients of adequate social learning experiences that normally drive typical development of social brain networks.

    “With respect to ASD, it has been postulated that early-life impairments in social attention/orienting may deprive patients of adequate social learning experiences that normally drive the typical development of social brain networks [15].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Chevallier C, Kohls G, Troiani V, Brodkin ES, Schultz RT. The social motivation theory of autism. Trends Cogn Sci [Internet]. 2012;16(4):231–8 Available from: https://doi.org/10.1016/j.tics.2012.02.007. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Rutgers et al. suggested that most children with ASD (53%) are able to form a secure attachment to caregivers, but that they are significantly less likely to do so compared to typically developing children.

    “With respect to ASD, Rutgers et al. [21] suggested that most children with ASD (53%) are able to form a secure attachment to caregivers, but that they are significantly less likely to do so compared to typically developing children.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Rutgers AH, Bakermans-Kranenburg MJ, Van Ijzendoorn MH, Van Berckelaer-Onnes IA. Autismand attachment: ameta-analytic review. J Child Psychol Psychiatry. 2004;45(6):1123–34. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Oxytocin is hypothesized to increase the saliency of social cues.

    “Considering that OT is hypothesized to increase the saliency of social cues [16], OT therapy might induce an enrichment of social experiences that stimulates long-term adaptations in social behaviors.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [16] Shamay-Tsoory SG, Abu-Akel A. The social salience hypothesis of oxytocin. Biol Psychiatry [Internet]. 2015 Aug [cited 2015 Aug 7];79(3):194–202. Available from: http://www.sciencedirect.com/science/article/pii/S0006322315006393 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Participants were assigned to receive oxytocin or placebo based on a computer-generated randomized order.

    “Participants were assigned to receive the OT or PL treatment based on a computer-generated randomized order.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Data were analyzed using an intention-to-treat format with last-observations-carried-forward to replace missing data.

    “An intention-to-treat format and last-observations-carried-forward to replace missing data was adopted.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Except for the manager of randomization, all research staff conducting the trial, participants, and their parents and/or partners were blinded to treatment allocation.

    “Except for the manager of randomization, all research staff conducting the trial, participants, and their parents and/or partners were blinded to treatment allocation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    No significant baseline differences were revealed between participants allocated to the oxytocin or placebo group for any of the questionnaires or in terms of participant characteristics.

    “No significant baseline differences were revealed between participants allocated to the OT or PL group for any of the questionnaires (see Additional file 1: Table S3) or in terms of participant characteristics (see Table 1).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    No primary time point was pre-specified.

    “Given that this is an exploratory pilot study evaluating the possibility of long-term retention effects of OT treatment, no primary time point was pre-specified.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductreasoning

    The significance level was set at p < .05 for all analyses, without correction for multiple comparisons.

    “Given that this is an exploratory pilot study evaluating long-term effects of OT treatment, the significance level was set at p < .05 for all analyses, without correction for multiple comparisons.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The initial sample size (n = 40) was set to be comparable to three prior studies showing significant effects of multiple-dose oxytocin treatment on similar outcome measures.

    “The initial sample size (n = 40) was set to be comparable to three prior studies showing significant effects of multiple-dose OT treatment on similar outcome measures [8, 9, 17].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [8] Anagnostou E, Soorya L, Chaplin W, Bartz J, Halpern D, Wasserman S, et al. Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial. Mol Autism [Internet]. 2012;3(1):16 Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3539865&tool=pmcentrez&rendertype=abstract. source

      Not checked in the free run.

    • cites [9] Watanabe T, Kuroda M, Kuwabara H, Aoki Y, Iwashiro N, Tatsunobu N, et al. Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism. Brain [Internet]. 2015 [cited 2016 Jan 6];138(Pt 11):3400–3412. Available from: http://brain.oxfordjournals.org/content/138/11/3400 source

      Not checked in the free run.

    • cites [17] Bernaerts S, Prinsen J, Berra E, Bosmans G, Steyaert J, Alaerts K. Long-term oxytocin administration enhances the experience of attachment. Psychoneuroendocrinology. 2017;78:1–9. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    One 1-week trial with adult men with ASD did not show OT-specific improvements on informant-based reports of repetitive behaviors.

    “Note however that one 1-week trial with adult men with ASD did not show OT-specific improvements on informant-based reports of repetitive behaviors [9].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [9] Watanabe T, Kuroda M, Kuwabara H, Aoki Y, Iwashiro N, Tatsunobu N, et al. Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism. Brain [Internet]. 2015 [cited 2016 Jan 6];138(Pt 11):3400–3412. Available from: http://brain.oxfordjournals.org/content/138/11/3400 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Previous studies showed beneficial effects of a single dose of OT on attachment security, development of trust and cooperation, and improved communal traits and altered agency.

    “Our findings also extend previous studies showing beneficial effects of a single dose of OT on attachment security [20], development of trust and cooperation [18], and improved communal traits and altered agency [19].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [20] Buchheim A, Heinrichs M, George C, Pokorny D, Koops E, Henningsen P, et al. Oxytocin enhances the experience of attachment security. Psychoneuroendocrinology [Internet]. 2009;34(9):1417–22 Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3138620&tool=pmcentrez&rendertype=abstract. source

      Not checked in the free run.

    • cites [18] De Dreu CKW. Oxytocin modulates the link between adult attachment and cooperation through reduced betrayal aversion. Psychoneuroendocrinology [Internet]. 2012[cited 2015 Dec 9];37(7):871–880. Available from: http://www.sciencedirect.com/science/article/pii/S0306453011003064 source

      Not checked in the free run.

    • cites [19] Bartz JA, Lydon JE, Kolevzon A, Zaki J, Hollander E, Ludwig N, et al. Differential effects of oxytocin on agency and communion for anxiously and avoidantly attached individuals. Psychol Sci [Internet]. 2015:1–10 Available from: http://pss.sagepub.com/lookup/doi/10.1177/0956797615580279. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    One explanation for unspecific effects in OT trials may be the presence of a placebo response, which has been shown to occur frequently in pediatric autism pharmacological and dietary placebo-controlled trials.

    “As suggested by Yatawara et al. (2016), one explanation for these unspecific effects may be the presence of a placebo response which has been shown to occur frequently in pediatric autism pharmacological and dietary placebo-controlled trials [37].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Yatawara et al. (2016)

      Not checked in the free run.

    • cites [37] Masi A, Lampit A, Glozier N, Hickie IB, Guastella AJ. Predictors of placebo response in pharmacological and dietary supplement treatment trials in pediatric autism spectru disorder: a meta-analysis. Transl Psychiatry [Internet]. 2015;5(9):e640–9 Available from: https://doi.org/10.1038/tp.2015.143. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The lack of a treatment-specific effect in this trial versus previous trials in children might relate to the frequency of contact of children versus adult populations with their respective informants.

    “The lack of a treatment-specific effect in our trial versus previous trials in children might relate to the frequency of contact of children versus adult populations with their respective informants (i.e., more frequent, sustained child-informant contact), potentially rendering more subtle improvements in social functioning in the adult population to remain undetected by informants.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The results suggest that the 4-week OT treatment predominantly improved a person's reluctance toward closeness or trust in others (attachment avoidance), but could not induce significant long-term alterations in a person's feelings of insecurity about one's own abilities (attachment anxiety).

    “our results suggest that the 4-week OT treatment predominantly improved a person’s reluctance toward closeness or trust in others (i.e., attachment avoidance), but that it could not induce significant long-term alterations in a person’s feelings of insecurity about one’s own abilities (i.e., attachment anxiety).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Beneficial effects of OT treatment on repetitive behaviors were mostly demonstrated in studies that adopted assessments based on self-reports, whereas no beneficial effects were evident in studies adopting informant-based reports of repetitive behavior.

    “In this view, it appears that beneficial effects of OT treatment on repetitive behaviors were mostly demonstrated in studies that adopted assessments based on self-reports (current study, [4, 8]), whereas no beneficial effects were evident in studies adopting informant-based reports of repetitive behavior [9–14].”
    Quote in the paperSubstantial claim0 of 8 sources checked
    • cites [4] Hollander E, Novotny S, Hanratty M, Yaffe R, DeCaria CM, Aronowitz BR, et al. Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger’s disorders. Neuropsychopharmacology. 2003;28(1):193–8. source

      Not checked in the free run.

    • cites [8] Anagnostou E, Soorya L, Chaplin W, Bartz J, Halpern D, Wasserman S, et al. Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial. Mol Autism [Internet]. 2012;3(1):16 Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3539865&tool=pmcentrez&rendertype=abstract. source

      Not checked in the free run.

    • cites [9] Watanabe T, Kuroda M, Kuwabara H, Aoki Y, Iwashiro N, Tatsunobu N, et al. Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism. Brain [Internet]. 2015 [cited 2016 Jan 6];138(Pt 11):3400–3412. Available from: http://brain.oxfordjournals.org/content/138/11/3400 source

      Not checked in the free run.

    • cites [10] Yamasue H, Okada T, Munesue T, Kuroda M, Fujioka T, Uno Y, et al. Effect of intranasal oxytocin on the core social symptoms of autism spectrum disorder: a randomized clinical trial. Mol Psychiatry [Internet]. 2018;1 Available from: http://www.nature.com/articles/s41380-018-0097-2.

      Not checked in the free run.

    • cites [11] Dadds MR, MacDonald E, Cauchi A, Williams K, Levy F, Brennan J. Nasal oxytocin for social deficits in childhood autism: a randomized controlled trial. J Autism Dev Disord [Internet]. 2014[cited 2016 Aug 1];44(3):521–531. Available from: http://link.springer.com/10.1007/s10803-013-1899-3 source

      Not checked in the free run.

    • cites [12] Guastella AJ, Gray KM, Rinehart NJ, Alvares GA, Tonge BJ, Hickie IB, et al. The effects of a course of intranasal oxytocin on social behaviors in youth diagnosed with autism spectrum disorders: A randomized controlled trial. J Child Psychol Psychiatry Allied Discip. 2015;4:444–52. source

      Not checked in the free run.

    • cites [13] Yatawara CJ, Einfeld SL, Hickie IB, Davenport TA, Guastella AJ. The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial. Mol Psychiatry [Internet]. 2016;(August):1–7. Available from: http://www.nature.com.are.uab.cat/mp/journal/vaop/ncurrent/full/mp2015162a.html%5Cn. http://www.nature.com/doifinder/10.1038/mp.2015.162

      Not checked in the free run.

    • cites [14] Parker KJ, Oztan O, Libove RA, Sumiyoshi RD, Jackson LP, Karhson DS, et al. Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism. Proc Natl Acad Sci [Internet]. 2017;114(30):201705521 Available from: http://www.pnas.org/lookup/doi/10.1073/pnas.1705521114.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In three previous long-term administration trials, improvements in social symptoms were identified both in participants receiving OT and in those receiving placebo, but with no significant difference between the two groups.

    “Correspondingly, in three previous long-term administration trials, improvements in social symptoms (SRS-A: [9, 12]) (ADOS subscale assessing social reciprocity: 10) were identified both in participants receiving the OT treatment and in those receiving the placebo treatment, but with no significant difference between the two groups.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [9] Watanabe T, Kuroda M, Kuwabara H, Aoki Y, Iwashiro N, Tatsunobu N, et al. Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism. Brain [Internet]. 2015 [cited 2016 Jan 6];138(Pt 11):3400–3412. Available from: http://brain.oxfordjournals.org/content/138/11/3400 source

      Not checked in the free run.

    • cites [12] Guastella AJ, Gray KM, Rinehart NJ, Alvares GA, Tonge BJ, Hickie IB, et al. The effects of a course of intranasal oxytocin on social behaviors in youth diagnosed with autism spectrum disorders: A randomized controlled trial. J Child Psychol Psychiatry Allied Discip. 2015;4:444–52. source

      Not checked in the free run.

    • cites [10] Yamasue H, Okada T, Munesue T, Kuroda M, Fujioka T, Uno Y, et al. Effect of intranasal oxytocin on the core social symptoms of autism spectrum disorder: a randomized clinical trial. Mol Psychiatry [Internet]. 2018;1 Available from: http://www.nature.com/articles/s41380-018-0097-2.

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductreasoning

    The findings of long-term improvements in repetitive behaviors, attachment avoidance, and vigor mood state should be interpreted with caution because this is an initial pilot study exploring long-term effects of OT treatment without correction for multiple comparisons.

    “Indeed, considering this is an initial pilot study exploring long-term effects of OT treatment (without correction for multiple comparisons), the findings of long-term improvements in repetitive behaviors; attachment avoidance and vigor mood state should be interpreted with caution.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In the current study, participants administered the OT nasal spray once a day (in the morning) while the majority of prior multiple-dose OT studies administered two doses/day.

    “Second, in the current study, participants administered the OT nasal spray once a day (in the morning) while the majority of prior multiple-dose OT studies administered two doses/day (one in the morning and one in the afternoon) ([8–10, 12–14], but see [11]).”
    Quote in the paperNot a substantial claim0 of 7 sources checked
    • cites [8] Anagnostou E, Soorya L, Chaplin W, Bartz J, Halpern D, Wasserman S, et al. Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial. Mol Autism [Internet]. 2012;3(1):16 Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3539865&tool=pmcentrez&rendertype=abstract. source

      Not checked in the free run.

    • cites [9] Watanabe T, Kuroda M, Kuwabara H, Aoki Y, Iwashiro N, Tatsunobu N, et al. Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism. Brain [Internet]. 2015 [cited 2016 Jan 6];138(Pt 11):3400–3412. Available from: http://brain.oxfordjournals.org/content/138/11/3400 source

      Not checked in the free run.

    • cites [10] Yamasue H, Okada T, Munesue T, Kuroda M, Fujioka T, Uno Y, et al. Effect of intranasal oxytocin on the core social symptoms of autism spectrum disorder: a randomized clinical trial. Mol Psychiatry [Internet]. 2018;1 Available from: http://www.nature.com/articles/s41380-018-0097-2.

      Not checked in the free run.

    • cites [12] Guastella AJ, Gray KM, Rinehart NJ, Alvares GA, Tonge BJ, Hickie IB, et al. The effects of a course of intranasal oxytocin on social behaviors in youth diagnosed with autism spectrum disorders: A randomized controlled trial. J Child Psychol Psychiatry Allied Discip. 2015;4:444–52. source

      Not checked in the free run.

    • cites [13] Yatawara CJ, Einfeld SL, Hickie IB, Davenport TA, Guastella AJ. The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial. Mol Psychiatry [Internet]. 2016;(August):1–7. Available from: http://www.nature.com.are.uab.cat/mp/journal/vaop/ncurrent/full/mp2015162a.html%5Cn. http://www.nature.com/doifinder/10.1038/mp.2015.162

      Not checked in the free run.

    • cites [14] Parker KJ, Oztan O, Libove RA, Sumiyoshi RD, Jackson LP, Karhson DS, et al. Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism. Proc Natl Acad Sci [Internet]. 2017;114(30):201705521 Available from: http://www.pnas.org/lookup/doi/10.1073/pnas.1705521114.

      Not checked in the free run.

    • cites [11] Dadds MR, MacDonald E, Cauchi A, Williams K, Levy F, Brennan J. Nasal oxytocin for social deficits in childhood autism: a randomized controlled trial. J Autism Dev Disord [Internet]. 2014[cited 2016 Aug 1];44(3):521–531. Available from: http://link.springer.com/10.1007/s10803-013-1899-3 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Recent reviews stated that most individuals with ASD have poor quality of life or lower quality of life than typically developing adults.

    “Importantly, recent reviews stated that most individuals with ASD have poor quality of life (note that most studies included children with ASD) [41] or lower quality of life than typically developing adults [42].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [41] Chiang HM, Wineman I. Factors associated with quality of life in individuals with autism spectrum disorders: a review of literature. Res Autism Spectr Disord [Internet]. 2014;8(8):974–86 Available from: https://doi.org/10.1016/j.rasd.2014.05.003. source

      Not checked in the free run.

    • cites [42] Ayres M, Parr JR, Rodgers J, Mason D, Avery L, Flynn D. A systematic review of quality of life of adults on the autism spectrum. Autism. 2017. source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    Participants' own beliefs about the received treatment were assessed and inclusion of this factor did not modulate the identified treatment effects.

    “Participants’ own beliefs about the received treatment, however, were assessed and inclusion of this factor did not modulate the identified treatment effects.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In a previous study from our lab, the POMS revealed no treatment-specific changes in vigor but OT-specific reductions in feelings of tension and anger after a 2-week OT treatment in neurotypical men.

    “In a previous study from our lab [17], the POMS was also adopted to evaluate the effects of a 2-week OT treatment in neurotypical men, and while here, no treatment-specific changes in vigor were detected, the POMS revealed OT-specific reductions in feelings of tension and anger.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Bernaerts S, Prinsen J, Berra E, Bosmans G, Steyaert J, Alaerts K. Long-term oxytocin administration enhances the experience of attachment. Psychoneuroendocrinology. 2017;78:1–9. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Anagnostou et al. reported an OT-specific improvement in quality of life (socio-emotional section) after a 6-week treatment in adult men with ASD.

    “Contrary to our findings, Anagnostou et al. [8] reported an OT-specific improvement in quality of life (socio-emotional section) after a 6-week treatment in adult men with ASD.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [8] Anagnostou E, Soorya L, Chaplin W, Bartz J, Halpern D, Wasserman S, et al. Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial. Mol Autism [Internet]. 2012;3(1):16 Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3539865&tool=pmcentrez&rendertype=abstract. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Evidence on the effects of OT on quality of life is relatively scarce since only two prior studies have addressed this topic.

    “To date, evidence on the effects of OT on quality of life is relatively scarce since only two prior studies have addressed this topic.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    To date there is no comprehensive ASD-specific quality of life assessment tool validated, and the tools used in the general population might not be the most adequate to assess quality of life in ASD.

    “Note, however, that to date there is no comprehensive ASD-specific quality of life assessment tool validated and consequently, the tools used in the general population (i.e., WHO-QOL) might not be the most adequate to assess quality of life in ASD (and thus changes in quality of life after intervention) [42].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] Ayres M, Parr JR, Rodgers J, Mason D, Avery L, Flynn D. A systematic review of quality of life of adults on the autism spectrum. Autism. 2017. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The current findings of significant ameliorations in attachment avoidance, but no treatment-specific effects on social responsiveness, are in line with the affiliative-motivation hypothesis and suggest that attachment characteristics may be more sensitive for evaluating treatment responses compared to evaluations based on core autism characteristics alone.

    “The current findings of significant ameliorations in attachment avoidance, but no treatment-specific effects on social responsiveness, are in line with this notion and together suggest that attachment characteristics may be more sensitive for evaluating treatment responses, as compared to evaluations based on core autism characteristics alone.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [38] Bartz JA. Oxytocin and the pharmacological dissection of affiliation. Curr Dir Psychol Sci [Internet]. 2016;25(2):104–10 Available from: http://cdp.sagepub.com/lookup/doi/10.1177/0963721415626678. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The overall mitigation of repetitive behavior symptoms and increased feelings of social approachability by the OT treatment may have been accompanied with overall higher reports of feeling 'energetic,' 'active,' 'lively' in the OT group compared to the PL group.

    “The overall mitigation of repetitive behavior symptoms and increased feelings of social approachability by the OT treatment may therefore have been accompanied with overall higher reports of feeling “energetic,” “active,” “lively” in the OT group, compared to the PL group.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Other studies showed more insecure attachment toward parents or romantic partners in unmarried or married adults with ASD.

    “as well as by other studies showing more insecure attachment toward parents or romantic partners in unmarried [43] or married adults with ASD [44], respectively.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [43] Taylor EL, Target M, Charman T. Attachment in adults with high-functioning autism. Attach Hum Dev. 2008;10(2):143–63. source

      Not checked in the free run.

    • cites [44] Lau W, Peterson CC. Adults and children with Asperger syndrome: exploring adult attachment style, marital satisfaction and satisfaction with parenthood. Res Autism Spectr Disord [Internet]. 2011 [cited 2018 Jun 20];5(1):392–399. Available from: https://www.sciencedirect.com/science/article/pii/S1750946710000887 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Elevated levels of OT have been demonstrated up to 7 h after a single-dose administration.

    “While elevated levels of OT have been demonstrated up to 7 h after a single-dose administration [45]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] van Ijzendoorn MH, Bhandari R, van der Veen R, Grewen KM, Bakermans-Kranenburg MJ. Elevated salivary levels of oxytocin persist more than 7 h after intranasal administration. Front Neurosci [Internet]. 2012 [cited 2019 Mar 20];6:174. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23233832 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A recent meta-analysis showed an association between the severity of autism characteristics and less secure attachment in children with ASD.

    “a notion that is generally supported by a recent meta-analysis showing an association between the severity of autism characteristics and less secure attachment in children with ASD [22]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Teague SJ, Gray KM, Tonge BJ, Newman LK. Attachment in children with autism spectrum disorder: a systematic review. Res Autism Spectr Disord [Internet]. 2017;35:35–50 Available from: https://doi.org/10.1016/j.rasd.2016.12.002. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Our sample size was comparable to that of prior similar clinical trials.

    “First, although our sample size was comparable to that of prior similar clinical trials, studies with larger samples are warranted.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Considering the adopted evaluations were predominantly based on self-report questionnaires, the possibility of subjective bias cannot be ruled out.

    “Third, considering the adopted evaluations were predominantly based on self-report questionnaires, the possibility of subjective bias cannot be ruled out.”
    Quote in the paperNot a substantial claim
54 of 54

  • The paper relies on this without support.

    Oxytocin enhances the salience of socially relevant cues, reduces social stress and anxiety, and modulates approach/avoidance motivational tendencies, presumably by impacting on limbic circuits and the central reward system.

    “OT has been implicated in enhancing the salience of socially relevant cues, inducing reductions in (social) stress and anxiety, and modulating approach/avoidance motivational tendencies, presumably by impacting on limbic circuits (e.g., amygdala) and the central reward system (e.g., nucleus accumbens).”

  • The paper relies on this without support.

    The human oxytocinergic system plays a central role in interpersonal bonding, trust, and attachment.

    “In line with the central role of the human oxytocinergic system in interpersonal bonding, trust, and attachment, the current observations may therefore urge future multiple-dose clinical trials to continue to include characterizations of attachment-related constructs when evaluating the potential of OT treatment for ASD.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • A recent randomised, placebo-controlled, double-blind study in adults with ASD showed improvements in self-reported repetitive behaviors and positive mood at 1 year post treatment after an initial 4 weeks of oxytocin treatment.

    “A recent randomised, placebo-controlled, double-blind study in adults with ASD showed improvements in self-reported repetitive behaviors and positive mood at 1 year post treatment after an initial 4 weeks of oxytocin treatment [78].”

    From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [78]

  • In the same study, there were no significant treatment benefits for social responsiveness with OXT.

    “However, in this same study, there were no significant treatment benefits for social responsiveness with OXT [78].”

    From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [78]

Statistics that don’t add up

Each reported p-value recomputed from its test statistic and degrees of freedom.

  • Inconsistent p-value: F(1,76) = 4.09, p = .03

    Minor

    The paper reports p = .03 here; recomputing from the test statistic and its degrees of freedom gives p = .047. The check cannot tell whether the statistic or the p-value is the misprint.

    Reported p = .03 · recomputed p = .047

1 of 1

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • Doesn’t add upF(1, 76) = 4.09reported p = .03 · recomputed p = .047

    “F(1,76) = 4.09, p = .03”

  • Not confirmedF(2, 76) = 1.566reported p = .1 · recomputed p = .216

    “F(2,76) = 1.566, p = .10”

  • ConsistentF(1, 76) = 0.12reported p = .37 · recomputed p = .730

    “F(1,76) = .12, p = .37”

    The paper states a one-tailed test

  • ConsistentF(2, 76) = 1.17reported p = .16 · recomputed p = .316

    “F(2,76) = 1.17, p = .16”

    The paper states a one-tailed F test

  • ConsistentF(1, 60) = 0.78reported p = .19 · recomputed p = .381

    “F(1, 60) = .78, p = .19”

    The paper states a one-tailed test

  • ConsistentF(2, 60) = 0.83reported p = .22 · recomputed p = .441

    “F(2, 60) = .83, p = .22”

    The paper states a one-tailed F test

  • ConsistentF(1, 74) = 3.2reported p = .04 · recomputed p = .078

    “F(1, 74) = 3.20, p = .04”

    The paper states a one-tailed test

  • ConsistentF(2, 74) = 1.04reported p = .18 · recomputed p = .359

    “F(2, 74) = 1.04, p = .18”

    The paper states a one-tailed F test

  • ConsistentF(1, 76) = 3.7reported p = .03 · recomputed p = .058

    “F(1,76) = 3.70, p = .03”

    The paper states a one-tailed test

  • ConsistentF(2, 76) = 0.27reported p = .38 · recomputed p = .764

    “F(2,76) = .27, p = .38”

    The paper states a one-tailed F test

  • ConsistentF(1, 76) = 0.88reported p = .18 · recomputed p = .351

    “F(1,76) = .88, p = .18”

    The paper states a one-tailed test

  • ConsistentF(2, 76) = 1.08reported p = .17 · recomputed p = .345

    “F(2,76) = 1.08, p = .17”

    The paper states a one-tailed F test

  • ConsistentF(1, 76) = 0.25reported p = .31 · recomputed p = .619

    “F(1,76) = .25, p = .31”

    The paper states a one-tailed test

  • ConsistentF(1, 76) = 0.2reported p = .33 · recomputed p = .656

    “F(1,76) = .20, p = .33”

    The paper states a one-tailed test

  • ConsistentF(1, 74) = 0.57reported p = .23 · recomputed p = .453

    “F(1,74) = .57, p = .23”

    The paper states a one-tailed test

  • ConsistentF(1, 74) = 0.78reported p = .19 · recomputed p = .380

    “F(1,74) = .78, p = .19”

    The paper states a one-tailed test

  • ConsistentF(2, 74) = 0.32reported p = .36 · recomputed p = .727

    “F(2,74) = .32, p = .36”

    The paper states a one-tailed F test

  • ConsistentF(2, 74) = 0.03reported p = .49 · recomputed p = .970

    “F(2,74) = .03, p = .49”

    The paper states a one-tailed F test

  • ConsistentF(1, 74) = 0.77reported p = .19 · recomputed p = .383

    “F(1,74) = .77, p = .19”

    The paper states a one-tailed test

  • ConsistentF(2, 74) = 0.96reported p = .19 · recomputed p = .388

    “F(2,74) = .96, p = .19”

    The paper states a one-tailed F test

  • ConsistentF(2, 76) = 0.04reported p = .96 · recomputed p = .961

    “F(2,76) = .04, p = .96”

  • Consistentt(76) = -2.51reported p = .014 · recomputed p = .014

    “t(76) = − 2.51, p = .014”

  • Consistentt(76) = 2.48reported p = .015 · recomputed p = .015

    “t(76) = 2.48, p = .015”

  • Consistentt(76) = 1.74reported p = .085 · recomputed p = .086

    “t(76) = 1.74, p = .085”

24 of 24

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Placebo-group vigor p value differs between text and table

    Minor

    The Results report p = .002 for the placebo group's T1 reduction in vigor, whereas Table 2 reports p = 0.003 for that change.

  • Attachment-security t statistic has the opposite sign from its mean change

    Minor

    At T3, the oxytocin group's mean change in attachment security is positive (+0.20), but its reported single-sample t statistic is negative (−0.62). A single-sample t test of that change against zero must have the same sign as the mean change.

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References 42 · Cited by 102

Research works printed but not linked: 2

  1. Wechsler D, Coalson D, Raiford S. WAIS IV Technical and Interpretive Manual. San Antonio: NCS Pearson; 2008.
  2. Constantino JN. Social Responsiveness Scale-Adult Research Version. Western Psychological Services: Lon Angeles; 2005.

Authors
Bernaerts, S., Boets, B., Bosmans, G., Steyaert, J., & Alaerts, K.
Affiliations
KU Leuven (BE)
Corresponding author
Alaerts, Kaat
ORCID
Venue
Molecular Autism
Publisher
Springer Science and Business Media LLC
Published
2020-01-15
Volume
11
Issue
1
Pages
6-6
ISSN
2040-2392 (ISSN-L)
DOI
10.1186/s13229-020-0313-1
PMC
PMC6964112
OpenAlex
W3007261060
Semantic Scholar
b2ceabcc2e47b7f6b1e0a0e730698b3fd0b03473
Cited by
102
References
42
Citations by year
2026: 12 · 2025: 12 · 2024: 12 · 2023: 19 · 2022: 23 · 2021: 14 · 2020: 10
FWCI
18.03
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Autism (publishedVersion, cc-by)
  • medRxiv (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Lirias (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Fonds Wetenschappelijk Onderzoek (G040112, KAN 1506716N, KAN 1521313N, G079017N)
  • Marguerite-Marie Delacroix Foundation (Not applicable)
  • Branco Weiss Fellowship of the Society in Science of ETH Zurich (Not applicable)
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
oxytocin, autism spectrum disorder, intranasal administration, long-term treatment outcomes, social responsiveness, repetitive behavior, attachment, social avoidance, mood states, retention effects, Social Responsiveness Scale, Profile of Mood States
MeSH terms
Administration, Intranasal, Adult, Autistic Disorder, Behavior, Double-Blind Method, Follow-Up Studies, Humans, Male, Oxytocin, Young Adult

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