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Cited by 111Neuroendocrine regulation and behaviorAutism Spectrum Disorder ResearchFace Recognition and Perception

Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial

Open access
Quintana, D S, Westlye, L T, Hope, S, Nærland, T, Elvsåshagen, T, Dørum, E, Rustan, Ø, Valstad, M +8 more·2017·Translational Psychiatry
DOI 10.1038/tp.2017.103PMC PMC5584522
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Abstract

The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin’s dose–response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequence of single-dose sessions, 17 male adults with ASD received 8 international units (IU) oxytocin, 24IU oxytocin or placebo followed by four social-cognitive tasks. We observed an omnibus main effect of treatment on the primary outcome measure of overt emotion salience as measured by emotional ratings of faces (η2=0.18). Compared to placebo, 8IU treatment increased overt emotion salience (P=0.02, d=0.63). There was no statistically significant increase after 24IU treatment (P=0.12, d=0.4). The effects after 8IU oxytocin were observed despite no significant increase in peripheral blood plasma oxytocin concentrations. We found no significant effects for reading the mind in the eyes task performance or secondary outcome social-cognitive tasks (emotional dot probe and face-morphing). To our knowledge, this is the first trial to assess the dose-dependent effects of a single oxytocin administration in autism, with results indicating that a low dose of oxytocin can significantly modulate overt emotion salience despite minimal systemic exposure.

AI snapshot

Written from the paper’s full text.

TL;DR

In a randomized, double-blind, placebo-controlled 3-way crossover trial in 17 male adults with ASD, intranasal oxytocin 8 IU delivered by a Breath Powered device increased overt emotion salience for happiness in ambiguous faces versus placebo, whereas 24 IU did not significantly differ from placebo. The 8 IU effect occurred without a significant increase in peripheral plasma oxytocin concentrations.

Key findings

  • Treatment had a significant main effect on happiness ratings of ambiguous faces, χ²(2)=6.71, P=0.03; 8 IU oxytocin increased ratings versus placebo (P=0.02, d=0.63), while 24 IU versus placebo was not significant (P=0.12, d=0.4) and 8 IU versus 24 IU was not significant (P=0.8, d=0.18). Repeated-measures ANOVA showed a similar main effect, F(2,32)=3.49, P=0.04, η²=0.18.
  • For anger ratings of ambiguous faces, the treatment main effect was borderline, χ²(2)=4.83, P=0.09; 24 IU versus placebo was also borderline (P=0.07, d=0.64), with ANOVA η²=0.13.
  • No significant treatment effects were found for RMET performance (χ²(2)=3.83, P=0.15), dot-probe attentional bias for happy (P=0.29) or angry (P=0.68) faces, or face-morphing speed/accuracy for happy or angry faces.
  • Post-treatment peripheral oxytocin was higher after 24 IU than after 8 IU (P=0.01) and placebo (P<0.001), but there was no difference between 8 IU and placebo (P=0.45); AVP and cortisol showed no significant treatment effects.

Methods

  • Randomized, double-blind, placebo-controlled, three-period crossover trial in 17 male adults with ASD aged 19–35 years (M=24.76, s.d.=4.75; mean full-scale IQ=109.8, s.d.=12.1). Participants received single doses of 8 IU oxytocin, 24 IU oxytocin, or placebo via a Breath Powered intranasal device, with at least 24 h between treatments.
  • Primary outcomes were an overt emotion sensitivity task using happy, angry, and ambiguous faces and a Norwegian translation of the Reading the Mind in the Eyes Test (RMET). Secondary outcomes were an emotional dot probe task and an emotional face-morphing task; plasma oxytocin, AVP, cortisol, and state anxiety were also measured.
  • Main analyses used multilevel linear mixed models comparing null versus main-effect models, with likelihood-ratio P-values and Tukey-adjusted post-hoc tests; repeated-measures ANOVAs and η² were also reported. A power analysis indicated 18 participants would provide 90% power for a large effect size (partial η²=0.14).

Limitations

  • The paper states that the sample was young adult males without intellectual disability, limiting generalizability to the wider ASD population; no measure of disorder severity was collected; and the sample, although matching the median for oxytocin crossover studies, may still be considered small.
  • The paper notes that secondary tasks may have been underpowered and that their timing (~60–80 min post-administration) may have missed peak central oxytocin concentrations, thought to be around 35–50 min post-administration; RMET results may reflect ceiling effects because placebo performance was 65.7% correct versus approximately 45% in prior ASD oxytocin research and 61% in ASD norms.
  • Evident from the text: the trial assessed only single-dose administration in males, did not directly compare the Breath Powered device with traditional nasal spray devices, and did not measure central oxytocin directly.

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

Integrity signals

Registry

Crossref · 10.1038/tp.2017.103

Cites

75 of 75 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

0 of 55 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Treatment condition had a statistically significant main effect on the primary outcome of overt emotion salience as measured by emotional ratings of faces (η2=0.18).

    “We observed an omnibus main effect of treatment on the primary outcome measure of overt emotion salience as measured by emotional ratings of faces (η2=0.18).”
    • Also stated in: § Primary outcome measures · plain
      “Treatment condition had a statistically significant effect on the perception of happiness in ambiguous faces, χ2(2)=6.71, P=0.03”
    • Also stated in: § Primary outcome measures · plain
      “For comparison, a repeated measures ANOVA revealed a similar outcome to the LMM with a significant main effect (F(2, 32)=3.49, P=0.04), which was associated with a large effect size (η2=0.18).”
    Quote in the paperSubstantial claim
  • Findingown data

    There was a main effect of treatment on perception of anger in ambiguous faces that was on the border of statistical significance (χ2(2)=4.83, P=0.09).

    “There was also evidence of a main effect of treatment on the perception of anger in ambiguous faces, but this was on the border of statistical significance, χ2(2)=4.83, P=0.09”
    Quote in the paperNot a substantial claim
  • Findingown data

    There was no significant effect of treatment on happy ratings of happy faces (χ2(2)=1.19, P=0.55).

    “There was no significant effect of treatment on the happy ratings of happy faces (χ2(2)=1.19, P=0.55”
    Quote in the paperNot a substantial claim
  • Findingown data

    The increase in anger ratings after 24IU oxytocin compared to placebo was on the border of statistical significance (P=0.07, d=0.64).

    “Tukey-adjusted multiple comparisons revealed that the increase in anger ratings after 24IU compared to placebo treatments was also on the border of statistical significance (P=0.07, d=0.64).”
    Quote in the paperNot a substantial claim
  • Findingown data

    There was no statistically significant increase in overt emotion salience after 24IU oxytocin compared to placebo (P=0.12, d=0.4).

    “There was no statistically significant increase after 24IU treatment (P=0.12, d=0.4).”
    • Also stated in: § Primary outcome measures · plain
      “There was no significant difference in the perception of happiness between 24IU and placebo (P=0.12, d=0.4)”
    Quote in the paperSubstantial claim
  • May combine two claims. 14
  • Classified as probably not a substantial claim. 25

  • May combine two claims.

    Findingown data

    Exploratory post-hoc analysis suggested that anger ratings were increased after 24IU oxytocin treatment compared to placebo, a difference coupled with a medium effect size, albeit non-significant.

    “Exploratory post-hoc analysis, albeit non-significant, suggested that anger ratings were increased after 24IU oxytocin treatment compared to placebo, a difference coupled with a medium effect size.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    There was no effect of treatment group on the total volume of the nasal cavity 2-5 cm deep from the nostrils.

    “There was also no effect of treatment group on nasal valve dimensions (χ2(2)=2.65, P=0.27), or the total volume of the nasal cavity 2–5 cm deep from the nostrils (χ2(2)=1.23, P=0.54).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There was a main effect of treatment condition on the perception of anger associated with a medium-to-large effect size, but it was on the border of statistical significance.

    “There was also a main effect of treatment condition on the perception of anger associated with a medium-to-large effect size; however, this was on the border of statistical significance, making conclusions less clear.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    There was a significant time effect on state anxiety with a reduction of ratings from baseline to the conclusion of testing.

    “There was no significant main effect of treatment condition on state anxiety, as measured by the STAI-state questionnaire, (χ2(2)=0.65, P=0.72) but a significant time effect (χ2(1)=17.45, P<0.001) with a reduction of ratings from baseline to the conclusion of testing.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    There was no effect of treatment group on nasal valve dimensions.

    “There was also no effect of treatment group on nasal valve dimensions (χ2(2)=2.65, P=0.27), or the total volume of the nasal cavity 2–5 cm deep from the nostrils (χ2(2)=1.23, P=0.54).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    The oxytocin system is important in mammalian social behaviors including social memory, recognition and attachment.

    “The importance of the oxytocin system in mammalian social behaviors including social memory, recognition and attachment has been established using a variety of animal models since 1980s.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [10] Pedersen CA, Ascher JA, Monroe YL, Prange AJ . Oxytocin induces maternal behavior in virgin female rats. Science 1982; 216: 648–650. source

      Not checked in the free run.

    • cites [11] Fahrbach S, Morrell J, Pfaff D . Possible role for endogenous oxytocin in estrogen-facilitated maternal behavior in rats. Neuroendocrinology 1985; 40: 526–532. source

      Not checked in the free run.

    • cites [12] Winslow JT, Insel TR . The social deficits of the oxytocin knockout mouse. Neuropeptides 2002; 36: 221–229. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisereasoning

    There is no justification for selecting the 24 IU dose beyond precedence.

    “yet there is no justification for selecting this dose beyond precedence”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Oxytocin modulates neural circuitry for social cognition in humans.

    “modulates neural circuitry for social cognition in humans,15”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Kirsch P, Esslinger C, Chen Q, Mier D, Lis S, Siddhanti S et al. Oxytocin modulates neural circuitry for social cognition and fear in humans. J Neurosci 2005; 25: 11489–11493. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    A succession of studies reported modest improvements in social cognition after use of nasal oxytocin spray in both neurotypical and psychiatric populations.

    “A succession of studies reported modest improvements in social cognition after use of nasal oxytocin spray in both neurotypical16, 17, 18 and psychiatric19, 20, 21 populations”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [16] Guastella AJ, Mitchell PB, Dadds MR . Oxytocin increases gaze to the eye region of human faces. Biol Psychiatry 2008; 63: 3–5. source

      Not checked in the free run.

    • cites [17] Domes G, Heinrichs M, Michel A, Berger C, Herpertz SC . Oxytocin Improves “Mind-Reading” in Humans. Biol Psychiatry 2007; 61: 731–733. source

      Not checked in the free run.

    • cites [18] Guastella AJ, Mitchell PB, Mathews F . Oxytocin enhances the encoding of positive social memories in humans. Biol Psychiatry 2008; 64: 256–258. source

      Not checked in the free run.

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

    Premisecitation

    Converging evidence suggests that oxytocin increases social salience and approach-related behaviors, regardless of valence.

    “with converging evidence suggesting that oxytocin increases social salience30 and approach-related behaviors,31 regardless of valence.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [30] Bartz JA, Zaki J, Bolger N, Ochsner KN . Social effects of oxytocin in humans: context and person matter. Trends Cogn Sci 2011; 15: 301–309.

      Not checked in the free run.

    • cites [31] Kemp AH, Guastella AJ . The role of oxytocin in human affect a novel hypothesis. Curr Dir Psychol Sci 2011; 20: 222–231. source

      Not checked in the free run.

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

    Premisecitation

    A series of negative results, mixed meta-analytic results and doubts surrounding oxytocin research methods dampened initial enthusiasm.

    “However, a series of negative results,24, 25, 26 mixed meta-analytic results27 and doubts surrounding oxytocin research methods28 somewhat dampened initial enthusiasm.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [24] 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 2014; 44: 521–531. source

      Not checked in the free run.

    • cites [25] Davis MC, Green MF, Lee J, Horan WP, Senturk D, Clarke AD et al. Oxytocin-augmented social cognitive skills training in schizophrenia. Neuropsychopharmacology 2014; 39: 2070–2077. source

      Not checked in the free run.

    • cites [26] Cacciotti-Saija C, Langdon R, Ward PB, Hickie IB, Scott E, Naismith SL et al. A double-blind randomized controlled trial of oxytocin nasal spray and social cognition training for young people with early psychosis. Schizophr Bull 2015; 41: 483–493. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisereasoning

    Intranasal oxytocin has emerged as a potential treatment addressing social dysfunction.

    “Intranasal oxytocin has emerged as a potential treatment addressing social dysfunction.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Oxytocin increases trust in humans.

    “reports that oxytocin increases trust14”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14] Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E . Oxytocin increases trust in humans. Nature 2005; 435: 673–676. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The corresponding average false-negative rate in oxytocin studies is large (88%), which probably contributes to poor replication rates.

    “Therefore, the corresponding average false-negative rate is large (88%), which probably contributes to poor replication rates.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28] Walum H, Waldman ID, Young LJ . Statistical and methodological considerations for the interpretation of intranasal oxytocin studies. Biol Psychiatry 2016; 79: 251–257. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A single administration of intranasal 8IU oxytocin modulated social cognition in neurotypical adult males, whereas intravenous administration did not, despite comparable peripheral blood concentrations of oxytocin after intranasal and intravenous oxytocin administration.

    “A single administration of intranasal 8IU oxytocin-modulated social cognition, whereas intravenous administration did not, despite comparable peripheral blood concentrations of oxytocin after intranasal and intravenous oxytocin administration.40”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [40] Quintana DS, Westlye LT, Rustan ØG, Tesli N, Poppy CL, Smevik H et al. Low dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized 4-way crossover trial with nasal cavity dimension assessment. Transl Psychiatry 2015; 5: 1–9. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The trial used a randomized, placebo-controlled, double-blind, three-period crossover design.

    “in a double-blind, crossover, randomized, placebo-controlled trial.”
    • Also stated in: § Study design · plain
      “Participants received 8IU oxytocin intranasally, 24IU oxytocin intranasally, and an intranasal placebo treatment in a randomized, placebo-controlled, double-blind, three-period crossover design.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    Post-hoc tests used Tukey adjustment of critical P-values to correct for multiple comparisons.

    “For any significant main effects (P<0.05), post-hoc tests were performed to compare each treatment condition (with Tukey adjustment of critical P-values to correct for multiple comparisons).”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    The study is registered at the EU Clinical Trials register.

    “The study is registered at the EU Clinical Trials register (EudraCT no.: 2014-005452-26).”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    Both participants and the research team were blinded to treatment.

    “and both the participants and the research team were blinded to treatment.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Participants were randomized to one of six treatment sequences using a three-period, three-treatment Latin square method.

    “Participants were randomized to one of six treatment sequences, using a three-period, three-treatment Latin square method (ABC—ACB—BAC—BCA—CAB—CBA in a 1:1:1 ratio; Supplementary Figure S1)”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    An independent statistician provided the randomization code.

    “An independent statistician (Smerud Medical Research International, Oslo, Norway) provided the randomization code”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    The trial was approved by the Regional Committee for Medical and Health Research Ethics.

    “This trial was approved by the Regional Committee for Medical and Health Research Ethics (REC South East) and participants provided written informed consent before they participated.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Every randomized participant completed all three treatments.

    “Every randomized participant completed all three treatments.”
    Quote in the paperSubstantial claim

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

    Study design and conductreasoning

    LMMs were chosen as repeated-measure analyses to assess main effects because they do not rely on complete data sets or the assumption of compound symmetry.

    “LMMs were chosen as repeated-measure analyses to assess main effects because they do not rely on complete data sets or the assumption of compound symmetry.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    We previously observed a reduction in angry ratings of ambiguous faces after 8IU administration, but this was found in a sample of neurotypical adults tested in a unique fMRI environment.

    “Although we previously observed a reduction in angry ratings of ambiguous faces after 8IU administration,40 this was found in a sample of neurotypical adults tested in a unique fMRI environment.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Quintana DS, Westlye LT, Rustan ØG, Tesli N, Poppy CL, Smevik H et al. Low dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized 4-way crossover trial with nasal cavity dimension assessment. Transl Psychiatry 2015; 5: 1–9. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    The participant sample was a population of young adult males without intellectual disability.

    “First, the participant sample was a population of young adult males without intellectual disability.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    As traditional nasal spray devices deliver less liquid to nose-to-brain targets in the upper-posterior region of the nasal cavity, this could limit the fraction reaching the brain and central activity.

    “As traditional nasal spray devices deliver less liquid to nose-to-brain targets in the upper-posterior region of the nasal cavity, this could limit the fraction reaching the brain and central activity.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    An alternative explanation is that the timing of these two tasks (~60-80 min post-administration) may have missed peak central concentrations of oxytocin, which is thought to be around 35-50 min post-administration.

    “An alternative explanation is that the timing of these two tasks (~60–80 min post-administration) may have missed peak central concentrations of oxytocin, which is thought to be around 35–50 min post-administration.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Peak central concentrations of oxytocin occur around 35–50 min post-administration.

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

    Interpretationreasoning

    24IU oxytocin delivered via traditional nasal devices may offer equivalent central levels because of substantial loss of the delivered drug.

    “Alternatively, 24IU oxytocin delivered via traditional nasal devices may offer equivalent central levels because of substantial loss of the delivered drug.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    This suggests that exogenous oxytocin might not influence the emotional salience of covert stimuli or the speed of recognizing overt emotional stimuli in young male adults with ASD.

    “This suggests that exogenous oxytocin might not influence the emotional salience of covert stimuli or the speed of recognizing overt emotional stimuli in young male adults with ASD.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Even if 24IU oxytocin delivered with traditional device provides equivalent central activity as 8IU delivered with the Breath Powered device, the latter device appears to reduce peripheral exposure to oxytocin.

    “Regardless, even if 24IU oxytocin delivered with traditional device provides equivalent central activity as 8IU delivered with the Breath Powered device, the latter device appears to reduce peripheral exposure to oxytocin.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The pattern of 8 IU oxytocin delivered with the Breath Powered device increasing emotion sensitivity without significantly elevating peripheral oxytocin supports the possibility of direct nose-to-brain transport with this delivery mechanism.

    “This suggests that 8 IU oxytocin delivered with the Breath Powered device increased emotion sensitivity without significantly elevating peripheral oxytocin, which supports the possibility of direct nose-to-brain transport with this delivery mechanism and potential to achieve therapeutic benefit while minimizing adverse effects due to peripheral oxytocin receptor activation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    There was no difference in AVP levels, suggesting no peripheral cross-reactivity.

    “There was also no difference in AVP levels, suggesting no peripheral cross-reactivity, which is more likely to occur with higher levels of oxytocin exposure.71”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [71] Manning M, Misicka A, Olma A, Bankowski K, Stoev S, Chini B et al. Oxytocin and vasopressin agonists and antagonists as research tools and potential therapeutics. J Neuroendocrinol 2012; 24: 609–628. source

      Not checked in the free run.

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

    Study design and conductcitation

    Although our sample size matched the median sample size for oxytocin crossover studies, this still may be considered as small.

    “Second, although our sample size matched the median sample size for oxytocin crossover studies,35 this still may be considered as small.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Alvares GA, Quintana DS, Whitehouse AJ . Beyond the hype and hope: critical considerations for intranasal oxytocin research in autism spectrum disorder. Autism Res 2016; 10: 25–41. source

      Not checked in the free run.

34 of 34

  • The authors state this as an assumption.

    Oxytocin travels via olfactory and trigeminal nerves to the brain rather than across the blood–brain barrier via circulating blood.

    “Although it is assumed that oxytocin travels via olfactory and trigeminal nerves to the brain rather than across the blood–brain barrier via circulating blood, this has not been directly tested in humans.”

  • The paper relies on this without support.

    Social cognition is a complex suite of processes that cannot be encapsulated by a single experimental task.

    “Social cognition is a complex suite of processes that cannot be encapsulated by a single experimental task.”

  • The paper relies on this without support.

    Research has yet to investigate the dose-dependent response to intranasal oxytocin in ASD using optimized intranasal delivery.

    “Research has yet to investigate the dose-dependent response to intranasal oxytocin in ASD using optimized intranasal delivery.”

  • The paper relies on this without support.

    The optimal oxytocin dose for humans is unknown.

    “Second, the optimal oxytocin dose for humans is unknown.”

  • The paper relies on this without support.

    Peak central concentrations of oxytocin occur around 35–50 min post-administration.

    “which is thought to be around 35–50 min post-administration.”
5 of 5

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?

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.

  • Consistentχ²(2) = 6.71reported p = .03 · recomputed p = .035

    “χ2(2)=6.71, p = .03”

  • ConsistentF(2, 32) = 3.49reported p = .04 · recomputed p = .043

    “F(2, 32)=3.49, p = .04”

  • Consistentχ²(2) = 4.83reported p = .09 · recomputed p = .089

    “χ2(2)=4.83, p = .09”

  • Consistentχ²(2) = 1.19reported p = .55 · recomputed p = .552

    “χ2(2)=1.19, p = .55”

  • Consistentχ²(2) = 0.22reported p = .89 · recomputed p = .896

    “χ2(2)=0.22, p = .89”

  • Consistentχ²(2) = 3.83reported p = .15 · recomputed p = .147

    “χ2(2)=3.83, p = .15”

  • Consistentχ²(2) = 1.79reported p = .41 · recomputed p = .409

    “χ2(2)=1.79, p = .41”

  • Consistentχ²(2) = 0.02reported p = .99 · recomputed p = .990

    “χ2(2)=0.02, p = .99”

  • Consistentχ²(2) = 0.43reported p = .8 · recomputed p = .807

    “χ2(2)=0.43, p = .8”

  • Consistentχ²(2) = 0.23reported p = .89 · recomputed p = .891

    “χ2(2)=0.23, p = .89”

  • Consistentχ²(2) = 5.39reported p = .07 · recomputed p = .068

    “χ2(2)=5.39, p = .07”

  • Consistentχ²(2) = 2.8reported p = .25 · recomputed p = .247

    “χ2(2)=2.8, p = .25”

  • Consistentχ²(2) = 0.18reported p = .91 · recomputed p = .914

    “χ2(2)=0.18, p = .91”

  • Consistentχ²(2) = 2.48reported p = .29 · recomputed p = .289

    “χ2(2)=2.48, p = .29”

  • Consistentχ²(2) = 0.76reported p = .68 · recomputed p = .684

    “χ2(2)=0.76, p = .68”

  • Consistentχ²(2) = 5.48reported p = .06 · recomputed p = .065

    “χ2(2)=5.48, p = .06”

  • Consistentχ²(1) = 0.3reported p = .58 · recomputed p = .584

    “χ2(1)=0.3, p = .58”

  • Consistentχ²(2) = 5.37reported p = .07 · recomputed p = .068

    “χ2(2)=5.37, p = .07”

  • Consistentχ²(2) = 0.17reported p = .92 · recomputed p = .919

    “χ2(2)=0.17, p = .92”

  • Consistentχ²(2) = 13.79reported p = .001 · recomputed p = .001

    “χ2(2)=13.79, p = .001”

  • Consistentχ²(2) = 2.03reported p = .36 · recomputed p = .362

    “χ2(2)=2.03, p = .36”

  • Consistentχ²(1) = 1.89reported p = .17 · recomputed p = .169

    “χ2(1)=1.89, p = .17”

  • Consistentχ²(2) = 4.2reported p = .12 · recomputed p = .122

    “χ2(2)=4.2, p = .12”

  • Consistentχ²(2) = 0.24reported p = .89 · recomputed p = .887

    “χ2(2)=0.24, p = .89”

  • Consistentχ²(1) = 1.65reported p = .2 · recomputed p = .199

    “χ2(1)=1.65, p = .2”

  • Consistentχ²(2) = 0.34reported p = .84 · recomputed p = .844

    “χ2(2)=0.34, p = .84”

  • Consistentχ²(2) = 0.65reported p = .72 · recomputed p = .723

    “χ2(2)=0.65, p = .72”

  • Consistentχ²(1) = 17.45reported p < .001 · recomputed p < .001

    “χ2(1)=17.45, p < .001”

  • Consistentχ²(2) = 0.5reported p = .78 · recomputed p = .779

    “χ2(2)=0.5, p = .78”

  • Consistentχ²(2) = 2.65reported p = .27 · recomputed p = .266

    “χ2(2)=2.65, p = .27”

  • Consistentχ²(2) = 1.23reported p = .54 · recomputed p = .541

    “χ2(2)=1.23, p = .54”

  • Consistentχ²(2) = 2.57reported p = .28 · recomputed p = .277

    “χ2 (2)=2.57, p = .28”

32 of 32

Self-check

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

Self-check results appear here once an independent check has confirmed them.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Cohen J . Statistical Power Analysis for the Behavioural Sciences. Lawrence Earlbaum Associates: Mahwah, NJ, 1988.

Cited by

Sorted by citations

Related

Authors
Quintana, D. S., Westlye, L. T., Hope, S., Nærland, T., Elvsåshagen, T., Dørum, E., Rustan, Ø., Valstad, M., Rezvaya, L., Lishaugen, H., Stensønes, E., Yaqub, S., Smerud, K. T., Mahmoud, R. A., Djupesland, P. G., & Andreassen, O. A.
Affiliations
  • Oslo University Hospital (NO)
  • Smerud Medical Research (Norway) (NO)
  • OptiNose (United States) (US)
  • OptiNose (Norway) (NO)
Corresponding author
Andreassen, O A
ORCID
Venue
Translational Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2017-05-23
Volume
7
Issue
5
Pages
e1136-e1136
ISSN
2158-3188 (ISSN-L)
DOI
10.1038/tp.2017.103
PMC
PMC5584522
OpenAlex
W2618490415
Semantic Scholar
324d0cf4b04a0fb6cfeb1103862e432ecaa6991a
Cited by
111
References
75
Citations by year
2026: 8 · 2025: 10 · 2024: 9 · 2023: 11 · 2022: 13 · 2021: 18 · 2020: 16 · 2019: 10 · 2018: 11 · 2017: 5
FWCI
16.44
Type
journal article
Language
en
Open access
Licence
Locations
  • Translational Psychiatry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
Funders
  • Novo Nordisk (NNF16OC0019856)
  • Universitetet i Oslo
  • Norges Forskningsråd (223273, 219483)
  • Novo Nordisk Fonden (NNF16OC0019856)
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Face Recognition and Perception
Keywords
oxytocin, autism spectrum disorder, intranasal drug delivery, dose-response relationship, social cognition, face perception, Reading the Mind in the Eyes Test, autistic adults
MeSH terms
Autism Spectrum Disorder, Administration, Intranasal, Adolescent, Adult, Cognition, Emotions, Facial Expression, Humans, Male, Oxytocics, Oxytocin, Social Behavior, Outcome Assessment, Health Care, Cross-Over Studies, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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