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Cited by 94Neuroendocrine regulation and behaviorOlfactory and Sensory Function StudiesStress Responses and Cortisol

Salivary oxytocin concentrations in males following intranasal administration of oxytocin: a double-blind, cross-over study

Open access
Daughters, Katie, Manstead, Antony S. R., Hubble, Kelly, Rees, Aled, Thapar, Anita, van Goozen, Stephanie H. M.·2015·PLOS ONE
DOI 10.1371/journal.pone.0145104PMC PMC4684402
Open this paper in CoChat — free accountOpen PDF

Abstract

The use of intranasal oxytocin (OT) in research has become increasingly important over the past decade. Although researchers have acknowledged a need for further investigation of the physiological effects of intranasal administration, few studies have actually done so. In the present double-blind cross-over study we investigated the longevity of a single 24 IU dose of intranasal OT measured in saliva in 40 healthy adult males. Salivary OT concentrations were significantly higher in the OT condition, compared to placebo. This significant difference lasted until the end of testing, approximately 108 minutes after administration, and peaked at 30 minutes. Results showed significant individual differences in response to intranasal OT administration. To our knowledge this is the largest and first all-male within-subjects design study to demonstrate the impact of intranasal OT on salivary OT concentrations. The results are consistent with previous research in suggesting that salivary OT is a valid matrix for OT measurement. The results also suggest that the post-administration 'wait-time' prior to starting experimental tasks could be reduced to 30 minutes, from the 45 minutes typically used, thereby enabling testing during peak OT concentrations. Further research is needed to ascertain whether OT concentrations after intranasal administration follow similar patterns in females, and different age groups.

AI snapshot

Written from the paper’s full text.

TL;DR

In a double-blind cross-over study of 40 healthy adult males, a single 24 IU dose of intranasal oxytocin significantly increased salivary oxytocin concentrations compared with placebo, peaking at 30 minutes and remaining significantly elevated through 108 minutes. The authors conclude salivary oxytocin is a valid measurement matrix and suggest reducing the usual post-administration wait-time to 30 minutes.

Key findings

  • Salivary oxytocin was significantly higher in the oxytocin condition than placebo at every post-administration sample: 30 min 999.52 (SD 813.95) vs 37.45 (21.24), 60 min 951.98 (772.96) vs 46.43 (33.54), 90 min 531.29 (538.76) vs 39.58 (29.77), 105 min 417.41 (366.88) vs 44.88 (33.47), and 108 min 355.17 (235.69) vs 34.08 (25.97); all post-baseline comparisons had p < .001.
  • Baseline samples did not differ significantly, though the difference approached significance: oxytocin 77.93 (74.46) vs placebo 45.96 (33.27), Z = -1.91, p = .056.
  • Concentrations peaked at 30 minutes after administration and the significant difference lasted until the end of testing, approximately 108 minutes after administration.
  • The authors report considerable individual differences in response to intranasal oxytocin, reflected in large standard deviations, and recommend that experimental testing begin at 30 minutes rather than the 45 minutes typically used.

Methods

  • Double-blind, cross-over, within-subjects design with 40 healthy male students from Cardiff University (M age = 20.98, SD = 4.55); participants received 24 IU intranasal oxytocin or placebo in two sessions separated by approximately 2 weeks, with a maximum interval of 35 days.
  • Saliva samples were collected at baseline and at 30, 60, 90, 105, and 108 minutes after administration; samples were lyophilized, concentrated four-fold, and analyzed with a 96-well oxytocin ELISA kit (Enzo Life Sciences), with the international oxytocin correction applied.
  • Because 9 of 12 samples violated normality, non-parametric tests were used: related-samples Friedman’s two-way ANOVA followed by Wilcoxon signed rank tests; data were winsorized before analysis because some samples were more than three standard deviations above the mean.

Limitations

  • The paper states that baseline oxytocin concentrations were higher than placebo baseline concentrations and the difference was close to significance (p = .056); four participants had noticeably higher oxytocin baseline values, and removing them reduced the oxytocin baseline mean to 51.13 (SD = 30.86) pg/ml, closer to the placebo mean of 45.96 pg/ml, but the authors retained the winsorized values.
  • The paper states that placebo-condition concentrations were 30–40 pg/ml, higher than typical values of <10 pg/ml reported previously, and that no standard operating procedure for saliva collection makes comparisons between studies difficult; it also states that samples could not be collected beyond 108 minutes due to logistical and financial restrictions.
  • Evident from the text: the sample was all male, young adult university students, so findings may not generalize to females, older adults, or children; participants’ nasal cavities were not medically examined; and some samples had sufficient volume for only a single analysis rather than duplicates.

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

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0145104

Cites

33 of 33 references verified0 citation errors · 0 not checkable

Statistics

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

Claims the paper makes

0 of 37 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    There were considerable individual differences in salivary oxytocin response to intranasal oxytocin administration.

    “Results showed significant individual differences in response to intranasal OT administration.”
    • Also stated in: § Results · plain
      “Large standard deviations showed that there were considerable individual differences in OT concentrations after In-OT.”
    • Also stated in: § Discussion · plain
      “The extent of individual differences in response to IN-OT is considerable and thus far unaddressed in the literature.”
    Quote in the paperSubstantial claim
  • Findingown data

    In healthy adult males, a single 24 IU dose of intranasal oxytocin produced significantly higher salivary oxytocin concentrations than placebo from 30 minutes through 108 minutes after administration.

    “Salivary OT concentrations were significantly higher in the OT condition, compared to placebo. This significant difference lasted until the end of testing, approximately 108 minutes after administration, and peaked at 30 minutes.”
    • Also stated in: § Results · plain
      “There were significant differences between all the remaining samples.”
    • Also stated in: § Discussion · plain
      “As expected, participants had significantly higher salivary OT concentrations after OT administration, compared to their placebo session.”
    Quote in the paperSubstantial claim
  • Findingown data

    Salivary oxytocin concentrations peaked at 30 minutes after intranasal oxytocin administration.

    “This significant difference lasted until the end of testing, approximately 108 minutes after administration, and peaked at 30 minutes.”
    • Also stated in: § Discussion · plain
      “In line with previous research [18, 25–27], maximum OT concentrations were detected 30 minutes after administration.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [18] A Gossen, 2012, Oxytocin plasma concentrations after single intranasal oxytocin administration—A study in healthy men, Neuropeptides source

      Not checked in the free run.

    • cites [25] MG Kirkpatrick, 2014, Plasma oxytocin concentrations following MDMA or intranasal oxytocin in humans, Psychoneuroendocrinology source

      Not checked in the free run.

    • cites [26] ID Neumann, 2013, Increased brain and plasma oxytocin after nasal and peripheral administration in rats and mice, Psychoneuroendocrinology source

      Not checked in the free run.

    • cites [27] Y Paloyelis, 2014, A Spatiotemporal Profile of In Vivo Cerebral Blood Flow Changes Following Intranasal Oxytocin in Humans, Biological psychiatry

      Not checked in the free run.

  • Findingown data

    There was no significant difference between the baseline saliva samples.

    “There was no significant difference between the baseline samples.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Related-samples Friedman's two-way analysis of variance revealed a significant difference between samples, χ2(11) = 286.75, p <0.001.

    “Related-samples Friedman’s two-way analysis of variance revealed a significant difference between samples, χ2(11) = 286.75, p <0.001.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 18
  • Classified as probably not a substantial claim. 19
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingown data

    Removing four participants with noticeably higher oxytocin baseline concentrations decreases the oxytocin baseline mean to 51.13 (SD = 30.86) pg/ml, closer to the placebo baseline mean of 45.96 pg/ml.

    “Within the winsorized dataset, there were four participants with noticeably higher OT baseline concentrations; if their values are removed the OT baseline mean decreases to 51.13 (SD = 30.86) pg/ml, much closer to the placebo baseline mean of 45.96 pg/ml.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Baseline oxytocin concentrations were higher in the oxytocin condition than in the placebo condition, but the difference was not statistically significant.

    “First, although the baseline concentrations are statistically similar, the difference does not fall very far short of statistical significance, with OT baseline concentrations being higher than placebo baseline concentrations.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Placebo oxytocin concentrations in the present study were 30-40 pg/ml across the testing session, higher than typical previous values of <10 pg/ml under placebo conditions.

    “In the present study we found concentrations of 30–40 pg/ml across the testing session.”
    • Also stated in: § Discussion · hedged
      “Typical values observed in previous research suggest that OT concentrations in peripheral bodily fluid are <10 pg/ml under placebo conditions [e.g., [35]].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] KM Grewen, 2005, Effects of partner support on resting oxytocin, cortisol, norepinephrine, and blood pressure before and after warm partner contact, Psychosomatic medicine source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    This study is the largest and first all-male within-subjects design study to demonstrate the impact of intranasal oxytocin on salivary oxytocin concentrations.

    “To our knowledge this is the largest and first all-male within-subjects design study to demonstrate the impact of intranasal OT on salivary OT concentrations.”
    • Also stated in: § Discussion · hedged
      “To our knowledge, this is the largest within-subjects design study to date demonstrating that intranasal administration of OT has significant effects on salivary OT concentrations in males.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    In a double-blind between-subjects study of 46 females, salivary oxytocin was still elevated 7 hours after intranasal oxytocin administration.

    “One study [12] found that salivary OT was still elevated 7 hours after administration in a double-blind, between-subjects study (n = 46; all female).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] MH Van IJzendoorn, 2012, Elevated salivary levels of oxytocin persist more than 7 h after intranasal administration, Frontiers in neuroscience source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Intranasal oxytocin reaches specific brain regions and crosses the blood-brain barrier in rats and mice.

    “A pioneering study [26] showed that IN-OT does reach specific brain regions in rats and mice, demonstrating that IN-OT does cross the blood-brain barrier, thereby addressing one of the main concerns [28].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] ID Neumann, 2013, Increased brain and plasma oxytocin after nasal and peripheral administration in rats and mice, Psychoneuroendocrinology source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The latest commercial saliva ELISA kit has reduced non-specific binding, alleviating artificially elevated oxytocin concentrations.

    “The latest ELISA kit [11] has reduced non-specific binding, and thereby alleviates this problem.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11] Product Technical Bulletin: Enzo Life Sciences; 2014. Available: <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://static.enzolifesciences.com/fileadmin/files/technicalbulletin/ADI-901-153A_tech-bulletin.pdf" xlink:type="simple">http://static.enzolifesciences.com/fileadmin/files/technicalbulletin/ADI-901-153A_tech-bulletin.pdf</ext-link>.

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisenone given

    The longevity of intranasal oxytocin effects on peripheral bodily fluids is not established.

    “As previously stated, the longevity of IN-OT effects on peripheral bodily fluids is not established.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    The psychological tasks were matched in the oxytocin and placebo conditions with respect to timing and content.

    “These tasks were matched in the OT and placebo conditions with respect to timing and content.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The small and non-significant baseline difference cannot account for the much larger and highly significant difference in salivary oxytocin concentrations following intranasal administration, and does not detract from the main result.

    “It is worth emphasizing that this small and non-significant difference in baseline values cannot account for the much larger and highly significant difference in salivary OT concentrations following intranasal administration, and therefore does not detract from the main result of the present study.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The study used a within-subjects design.

    “An important attribute of the present study is its use of a within-subjects design.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Plasma oxytocin is significantly elevated 15 minutes after intranasal oxytocin administration.

    “A recent study [15] investigating the relationship between IN-OT and its impact on OT concentrations in plasma and cerebrospinal fluid found that plasma OT was significantly elevated 15 minutes post-administration.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] N Striepens, 2013, Elevated cerebrospinal fluid and blood concentrations of oxytocin following its intranasal administration in humans, Scientific reports source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    The present study obtained intra-assay and inter-assay coefficients of variability of <8% and 10.6-14.5%, respectively, within accepted values.

    “The present study obtained intra-assay and inter-assay coefficients of <8% and 10.6–14.5%, respectively.”
    • Also stated in: § Oxytocin Sampling and Analysis · plain
      “Accepted values for coefficients of variability are <10% for intra-assay and <15% for inter-assay variability [24].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Inter- and intra-assay coefficients of variability: Salimetrics; 2014 [cited 2014]. Technical Report]. Available: <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.salimetrics.com/assets/documents/Spit_Tips_Inter__Intra_Assay_Coefficients_of_Variability.pdf?/documents/Spit_Tips_-_Inter__Intra_Assay_Coefficients_of_Variability.pdf" xlink:type="simple">http://www.salimetrics.com/assets/documents/Spit_Tips_Inter__Intra_Assay_Coefficients_of_Variability.pdf?/documents/Spit_Tips_-_Inter__Intra_Assay_Coefficients_of_Variability.pdf</ext-link>.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Few studies have addressed the longevity and pattern of salivary oxytocin after intranasal oxytocin, and many intranasal oxytocin administration studies do not include any assessment of participants' oxytocin concentrations.

    “Few studies have addressed these questions, and many IN-OT administration studies do not include any assessment of participants’ OT concentrations.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [1] JG Veening, 2013, Intranasal administration of oxytocin: behavioral and clinical effects, a review, Neuroscience & Biobehavioral Reviews source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    There is a lack of evidence concerning both the longevity of intranasal oxytocin effects on peripheral oxytocin concentrations and the pattern of concentrations during these effects.

    “In particular, there is a lack of evidence concerning both the longevity of the effects of intranasal spray on peripheral OT concentrations and the pattern of concentrations during these effects [1].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [1] JG Veening, 2013, Intranasal administration of oxytocin: behavioral and clinical effects, a review, Neuroscience & Biobehavioral Reviews source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted).

    Interpretationreasoning

    At 15 minutes after intranasal oxytocin, measured salivary oxytocin may include synthetic oxytocin spray that has trickled from the nasal cavity to the back of the throat, causing an artificial spike.

    “Given the mode of delivery, is it possible that at 15 minutes what is actually being measured is Syntocinon (synthetic OT) spray that has trickled down from the nasal cavity to the back of the throat, causing an artificial ‘spike’ in OT concentrations in the saliva.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The study used a double-blind, cross-over design.

    “We used a double-blind, cross-over design.”
    • Also stated in: § Discussion · plain
      “The study was double-blind; participants were randomly assigned to their drug order; there were no significant order effects; and all data points were winsorized (therefore there were no statistical outliers).”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Oxytocin concentrations may peak earlier than 30 minutes, as is the case for many other small peptides.

    “It is nonetheless worth noting that concentrations may peak earlier than 30 minutes, as is the case for many other small peptides [1], and can be reliably measured in other matrices.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] JG Veening, 2013, Intranasal administration of oxytocin: behavioral and clinical effects, a review, Neuroscience & Biobehavioral Reviews source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    The two testing sessions were timed to take place at the same time of day to control for potential diurnal effects.

    “The two sessions were timed to take place at the same time of day to control for any potential diurnal effects.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    Nine out of 12 samples violated the assumption of normality, so non-parametric tests were used.

    “Initial analysis revealed that 9 out of 12 samples violated the assumption of normality (see S1 Table). We therefore used non-parametric tests to assess whether there was a significant effect of drug on salivary OT concentrations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisereasoning

    Because salivary oxytocin can degrade very quickly and there is no standardised collection procedure, it is difficult to compare oxytocin concentrations between studies.

    “Given that salivary OT can degrade very quickly and the lack of a standardised procedure for its collection, it is difficult to compare concentrations between studies.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    The study used the largest within-subjects sample size published to date.

    “By using a within-subjects design, and the largest, within-subjects, sample size published to date, we aimed to address both types of concerns.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    In a study of 57 females, salivary oxytocin concentrations were still significantly elevated 2.25 hours after intranasal oxytocin administration compared to placebo.

    “Salivary OT concentrations were still significantly elevated 2.25 hours after administration, compared to placebo concentrations.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] R Huffmeijer, 2011, Salivary levels of oxytocin remain elevated for more than two hours after intranasal oxytocin administration, Neuro endocrinology letters

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    The precise salivary oxytocin values reported at 15 minutes post-administration should be treated with caution.

    “Although Weisman et al. [13] reported a significant increase in salivary OT at 15 minutes post-administration, the precise values should be treated with caution.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] O Weisman, 2012, Intranasal oxytocin administration is reflected in human saliva, Psychoneuroendocrinology source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    Lyophilization has been found to significantly increase the validity of measuring oxytocin via ELISA, so lyophilisation was used instead of the chemical concentration process.

    “Lyophilization has also been found to significantly increase the validity of measuring OT via ELISA [7, 21, 22]. Therefore, we used the lyophilisation process instead of the chemical process outlined in the manual.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [7] ME McCullough, 2013, Problems with measuring peripheral oxytocin: can the data on oxytocin and human behavior be trusted?, Neuroscience & Biobehavioral Reviews source

      Not checked in the free run.

    • cites [21] JC Christensen, 2014, Lack of Association between Human Plasma Oxytocin and Interpersonal Trust in a Prisoner’s Dilemma Paradigm, PLoS one source

      Not checked in the free run.

    • cites [22] G Leng, 2015, Intranasal oxytocin: myths and delusions, Biological Psychiatry

      Not checked in the free run.

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

    Premisecitation

    In that study, both the 24 IU and 16 IU intranasal oxytocin conditions had significantly higher salivary oxytocin concentrations after 7 hours than placebo.

    “Participants in both the high dose (24 IU; n = 10) and low dose (16 IU; n = 18) IN-OT conditions still had significantly higher salivary OT concentrations after 7 hours, compared to participants in the placebo condition.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] MH Van IJzendoorn, 2012, Elevated salivary levels of oxytocin persist more than 7 h after intranasal administration, Frontiers in neuroscience source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Participants were randomly assigned to their drug order.

    “The study was double-blind; participants were randomly assigned to their drug order; there were no significant order effects; and all data points were winsorized (therefore there were no statistical outliers).”
    Quote in the paperSubstantial claim

  • May combine two claims. The quote only partly states this claim.

    Study design and conductcitation

    The ELISA kit used had recently undergone modification and rigorous validation, giving greater specificity than the earlier version.

    “This kit has been used in several OT studies [12, 13] although as noted above the kit has recently (September 2013) undergone modification and “rigorous validation” [[11] p, 1].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] Product Technical Bulletin: Enzo Life Sciences; 2014. Available: <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://static.enzolifesciences.com/fileadmin/files/technicalbulletin/ADI-901-153A_tech-bulletin.pdf" xlink:type="simple">http://static.enzolifesciences.com/fileadmin/files/technicalbulletin/ADI-901-153A_tech-bulletin.pdf</ext-link>.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    There was a significant decrease in salivary oxytocin between 30 and 45 minutes post-administration, followed by a plateau from 45 to 120 minutes after administration.

    “There was a significant decrease in salivary OT between 30 minutes and 45 minutes post-administration, followed by a plateau phase lasting from 45 minutes to 120 minutes after administration.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] O Weisman, 2012, Intranasal oxytocin administration is reflected in human saliva, Psychoneuroendocrinology 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

    Recommendations regarding administration procedures made by Guastella et al. were followed, although participants' nasal cavities were not medically examined.

    “Recommendations regarding administration procedures made by Guastella et al. [19] were followed, although participants’ nasal cavities were not medically examined.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] AJ Guastella, 2013, Recommendations for the standardisation of oxytocin nasal administration and guidelines for its reporting in human research, Psychoneuroendocrinology source

      Not checked in the free run.

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

    Premisecitation

    The impact of intranasal oxytocin lasts for at least 90 minutes in both plasma and saliva.

    “except to corroborate other evidence that the impact of IN-OT lasts for at least 90 minutes in both plasma and saliva [18].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] A Gossen, 2012, Oxytocin plasma concentrations after single intranasal oxytocin administration—A study in healthy men, Neuropeptides 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 conductreasoning

    All data points were winsorized, so there were no statistical outliers.

    “The study was double-blind; participants were randomly assigned to their drug order; there were no significant order effects; and all data points were winsorized (therefore there were no statistical outliers).”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    The primary effects found in the present study are the same as those observed in other studies.

    “3) the primary effects found in the present study are the same as those observed in other studies.”
    Quote in the paperNot a substantial claim
33 of 33

  • The paper relies on this without support.

    Substances not absorbed across the nasal membrane are moved to the back of the throat and swallowed within about 15 minutes, so they can no longer spike saliva.

    “When substances are brought to the back of the throat, they do not remain there indefinitely; instead, the swallow reflex is activated and moves substances from the throat into the oesophagus and down to the stomach.”

  • The paper relies on this without support.

    The sample of 40 male university students is representative of healthy adult males for salivary oxytocin response to intranasal oxytocin.

    “Forty healthy male students (M age = 20.98; SD = 4.55) from Cardiff University took part in the study.”
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?

Statistics that don’t add up

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

  • Inconsistent p-value: r(6) = .96, p = .002

    Minor

    The paper reports p = .002 here; recomputing from the test statistic and its degrees of freedom gives p < .001 (two-tailed). The check cannot tell whether the statistic or the p-value is the misprint.

    Reported p = .002 · recomputed p < .001

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 upr(6) = 0.96reported p = .002 · recomputed p < .001

    “r(6) = .96, p = .002”

  • Consistentχ²(11) = 286.75reported p < .001 · recomputed p < .001

    “χ2(11) = 286.75, p < .001”

2 of 2

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.

  • Reported placebo range excludes several table means

    Minor

    The discussion describes placebo concentrations as 30-40 pg/ml across the session, but Table 1 reports means above 40 pg/ml at baseline, 60 minutes, and 105 minutes.

1 of 1

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Related

Authors
Daughters, K., Manstead, A. S. R., Hubble, K., Rees, A., Thapar, A., & van Goozen, S. H. M.
Affiliations
Cardiff University (GB)
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2015-12-15
Volume
10
Issue
12
Pages
e0145104
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0145104
PMC
PMC4684402
OpenAlex
W2202540184
Cited by
92
References
34
Citations by year
2026: 1 · 2025: 4 · 2024: 24 · 2023: 2 · 2022: 8 · 2021: 17 · 2020: 9 · 2019: 4 · 2018: 7 · 2017: 9 · 2016: 5 · 2015: 1
FWCI
12.03
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Open Access at Essex (University of Essex) (acceptedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Wellcome Trust
  • Cardiff University
  • Medical Research Council (MR/L010305/1)
  • Economic and Social Research Council (ES/J500197, 1085185, 1228040, ES/J500197/1)
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
intranasal oxytocin, salivary oxytocin, healthy men
MeSH terms
Administration, Intranasal, Double-Blind Method, Humans, Male, Oxytocin, Placebos, Cross-Over Studies

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 2026-10-08.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-08.

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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