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Cited by 23Neuroendocrine regulation and behaviorAutism Spectrum Disorder ResearchAction Observation and Synchronization

Randomized clinical trial shows no substantial modulation of empathy-related neural activation by intranasal oxytocin in autism

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Mayer, Annalina V., Wermter, Anne-Kathrin, Stroth, Sanna, Alter, Peter, Haberhausen, Michael, Stehr, Thomas, Paulus, Frieder M., Krach, Sören +1 more·2021·Scientific Reports
DOI 10.1038/s41598-021-94407-xPMC PMC8302641
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Abstract

Evidence suggests that intranasal application of oxytocin facilitates empathy and modulates its underlying neural processes, which are often impaired in individuals with autism spectrum disorders (ASD). Oxytocin has therefore been considered a promising candidate for the treatment of social difficulties in ASD. However, evidence linking oxytocin treatment to social behavior and brain function in ASD is limited and heterogeneous effects might depend on variations in the oxytocin-receptor gene (OXTR). We examined 25 male ASD patients without intellectual disability in a double-blind, cross-over, placebo-controlled fMRI-protocol, in which a single dose of oxytocin or placebo was applied intranasally. Patients performed three experiments in the MRI examining empathy for other’s physical pain, basic emotions, and social pain. All participants were genotyped for the rs53576 single-nucleotide polymorphism of the OXTR. Oxytocin increased bilateral amygdala responsiveness during the physical pain task for both painful and neutral stimuli. Other than that, there were no effects of oxytocin treatment. OXTR genotype did not significantly interact with oxytocin treatment. Our results contribute to the growing body of empirical literature suggesting heterogenous effects of oxytocin administration in ASD. To draw clinically relevant conclusions regarding the usefulness of oxytocin treatment, however, empirical studies need to consider methods of delivery, dose, and moderating individual factors more carefully in larger samples.

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Written from the paper’s full text.

TL;DR

In a randomized, double-blind, placebo-controlled crossover fMRI trial in 25 male autistic adults/adolescents without intellectual disability, a single intranasal oxytocin dose did not substantially modulate empathy-related neural activation. The only significant oxytocin effect was increased bilateral amygdala responsiveness during the physical pain task, and OXTR rs53576 genotype did not significantly interact with treatment.

Key findings

  • Oxytocin increased bilateral amygdala responsiveness during the physical pain task for both painful and neutral stimuli: whole-brain right amygdala cluster k = 11, t(94) = 5.12, pFWE = 0.017; left hippocampus k = 10, t(94) = 5.10, pFWE = 0.019; ROI left amygdala k = 29, t(94) = 3.95, pFWE = 0.007; right amygdala k = 131, pFWE < 0.001.
  • Other than that, there were no effects of oxytocin treatment across the basic emotions and social pain experiments, and no significant treatment effects in whole-brain or ROI analyses for those tasks.
  • OXTR rs53576 genotype did not significantly interact with oxytocin treatment in the hypothesized regions; exploratory whole-brain genotype–treatment interactions appeared in left precuneus and left frontal inferior orbital white matter, where genotype was more strongly associated with activation under placebo than oxytocin.
  • Behavioral ratings showed strong stimulus-category effects in all three tasks, but no significant main effects of treatment or OXTR genotype and no significant interaction effects after correction.

Methods

  • Monocentric, randomized, double-blind, placebo-controlled crossover trial; preregistered (EudraCT 2012-003750-89), stopped prematurely because of poor recruitment. Twenty-seven male ASD patients aged 15–33 years were recruited; 25 were analyzed after exclusions.
  • Participants received a single intranasal dose of oxytocin or placebo (24 IU for those aged ≥ 18 years, n = 20; 18 IU for ages 15–17, n = 5), then entered MRI 45 min later and completed three fMRI experiments: physical pain, basic emotions, and social pain. All were genotyped for OXTR rs53576.
  • fMRI data were analyzed in SPM12 using mixed-effects models with treatment and stimulus category as within-subject factors and genotype as a covariate; results were FWE-corrected at voxel level for whole-brain and anatomically defined ROI analyses (ACC, anterior insula, amygdala). Behavioral ratings were analyzed with repeated-measures ANOVAs and Holm–Bonferroni correction.

Limitations

  • The paper states that the sample of 25 analyzed datasets lacked sufficient statistical power to reliably detect possible small effects, and that the sample was relatively homogeneous (males without intellectual disability, moderate symptomatology), limiting representativeness.
  • The authors note that baseline oxytocin levels and anxiety were not measured, age range was unbalanced, homozygous A-allele carriers were rare, and single-SNP rather than haplotype analyses may have limited detection of genetic moderation.
  • The paper also states that prior interventions may have produced a ceiling effect, epigenetic processes may influence oxytocin sensitivity, and effect sizes in the oxytocin literature may have been overestimated; the text makes evident that the sole significant neural finding was among many contrasts and should be considered speculative.

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

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Registry

Crossref · 10.1038/s41598-021-94407-x

Cites

114 of 114 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

0 of 77 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Whole brain analyses indicated that physical pain compared to physical neutral induced strong and consistent activations of brain regions previously implicated in empathy for physical pain, including ACC, anterior insula and supramarginal gyrus.

    “Whole brain analyses indicated that PP, compared to PN, induced strong and consistent activations of brain regions that have been previously implicated in empathy for or others’ physical pain79, including ACC, anterior insula and supramarginal gyrus (Supplementary Table S5, Fig. 2B).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Other than the increased bilateral amygdala responsiveness during the physical pain task, there were no effects of oxytocin treatment.

    “Other than that, there were no effects of oxytocin treatment.”
    Quote in the paperSubstantial claim
  • Findingown data

    Whole-brain analyses showed significant genotype-treatment interactions in the left precuneus and white matter within the left frontal inferior orbital region.

    “Whole-brain analyses however showed significant genotype-treatment interactions in the left precuneus (k = 50, − 2/− 46/10, t(94) = 5.68, pFWE = 0.002) and white matter within the left frontal inferior orbital region (k = 10, − 24/30/− 6, t(94) = 5.42, pFWE = 0.006).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Participants with ASD clearly distinguished between physical pain and physical neutral stimuli, as indicated by a significant main effect of category on stimulus ratings.

    “Participants with ASD clearly distinguished between PP and PN, as indicated by a significant main effect of category on stimulus ratings (F(1,23) = 901.89, p < 0.001, partial η2 = 0.975).”
    Quote in the paperNot a substantial claim
  • Findingown data

    OXTR genotype did not significantly interact with oxytocin treatment.

    “OXTR genotype did not significantly interact with oxytocin treatment.”
    Quote in the paperSubstantial claim
  • May combine two claims. 29
  • Classified as probably not a substantial claim. 32
  • The quote only partly states this claim. 2

  • May combine two claims.

    Findingown data

    There were no significant interactions of stimulus category and treatment, and no main effects of OXTR genotype, both in whole-brain and ROI analyses for physical pain.

    “There were no significant interactions of stimulus category and treatment, and no main effects of OXTR genotype, both in whole-brain and ROI analyses.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    ROI analyses revealed that oxytocin increased average left amygdala activation, with the effect more pronounced in the right amygdala.

    “ROI analyses revealed that oxytocin also increased average left amygdala activation (k = 29, − 22/− 2/− 12, t(94) = 3.95 pFWE = 0.007), although this effect was more pronounced in the right amygdala (k = 131, pFWE < 0.001).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There were no significant main effects of treatment or OXTR genotype, and no significant interaction effects on physical pain ratings.

    “There were no significant main effects of treatment or OXTR genotype, and no significant interaction effects.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Oxytocin enhanced average activation within the right amygdala and inferior temporal gyrus, and left hippocampus compared to placebo.

    “oxytocin was found to enhance average activation within the right amygdala and inferior temporal gyrus (k = 11, MNI coordinates: 34/0/− 26, t(94) = 5.12, pFWE = 0.017), and left hippocampus (k = 10, − 34/− 8/− 22, t(94) = 5.10, pFWE = 0.019) compared to placebo.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Whole-brain analyses showed that on average, genotype was significantly associated with a small cluster within the right primary visual cortex.

    “Whole-brain analyses showed that on average, genotype was significantly associated with a small cluster within the right primary visual cortex (k = 2, 20/− 100/0, F(1,130) = 25.21, pFWE = 0.031).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There were no significant treatment effects in both whole-brain analyses and ROI analyses, and no significant effects of genotype or genotype-treatment interactions for social pain.

    “Again, there were no significant treatment effects in both whole-brain analyses and ROI analyses, and no significant effects of genotype or genotype-treatment interactions.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There were no effects of oxytocin treatment in both whole-brain analyses and ROI analyses for basic emotions.

    “There were no effects of treatment in both whole-brain analyses and ROI analyses.”
    Quote in the paperSubstantial claim

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

    Findingown data

    There were no significant main effects of treatment or OXTR genotype, and no significant interaction effects on social pain ratings.

    “There were no significant main effects of treatment or OXTR genotype, and no significant interaction effects.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    There were no significant main effects of treatment or OXTR genotype, and no significant interaction effects on basic emotions ratings.

    “There were no significant main effects of treatment or OXTR genotype, and no significant interaction effects.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The only significant oxytocin effect on brain activation was found during the physical pain experiment, where oxytocin, compared to placebo, enhanced activation in bilateral amygdala and left hippocampus, irrespective of whether the pictures showed painful scenes or not.

    “The only significant oxytocin effect on brain activation was found during the physical pain experiment, where oxytocin, compared to placebo, enhanced activation in bilateral amygdala and left hippocampus, irrespective of whether the pictures showed painful scenes or not.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Across all analyses across three experiments, including analyses restricted to anatomically defined search areas, only one significant effect of oxytocin on brain activation was found; all other comparisons were non-significant.

    “Of all analyses across three experiments, including analyses restricted to anatomically defined search areas, we found only one significant effect of oxytocin on brain activation. All other comparisons yielded non-significant results.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    The sample is larger than the average sample size of previous studies examining oxytocin effects on brain function in ASD and comparable to the average sample size in clinical trials examining oxytocin effects across different neurodevelopmental disorders.

    “However, it must be noted that our sample is larger than the average sample size of previous studies examining oxytocin effects on brain function in ASD44, and comparable to the average sample size in clinical trials examining oxytocin effects across different neurodevelopmental disorders83.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [44] Ooi, Y., Weng, S.-J., Kossowsky, J., Gerger, H. & Sung, M. Oxytocin and autism spectrum disorders: A systematic review and meta-analysis of randomized controlled trials. Pharmacopsychiatry 50, 5–13 (2016). source

      Not checked in the free run.

    • cites [83] Keech, B., Crowe, S. & Hocking, D. R. Intranasal oxytocin, social cognition and neurodevelopmental disorders: A meta-analysis. Psychoneuroendocrinology 87, 9–19 (2018). source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Carriers of the rs53576 A allele showed higher levels of ASD symptomatology in their childhood compared to non-carriers, but both groups displayed comparable symptom levels at the time of study participation.

    “Interestingly, carriers of the rs53576 A allele showed higher levels of ASD symptomatology in their childhood compared to non-carriers, but both groups displayed comparable symptom levels at the time of study participation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The sample was relatively homogeneous, including only males without intellectual disability and with moderate levels of symptomatology at the time of data collection.

    “Second, the sample was relatively homogeneous, including only males without intellectual disability and with moderate levels of symptomatology at the time of data collection, which cannot be considered representative for the heterogeneous phenotype of ASD.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The age range in this sample was 15-33 years, with a significantly larger proportion of adults (18 years or older).

    “For example, the age range in this sample was 15–33 years, with a significantly larger proportion of adults (18 years or older).”
    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 stopped prematurely because of poor recruitment.

    “The trial was stopped prematurely because of poor recruitment (see Supplementary Methods).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    All fMRI results were family-wise error (FWE)-corrected for multiple comparisons on the voxel-level in both whole-brain and regions of interest (ROI) analyses.

    “All fMRI results were family-wise error (FWE)-corrected for multiple comparisons on the voxel-level in both whole-brain and regions of interest (ROI) analyses.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    These difficulties have been associated with anatomical and functional differences in the empathy network.

    “These difficulties have been associated with anatomical and functional differences in the empathy network5–10.”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [5] Gallese, V., Rochat, M. J. & Berchio, C. The mirror mechanism and its potential role in autism spectrum disorder. Dev. Med. Child Neurol. 55, 15–22 (2013). source

      Not checked in the free run.

    • cites [6] Keysers, C. & Gazzola, V. Expanding the mirror: Vicarious activity for actions, emotions, and sensations. Curr. Opin. Neurobiol. 19, 666–671 (2009). source

      Not checked in the free run.

    • cites [7] Krach, S. et al. Evidence from pupillometry and fMRI indicates reduced neural response during vicarious social pain but not physical pain in autism. Hum. Brain Mapp. 36, 4730–4744 (2015). source

      Not checked in the free run.

    • cites [8] Oberman, L. M. et al. EEG evidence for mirror neuron dysfunction in autism spectrum disorders. Cogn. Brain Res. 24, 190–198 (2005). source

      Not checked in the free run.

    • cites [9] Hadjikhani, N., Joseph, R. M., Snyder, J. & Tager-Flusberg, H. Anatomical differences in the mirror neuron system and social cognition network in autism. Cereb. Cortex 16, 1276–1282 (2006). source

      Not checked in the free run.

    • cites [10] Dapretto, M. et al. Understanding emotions in others: Mirror neuron dysfunction in children with autism spectrum disorders. Nat. Neurosci. 9, 28–30 (2006). source

      Not checked in the free run.

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

    Study design and conductcitation

    The study used a validated three-cluster parcellation scheme to obtain a valid anterior insula mask.

    “we used a validated three-cluster parcellation scheme to obtain a valid anterior insula mask76.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [76] Kelly, C. et al. A convergent functional architecture of the insula emerges across imaging modalities. Neuroimage 61, 1129–1142 (2012). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Patients were randomly assigned to receive oxytocin or placebo first.

    “Patients were randomly assigned to receive oxytocin (n = 14) or placebo (n = 11) first.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    One symptom reported by individuals with ASD are difficulties in intuitively empathizing with others' emotional states, especially in situations that require an integration of complex social information.

    “One symptom reported by individuals with ASD are difficulties in intuitively empathizing with others’ emotional states, especially in situations that require an integration of complex social information3,4.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [3] Brewer, N., Young, R. L. & Barnett, E. Measuring theory of mind in adults with autism spectrum disorder. J. Autism Dev. Disord. 47, 1927–1941 (2017). source

      Not checked in the free run.

    • cites [4] Senju, A. Atypical development of spontaneous social cognition in autism spectrum disorders. Brain Dev. 35, 96–101 (2013). source

      Not checked in the free run.

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

    Study design and conductown data

    Two patients were excluded after the first study visit, leaving data from n = 25 patients to be analyzed.

    “Two patients were excluded after the first study visit because of unexpected clinical findings in one case and subjective negative experiences (nightmares) in another case, leaving data from n = 25 patients to be analyzed.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    This randomized controlled trial was preregistered at the European Union Clinical Trials Register.

    “This randomized controlled trial was preregistered at the European Union Clinical Trials Register (EudraCT 2012-003750-89; https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-003750-89/DE; registered 21/11/2012).”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    This was a monocentric, randomized, double-blind, placebo-controlled, cross-over study.

    “This was a monocentric, randomized, double-blind, placebo-controlled, cross-over study.”
    Quote in the paperSubstantial claim

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

    Study design and conductown data

    Due to technical difficulties during the MRI scan, two patients were excluded from the analyses of the basic emotions experiment, and four were excluded from the analyses of the social pain experiment.

    “Due to technical difficulties during the MRI scan, two patients were excluded from the analyses of the basic emotions experiment, and four were excluded from the analyses of the social pain experiment (see Supplementary Fig. S1 for CONSORT diagram of patient recruitment and study flow).”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    The insula and amygdala seem to be key target regions in the brain, with oxytocin modulating amygdala responsiveness to emotional faces or social stimuli in general.

    “In this context, the insula17 as well as the amygdala seem to be key target regions in the brain, with oxytocin modulating amygdala responsiveness to emotional faces18–22 or social stimuli in general23.”
    Quote in the paperSubstantial claim0 of 7 sources checked
    • cites [17] Wigton, R. et al. Neurophysiological effects of acute oxytocin administration: Systematic review and meta-analysis of placebo-controlled imaging studies. J. Psychiatry Neurosci. 40, E1–E22 (2015). source

      Not checked in the free run.

    • cites [18] Domes, G. et al. Oxytocin attenuates amygdala responses to emotional faces regardless of valence. Biol. Psychiatry 62, 1187–1190 (2007). source

      Not checked in the free run.

    • cites [19] Quintana, D. S. et al. Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled within-subjects randomized dose-response fMRI trial. Psychoneuroendocrinology 69, 180–188 (2016). source

      Not checked in the free run.

    • cites [20] Kirsch, P. Oxytocin modulates neural circuitry for social cognition and fear in humans. J. Neurosci. 25, 11489–11493 (2005). source

      Not checked in the free run.

    • cites [21] Gamer, M., Zurowski, B. & Büchel, C. Different amygdala subregions mediate valence-related and attentional effects of oxytocin in humans. Proc. Natl. Acad. Sci. 107, 9400–9405 (2010). source

      Not checked in the free run.

    • cites [22] Petrovic, P., Kalisch, R., Singer, T. & Dolan, R. J. Oxytocin attenuates affective evaluations of conditioned faces and amygdala activity. J. Neurosci. 28, 6607–6615 (2008). source

      Not checked in the free run.

    • cites [23] Geng, Y. et al. Oxytocin enhancement of emotional empathy: Generalization across cultures and effects on amygdala activity. Front. Neurosci. 12, 1–14 (2018). source

      Not checked in the free run.

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

    Premisecitation

    Variations of the OXTR have been associated with individual differences in the capacity and tendency to empathize with others' emotional states in healthy individuals and related brain function in individuals with ASD.

    “Further, variations of the oxytocin receptor gene (OXTR) have been associated with individual differences in the capacity and tendency to empathize with others’ emotional states in healthy individuals25–30 and related brain function in individuals with ASD31.”
    Quote in the paperNot a substantial claim0 of 7 sources checked
    • cites [25] Rodrigues, S. M., Saslow, L. R., Garcia, N., John, O. P. & Keltner, D. Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans. Proc. Natl. Acad. Sci. 106, 21437–21441 (2009). source

      Not checked in the free run.

    • cites [26] Smith, K. E., Porges, E. C., Norman, G. J., Connelly, J. J. & Decety, J. Oxytocin receptor gene variation predicts empathic concern and autonomic arousal while perceiving harm to others. Soc. Neurosci. 9, 1–9 (2014). source

      Not checked in the free run.

    • cites [27] Li, J. et al. Association of oxytocin receptor gene (OXTR) rs53576 polymorphism with sociality: A meta-analysis. PLoS One 10, 1–16 (2015).

      Not checked in the free run.

    • cites [28] Uzefovsky, F. et al. Oxytocin receptor and vasopressin receptor 1a genes are respectively associated with emotional and cognitive empathy. Horm. Behav. 67, 60–65 (2015). source

      Not checked in the free run.

    • cites [29] Gong, P. et al. Revisiting the impact of OXTR rs53576 on empathy: A population-based study and a meta-analysis. Psychoneuroendocrinology 80, 131–136 (2017). source

      Not checked in the free run.

    • cites [30] Flasbeck, V., Moser, D., Kumsta, R. & Brüne, M. The OXTR single-nucleotide polymorphism rs53576 moderates the impact of childhood maltreatment on empathy for social pain in female participants: Evidence for differential susceptibility. Front. Psychiatry 9, 1–9 (2018). source

      Not checked in the free run.

    • cites [31] Uzefovsky, F. et al. The oxytocin receptor gene predicts brain activity during an emotion recognition task in autism. Mol. Autism 10, 12 (2019). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The empathy network, including the ACC and anterior insula, encodes for both one's own, as well as others' bodily, mental, and emotional states.

    “This network, including the anterior cingulate cortex (ACC) and the anterior insula, encodes for both one’s own, as well as others’ bodily, mental, and emotional states11.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11] Kanske, P., Böckler, A. & Singer, T. Models, Mechanisms and Moderators Dissociating Empathy and Theory of Mind. 193–206. https://doi.org/10.1007/7854_2015_412 (Springer, 2015). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Intranasal administration of oxytocin has been found to enhance the ability to share others' affective and mental states in healthy individuals.

    “Importantly, intranasal administration of oxytocin has also been found to enhance the ability to share others’ affective and mental states in healthy individuals15,16.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [15] Domes, G., Heinrichs, M., Michel, A., Berger, C. & Herpertz, S. C. Oxytocin improves ‘mind-reading’ in humans. Biol. Psychiatry 61, 731–733 (2007). source

      Not checked in the free run.

    • cites [16] Hurlemann, R. et al. Oxytocin enhances amygdala-dependent, socially reinforced learning and emotional empathy in humans. J. Neurosci. 30, 4999–5007 (2010). source

      Not checked in the free run.

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

    Premisecitation

    Several clinical studies have investigated intranasal oxytocin as a treatment for ASD, but cannot provide a certain conclusion about its therapeutic potential.

    “Several clinical studies have also investigated the potential of intranasal oxytocin as a treatment for socio-cognitive, behavioral, and socio-affective symptoms of ASD. So far, these studies cannot provide a certain conclusion about oxytocin’s therapeutic potential43–47.”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [43] Alvares, G. A., Quintana, D. S. & Whitehouse, A. J. O. Beyond the hype and hope: Critical considerations for intranasal oxytocin research in autism spectrum disorder. Autism Res. 10, 25–41 (2017). source

      Not checked in the free run.

    • cites [44] Ooi, Y., Weng, S.-J., Kossowsky, J., Gerger, H. & Sung, M. Oxytocin and autism spectrum disorders: A systematic review and meta-analysis of randomized controlled trials. Pharmacopsychiatry 50, 5–13 (2016). source

      Not checked in the free run.

    • cites [45] Guastella, A. J. & Hickie, I. B. Oxytocin treatment, circuitry, and autism: A critical review of the literature placing oxytocin into the autism context. Biol. Psychiatry 79, 234–242 (2016). source

      Not checked in the free run.

    • cites [46] Bakermans-Kranenburg, M. J. & van IJzendoorn, M. H. Sniffing around oxytocin: Review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy. Transl. Psychiatry 3, e258 (2013). source

      Not checked in the free run.

    • cites [47] Yamasue, H. Promising evidence and remaining issues regarding the clinical application of oxytocin in autism spectrum disorders. Psychiatry Clin. Neurosci. 70, 89–99 (2016). source

      Not checked in the free run.

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

    Premisecitation

    A allele carriers have reduced amygdala activation during the processing of faces compared to non-carriers.

    “Specifically, it has been shown that A allele carriers have reduced amygdala activation during the processing of faces compared to non-carriers42.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] Tost, H. et al. A common allele in the oxytocin receptor gene (OXTR) impacts prosocial temperament and human hypothalamic-limbic structure and function. Proc. Natl. Acad. Sci. 107, 13936–13941 (2010). source

      Not checked in the free run.

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

    Premisecitation

    The rs53576 SNP (G > A) has been shown to modulate social cognition both within ASD and the general population.

    “Especially the rs53576 SNP (G > A) has been shown to modulate social cognition both within ASD and the general population40.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Wilczyński, K. M., Siwiec, A. & Janas-Kozik, M. Systematic review of literature on single-nucleotide polymorphisms within the oxytocin and vasopressin receptor genes in the development of social cognition dysfunctions in individuals suffering from autism spectrum disorder. Front. Psychiatry 10, 380 (2019). source

      Not checked in the free run.

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

    Premisecitation

    Oxytocin has been shown to increase gazing time on the eye region, and to improve performance on the Reading the Mind in the Eyes Task in adults and adolescents with ASD.

    “For example, oxytocin has been shown to increase gazing time on the eye region33, and to improve performance on the Reading the Mind in the Eyes Task in adults and adolescents with ASD48,49.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [33] Andari, E. et al. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc. Natl. Acad. Sci. U. S. A. 107, 4389–4394 (2010). source

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    • cites [48] Guastella, A. J. et al. Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders. Biol. Psychiatry 67, 692–694 (2010). source

      Not checked in the free run.

    • cites [49] Anagnostou, E. et al. Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: A randomized controlled trial. Mol. Autism 3, 16 (2012). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Imaging studies have provided preliminary evidence that oxytocin influences the ability to understand others' mental and emotional states by enhancing activation of brain regions within the empathy network, such as the anterior insula.

    “Imaging studies have provided preliminary evidence that oxytocin influences the ability to understand others’ mental and emotional states by enhancing activation of brain regions within the empathy network, such as the anterior insula50.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [50] Aoki, Y. et al. Oxytocin improves behavioural and neural deficits in inferring others’ social emotions in autism. Brain 137, 3073–3086 (2014). source

      Not checked in the free run.

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

    Premisecitation

    Oxytocin administration has been shown to increase amygdala activation during face processing specifically in adults with ASD, accompanied by improvements in emotion recognition.

    “Similarly, oxytocin administration has been shown to increase amygdala activation during face processing specifically in adults with ASD, accompanied by improvements in emotion recognition51,52.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [51] Domes, G. et al. Effects of intranasal oxytocin on the neural basis of face processing in autism spectrum disorder. Biol. Psychiatry 74, 164–171 (2013). source

      Not checked in the free run.

    • cites [52] Domes, G., Kumbier, E., Heinrichs, M. & Herpertz, S. C. Oxytocin promotes facial emotion recognition and amygdala reactivity in adults with asperger syndrome. Neuropsychopharmacology 39, 698–706 (2014). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Several studies suggest that oxytocin effects on behavior and brain function are modulated by OXTR genotype.

    “Several studies indeed suggest that oxytocin effects on behavior54–56 and brain function57–59 are modulated by OXTR genotype.”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [54] Marsh, A. A. et al. The influence of oxytocin administration on responses to infant faces and potential moderation by OXTR genotype. Psychopharmacology 224, 469–476 (2012). source

      Not checked in the free run.

    • cites [55] Chen, F. S. et al. Genetic modulation of oxytocin sensitivity: A pharmacogenetic approach. Transl. Psychiatry 5, e664–e664 (2015). source

      Not checked in the free run.

    • cites [56] Kosaka, H. et al. Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: A 24-week randomized clinical trial. Transl. Psychiatry 6, e872 (2016). source

      Not checked in the free run.

    • cites [57] Feng, C. et al. A common oxytocin receptor gene (OXTR) polymorphism modulates intranasal oxytocin effects on the neural response to social cooperation in humans. Genes Brain Behav. 14, 516–525 (2015). source

      Not checked in the free run.

    • cites [58] Montag, C., Sauer, C., Reuter, M. & Kirsch, P. An interaction between oxytocin and a genetic variation of the oxytocin receptor modulates amygdala activity toward direct gaze: Evidence from a pharmacological imaging genetics study. Eur. Arch. Psychiatry Clin. Neurosci. 263, 169–175 (2013). source

      Not checked in the free run.

    • cites [59] Watanabe, T. et al. Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism. Soc. Cogn. Affect. Neurosci. 12, 496–506 (2017). source

      Not checked in the free run.

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

    Premisecitation

    The effects of intranasal oxytocin may not be the same for all individuals, but instead depend on stable individual differences, which might reflect variation in the endogenous oxytocin system, including genetic factors.

    “However, it has been discussed that the effects of intranasal oxytocin may not be the same for all individuals, but instead depend on stable individual differences, which might reflect variation in the endogenous oxytocin system, including genetic factors53.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [53] Bartz, J. A., Zaki, J., Bolger, N. & Ochsner, K. N. Social effects of oxytocin in humans: Context and person matter. Trends Cogn. Sci. 15, 301–309 (2011).

      Not checked in the free run.

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

    Premisecitation

    Most studies examining oxytocin effects have too small sample sizes to even detect medium effects and are therefore substantially underpowered.

    “It has been criticized that most studies examining oxytocin effects have too small sample sizes to even detect medium effects and are therefore substantially underpowered98.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [98] Walum, H., Waldman, I. D. & Young, L. J. Statistical and methodological considerations for the interpretation of intranasal oxytocin studies. Biol. Psychiatry 79, 251–257 (2016). source

      Not checked in the free run.

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

    Premisecitation

    Oxytocin has been shown to influence brain and behavior differently at different developmental stages.

    “Since oxytocin has been shown to influence brain and behavior differently at different developmental stages94, oxytocin efficacy might differ between adults and adolescents.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [94] Miller, T. V. & Caldwell, H. K. Oxytocin during development: Possible organizational effects on behavior. Front. Endocrinol. (Lausanne) 6, 76 (2015). source

      Not checked in the free run.

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

    Interpretationcitation

    An alternative explanation for the absence of a general treatment effect in this study relates to an overestimation of effect sizes of intranasal oxytocin treatment based on earlier studies.

    “An alternative explanation for the absence of a general treatment effect in this study relates to an overestimation of effect sizes of intranasal oxytocin treatment based on earlier studies.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    If the effects found in previous studies are true effects with roughly accurate effect size estimates, we would expect to find them even within our sample.

    “If the effects found in these studies are true effects with roughly accurate effect size estimates, we would expect to find them even within in our sample.”
    Quote in the paperSubstantial claim

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

    Interpretationcitation

    Oxytocin efficacy might differ between adults and adolescents.

    “Since oxytocin has been shown to influence brain and behavior differently at different developmental stages94, oxytocin efficacy might differ between adults and adolescents.”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning

    Other potential moderating factors could not be addressed in this study, which might have led to overall non-significant effects.

    “Although this study explicitly examined potential moderating influences of OXTR genotype, other potential moderating factors could not be addressed, which might have led to overall non-significant effects.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The effects of a single dose of intranasal oxytocin might have been too small to lead to a detectable change in brain function and affective experience in the sample of 25 individuals, which might suggest that its use as a therapeutic intervention alone may be limited.

    “The effects of a single dose of intranasal oxytocin might have been too small to lead to a detectable change in brain function and affective experience in our sample of 25 individuals, which might suggest that its use as a therapeutic intervention alone may be limited.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Intranasal oxytocin at the dose and route used in this study can reach the brain and modulate neural activity.

  • May combine two claims.

    Premisecitation

    Effect sizes of studies using intranasal oxytocin seem to be smaller than initially assumed, reflected in unsuccessful attempts to replicate earlier findings of oxytocin effects on trust and mind-reading in healthy populations.

    “Generally, effect sizes of studies using intranasal oxytocin seem to be smaller than initially assumed99, a finding that is also reflected in unsuccessful attempts to replicate earlier findings of oxytocin effects on trust100,101 and mind-reading in healthy populations102.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [99] Tabak, B. A. et al. Null results of oxytocin and vasopressin administration across a range of social cognitive and behavioral paradigms: Evidence from a randomized controlled trial. Psychoneuroendocrinology https://doi.org/10.1016/J.PSYNEUEN.2019.04.019 (2019). source

      Not checked in the free run.

    • cites [100] Lane, A. et al. Failed replication of oxytocin effects on trust: The envelope task case. PLoS One 10, 1–10 (2015).

      Not checked in the free run.

    • cites [101] Declerck, C. H., Boone, C., Pauwels, L., Vogt, B. & Fehr, E. A registered replication study on oxytocin and trust. Nat. Hum. Behav. https://doi.org/10.1038/s41562-020-0878-x (2020). source

      Not checked in the free run.

    • cites [102] Radke, S. & de Bruijn, E. R. A. Does oxytocin affect mind-reading? A replication study. Psychoneuroendocrinology https://doi.org/10.1016/j.psyneuen.2015.06.006 (2015). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Intranasal oxytocin has no significant effect on emotion recognition and empathy.

    “Importantly, our findings are in line with recent meta-analytical evidence indicating that intranasal oxytocin only leads to small but non-significant changes in overall social cognition in ASD44, but has no significant effect on emotion recognition and empathy83.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [83] Keech, B., Crowe, S. & Hocking, D. R. Intranasal oxytocin, social cognition and neurodevelopmental disorders: A meta-analysis. Psychoneuroendocrinology 87, 9–19 (2018). source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Whether or not oxytocin nasal spray may benefit individuals with ASD, either as a discrete treatment option or in combination with behavioral therapy, cannot be assessed to date.

    “Whether or not oxytocin nasal spray may benefit individuals with ASD, either as a discrete treatment option or in combination with behavioral therapy, cannot be assessed to date.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Our findings are in line with recent meta-analytical evidence indicating that intranasal oxytocin only leads to small but non-significant changes in overall social cognition in ASD, but has no significant effect on emotion recognition and empathy.

    “Importantly, our findings are in line with recent meta-analytical evidence indicating that intranasal oxytocin only leads to small but non-significant changes in overall social cognition in ASD44, but has no significant effect on emotion recognition and empathy83.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [44] Ooi, Y., Weng, S.-J., Kossowsky, J., Gerger, H. & Sung, M. Oxytocin and autism spectrum disorders: A systematic review and meta-analysis of randomized controlled trials. Pharmacopsychiatry 50, 5–13 (2016). source

      Not checked in the free run.

    • cites [83] Keech, B., Crowe, S. & Hocking, D. R. Intranasal oxytocin, social cognition and neurodevelopmental disorders: A meta-analysis. Psychoneuroendocrinology 87, 9–19 (2018). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Most randomized clinical trials have found some oxytocin effects on ASD symptoms and brain function, but not all trials have reported effects.

    “While most randomized clinical trials have found some oxytocin effects on ASD symptoms33,50–52 and brain function50–52,80,81, not all trials have reported effects82.”
    Quote in the paperNot a substantial claim0 of 7 sources checked
    • cites [33] Andari, E. et al. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc. Natl. Acad. Sci. U. S. A. 107, 4389–4394 (2010). source

      Not checked in the free run.

    • cites [50] Aoki, Y. et al. Oxytocin improves behavioural and neural deficits in inferring others’ social emotions in autism. Brain 137, 3073–3086 (2014). source

      Not checked in the free run.

    • cites [51] Domes, G. et al. Effects of intranasal oxytocin on the neural basis of face processing in autism spectrum disorder. Biol. Psychiatry 74, 164–171 (2013). source

      Not checked in the free run.

    • cites [52] Domes, G., Kumbier, E., Heinrichs, M. & Herpertz, S. C. Oxytocin promotes facial emotion recognition and amygdala reactivity in adults with asperger syndrome. Neuropsychopharmacology 39, 698–706 (2014). source

      Not checked in the free run.

    • cites [80] Aoki, Y. et al. Oxytocin’s neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: A randomized controlled trial. Mol. Psychiatry 20, 447–453 (2015). source

      Not checked in the free run.

    • cites [81] Andari, E., Richard, N., Leboyer, M. & Sirigu, A. Adaptive coding of the value of social cues with oxytocin, an fMRI study in autism spectrum disorder. Cortex 76, 79–88 (2016). source

      Not checked in the free run.

    • cites [82] Dadds, M. R. et al. Nasal oxytocin for social deficits in childhood autism: A randomized controlled trial. J. Autism Dev. Disord. 44, 521–531 (2014). source

      Not checked in the free run.

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

    Interpretationown data

    Our results are part of a growing number of studies that report heterogeneous effects of intranasal oxytocin in the context of ASD.

    “Overall, our results are part of a growing number of studies that report heterogeneous effects of intranasal oxytocin in the context of ASD.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Oxytocin administration leads to an increase in amygdala activation during the processing of faces in men with ASD.

    “While this finding fits with previous reports that oxytocin administration leads to an increase in amygdala activation during the processing of faces in men with ASD51,52, these findings are not consistent with studies that examine neural responses to aversive stimuli in men without an ASD diagnosis.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [51] Domes, G. et al. Effects of intranasal oxytocin on the neural basis of face processing in autism spectrum disorder. Biol. Psychiatry 74, 164–171 (2013). source

      Not checked in the free run.

    • cites [52] Domes, G., Kumbier, E., Heinrichs, M. & Herpertz, S. C. Oxytocin promotes facial emotion recognition and amygdala reactivity in adults with asperger syndrome. Neuropsychopharmacology 39, 698–706 (2014). source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Studies examining neural responses to aversive stimuli in men without an ASD diagnosis have repeatedly demonstrated decreased amygdala activation, interpreted as a neural mechanism underlying oxytocin's anxiolytic effects.

    “These studies have repeatedly demonstrated decreased amygdala activation, which has been interpreted as a neural mechanism underlying oxytocin’s anxiolytic effects18,20,21.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [18] Domes, G. et al. Oxytocin attenuates amygdala responses to emotional faces regardless of valence. Biol. Psychiatry 62, 1187–1190 (2007). source

      Not checked in the free run.

    • cites [20] Kirsch, P. Oxytocin modulates neural circuitry for social cognition and fear in humans. J. Neurosci. 25, 11489–11493 (2005). source

      Not checked in the free run.

    • cites [21] Gamer, M., Zurowski, B. & Büchel, C. Different amygdala subregions mediate valence-related and attentional effects of oxytocin in humans. Proc. Natl. Acad. Sci. 107, 9400–9405 (2010). source

      Not checked in the free run.

52 of 52

  • The paper relies on this without support.

    It is still unclear whether OXTR genotype moderates the effects of intranasal oxytocin on neural activity when empathizing with others.

    “To date, it is still unclear whether OXTR genotype moderates the effects of intranasal oxytocin on neural activity when empathizing with others.”

  • The paper relies on this without support.

    Oxytocin has been considered a promising candidate for the treatment of social difficulties in ASD.

    “Oxytocin has therefore been considered a promising candidate for the treatment of social difficulties in ASD.”

  • The paper relies on this without support.

    Intranasal oxytocin at the dose and route used in this study can reach the brain and modulate neural activity.

    “The present study examined the influence of acute oxytocin administration on neural correlates of empathy in individuals with ASD and how these effects are modulated by OXTR genotype.”
3 of 3

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?

  • Another recent study in young adults with ASD did not demonstrate any immediate benefits of OXT on empathy and social perception.

    “Another recent study in young adults with ASD also did not demonstrate any immediate benefits of OXT on empathy and social perception [79].”

    From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [79]

  • The effects of OXT in ASD are likely modulated by age, gender, and possibly genetic factors.

    “It is also likely that the effects of OXT in ASD are modulated by age, gender, and possibly genetic factors [77, 79, 90].”

    From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [79]

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.

  • ConsistentF(1, 23) = 901.89reported p < .001 · recomputed p < .001

    “F(1,23) = 901.89, p < .001”

  • ConsistentF(1, 22) = 6.49reported p = .018 · recomputed p = .018

    “F(1,22) = 6.49, p = .018”

  • Consistentr(23) = 0.49reported p = .012 · recomputed p = .013

    “r(23) = 0.49, p = .012”

  • ConsistentF(1, 22) = 10.95reported p = .003 · recomputed p = .003

    “F(1,22) = 10.95, p = .003”

  • ConsistentF(2, 42) = 486.8reported p < .001 · recomputed p < .001

    “F(2,42) = 486.8, p < .001”

  • ConsistentF(2, 42) = 8.1reported p = .001 · recomputed p = .001

    “F(2,42) = 8.10, p = .001”

  • ConsistentF(1, 20) = 7.65reported p = .012 · recomputed p = .012

    “F(1,20) = 7.65, p = .012”

  • ConsistentF(1, 19) = 1413.25reported p < .001 · recomputed p < .001

    “F(1,19) = 1413.25, p < .001”

8 of 8

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.

  • Abstract denies a genotype-treatment interaction reported in the results

    Minor

    The abstract says OXTR genotype did not significantly interact with treatment, but the physical-pain whole-brain analysis reports two significant genotype-treatment interactions. The abstract does not limit its claim to the prespecified regions of interest.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 3

  1. Rutter, M., Le Couteur, A. & Lord, C. Autism Diagnostic Interview-Revised (ADI-R). (Western Psychological Services, 2003).
  2. Wechsler, D. Wechsler Intelligence Scale for Children—Fourth Edition (WISC-IV). (The Psychological Corporation, 2003).
  3. Wermter, A. K. et al. Evidence for the involvement of genetic variation in the oxytocin receptor gene (OXTR) in the etiology of autistic disorders on high-functioning level. Am. J. Med. Genet. Part B Neuropsychiatr. Genet. https://doi.org/10.1002/ajmg.b.31032 (2010). · DOI · Paper page

Cited by

Sorted by citations

Related

Authors
Mayer, A. V., Wermter, A.-K., Stroth, S., Alter, P., Haberhausen, M., Stehr, T., Paulus, F. M., Krach, S., & Kamp-Becker, I.
Affiliations
  • Social Neuroscience Lab (DE)
  • Philipps University of Marburg (DE)
Corresponding author
Mayer, Annalina V.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2021-07-23
Volume
11
Issue
1
Pages
15056-15056
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-021-94407-x
PMC
PMC8302641
OpenAlex
W3186792749
Semantic Scholar
5eb583acdaa15edf39811bdf81e0cc209e8a079d
Cited by
23
References
114
Citations by year
2026: 3 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 7 · 2021: 1
FWCI
4.16
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Deutsche Forschungsgemeinschaft (WE 5076/1-1)
  • Universität zu Lübeck
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Social Sciences › Psychology › Social Psychology › Action Observation and Synchronization
Keywords
autism spectrum disorder, intranasal oxytocin, empathy, amygdala, social pain, bodily pain, emotion recognition, social cognition, treatment effect heterogeneity
MeSH terms
Autism Spectrum Disorder, Administration, Intranasal, Adolescent, Adult, Brain, Double-Blind Method, Empathy, Genotype, Humans, Magnetic Resonance Imaging, Male, Oxytocin, Social Behavior, Receptors, Oxytocin, Young Adult, Translational Research, Biomedical

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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