The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Mitigation of Sociocommunicational Deficits of Autism Through Oxytocin-Induced Recovery of Medial Prefrontal Activity: A Randomized Trial
Abstract
IMPORTANCE: Sociocommunicational deficits make it difficult for individuals with autism spectrum disorders (ASD) to understand communication content with conflicting verbal and nonverbal information. Despite growing prospects for oxytocin as a therapeutic agent for ASD, no direct neurobiological evidence exists for oxytocin's beneficial effects on this core symptom of ASD. This is slowing clinical application of the neuropeptide. OBJECTIVE: To directly examine whether oxytocin has beneficial effects on the sociocommunicational deficits of ASD using both behavioral and neural measures. DESIGN, SETTING, AND PARTICIPANTS: At the University of Tokyo Hospital, we conducted a randomized, double-blind, placebo-controlled, within-subject-crossover, single-site experimental trial in which intranasal oxytocin and placebo were administered. A total of 40 highly functioning men with ASD participated and were randomized in the trial. INTERVENTIONS: Single-dose intranasal administration of oxytocin (24 IU) and placebo. MAIN OUTCOMES AND MEASURES: Using functional magnetic resonance imaging, we examined effects of oxytocin on behavioral neural responses of the participants to a social psychological task. In our previous case-control study using the same psychological task, when making decisions about social information with conflicting verbal and nonverbal contents, participants with ASD made judgments based on nonverbal contents less frequently with longer time and could not induce enough activation in the medial prefrontal cortex. Therefore, our main outcomes and measures were the frequency of the nonverbal information-based judgments (NVJs), the response time for NVJs, and brain activity of the medial prefrontal cortex during NVJs. RESULTS: Intranasal oxytocin enabled the participants to make NVJs more frequently (P = .03) with shorter response time (P = .02). During the mitigated behavior, oxytocin increased the originally diminished brain activity in the medial prefrontal cortex (P < .001). Moreover, oxytocin enhanced functional coordination in the area (P < .001), and the magnitude of these neural effects was predictive of the behavioral effects (P ≤ .01). CONCLUSIONS AND RELEVANCE: These findings provide the first neurobiological evidence for oxytocin's beneficial effects on sociocommunicational deficits of ASD and give us the initial account for neurobiological mechanisms underlying any beneficial effects of the neuropeptide. TRIAL REGISTRATION: umin.ac.jp/ctr Identifier: UMIN000002241 and UMIN000004393.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“These results have been supported by functional neuroimaging studies involving persons with autism spectrum disorder, which have shown differences in regional brain activation in response to social stimuli after the administration of intranasal oxytocin, as compared with placebo.11,15–17”
From Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder (2021) · cites this paper as [11]
In the citing paper
“Several trials have shown that a single dose of intranasal oxytocin enhanced performance on measures of social cognition10,11 or motivation,12–14 as compared with placebo, in persons with autism spectrum disorder.”
From Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder (2021) · cites this paper as [11]
In the citing paper
“Oxytocin has received substantial interest as a potential treatment for psychiatric conditions such as autism spectrum conditions (ASC; henceforth autism),3 although clinical trials show modest effects.4, 5, 6”
From Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women (2017) · cites this paper as [4]
In the citing paper
“Moreover, previous studies showing oxytocin effects on emotion recognition, empathy, or face processing in adults with ASD had an average sample size of 21.5 participants48,50,51,86–88.”
From Randomized clinical trial shows no substantial modulation of empathy-related neural activation by intranasal oxytocin in autism (2021) · cites this paper as [86]
Citations
Cites
Diagnostic and Statistical Manual of Mental Disorders
Williams, J. B. W., & First, M. B. (2013) · Oxford University Press eBooks · doi:10.1093/acrefore/9780199975839.013.104 · Cited by 109,845
Lord, C., Rutter, M., & Le Couteur, A. (1994) · Journal of Autism and Developmental Disorders · doi:10.1007/bf02172145 · Cited by 9,065
Lord, C., Risi, S., Lambrecht, L., Cook, E. H., Leventhal, B. L., DiLavore, P. C., Pickles, A., & Rutter, M. (2000) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1005592401947 · Cited by 7,520
Oxytocin increases trust in humans
Kosfeld, M., Heinrichs, M., Zak, P. J., Fischbacher, U., & Fehr, E. (2005) · Nature · doi:10.1038/nature03701 · Cited by 3,690
Psychophysiological and Modulatory Interactions in Neuroimaging
Friston, K. J., Buechel, C., Fink, G. R., Morris, J., Rolls, E., & Dolan, R. J. (1997) · NeuroImage · doi:10.1006/nimg.1997.0291 · Cited by 3,097
Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine
Meyer-Lindenberg, A., Domes, G., Kirsch, P., & Heinrichs, M. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3044 · Cited by 1,688
Oxytocin, vasopressin, and the neurogenetics of sociality
Donaldson, Z. R., & Young, L. J. (2008) · Science · doi:10.1126/science.1158668 · Cited by 1,645
Oxytocin Modulates Neural Circuitry for Social Cognition and Fear in Humans
Kirsch, P., Esslinger, C., Chen, Q., Mier, D., Lis, S., Siddhanti, S., Gruppe, H., Mattay, V. S., Gallhofer, B., & Meyer-Lindenberg, A. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.3984-05.2005 · Cited by 1,639
Social effects of oxytocin in humans: context and person matter
Bartz, J. A., Zaki, J., Bolger, N., & Ochsner, K. N. (2011) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2011.05.002 · Cited by 1,581
The neurobiology of pair bonding.
Young, L. J., & Wang, Z. (2004) · Nature Neuroscience · doi:10.1038/nn1327 · Cited by 1,523
Sniffing neuropeptides: A transnasal approach to the human brain
Born, J., Lange, T., Kern, W., McGregor, G. P., Bickel, U., & Fehm, H. L. (2002) · Nature Neuroscience · doi:10.1038/nn0602-849 · Cited by 1,356
Oxytocin improves “mind-reading” in humans
Domes, G., Heinrichs, M., Michel, A., Berger, C., & Herpertz, S. C. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.07.015 · Cited by 1,298
Oxytocin shapes the neural circuitry of trust and trust adaptation in humans
Baumgartner, T., Heinrichs, M., Vonlanthen, A., Fischbacher, U., & Fehr, E. (2008) · Neuron · doi:10.1016/j.neuron.2008.04.009 · Cited by 1,258
Communicative competence and theory of mind in autism: A test of relevance theory
Happe, F. G. E. (1993) · Cognition · doi:10.1016/0010-0277(93)90026-r · Cited by 1,161
Evoked axonal oxytocin release in the central amygdala attenuates fear response
Knobloch, H. S., Charlet, A., Hoffmann, L. C., Eliava, M., Khrulev, S., Cetin, A. H., Osten, P., Schwarz, M. K., Seeburg, P. H., Stoop, R., et al. (2012) · Neuron · doi:10.1016/j.neuron.2011.11.030 · Cited by 1,049
Insel, T. R. (2010) · Neuron · doi:10.1016/j.neuron.2010.03.005 · Cited by 1,044
Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders.
Guastella, A. J., Einfeld, S. L., Gray, K. M., Rinehart, N. J., Tonge, B. J., Lambert, T. J., & Hickie, I. B. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.09.020 · Cited by 962
Promoting social behavior with oxytocin in high-functioning autism spectrum disorders.
Andari, E., Duhamel, J.-R., Zalla, T., Herbrecht, E., Leboyer, M., & Sirigu, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910249107 · Cited by 941
Oxytocin enhances amygdala-dependent, socially reinforced learning and emotional empathy in humans
Hurlemann, R., Patin, A., Onur, O. A., Cohen, M. X., Baumgartner, T., Metzler, S., Dziobek, I., Gallinat, J., Wagner, M., Maier, W., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5538-09.2010 · Cited by 771
Mindblind eyes: an absence of spontaneous theory of mind in Asperger syndrome
Senju, A., Southgate, V., White, S., & Frith, U. (2009) · Science · doi:10.1126/science.1176170 · Cited by 769
Oxytocin Increases Retention of Social Cognition in Autism
Hollander, E., Bartz, J., Chaplin, W., Phillips, A., Sumner, J., Soorya, L., Anagnostou, E., & Wasserman, S. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.05.030 · Cited by 693
Oxytocin Infusion Reduces Repetitive Behaviors in Adults with Autistic and Asperger's Disorders
Hollander, E., Novotny, S., Hanratty, M., Yaffe, R., DeCaria, C. M., Aronowitz, B. R., & Mosovich, S. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300021 · Cited by 689
CD38 is critical for social behaviour by regulating oxytocin secretion
Jin, D., Liu, H.-X., Hirai, H., Torashima, T., Nagai, T., Lopatina, O., Shnayder, N. A., Yamada, K., Noda, M., Seike, T., et al. (2007) · Nature · doi:10.1038/nature05526 · Cited by 665
Tost, H., Kolachana, B., Hakimi, S., Lemaitre, H., Verchinski, B. A., Mattay, V. S., Weinberger, D. R., & Meyer–Lindenberg, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003296107 · Cited by 564
Different amygdala subregions mediate valence-related and attentional effects of oxytocin in humans
Gamer, M., Zurowski, B., & Büchel, C. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000985107 · Cited by 487
Neural basis of irony comprehension in children with autism: the role of prosody and context
Wang, A. T., Lee, S. S., Sigman, M., & Dapretto, M. (2006) · Brain · doi:10.1093/brain/awl032 · Cited by 447
Neural basis of eye gaze processing deficits in autism
Pelphrey, K. A., Morris, J. P., & McCarthy, G. (2005) · Brain · doi:10.1093/brain/awh404 · Cited by 441
Sex differences in oxytocin and vasopressin: Implications for autism spectrum disorders?
CARTER, C. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2006.08.025 · Cited by 432
Oxytocin Attenuates Affective Evaluations of Conditioned Faces and Amygdala Activity
Petrovic, P., Kalisch, R., Singer, T., & Dolan, R. J. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.4572-07.2008 · Cited by 424
Oxytocin Selectively Gates Fear Responses Through Distinct Outputs from the Central Amygdala
Viviani, D., Charlet, A., van den Burg, E., Robinet, C., Hurni, N., Abatis, M., Magara, F., & Stoop, R. (2011) · Science · doi:10.1126/science.1201043 · Cited by 381
Van IJzendoorn, M. H., & Bakermans-Kranenburg, M. J. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.07.008 · Cited by 365
Anagnostou, E., Soorya, L., Chaplin, W., Bartz, J., Halpern, D., Wasserman, S., Wang, A. T., Pepa, L., Tanel, N., Kushki, A., et al. (2012) · Molecular Autism · doi:10.1186/2040-2392-3-16 · Cited by 350
The Neuroanatomical Basis of Understanding Sarcasm and Its Relationship to Social Cognition.
Shamay‐Tsoory, S., Tomer, R., & Aharon‐Peretz, J. (2005) · Neuropsychology · doi:10.1037/0894-4105.19.3.288 · Cited by 332
Theodoridou, A., Rowe, A. C., Penton-Voak, I. S., & Rogers, P. J. (2009) · Hormones and Behavior · doi:10.1016/j.yhbeh.2009.03.019 · Cited by 318
Oxytocin Modulates Social Distance between Males and Females
Scheele, D., Striepens, N., Güntürkün, O., Deutschländer, S., Maier, W., Kendrick, K. M., & Hurlemann, R. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.2755-12.2012 · Cited by 301
Bethlehem, R. A. I., van Honk, J., Auyeung, B., & Baron-Cohen, S. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.10.011 · Cited by 285
Singer, T., Snozzi, R., Bird, G., Petrovic, P., Silani, G., Heinrichs, M., & Dolan, R. J. (2008) · Emotion · doi:10.1037/a0014195 · Cited by 248
Oxytocin facilitates protective responses to aversive social stimuli in males
Striepens, N., Scheele, D., Kendrick, K. M., Becker, B., Schäfer, L., Schwalba, K., Reul, J., Maier, W., & Hurlemann, R. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1208852109 · Cited by 242
Wang, A. T., Lee, S. S., Sigman, M., & Dapretto, M. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.6.698 · Cited by 227
Language and communication in autistic disorders
Frith, U., & Happe, F. G. E. (1994) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.1994.0133 · Cited by 160
Variant in oxytocin receptor gene is associated with amygdala volume
Furman, D. J., Chen, M. C., & Gotlib, I. H. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2010.12.004 · Cited by 151
Yamasue, H., Yee, J. R., Hurlemann, R., Rilling, J. K., Chen, F. S., Meyer-Lindenberg, A., & Tost, H. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.3327-12.2012 · Cited by 149
Self-citationDiminished Medial Prefrontal Activity behind Autistic Social Judgments of Incongruent Information
Watanabe, T., Yahata, N., Abe, O., Kuwabara, H., Inoue, H., Takano, Y., Iwashiro, N., Natsubori, T., Aoki, Y. Y., Takao, H., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039561 · Cited by 88
Self-citationNeurogenetic effects of OXTR rs2254298 in the extended limbic system of healthy Caucasian adults
Tost, H., Kolachana, B., Verchinski, B. A., Bilek, E., Goldman, A. L., Mattay, V. S., Weinberger, D. R., & Meyer-Lindenberg, A. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.06.034 · Cited by 77
Can Autistic Children Distinguish Lies from Jokes? A Second Look at Second‐order Belief Attribution
Leekam, S., & Prior, M. (1994) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.1994.tb02301.x · Cited by 64
Learning affective values for faces is expressed in amygdala and fusiform gyrus
Petrović, P., Kalisch, R., Pessiglione, M., Singer, T., & Dolan, R. J. (2008) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsn002 · Cited by 45
Oxytocin Increases Trust in Humans Nature
Kosfeld, M., Heinrichs, M., Zak, P. J., Fischbacher, U., & Fehr, E. (2015) · Cited by 30
Watanabe, T., Kimura, H. M., Hirose, S., Wada, H., Imai, Y., Machida, T., Shirouzu, I., Miyashita, Y., & Konishi, S. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.5553-11.2012 · Cited by 28
Self-citationScientists Probe Oxytocin Therapy for Social Deficits in Autism, Schizophrenia
Kuehn, B. M. (2011) · JAMA · doi:10.1001/jama.2011.117 · Cited by 27
Cited by
Sorted by citations
Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism
Peñagarikano, O., Lázaro, M. T., Lu, X.-H., Gordon, A., Dong, H., Lam, H. A., Peles, E., Maidment, N. T., Murphy, N. P., Yang, X. W., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.3010257 · Cited by 378
Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder
Sikich, L., Kolevzon, A., King, B. H., McDougle, C. J., Sanders, K. B., Kim, S.-J., Spanos, M., Chandrasekhar, T., Trelles, M. D. P., Rockhill, C. M., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2103583 · Cited by 298
Nakajima, M., Görlich, A., & Heintz, N. (2014) · Cell · doi:10.1016/j.cell.2014.09.020 · Cited by 262
Baribeau, D. A., & Anagnostou, E. A. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00335 · Cited by 241
Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism
Watanabe, T., Kuroda, M., Kuwabara, H., Aoki, Y., Iwashiro, N., Tatsunobu, N., Takao, H., Nippashi, Y., Kawakubo, Y., Kunimatsu, A., et al. (2015) · Brain · doi:10.1093/brain/awv249 · Cited by 222
Self-citation
Metadata
- Authors
- Watanabe, T., Abe, O., Kuwabara, H., Yahata, N., Takano, Y., Iwashiro, N., Natsubori, T., Aoki, Y., Takao, H., Kawakubo, Y., Kamio, Y., Kato, N., Miyashita, Y., Kasai, K., & Yamasue, H.
- Affiliations
- The University of Tokyo (JP)
- Nihon University (JP)
- National Center of Neurology and Psychiatry (JP)
- SHOWA Medical University (JP)
- ORCID
- Venue
- JAMA Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2014-02-01
- Volume
- 71
- Issue
- 2
- Pages
- 166
- ISSN
- 2168-622X (ISSN-L)
- OpenAlex
- W1985576902
- Cited by
- 183
- References
- 50
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 12 · 2023: 11 · 2022: 15 · 2021: 16 · 2020: 19 · 2019: 11 · 2018: 19 · 2017: 19 · 2016: 15 · 2015: 21 · 2014: 12
- FWCI
- 23.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (22689034)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › 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, oxytocin, medial prefrontal cortex, intranasal administration, social decision-making, placebo-controlled crossover trial, neuropeptide therapy, reaction time (psychology), functional connectivity
- MeSH terms
- Administration, Intranasal, Adult, Child Development Disorders, Pervasive, Double-Blind Method, Humans, Magnetic Resonance Imaging, Male, Oxytocin, Social Behavior, Placebo Effect, Treatment Outcome, Prefrontal Cortex, 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.
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 ›
Are you an author, or do you see a problem with this page? Request a review
