Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism
Abstract
Autism spectrum disorder is a prevalent neurodevelopmental disorder with no established pharmacological treatment for its core symptoms. Although previous literature has shown that single-dose administration of oxytocin temporally mitigates autistic social behaviours in experimental settings, it remains in dispute whether such potentially beneficial responses in laboratories can result in clinically positive effects in daily life situations, which are measurable only in long-term observations of individuals with the developmental disorder undergoing continual oxytocin administration. Here, to address this issue, we performed an exploratory, randomized, double-blind, placebo-controlled, crossover trial including 20 high-functional adult males with autism spectrum disorder. Data obtained from 18 participants who completed the trial showed that 6-week intranasal administration of oxytocin significantly reduced autism core symptoms specific to social reciprocity, which was clinically evaluated by Autism Diagnostic Observation Scale (P = 0.034, PFDR < 0.05, Cohen's d = 0.78). Critically, the improvement of this clinical score was accompanied by oxytocin-induced enhancement of task-independent resting-state functional connectivity between anterior cingulate cortex and dorso-medial prefrontal cortex (rho = -0.60, P = 0.011), which was measured by functional magnetic resonance imaging. Moreover, using the same social-judgement task as used in our previous single-dose oxytocin trial, we confirmed that the current continual administration also significantly mitigated behavioural and neural responses during the task, both of which were originally impaired in autistic individuals (judgement tendency: P = 0.019, d = 0.62; eye-gaze effect: P = 0.03, d = 0.56; anterior cingulate activity: P = 0.00069, d = 0.97; dorso-medial prefrontal activity: P = 0.0014, d = 0.92; all, PFDR < 0.05). Furthermore, despite its longer administration, these effect sizes of the 6-week intervention were not larger than those seen in our previous single-dose intervention. These findings not only provide the evidence for clinically beneficial effects of continual oxytocin administration on the core social symptoms of autism spectrum disorder with suggesting its underlying biological mechanisms, but also highlight the necessity to seek optimal regimens of continual oxytocin treatment in future studies.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Small randomized controlled trials of intranasal oxytocin administered for 4 to 24 weeks in persons with autism spectrum disorder have had equivocal results regarding improvements in social functioning, social cognition, or social attention.
“Small, randomized, controlled trials of intranasal oxytocin administered for 4 to 24 weeks in persons with autism spectrum disorder have had equivocal results with regard to oxytocin-associated improvements in social functioning, social cognition, or social attention.18–21”
From Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder (2021) · cites this paper as [19]
Oxytocin has received substantial interest as a potential treatment for psychiatric conditions such as autism, although clinical trials show modest effects.
“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 [5]
The small number of existing rsfMRI oxytocin-administration studies use seed-based analyses that do not allow for hypothesis-free examination across the connectome.
“the small number of existing rsfMRI oxytocin-administration studies5, 13, 19, 20 use seed-based analyses that do not allow for hypothesis-free examination across the connectome.”
From Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women (2017) · cites this paper as [5]
Six-weeks of IN-OT treatment in ASD patients rescued social reciprocity deficits and enhanced task-dependent functional connectivity between anterior cingulate cortex and PFC.
“Six-weeks of IN-OT treatment in ASD patients rescued social reciprocity deficits and enhanced task-dependent functional connectivity between anterior cingulate cortex and PFC [48].”
From Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry (2021) · cites this paper as [48]
The improvement was accompanied by increased resting state functional connectivity between ACC and dmPFC and increased eye gaze during a social-judgment task.
“The improvement was accompanied by increased resting state functional connectivity between ACC and dmPFC in addition to an increased eye gaze during a social-judgment task.”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Watanabe et al. 2015
IN-OT significantly reduced autism core symptoms in social reciprocity following a 6-week intranasal oxytocin regimen.
“For instance, Watanabe et al. (2015) showed that IN-OT significantly reduced autism core symptoms in social reciprocity following a 6-week intranasal oxytocin regimen (Watanabe et al. 2015).”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Watanabe et al. 2015
Watanabe et al. showed significant improvements in social reciprocity and social functioning after 6 weeks of intranasal oxytocin treatment in 20 adult men with ASD.
“In another study with 20 adult men with ASD, Watanabe et al. [9] studied the effects of 6 weeks of intranasal OT administration on core autism characteristics and showed significant improvements in social reciprocity and social functioning (social-judgment task).”
From Behavioral effects of multiple-dose oxytocin treatment in autism: a randomized, placebo-controlled trial with long-term follow-up (2020) · cites this paper as [9]
Taken together, initial multiple-dose trials provided indications for a more consistent positive pattern of results for oxytocin trials with adults with ASD compared to trials with children with ASD.
“Taken together, findings of these initial multiple-dose trials provided indications for a more consistent (positive) pattern of results for OT trials with adults with ASD [8–10], compared to trials with children with ASD [11–14].”
From Behavioral effects of multiple-dose oxytocin treatment in autism: a randomized, placebo-controlled trial with long-term follow-up (2020) · cites this paper as [9]
The initial sample size (n = 40) was set to be comparable to three prior studies showing significant effects of multiple-dose oxytocin treatment on similar outcome measures.
“The initial sample size (n = 40) was set to be comparable to three prior studies showing significant effects of multiple-dose OT treatment on similar outcome measures [8, 9, 17].”
From Behavioral effects of multiple-dose oxytocin treatment in autism: a randomized, placebo-controlled trial with long-term follow-up (2020) · cites this paper as [9]
One 1-week trial with adult men with ASD did not show OT-specific improvements on informant-based reports of repetitive behaviors.
“Note however that one 1-week trial with adult men with ASD did not show OT-specific improvements on informant-based reports of repetitive behaviors [9].”
From Behavioral effects of multiple-dose oxytocin treatment in autism: a randomized, placebo-controlled trial with long-term follow-up (2020) · cites this paper as [9]
In three previous long-term administration trials, improvements in social symptoms were identified both in participants receiving OT and in those receiving placebo, but with no significant difference between the two groups.
“Correspondingly, in three previous long-term administration trials, improvements in social symptoms (SRS-A: [9, 12]) (ADOS subscale assessing social reciprocity: 10) were identified both in participants receiving the OT treatment and in those receiving the placebo treatment, but with no significant difference between the two groups.”
From Behavioral effects of multiple-dose oxytocin treatment in autism: a randomized, placebo-controlled trial with long-term follow-up (2020) · cites this paper as [9]
Beneficial effects of OT treatment on repetitive behaviors were mostly demonstrated in studies that adopted assessments based on self-reports, whereas no beneficial effects were evident in studies adopting informant-based reports of repetitive behavior.
“In this view, it appears that beneficial effects of OT treatment on repetitive behaviors were mostly demonstrated in studies that adopted assessments based on self-reports (current study, [4, 8]), whereas no beneficial effects were evident in studies adopting informant-based reports of repetitive behavior [9–14].”
From Behavioral effects of multiple-dose oxytocin treatment in autism: a randomized, placebo-controlled trial with long-term follow-up (2020) · cites this paper as [9]
Watanabe et al. observed only a trend toward improvement in quality of life immediately after a 6-week trial in adult men with ASD.
“Watanabe et al. [9] on the other hand, only observed a trend toward improvement in quality of life immediately after a 6-week trial in adult men with ASD.”
From Behavioral effects of multiple-dose oxytocin treatment in autism: a randomized, placebo-controlled trial with long-term follow-up (2020) · cites this paper as [9]
In the current study, participants administered the OT nasal spray once a day (in the morning) while the majority of prior multiple-dose OT studies administered two doses/day.
“Second, in the current study, participants administered the OT nasal spray once a day (in the morning) while the majority of prior multiple-dose OT studies administered two doses/day (one in the morning and one in the afternoon) ([8–10, 12–14], but see [11]).”
From Behavioral effects of multiple-dose oxytocin treatment in autism: a randomized, placebo-controlled trial with long-term follow-up (2020) · cites this paper as [9]
Long-term oxytocin administration can alleviate symptoms of autism spectrum disorder.
“Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD)”
Long-term oxytocin administration improves social-communicative skills in individuals with ASD.
“Previous findings also suggested that social-communicative skills, that is, Autism Diagnostic Observation Schedule reciprocity score5 and social interactions during the play sessions and daily life,6 were improved by long-term oxytocin administration;5, 6”
Oxytocin administration improves eye contact during naturalistic social interaction.
“Previous studies have found that oxytocin administration improves eye contact during naturalistic social interaction.5, 45”
The failure to detect changes in social-communicative behaviors by IRSA may be because the assessment procedure used a videotaped interaction.
“Therefore, we could not detect changes in social-communicative behaviors by IRSA possibly because the assessment procedure used a videotaped interaction, in contrast to our findings of CGI-I score and those of previous trials.5, 6”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The CES-D Scale: A Self-Report Depression Scale for Research in the General Population
Radloff, L. S. (1977) · Applied Psychological Measurement · doi:10.1177/014662167700100306 · Cited by 53,267 · see citing works
A default mode of brain function
Raichle, M. E., MacLeod, A. M., Snyder, A. Z., Powers, W. J., Gusnard, D. A., & Shulman, G. L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.2.676 · Cited by 12,190 · see citing works
Functional connectivity in the motor cortex of resting human brain using echo‐planar mri
Biswal, B., Zerrin Yetkin, F., Haughton, V. M., & Hyde, J. S. (1995) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910340409 · Cited by 9,812 · see citing works
Lord, C., Rutter, M., & Le Couteur, A. (1994) · Journal of Autism and Developmental Disorders · doi:10.1007/bf02172145 · Cited by 9,065 · see citing works
(1995) · Social Science & Medicine · doi:10.1016/0277-9536(95)00112-k · Cited by 7,643 · see citing works
Baron-Cohen, S., Wheelwright, S., Skinner, R., Martin, J., & Clubley, E. (2001) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1005653411471 · Cited by 6,450 · cited 1× · see citing works
“Other secondary outcomes comprised Autism Spectrum Quotient (AQ) (Baron-Cohen et al., 2001), Social Responsiveness Scale (SRS) (Constantino et al.”
BackgroundCohen, J. (1992) · Current Directions in Psychological Science · doi:10.1111/1467-8721.ep10768783 · Cited by 5,870 · see citing works
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 · see citing works
Di Martino, A., Yan, C.-G., Li, Q., Denio, E., Castellanos, F. X., Alaerts, K., Anderson, J. S., Assaf, M., Bookheimer, S. Y., Dapretto, M., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.78 · Cited by 2,780 · see citing works
STAI manual for the State-trait anxiety inventory
Cd, S. (1970) · Medical Entomology and Zoology · Cited by 2,433 · see citing works
Lord, C., Rutter, M., Goode, S., Heemsbergen, J., Jordan, H., Mawhood, L., & Schopler, E. (1989) · Journal of Autism and Developmental Disorders · doi:10.1007/bf02211841 · Cited by 2,030 · see citing works
Constantino, J. N., Davis, S. A., Todd, R. D., Schindler, M. K., Gross, M. M., Brophy, S. L., Metzger, L. M., Shoushtari, C. S., Splinter, R., & Reich, W. (2003) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1025014929212 · Cited by 1,611 · see citing works
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 1,572 · see citing works
Shamay-Tsoory, S. G., Aharon-Peretz, J., & Perry, D. (2009) · Brain · doi:10.1093/brain/awn279 · Cited by 1,544 · see citing works
On the adaptive control of the false discovery rate in multiple testing with independent statistics
Benjamini, Y., & Hochberg, Y. (2000) · Journal of Educational and Behavioral Statistics · doi:10.3102/10769986025001060 · Cited by 1,349 · see citing works
Type I and Type II error concerns in fMRI research: re-balancing the scale
Lieberman, M. D., & Cunningham, W. A. (2009) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsp052 · Cited by 1,342 · see citing works
Summary of notifiable diseases--United States, 2012.
Adams, D. A., Jajosky, R. A., Ajani, U. A., Kriseman, J., Sharp, P., Onwen, D. H., Schley, A. W., Anderson, W. J., Grigoryan, A., Aranas, A. E., et al. (2014) · PubMed · Cited by 1,342 · see citing works
The maturing architecture of the brain's default network
Fair, D. A., Cohen, A. L., Dosenbach, N. U. F., Church, J. A., Miezin, F. M., Barch, D. M., Raichle, M. E., Petersen, S. E., & Schlaggar, B. L. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800376105 · Cited by 1,314 · see citing works
The Neuropeptide Oxytocin Regulates Parochial Altruism in Intergroup Conflict Among Humans
De Dreu, C. K. W., Greer, L. L., Handgraaf, M. J. J., Shalvi, S., Van Kleef, G. A., Baas, M., Ten Velden, F. S., Van Dijk, E., & Feith, S. W. W. (2010) · Science · doi:10.1126/science.1189047 · Cited by 1,148 · see citing works
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 · see citing works
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 · see citing works
Green, J., Charman, T., McConachie, H., Aldred, C., Slonims, V., Howlin, P., Le Couteur, A., Leadbitter, K., Hudry, K., Byford, S., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60587-9 · Cited by 857 · see citing works
Oxytocin promotes human ethnocentrism
De Dreu, C. K. W., Greer, L. L., Van Kleef, G. A., Shalvi, S., & Handgraaf, M. J. J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1015316108 · Cited by 838 · see citing works
Lam, K. S. L., & Aman, M. G. (2007) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-006-0213-z · Cited by 793 · see citing works
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 · see citing works
Functional connectivity in a baseline resting-state network in autism
Cherkassky, V. L., Kana, R. K., Keller, T. A., & Just, M. A. (2006) · NeuroReport · doi:10.1097/01.wnr.0000239956.45448.4c · Cited by 622 · see citing works
Aldred, C., Green, J., & Adams, C. (2004) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2004.00338.x · Cited by 449 · see citing works
Bakermans-Kranenburg, M. J., & van IJzendoorn, M. H. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.34 · Cited by 383 · see citing works
Van IJzendoorn, M. H., & Bakermans-Kranenburg, M. J. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.07.008 · Cited by 365 · see citing works
Lynch, C. J., Uddin, L. Q., Supekar, K., Khouzam, A., Phillips, J. M., & Menon, V. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.12.013 · Cited by 357 · see citing works
Guidelines for rating Global Assessment of Functioning (GAF)
Aas, I. H. M. (2011) · Annals of General Psychiatry · doi:10.1186/1744-859x-10-2 · Cited by 346 · see citing works
Oxytocin enhances brain function in children with autism
Gordon, I., Vander Wyk, B. C., Bennett, R. H., Cordeaux, C., Lucas, M. V., Eilbott, J. A., Zagoory-Sharon, O., Leckman, J. F., Feldman, R., & Pelphrey, K. A. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1312857110 · Cited by 336 · see citing works
Cox, C. L., Uddin, L. Q., Di Martino, A., Castellanos, F. X., Milham, M. P., & Kelly, C. (2012) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsr051 · Cited by 333 · see citing works
Adjunctive intranasal oxytocin reduces symptoms in schizophrenia patients
Feifel, D., Macdonald, K., Nguyen, A., Cobb, P., Warlan, H., Galangue, B., Minassian, A., Becker, O., Cooper, J., Perry, W., et al. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.04.039 · Cited by 308 · see citing works
Guastella, A. J., Gray, K. M., Rinehart, N. J., Alvares, G. A., Tonge, B. J., Hickie, I. B., Keating, C. M., Cacciotti‐Saija, C., & Einfeld, S. L. (2015) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12305 · Cited by 299 · see citing works
Bales, K. L., Perkeybile, A. M., Conley, O. G., Lee, M. H., Guoynes, C. D., Downing, G. M., Yun, C. R., Solomon, M., Jacob, S., & Mendoza, S. P. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.08.025 · Cited by 265 · see citing works
Nasal oxytocin for social deficits in childhood autism: A randomized controlled trial
Dadds, M. R., MacDonald, E., Cauchi, A., Williams, K., Levy, F., & Brennan, J. (2014) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-013-1899-3 · Cited by 250 · see citing works
Howlin, P., Gordon, R. K., Pasco, G., Wade, A. M., & Charman, T. (2007) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2006.01707.x · Cited by 242 · see citing works
Oxytocin promotes group-serving dishonesty
Shalvi, S., & Dreu, C. K. W. D. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1400724111 · Cited by 225 · see citing works
Oxytocin improves behavioural and neural deficits in inferring others’ social emotions in autism
Aoki, Y., Yahata, N., Watanabe, T., Takano, Y., Kawakubo, Y., Kuwabara, H., Iwashiro, N., Natsubori, T., Inoue, H., Suga, M., et al. (2014) · Brain · doi:10.1093/brain/awu231 · Cited by 187 · see citing works
Self-citationWatanabe, T., Abe, O., Kuwabara, H., Yahata, N., Takano, Y., Iwashiro, N., Natsubori, T., Aoki, Y., Takao, H., Kawakubo, Y., et al. (2014) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2013.3181 · Cited by 183 · see citing works
Self-citationHuman neuroimaging of oxytocin and vasopressin in social cognition
Zink, C. F., & Meyer-Lindenberg, A. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2012.01.016 · Cited by 176 · see citing works
Intranasal administration of oxytocin: behavioral and clinical effects, a review
Veening, J. G., & Olivier, B. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.04.012 · Cited by 169 · see citing works
Domes, G., Kumbier, E., Heinrichs, M., & Herpertz, S. C. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2013.254 · Cited by 160 · see citing works
Anagnostou, E., Soorya, L., Brian, J., Dupuis, A., Mankad, D., Smile, S., & Jacob, S. (2014) · Brain Research · doi:10.1016/j.brainres.2014.01.049 · Cited by 155 · see citing works
Stallen, M., Dreu, C. K. W. D., Shalvi, S., Smidts, A., & Sanfey, A. G. (2012) · Psychological Science · doi:10.1177/0956797612446026 · Cited by 152 · see citing works
Tachibana, M., Kagitani-Shimono, K., Mohri, I., Yamamoto, T., Sanefuji, W., Nakamura, A., Oishi, M., Kimura, T., Onaka, T., Ozono, K., et al. (2013) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2012.0048 · Cited by 151 · see citing works
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 · see citing works
Self-citationAltered Network Topologies and Hub Organization in Adults with Autism: A Resting-State fMRI Study
Itahashi, T., Yamada, T., Watanabe, H., Nakamura, M., Jimbo, D., Shioda, S., Toriizuka, K., Kato, N., & Hashimoto, R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0094115 · Cited by 139 · see citing works
Wong, V. C. N., & Kwok-loi, Q. K. (2009) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-009-0916-z · Cited by 130 · see citing works
Jung, M., Kosaka, H., Saito, D. N., Ishitobi, M., Morita, T., Inohara, K., Asano, M., Arai, S., Munesue, T., Tomoda, A., et al. (2014) · Molecular Autism · doi:10.1186/2040-2392-5-35 · Cited by 128 · see citing works
Multisite, Double-Blind, Placebo-Controlled Trial of Porcine Secretin in Autism
Owley, T. B., McMahon, W., Cook, E. H., Laulhere, T. M., South, M., Mays, L. Z., Shernoff, E. S., Lainhart, J. E., Modahl, C., Corsello, C. M., et al. (2001) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-200111000-00009 · Cited by 121 · see citing works
Bethlehem, R. A. I., Baron-Cohen, S., van Honk, J., Auyeung, B., & Bos, P. A. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00048 · Cited by 120 · see citing works
Aoki, Y., Watanabe, T., Abe, O., Kuwabara, H., Yahata, N., Takano, Y., Iwashiro, N., Natsubori, T., Takao, H., Kawakubo, Y., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.74 · Cited by 95 · see citing works
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 84 · see citing works
Self-citationWandschneider, B., Centeno, M., Vollmar, C., Symms, M. R., Thompson, P. J., Duncan, J. S., & Koepp, M. J. (2014) · Brain · doi:10.1093/brain/awu175 · Cited by 65 · see citing works
Suicidality and divalproex sodium: analysis of controlled studies in multiple indications
Redden, L., Pritchett, Y., Robieson, W., Kovacs, X., Garofalo, M. E., Tracy, K. A., & Saltarelli, M. (2011) · Annals of General Psychiatry · doi:10.1186/1744-859x-10-1 · Cited by 46 · see citing works
Lin, I.-F., Kashino, M., Ohta, H., Yamada, T., Tani, M., Watanabe, H., Kanai, C., Ohno, T., Takayama, Y., Iwanami, A., et al. (2014) · Molecular Autism · doi:10.1186/2040-2392-5-20 · Cited by 40 · see citing works
Network structure underlying resolution of conflicting non-verbal and verbal social information
Watanabe, T., Yahata, N., Kawakubo, Y., Inoue, H., Takano, Y., Iwashiro, N., Natsubori, T., Takao, H., Sasaki, H., Gonoi, W., et al. (2013) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nst046 · Cited by 25 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism
Parker, K. J., Oztan, O., Libove, R. A., Sumiyoshi, R. D., Jackson, L. P., Karhson, D. S., Summers, J. E., Hinman, K. E., Motonaga, K. S., Phillips, J. M., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705521114 · Cited by 349 · see citing works
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 314 · see citing works
Freeman, S. M., & Young, L. J. (2016) · Journal of Neuroendocrinology · doi:10.1111/jne.12382 · Cited by 196 · see citing works
“Indeed, IN-OT has been shown to acutely increase gaze to the eye region of human faces in autistic populations (65,66), although the benefit of chronic or developmental OT exposure is only beginning to be explored (67,68).”
BackgroundYamasue, H., Okada, T., Munesue, T., Kuroda, M., Fujioka, T., Uno, Y., Matsumoto, K., Kuwabara, H., Mori, D., Okamoto, Y., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-018-0097-2 · Cited by 185 · see citing works
Self-citationIntranasal oxytocin, social cognition and neurodevelopmental disorders: A meta-analysis
Keech, B., Crowe, S., & Hocking, D. R. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.09.022 · Cited by 145 · see citing works
Ma, Y., Shamay-Tsoory, S., Han, S., & Zink, C. F. (2016) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2015.10.009 · Cited by 131 · see citing works
Bolognani, F., del Valle Rubido, M., Squassante, L., Wandel, C., Derks, M., Murtagh, L., Sevigny, J., Khwaja, O., Umbricht, D., & Fontoura, P. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aat7838 · Cited by 128 · see citing works
Intranasal oxytocin in the treatment of autism spectrum disorders: A multilevel meta-analysis
Huang, Y., Huang, X., Ebstein, R. P., & Yu, R. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.12.028 · Cited by 119 · see citing works
Overview of human oxytocin research
Kendrick, K. M., Guastella, A. J., & Becker, B. (2017) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2017_19 · Cited by 121 · see citing works
Kosaka, H., Okamoto, Y., Munesue, T., Yamasue, H., Inohara, K., Fujioka, T., Anme, T., Orisaka, M., Ishitobi, M., Jung, M., et al. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.152 · Cited by 117 · see citing works
Self-citationGordon, I., Jack, A., Pretzsch, C. M., Vander Wyk, B., Leckman, J. F., Feldman, R., & Pelphrey, K. A. (2016) · Scientific Reports · doi:10.1038/srep35054 · Cited by 114 · see citing works
Oxytocin and Autism Spectrum Disorders
Yamasue, H., & Domes, G. (2017) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2017_24 · Cited by 109 · see citing works
Self-citationIntranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women
Bethlehem, R. A. I., Lombardo, M. V., Lai, M.-C., Auyeung, B., Crockford, S. K., Deakin, J., Soubramanian, S., Sule, A., Kundu, P., Voon, V, et al. (2017) · Translational Psychiatry · doi:10.1038/tp.2017.72 · Cited by 96 · see citing works
Bernaerts, S., Boets, B., Bosmans, G., Steyaert, J., & Alaerts, K. (2020) · Molecular Autism · doi:10.1186/s13229-020-0313-1 · Cited by 102 · see citing works
Wang, D., Yan, X., Li, M., & Ma, Y. (2017) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsx085 · Cited by 86 · see citing works
Alvares, G. A., Quintana, D. S., & Whitehouse, A. J. O. (2017) · Autism Research · doi:10.1002/aur.1692 · Cited by 91 · see citing works
Hara, Y., Ago, Y., Higuchi, M., Hasebe, S., Nakazawa, T., Hashimoto, H., Matsuda, T., & Takuma, K. (2017) · Hormones and Behavior · doi:10.1016/j.yhbeh.2017.09.013 · Cited by 61 · see citing works
Yamasue, H. (2016) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12364 · Cited by 58 · see citing works
Self-citationImaging-genetics of sex differences in ASD: distinct effects of OXTR variants on brain connectivity
Hernandez, L. M., Lawrence, K. E., Padgaonkar, N. T., Inada, M., Hoekstra, J. N., Lowe, J. K., Eilbott, J., Jack, A., Aylward, E., Gaab, N., et al. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0750-9 · Cited by 54 · see citing works
Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism
Watanabe, T., Otowa, T., Abe, O., Kuwabara, H., Aoki, Y., Natsubori, T., Takao, H., Kakiuchi, C., Kondo, K., Ikeda, M., et al. (2017) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsw150 · Cited by 54 · see citing works
Self-citationThe oxytocin receptor gene predicts brain activity during an emotion recognition task in autism
Uzefovsky, F., Bethlehem, R. A. I., Shamay-Tsoory, S., Ruigrok, A., Holt, R., Spencer, M., Chura, L., Warrier, V., Chakrabarti, B., Bullmore, E., et al. (2019) · Molecular Autism · doi:10.1186/s13229-019-0258-4 · Cited by 49 · see citing works
Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry
Ford, C. L., & Young, L. J. (2021) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2020.11.007 · Cited by 46 · see citing works
Neurochemical evidence for differential effects of acute and repeated oxytocin administration
Benner, S., Aoki, Y., Watanabe, T., Endo, N., Abe, O., Kuroda, M., Kuwabara, H., Kawakubo, Y., Takao, H., Kunimatsu, A., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-018-0249-4 · Cited by 40 · see citing works
Self-citationAdditive effects of oxytocin receptor gene polymorphisms on reward circuitry in youth with autism
Hernandez, L. M., Krasileva, K., Green, S. A., Sherman, L. E., Ponting, C., McCarron, R., Lowe, J. K., Geschwind, D. H., Bookheimer, S. Y., & Dapretto, M. (2017) · Molecular Psychiatry · doi:10.1038/mp.2016.209 · Cited by 43 · see citing works
Zhong, J., Amina, S., Liang, M., Akther, S., Yuhi, T., Nishimura, T., Tsuji, C., Tsuji, T., Liu, H.-X., Hashii, M., et al. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00304 · Cited by 42 · see citing works
A precision medicine approach to oxytocin trials
Andari, E., Hurlemann, R., & Young, L. J. (2017) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2017_29 · Cited by 40 · see citing works
Wang, Y., Wang, M.-J., Rong, Y., He, H.-Z., & Yang, C.-J. (2019) · Research in Autism Spectrum Disorders · doi:10.1016/j.rasd.2019.03.007 · Cited by 33 · see citing works
Yuhi, T., Kyuta, H., Mori, H.-A., Murakami, C., Furuhara, K., Okuno, M., Takahashi, M., Fuji, D., & Higashida, H. (2017) · Brain Sciences · doi:10.3390/brainsci7110152 · Cited by 32 · see citing works
The Potential of Nasal Oxytocin Administration for Remediation of Autism Spectrum Disorders
Okamoto, Y., Ishitobi, M., Wada, Y., & Kosaka, H. (2016) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527315666160413120845 · Cited by 33 · see citing works
Bridging the gap between rodents and humans: The role of non‐human primates in oxytocin research
Putnam, P. T., Young, L. J., & Gothard, K. M. (2018) · American Journal of Primatology · doi:10.1002/ajp.22756 · Cited by 28 · see citing works
Preckel, K., Kanske, P., Singer, T., Paulus, F. M., & Krach, S. (2016) · BMC Psychiatry · doi:10.1186/s12888-016-1036-x · Cited by 25 · see citing works
New therapeutic options for autism spectrum disorder: experimental evidences
Peñagarikano, O. (2015) · Experimental Neurobiology · doi:10.5607/en.2015.24.4.301 · Cited by 24 · see citing works
Effects of chronic oxytocin on attention to dynamic facial expressions in infant macaques
Parr, L. A., Brooks, J. M., Jonesteller, T., Moss, S., Jordano, J. O., & Heitz, T. R. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.08.028 · Cited by 23 · see citing works
- Authors
- Watanabe, T., Kuroda, M., Kuwabara, H., Aoki, Y., Iwashiro, N., Tatsunobu, N., Takao, H., Nippashi, Y., Kawakubo, Y., Kunimatsu, A., Kasai, K., & Yamasue, H.
- Affiliations
- University College London (GB)
- The University of Tokyo (JP)
- Japan Science and Technology Agency (JP)
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-09-03
- Volume
- 138
- Issue
- 11
- Pages
- 3400-3412
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2216419462
- Cited by
- 222
- References
- 60
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 10 · 2023: 21 · 2022: 19 · 2021: 22 · 2020: 22 · 2019: 19 · 2018: 29 · 2017: 29 · 2016: 22 · 2015: 8
- FWCI
- 48.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science (26250024, 25461751)
- Japan Science and Technology Agency
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- oxytocin, autism spectrum disorder, social reciprocity, resting-state functional connectivity, anterior cingulate cortex, dorsomedial prefrontal cortex, social judgment, gaze, high-functioning adults
- MeSH terms
- Autism Spectrum Disorder, Administration, Intranasal, Adult, Autistic Disorder, Brain, Double-Blind Method, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Neural Pathways, Oxytocics, Oxytocin, Social Behavior, Treatment Outcome, Prefrontal Cortex, Cross-Over Studies, Young Adult, Functional Neuroimaging
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
