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Intranasal oxytocin in the treatment of autism spectrum disorders: A multilevel meta-analysis
Abstract
Intranasal oxytocin has been shown to promote social functioning and has recently been applied as a treatment for autism spectrum disorders (ASD). The current meta-analysis aims to assess the crucial question of oxytocin's efficacy in the treatment of ASD. We performed a systematic literature search, including randomized, single- or double-blind/open-label and placebo-controlled clinical trials as well as single-arm, non-randomized and uncontrolled studies investigating exogenous oxytocin effect on ASD. A total of 28 studies (N = 726 ASD patients) met our predefined inclusion criteria. We used a multilevel meta-analytic model and found that oxytocin had beneficial effects on social functioning, but did not find strong evidence for symptoms improvement in the non-social domain. Our findings suggest that oxytocin administration can be regarded as an effective treatment for some core aspects of ASD, especially in the domain of social functioning, highlighting the promise of using oxytocin as a new-generation therapeutic to address core social impairments in ASD.
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“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 [90]
In the citing paper
“Nonetheless, as illustrated by a recent meta-analysis, there does seem to be overall beneficial effects of OXT on social symptoms of ASD, although this review included both children and adults [90].”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [90]
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“1Mus-deficient mice [104] Magel1-deficient mice [105] Magel2-deficient mice [106] Magel2-deficient mice [107] VPA rats and FRX mice [108] BALB/cByJ and C58/J mice [110,111] Oprm1−/− Mouse [112] HPC-1/Syntaxin1A Knockout Mice [113] Shank3-Deficient Rat [114] Intranasal OXT in adolescent boys [87] Intranasal OXT treatme…”
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“…contains 616 effect sizes from 15 meta-analyses on oxytocin intervention studies (Bakermans-Kranenburg & van IJzendoorn, 2013; Chen et al., 2021; Huang et al., 2021; Kang et al., 2022; Keech et al., 2018; Leppanen et al., 2017, 2018; Leslie et al., 2018; Ooi et al., 2017; Peled-Avron et al.,…”
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“For example, although the efficacy is controversial, some clinical evidence showed that functional training (53, 54) and nasal oxytocin (39) can effectively improve the social cognition of autistic patients, the mechanism of which might be the enhancement of neurogenesis in hippocampus.”
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Aboul‐Fotouh, S., Zohny, S. M., Elnahas, E. M., Habib, M. Z., & Hassan, G. A. M. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106019 · Cited by 5
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Bitsika, V., & Sharpley, C. F. (2024) · Advances in Neurodevelopmental Disorders · doi:10.1007/s41252-023-00364-z · Cited by 5
“%) by Huang et al. (2021) reported strong evidence of positive change in social, but not non-social behaviour (e.g., repetitive responses, stereotypies).”
Zhang, Y., Zhang, X., & Huang, L. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1477076 · Cited by 5
Winterdahl, M., Nielsen, E. N., Hansen, S. B., Dias, A. H., Vendelbo, M. H., Jakobsen, S., & Yeomans, D. C. (2025) · EJNMMI Research · doi:10.1186/s13550-025-01329-0 · Cited by 4
“Recent research has explored intranasal administration of oxytocin as a promising approach for managing disorders like craniofacial pain, autism spectrum disorder (ASD), schizophrenia, and posttraumatic stress disorder (PTSD) [3, 11, 31].”
Du, M., Shi, P., Liu, Z., Xu, Y., Liu, X., Liu, W., Liu, S., & Ming, D. (2026) · npj Digital Medicine · doi:10.1038/s41746-026-02375-1 · Cited by 4
Ricchiuti, G., Taillieu, A., Tuerlinckx, E., Prinsen, J., Debbaut, E., Steyaert, J. G., Boets, B., & Alaerts, K. (2025) · BMC Psychiatry · doi:10.1186/s12888-025-06617-6 · Cited by 4
“…points to disrupted oxytocinergic signaling as a potential factor in autism [4, 5], leading to increased interest in the intranasal administration of oxytocin as a pharmacological option aimed at improving stress regulation and alleviating the core social difficulties characterizing autism [6, 7].”
Sawares, A. S., Olver, J. S., Morcos, M., & Norman, T. R. (2024) · Australasian Psychiatry · doi:10.1177/10398562241291335 · Cited by 4
Pharmacotherapy of Disruptive Behaviors in Children with Intellectual Disabilities
Hodgins, G. E., Winsor, K., & Barnhill, J. (2022) · Pediatric Drugs · doi:10.1007/s40272-022-00517-y · Cited by 4
Qiao, Z., der Donck, S. V., Moerkerke, M., Dlhosova, T., Vettori, S., Dzhelyova, M. P., van Winkel, R., Alaerts, K., & Boets, B. (2022) · Brain Sciences · doi:10.3390/brainsci12091224 · Cited by 5
Alibek, K., Niyazmetova, L., Farmer, S., & Isakov, T. (2022) · Research Ideas and Outcomes · doi:10.3897/rio.8.e91179 · Cited by 4
“Pharmacologic interventions are limited and involve using antidepressant and antipsychotic medications to alleviate some psychiatric symptoms of autism (Huang et al. 2021).”
BackgroundShariatpanahi, M., Sojoudi, Z., Khodagholi, F., Rahmati, H., Jameie, S. B., Eftekharzadeh, M., Karizmeh, M. S., Shabani, M., & Zamani, E. (2023) · International Journal of Developmental Neuroscience · doi:10.1002/jdn.10286 · Cited by 4
“The efficacy and safety concerns of oxytocin whether single-dose or long-term administration have been investigated for ASD patients through the years (Huang et al., 2021; Yamasue et al., 2020).”
Angelopoulou, M., Siaperas, P., Livadas, S., Karantana, E., Papadimitriou, D. T., & Angelopoulos, N. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.09.009 · Cited by 4
Hausman-Cohen, S., LaValley, W., Way, H., Gutierrez, E., & Reeder, J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23042167 · Cited by 4
“All of the above findings, along with the published studies of intranasal oxytocin being used and having a demonstrated benefit in children with ASD [40], made oxytocin qualify to be listed as a potential intervention for SHANK3 for the genomic CDS described.”
ResultSaporta, L., Feldman, R., Levi, L. W., Davidson, M., Burshtein, S., Gur, R. C., Zagoory‐Sharon, O., Amiaz, R., Park, J., Davis, J. M., et al. (2024) · Schizophrenia Bulletin Open · doi:10.1093/schizbullopen/sgae022 · Cited by 2
Neuropeptidergic systems in psychiatric disorders
Hodzic, S., & Riedemann, T. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1654292 · Cited by 2
Wu, L., Zhang, X.-C., Liu, S., Gao, X., & Wang, J. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1722874 · Cited by 2
“Research indicated that listening to music is accompanied by an increase in oxytocin levels (60), Oxytocin is believed to enhance social brain function in areas typically identi fi ed as underactive in children with autism (61, 62).”
Oxytocin and autism – A precision medicine framework to unpack mechanisms and evidence
Boulton, K., & Guastella, A. J. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106746 · Cited by 2
Oxytocin Reactivity during a Wilderness Program without Parents in Adolescents
Morita, A., Shikano, A., Nakamura, K., Noi, S., & Fujiwara, T. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph192315437 · Cited by 2
Shevela, Е. Y., Loginova, T. A., Munkuev, A. S., Volskaya, T. E., Sergeeva, S. A., Ращупкин, И. М., Kafanova, M. Y., Degtyareva, V. G., Sosnovskaya, A. V., Ostanin, A. A., et al. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13113079 · Cited by 2
A multiverse meta-analysis of oxytocin administration studies
Kang, H., Deilhaug, E., Walle, K. M., Sartorius, A. M., & Quintana, D. S. (2025) · Biological Psychology · doi:10.1016/j.biopsycho.2025.109112 · Cited by 2
Janz, P., Knoflach, F., Bleicher, K., Belli, S., Biemans, B. A. M., Schnider, P., Ebeling, M., Grundschober, C., & Benekareddy, M. (2023) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1286552 · Cited by 2
Harris, J. C., & Coyle, J. T. (2024) · Oxford University Press eBooks · doi:10.1093/med/9780199928118.003.0016 · Cited by 2
Daniëls, N., Moerkerke, M., Steyaert, J. G., Bamps, A., Debbaut, E., Prinsen, J., Tang, T., der Donck, S. V., Boets, B., & Alaerts, K. (2022) · medRxiv · doi:10.1101/2022.04.20.22274106 · Cited by 2
Kaky, A. S., & Saleh, S. S. (2025) · Baghdad Journal of Biochemistry and Applied Biological Sciences · doi:10.47419/bjbabs.v6i01.331 · Cited by 1
“Skin-to-skin contact between parents and infants raises oxytocin levels and Affectionate touch and emotional support play a role in oxytocin release, while affectionate conversation with parents can boost oxytocin in children 35,36 .”
Paparella, R., Bei, A., Bernabei, I., Fiorentini, C., Iafrate, N., Lucibello, R., Marchetti, L., Pastore, F., Maglione, V., Niceta, M., et al. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47120982 · Cited by 1
Lv, C., Song, D., Ni, J., Qing, H., & Quan, Z. (2026) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2026.102892 · Cited by 2
Interdependency between oxytocin and dopamine in trust-based learning in mice
Budniok, S., Callaerts‐Vegh, Z., Bakermans‐Kranenburg, M. J., Bosmans, G., & D’Hooge, R. (2026) · Scientific Reports · doi:10.1038/s41598-026-38976-9 · Cited by 1
“For instance, OT has been proposed as adjunct pharmacotherapy for psychiatric disorders characterized by social deficits, such as autism spectrum disorder (ASD) 53,54 .”
Dayley, E. E., Durham, S. L., Palumbo, M., Lundell, J. F., & Freeman, S. M. (2026) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-026-09678-0 · Cited by 1
Early life adversity impairs visually evoked innate defensive behaviors via oxytocin signaling
Tan, H., Su, J., Ma, S., Chen, S., Liu, Q., Yang, X., & Wang, L. (2026) · Communications Biology · doi:10.1038/s42003-026-09738-0 · Cited by 1
Vattem, N., Snyder, M., Leschinsky, A., Aziz, A., Amin, J., Butt, M., Aburas, J., & Pierce, M. L. (2026) · NeuroSci · doi:10.3390/neurosci7050100 · Cited by 1
Metadata
- Authors
- Huang, Y., Huang, X., Ebstein, R. P., & Yu, R.
- Affiliations
- Lingnan University (HK)
- Peking University (CN)
- Southwestern University of Finance and Economics (CN)
- Hong Kong Baptist University (HK)
- Corresponding author
- Yu, Rongjun
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2021-03
- Volume
- 122
- Pages
- 18-27
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W3120256748
- Semantic Scholar
- f48f0f3b5ee61a8b063bae805b9f9d5c343c51ac
- Cited by
- 119
- References
- 80
- Citations by year
- 2026: 19 · 2025: 19 · 2024: 21 · 2023: 24 · 2022: 31 · 2021: 5
- FWCI
- 3.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Human-Animal Interaction Studies
- Keywords
- intranasal oxytocin, autism spectrum disorder, social functioning, social dysfunction, autism treatment
- MeSH terms
- Autism Spectrum Disorder, Administration, Intranasal, Double-Blind Method, Humans, Oxytocin, Randomized Controlled Trials as Topic, Treatment Outcome
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