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Plasma oxytocin concentrations and OXTR polymorphisms predict social impairments in children with and without autism spectrum disorder
Open accessAbstract
Significance: The neuropeptide oxytocin (OXT) is critically involved in mammalian social functioning, and initial clinical research suggests that OXT biology may be altered in individuals with autism spectrum disorder (ASD). Here we provide important evidence that blood OXT concentrations are highly heritable within families, yet also strongly predict social functioning in ASD children, their unaffected siblings, and healthy control children. These findings also extend to OXT receptor genotypes which are significantly associated with differences in social functioning independent of disease status. These findings indicate that dysregulated OXT biology is not uniquely associated with ASD social phenotypes as widely theorized, but instead variation in OXT biology contributes to important individual differences in human social functioning, including the severe social impairments which characterize ASD.
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“many of these genetic studies have found that polymorphisms in the human OXT receptor (OXTR) gene are significantly associated with an ASD diagnosis and/or predict the severity of ASD4–12.”
From Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain (2018) · cites this paper as [5]
In the citing paper
“Recent research in humans found that intronic OXTR variants predicted individual differences in functional connectivity between brain regions during the processing of social information (80, 81).”
From Variation in the Oxytocin Receptor Gene Predicts Brain Region–Specific Expression and Social Attachment (2016) · cites this paper as [81]
In the citing paper
“However, despite these above challenges, there is an increasing body of evidence showing that OT can be used as a biomarker of social functioning (Andari et al. 2014; Parker et al. 2014).”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Parker et al. 2014
In the citing paper
“Recently, Parker et al. (2014) reported that plasma oxytocin concentration and OTR polymorphisms correlate with social aptitudes in children with and without autism (Parker et al. 2014).”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Parker et al. 2014
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Highly Specific Detection of Oxytocin in Saliva
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“This may, in part, account for the successful use of peripheral OT measurement in social and behavioral research (Feldman, Gordon, & Zagoory-Sharon, 2011; Modahl et al., 1998; Parker et al., 2014; Rubin, et al., 2010; Wismer Fries, Ziegler, Kurian, Jacoris, & Pollak, 2005).”
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“The findings are also in agreement with Parker and colleagues [118] that showed no baseline plasma differences in OT in a large sample of participants indicating similar circulating concentration between children with ASD and non-ASD children.”
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“Common OXTR gene polymorphisms have been found to contribute to the development of social cognition impairments in humans, both with [7] and without autism spectrum disorder [18].”
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“[60], who observed that basal OT was highly predictive of theory of mind and social communication in a sample consisting of autistic and typically developing children.”
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“At the same time, the direct correlation that we established between the indicators of severe autistic disorders and high levels of saliva OT concentration in the group ID with ASD does not correspond to the materials of scientific publications on the reduced concentration of this hormone in autistic pathology (52).”
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“However, similarly high plasma oxytocin heritabilities ( h 2 = 0.86) were observed in humans, among sibling dyads where one child was diagnosed with autism spectrum disorder (Parker et al., 2014).”
BackgroundInfluentialZaidman‐Zait, A., Hollocks, M. J., Kerns, C. M., Magiati, I., McVey, A. J., Smith, I. M., Bedford, R., Bennett, T. A., Duku, E., Georgiades, S., et al. (2025) · Child and Adolescent Mental Health · doi:10.1111/camh.70026 · Cited by 7
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“Lower blood oxytocin levels in autistic children were associated with higher social deficits (Parker et al., 2014; Andariet al., 2010; Modahl et al., 1998).”
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“Similarly, plasma OT levels were associated with social communication capacities, implying that plasma OT concentrations and OXTR genotype exert independent and additive effects on social functioning of both children with ASD and typically developing children [Parker et al., 2014].”
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“Nevertheless, the results of research are still quite contradictory, from low oxytocin levels found in children with ASD (117) to the varying ones (118).”
BackgroundEditorial: Oxytocin's routes in social behavior: into the 21st century
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“OXTR density or distribution or gene polymorphisms can shape social behavior and can be a moderator of the degree of susceptibility to early adverse experiences (Anacker and Beery, 2013, this issue; Parker et al., 2014; Barrett et al., 2015).”
InfluentialUtility of Downstream Biomarkers to Assess and Optimize Intranasal Delivery of Oxytocin
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“Genetic alterations of oxytocin receptor (OXTR), coded by OXTR, might interact in the etiology and development of several mental disorders [3], along with associations with a differential response related to social behaviors [4].”
BackgroundCamerini, L., Zurchimitten, G., Bock, B. B., Xavier, J., Bastos, C. R., Martins, E., Ardais, A. P., Motta, J. V. D. S., Pires, A. J., de Matos, M. B., et al. (2022) · Child Psychiatry & Human Development · doi:10.1007/s10578-022-01419-3 · Cited by 6
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“Dysregulated OXT biology is not uniquely associated with ASD social phenotypes as widely theorized, but instead variation in OXT biology contributes to important indi‐ vidual differences in human social functioning, including the severe social impairments, which characterize ASD [169].”
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“Clinical reports suggest that dysregulated OXTR SNP (single-nucleotide polymorphism) may be a social impairment biomarker in ASD (Parker et al. 2014).”
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“Furthermore, oxytocin concentrations are positively predictive of theory of mind and social communication performance in both ASD and non-ASD cohorts, highlighting its role in social functioning in humans (Parker et al., 2014).”
BackgroundOxytocin improves maternal licking behavior deficits in autism-associated Shank3 mutant dogs
Lyu, W., Li, Y., Yao, A., Tan, Q.-Q., Zhang, R., Zhao, J., Guo, K., Jiang, Y., Tian, R., & Zhang, Y. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03296-5 · Cited by 5
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Self-citationA természetes és a szintetikus oxitocin szüléskor és szoptatáskor.
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Mathematical Models for Possible Roles of Oxytocin and Oxytocin Receptors in Autism
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“Data from the Stanford study [1] on the severity of autism and oxytocin blood levels in children, that has undergone normalizing mathematical operations, is compared with a normalized theoretical model based on very plausible considerations of autism severity and oxytocin receptor numbers.”
InfluentialMulti-dimensional social relationships shape social attention in monkeysPreprint
Liu, S., Huang, J., Chen, S., Platt, M. L., & Yang, Y. T. (2025) · eLife · doi:10.7554/elife.104460 · Cited by 3
“These findings resonate with prior work showing that individual variation in oxytocin concentration predicts social functioning in humans ( Parker et al., 2014 ) and that exogenous administration of oxytocin only improves social function in children with low endogenous levels of the peptide hormone…”
Dobewall, H., Keltikangas‐Järvinen, L., Saarinen, A., Lyytikäinen, L., Zwir, I., Cloninger, R., Raitakari, O. T., Lehtimäki, T., & Hintsanen, M. (2021) · Developmental Psychobiology · doi:10.1002/dev.22184 · Cited by 2
Osteopathic manipulative treatment for autism spectrum disorder: Three case reports
Wolf, K., Widjaja, F., O’Keefe, W., Chen, Y., Breard, M., Parenteau, C. I., Keys, J., Riemer, R., & Hendren, R. L. (2023) · International journal of osteopathic medicine · doi:10.1016/j.ijosm.2023.100700 · Cited by 2
Ghamari, R., Tahmaseb, M., Sarabi‐Jamab, A., Etesami, S.-A., Mohammadzadeh, A., Alizadeh, F., & Tehrani‐Doost, M. (2024) · BMC Psychiatry · doi:10.1186/s12888-023-05461-w · Cited by 2
“As an illustration, rs53576 is significantly associated with ASD [75], Asperger syndrome [76], and autism related social impairment and social communication difficulties [58, 77].”
BackgroundFunctional significance of some common oxytocin receptor SNPs involved in complex human traits
Ma, S. L., Bowen, M. T., & Dadds, M. R. (2025) · BMC Molecular and Cell Biology · doi:10.1186/s12860-024-00529-1 · Cited by 2
Yılmazer, E., Çınaroğlu, M., Köse, S. K., Ülker, S. V., & Tarlacı, S. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14196760 · Cited by 2
Ragusa, A. (2015) · Journal of pediatric and neonatal individualized medicine · doi:10.7363/040228 · Cited by 2
“Blood oxytocin concentrations are highly heritable within families; its level is a strong predictor of social functioning in autism spectrum disorder children, in their unaffected siblings, and healthy control children [65]; this study indicates that dysregulated oxytocin biology is not uniquely associated with ASD so…”
BackgroundMeasuring Affinity of Ligands to the Oxytocin Receptor Using Radioligand Binding
Werry, E. L., & Kassiou, M. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1759-5_14 · Cited by 2
Oxytocin and Oxytocin Receptor Gene Regulation in Williams Syndrome: A Systematic Review.
Çalışkan, E., Şahin, M. N., & Güldağ, M. A. (2021) · PubMed Central · Cited by 2
Oxytocin and its links through scientific lineage
Jacob, S. (2024) · Comprehensive Psychoneuroendocrinology · doi:10.1016/j.cpnec.2024.100230 · Cited by 2
“Later work highlighted that the level of social functioning versus diagnostic category may be a better phenotypic association with some of these OXTR SNPs [32].”
BackgroundАлымов, А. А., Капица, И. Г., & Воронина, Т. А. (2021) · Neurochemical Journal · doi:10.1134/s1819712421020033 · Cited by 2
Linked OXTR Variants Are Associated With Social Behavior Differences in Bonobos ( Pan paniscus )Preprint
Skiba, S. A., McCall, R., Byers, A., Waldron, S., Epping, A. J., & Taglialatela, J. P. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.12.22.573122 · Cited by 2
“…these findings suggest that specific OXTR variants might be promising biomarkers for social communication dysfunction in humans and highlight the need for alternative approaches to assessing the impact OXTR variants have on complex behavioral phenotypes, like those observed in ASD [95-97].”
Cai, X., Le, J., Shou, X., Wuyun, G., Wang, X., Han, S., Han, J., Kendrick, K. M., & Zhang, R. (2022) · Autism Research · doi:10.1002/aur.2714 · Cited by 1
“Several studies have reported that individuals with ASD tend to have lower basal blood concentrations of OXT than in TD individuals (Parker et al., 2014; Zhang et al., 2016).”
BackgroundResultPaparella, 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
“Genetic and epigenetic alterations of the OXTR gene—such as single nucleotide polymorphisms and promoter hypermethylation—have been associated with increased vulnerability to ASD, attention-deficit/hyperactivity disorder, and conduct disorder [53,65,100,101].”
Tales from the life and lab of a female social neuroscientist
Parker, K. J. (2023) · Comprehensive Psychoneuroendocrinology · doi:10.1016/j.cpnec.2023.100202 · Cited by 1
“…concentrations were highly heritable within families and that variation in oxytocin biology (oxytocin peptide concentrations; oxytocin receptor gene variants) contributes to important individual differences in human social functioning, including the social deficits that characterize autism [51].”
BackgroundSelf-citationLohrentz, C., Womersley, J. S., Swart, P., Sommer, J. E., Hinsberger, M., Elbert, T. R., Weierstall, R., Kaminer, D., Seedat, S., & Hemmings, S. M. J. (2024) · Aggressive Behavior · doi:10.1002/ab.22131 · Cited by 1
“In a study of autism in children, the presence of the rs2254298 A allele was associated with impaired social behavior (Parker et al., 2014).”
BackgroundOxytocin Receptor Polymorphism Is Associated With Sleep Apnea Symptoms
Goto, H., Yamamoto, Y., Tsujiguchi, H., Sato, T. K., Yamamoto, R., Takeshita, Y., Nakano, Y., Kannon, T., Hosomichi, K., Suzuki, K., et al. (2024) · Journal of the Endocrine Society · doi:10.1210/jendso/bvae198 · Cited by 2
Zappia, K. J., & Erickson, C. A. (2025) · Springer eBooks · doi:10.1007/978-3-031-78143-8_12 · Cited by 1
Role of oxytocin in social cognition in psychosis spectrum disorders
Benavides, C., Fred-Torres, S., Rutter, S., Larsen, E. M., Fastman, J., Bulbena‐Cabré, A., Lepow, L., Mahon, K., Russo, M., Ungar, A. K., et al. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-815315-4.00006-9 · Cited by 1
Kou, J., Zhang, Y., Zhou, F., Sindermann, C., Montag, C., Becker, B., & Kendrick, K. M. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/493387 · Cited by 1
Neuropeptides in mental health: CRF, AVP, and OXT
Hammock, E. A. D. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-91497-0.00211-3 · Cited by 1
Espino, C. C., & Vale-Martı́nez, A. (2015) · Revista de Neurología · doi:10.33588/rn.6109.2015219
Neuropeptides in Mental Health: CRF, AVP, and OXT
Hammock, E. A. D. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-397045-9.00137-3
The effects of oxytocin on social behaviour: the influence of context and individual differences
Daughters, K. (2016) · ORCA Online Research @Cardiff (Cardiff University)
Gross, T. J., Gross, T. F., & Blauth, S. L. (2017) · SAGE Open · doi:10.1177/2158244017726355
On oxytocin and social behavior
Hovey, D. (2018) · Gothenburg University Publications Electronic Archive (Gothenburg University)
Mathematical Models for Possible Roles of Oxytocin and Oxytocin Receptors in AutismPreprint
Gottlieb, M. M. (2019) · Preprints.org · doi:10.20944/preprints201904.0246.v2
The connection between oxytocin and autism, explained
Hess, P. (2022) · The Transmitter · doi:10.53053/nlau3623
Oxytocin, Arginine Vasopressin and Autism Spectrum Disorder
Bagasra, O., Heggen, C., & Hossain, M. I. (2018) · Wiley eBooks · doi:10.1002/9781119042280.ch4
Air pollutants reinforce autism–like behavior in the VPA-Induced – rat model of autismPreprint
Emam, B., Shahsavani, A., Khodagholi, F., Hopke, P. K., Abdollahifar, M., Hadei, M., & Mirbehbahani, S. H. (2020) · doi:10.21203/rs.3.rs-21729/v1
“Since initial clinical research suggests that OXTR may be biomarkers of social impairments in autism spectrum disorder [59], we used this biomarker to detect the autism spectrum disorder characteristics in rats.”
BackgroundMethodMathematical Models for Possible Roles of Oxytocin and Oxytocin Receptors in AutismPreprint
Gottlieb, M. (2019) · Preprints.org · doi:10.20944/preprints201904.0246.v1
Study of Oxytocin in Biopolitics
Jung, S. (2022) · Emerald Group Publishing Limited eBooks · doi:10.1108/s2042-994020220000013009
Mills-Koonce, R., Grewen, K., Gottfredson, N. C., Pearson, B. L., Strange, C. G., Meltzer-Brody, S. E., Guintivano, J., & Stuebe, A. M. (2023) · JMIR Research Protocols · doi:10.2196/51132
“Although speculative, research suggests that circulating oxytocin levels are comparable across boys and girls during the first 5 years of life [47,48]; however, oxytocin responsiveness to stress is significantly greater for girls who have a history of parental maltreatment as compared with girls…”
Background
Metadata
- Authors
- Parker, K. J., Garner, J. P., Libove, R. A., Hyde, S. A., Hornbeak, K. B., Carson, D. S., Liao, C.-P., Phillips, J. M., Hallmayer, J. F., & Hardan, A. Y.
- Affiliations
- Department of Psychiatry and Behavioral Sciences and
- Stanford Medicine (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-08-04
- Volume
- 111
- Issue
- 33
- Pages
- 12258-12263
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4143031
- OpenAlex
- W2093926419
- Cited by
- 215
- References
- 51
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 10 · 2023: 14 · 2022: 23 · 2021: 22 · 2020: 20 · 2019: 18 · 2018: 24 · 2017: 24 · 2016: 19 · 2015: 21 · 2014: 2
- FWCI
- 32.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Center for Research Resources (RR 000167, P51RR000167)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › 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, oxytocin receptor, autism spectrum disorder, OXTR polymorphisms, rs53576, rs2254298, social dysfunction, theory of mind, social communication, affect recognition, heritability, biomarkers, children
- MeSH terms
- Child, Child Development Disorders, Pervasive, Child, Preschool, Female, Humans, Male, Oxytocin, Phenotype, Polymorphism, Genetic, Social Behavior, Case-Control Studies, Receptors, Oxytocin
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