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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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The oxytocin receptor: from intracellular signaling to behavior
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BackgroundExogenous 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
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“Because idiopathic ASD is characterized by enormous heterogeneity, including substantial variability in blood OXT concentrations (27), we hypothesized that the prior ambiguous OXT clinical trial findings might be attributable, at least in part, to variability in participants’ pretreatment neuropeptide biology.”
BackgroundMethodInfluentialSelf-citationMarotta, R., Risoleo, M. C., Messina, G., Parisi, L., Carotenuto, M., Vetri, L., & Roccella, M. (2020) · Brain Sciences · doi:10.3390/brainsci10030163 · Cited by 279
“An association between the degree of methylation of the oxytocin receptor (OXTR) gene and autistic symptoms has been reported [112,113].”
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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