The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Early nurture epigenetically tunes the oxytocin receptor
Open accessAbstract
Mammalian sociality is regulated in part by the neuropeptide oxytocin. In prairie voles, subtle variation in early life experience changes oxytocin receptor-mediated social behaviors. We report that low levels of early care in voles leads to de novo DNA methylation at specific regulatory sites in the oxytocin receptor gene (Oxtr), impacting gene expression and protein distribution in the nucleus accumbens. DNA methylation state of the blood predicts expression in the brain indicating the utility of the blood as a biomarker for the transcription state of the brain. These experience-sensitive CpG sites are conserved in humans, are related to gene expression in the brain, and have been associated with psychiatric disorders and individual differences in neural response to social stimuli. These results identify a mechanism by which early care regulates later displays of typical prairie vole social behavior and suggest the potential for nurture driven epigenetic tuning of OXTR in humans.
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“Early-life nurturing is associated with epigenetic modifications to the oxytocin receptor gene (Oxtr) that may explain later differences in social behavior in adulthood.”
From The Neurobiology of Love and Pair Bonding from Human and Animal Perspectives (2023) · cites this paper as [68]
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“Prairie voles receiving lower levels of parental care have hypermethylation of the MT2 region, which is predictive of lower OXTR expression in the NAc [67,68].”
From The Neurobiology of Love and Pair Bonding from Human and Animal Perspectives (2023) · cites this paper as [68]
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Carter, C. S., Kenkel, W. M., MacLean, E. L., Wilson, S. R., Perkeybile, A. M., Yee, J. R., Ferris, C. F., Nazarloo, H. P., Porges, S. W., Davis, J. M., et al. (2020) · Pharmacological Reviews · doi:10.1124/pr.120.019398 · Cited by 394
Self-citationEllis, B. J., Horn, A. J., Carter, C. S., van IJzendoorn, M. H., & Bakermans‐Kranenburg, M. J. (2021) · Clinical Psychology Review · doi:10.1016/j.cpr.2021.101985 · Cited by 103
Self-citationAndari, E., Nishitani, S., Gopinath, K., Caceres, G. A., Morrier, M. J., Ousley, O., Smith, A. K., Cubells, J. F., & Young, L. J. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-0610-6 · Cited by 101
Oxytocin receptor DNA methylation and alterations of brain volumes in maltreated children
Fujisawa, T. X., Nishitani, S., Takiguchi, S., Shimada, K., Smith, A. K., & Tomoda, A. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0414-8 · Cited by 85
Genetic, epigenetic, and environmental factors controlling oxytocin receptor gene expression
Danoff, J. S., Wroblewski, K. L., Graves, A. J., Quinn, G. C., Perkeybile, A. M., Kenkel, W. M., Lillard, T. S., Parikh, H. I., Golino, H. F., Gregory, S. G., et al. (2021) · Clinical Epigenetics · doi:10.1186/s13148-021-01017-5 · Cited by 85
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Metadata
- Authors
- Perkeybile, A. M., Carter, C. S., Wroblewski, K. L., Puglia, M. H., Kenkel, W. M., Lillard, T. S., Karaoli, T., Gregory, S. G., Mohammadi, N., Epstein, L., Bales, K. L., & Connelly, J. J.
- Affiliations
- Indiana University Bloomington (US)
- University of Virginia (US)
- Duke University (US)
- University of California, Davis (US)
- Corresponding author
- Connelly, Jessica J.
- ORCID
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 99
- Pages
- 128-136
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC6231974
- OpenAlex
- W2889420339
- Cited by
- 160
- References
- 45
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 17 · 2023: 18 · 2022: 40 · 2021: 18 · 2020: 33 · 2019: 12
- FWCI
- 21.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Psychoneuroendocrinology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Funders
- Autism Speaks (#7110)
- NIH grant (HD075750, MH073022, HD060117)
- National Alliance for Autism Research
- NSF grant (0437523)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- oxytocin receptor, DNA methylation, early life experience, Microtus ochrogaster, social behavior, CpG sites, epigenetics, gene expression regulation, mental illness, sociality
- MeSH terms
- Animals, Brain, Arvicolinae, Female, Male, Maternal Behavior, Mothers, Nucleus Accumbens, Oxytocin, Pair Bond, Promoter Regions, Genetic, Social Behavior, Receptors, Oxytocin, CpG Islands, DNA Methylation
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