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The role of oxytocin receptor gene (OXTR) DNA methylation (DNAm) in human social and emotional functioning: a systematic narrative review
Open accessAbstract
BACKGROUND: The neuropeptide Oxytocin (OXT) plays a central role in birthing, mother-infant bonding and a broad range of related social behaviours in mammals. More recently, interest has extended to epigenetic programming of genes involved in oxytocinergic neurotransmission. This review brings together early findings in a rapidly developing field of research, examining relationships between DNA methylation (DNAm) of the Oxytocin Receptor Gene (OXTR) and social and emotional behaviour in human populations. METHOD: A systematic search across Web of Knowledge/Science, Scopus, Medline and EMBASE captured all published studies prior to June 2017 examining the association between OXTR DNAm and human social and emotional outcomes. Search terms included 'oxytocin gene' or 'oxytocin receptor gene' and 'epigenetics' or 'DNA methylation'. Any article with a focus on social and emotional functioning was then identified from this set by manual review. RESULTS: Nineteen studies met eligibility criteria. There was considerable heterogeneity of study populations, tissue samples, instrumentation, measurement, and OXTR site foci. Only three studies examined functional consequences of OXTR DNAm on gene expression and protein synthesis. Increases in OXTR DNAm were associated with callous-unemotional traits in youth, social cognitive deficits in Autistic Spectrum Disorder (ASD), rigid thinking in anorexia nervosa, affect regulation problems, and problems with facial and emotional recognition. In contrast, reductions in DNAm were associated with perinatal stress, postnatal depression, social anxiety and autism in children. CONCLUSIONS: Consistent with an emerging field of inquiry, there is not yet sufficient evidence to draw conclusions about the role of OXTR DNAm in human social and emotional behaviour. However, taken together, findings point to increased OXTR DNAm in general impairments in social, cognitive and emotional functioning, and decreased OXTR DNAm in specific patterns of impairment related to mood and anxiety disorders (but not in all). Future progress in this field would be enhanced by adequately powered designs, greater phenotypic precision, and methodological improvements including longitudinal studies with multiple time-points to facilitate causal inference.
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“In the endocrine system, OXT is secreted by the posterior pituitary into the bloodstream to support reproductive processes like uterine contraction and lactation (Grewen et al., 2010; Maud et al., 2018).”
From Music's context-dependent influence on oxytocin, social bonding, and emotion regulation: a systematic review (2026) · cites this paper as Maud et al., 2018
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“Specifically, increased OXTR DNA methylation seems to be associated with a reduced OXTR expression and, consequently, with social cognition impairments [17].”
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“The methylation of the OXTR gene has attracted considerable attention in the research of inter-individual differences in maternal behavior and social cognition [17,20].”
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“For example, it was recently shown how a higher OXTR methylation level is linked to enhanced infants’ brain responses (as measured via fNIRS) to angry and fearful faces [55], while other evidence suggests that higher OXTR methylation is associated with problems with facial and emotional recognition [56].”
BackgroundHopkins, W. D., Staes, N., Guevara, E. E., Mulholland, M. M., Sherwood, C. C., & Bradley, B. J. (2023) · Autism Research · doi:10.1002/aur.2895 · Cited by 8
“There have been fewer studies of the role of OXTR DNA methylation and ASD or social cognition and behavior, and results have been contradictory; studies have reported both hypermethylation and hypomethylation (Maud et al., 2018; Moerkerke et al., 2021).”
ResultChu, T.-H., & Tsai, C.-G. (2026) · Frontiers in cognition · doi:10.3389/fcogn.2025.1678665 · Cited by 8
“In the endocrine system, OXT is secreted by the posterior pituitary into the bloodstream to support reproductive processes like uterine contraction and lactation (Grewen et al., 2010; Maud et al., 2018).”
Marzoratti, A., Liu, M. E., Krol, K. M., Sjobeck, G. R., Lipscomb, D., Hofkens, T. L., Boker, S. M., Pelphrey, K. A., Connelly, J. J., & Evans, T. M. (2023) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2023.101302 · Cited by 8
“Both oxytocinergic activity (Cecil et al., 2020; Gordon et al., 2011; Maud et al., 2018) and INS (Feldman et al.”
BackgroundWeinstein, S. R., Erickson, E. N., Molina, R., & Bell, A. F. (2023) · Comprehensive Psychoneuroendocrinology · doi:10.1016/j.cpnec.2023.100209 · Cited by 6
“The majority of research on genetic and epigenetic variations of OXT and OXTR has focused on psychological outcomes, linking OXTR methylation with conditions such as autism, obsessive-compulsive disorder, and impaired attachment [28,30].”
BackgroundTorres, G., Mourad, M., & Leheste, J. R. (2020) · Heliyon · doi:10.1016/j.heliyon.2020.e04047 · Cited by 7
“Oxytocin exposure at birth appears to be associated with epigenetic phenomena as methylation of the oxytocin GPCR in the fetal nervous system can result in long-term changes in behavior, including behaviors that have traditionally been linked to endogenous oxytocin signaling (e.g., social affiliative behavior; Maud et…”
BackgroundLudwig, B., Carlberg, L., Kienesberger, K., Swoboda, P., Swoboda, M. M. M., Bernegger, A., Koller, R., Inaner, M., Fuxjäger, M., Zotter, M., et al. (2022) · BMC Psychiatry · doi:10.1186/s12888-022-04031-w · Cited by 7
Huisman, L., Ong, C., van de Werken, M., & Jan Treur, A. (2024) · IFIP advances in information and communication technology · doi:10.1007/978-3-031-63211-2_18 · Cited by 7
The epigenetic regulation of synaptic genes contributes to the etiology of autism
Srančíková, A., Bačová, Z., & Bakoš, J. (2021) · Reviews in the Neurosciences · doi:10.1515/revneuro-2021-0014 · Cited by 7
Methylation of OXT and OXTR genes, central oxytocin, and social behavior in female macaques
Leon, D. D., Nishitani, S., Walum, H., McCormack, K. M., Wilson, M. E., Smith, A. K., Young, L. J., & Sánchez, M. M. (2020) · Hormones and Behavior · doi:10.1016/j.yhbeh.2020.104856 · Cited by 7
“Indeed, epigenetic reports of OXTR are still in their infancy and methods and findings are variable (Maud et al., 2018).”
BackgroundGilani, M., Abak, N., & Saberian, M. (2024) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2024.173897 · Cited by 6
Fiaz, T., Nadeem, M. S., Afzal, O., Altamimi, A. S. A., Alzarea, S. I., Almalki, W. H., Khan, H. A., Ul‐Haq, I., Hanook, S., Kazmi, I. A., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232214097 · Cited by 6
“The role of OXTR is also established in regulating the stress response [31].”
BackgroundSünnetçi, E., Durankuş, F., Albayrak, Y., Erdoğan, M. A., Atasoy, Ö., & Erbaş, O. (2021) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.2021.19.1.84 · Cited by 6
“nasal oxytocin administration was demonstrated to improve social functioning and empathy in healthy individuals [47,49].”
BackgroundRung, J. M., Kidder, Q. A., Horta, M., Pournajafi‐Nazarloo, H., Carter, C. S., Berry, M. S., & Ebner, N. C. (2022) · Brain and Behavior · doi:10.1002/brb3.2425 · Cited by 6
The potentialities of oxytocin receptor inhibitors for endometriosis therapy
Yarmolinskaya, M. I., Khobets, V. V., Tral, T. G., & Tkachenko, N. N. (2020) · Gynecological Endocrinology · doi:10.1080/09513590.2020.1816722 · Cited by 6
On social health: Conceptualization, Correlates and PatterningPreprint
Doyle, D. M., & Link, B. G. (2022) · PsyArXiv (OSF Preprints) · doi:10.31234/osf.io/m2ypw · Cited by 6
Fonseca, P. A. D. S., Suárez‐Vega, A., Esteban‐Blanco, C., Marina, H., Pelayo, R., Gutiérrez‐Gil, B., & Arranz, J.-J. (2025) · BMC Genomics · doi:10.1186/s12864-025-11520-1 · Cited by 6
“In humans, the methylation of the OXTR is associated with a series of callous-unemo-tional traits in youth, such as rigid thinking in anorexia nervosa [82].”
Cheong, Y., Bae, J., Lee, S., Ro, J., Okazawa, H., Kosaka, H., & Jung, M. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03566-2 · Cited by 5
“By integrating neuroscience and epigenetics, remarkable break-throughs have been made in identifying reliable biomarkers [1, 2].”
Sun, Y., Qian, W., Zhang, L., Niu, H., Li, L., Li, L., Zhu, Y., Xiao, J., Liu, J., Han, X., et al. (2025) · Communications Biology · doi:10.1038/s42003-025-09208-z · Cited by 5
The role of protective caregiving in epigenetic regulation in human infants
Montirosso, R., Provenzi, L., & Mascheroni, E. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819262-7.00008-8 · Cited by 5
Heseding, H. M., Jahn, K., Eberlein, C. K., Wieting, J., Maier, H. B., Proskynitopoulos, P. J., Glahn, A., Bleich, S., Frieling, H., & Deest, M. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02014-9 · Cited by 5
“Likewise, epigenetic modification of the OXTR gene has been studied in regard to a wide range of human socioemotional functioning and psychiatric illnesses [22].”
BackgroundGuoynes, C. D., & Marler, C. A. (2022) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2023.114230 · Cited by 5
Epigenetics of Stress in Farmed Fish
Guinand, B., & Σαμαράς, Α. (2023) · Wiley eBooks · doi:10.1002/9781119821946.ch12 · Cited by 5
Functional characterization of OXTR -associated enhancers
Cintrón, D. L., Sheng, R. R., & Ahituv, N. (2025) · Human Molecular Genetics · doi:10.1093/hmg/ddaf022 · Cited by 4
Exploring the role of OXTR gene methylation in attachment development: A longitudinal study
Cuyvers, B., Ein‐Dor, T., Houbrechts, M., Freson, K., Goossens, L., Noortgate, W. V. D., Leeuwen, K. G. V., Bijttebier, P., Claes, S. J., Turner, J. D., et al. (2024) · Developmental Psychobiology · doi:10.1002/dev.22496 · Cited by 4
Brown, C. K., Coster, L. D., Lee, J., Lin, L. D., Mathalon, D. H., & Woolley, J. D. (2024) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2024.107228 · Cited by 4
Baptista, T. S. A., de Azeredo, L. A., Zaparte, A., Viola, T. W., Castro, S. C. C., Nagai, M. A., Mangone, F. R., Pavanelli, A. C., Schuch, J. B., Mardini, V., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.639287 · Cited by 6
Braithwaite, E., Cole, J., Murgatroyd, C., Wright, N., O’Farrelly, C., Barker, B., & Ramchandani, P. G. (2023) · Frontiers in Child and Adolescent Psychiatry · doi:10.3389/frcha.2023.1175299 · Cited by 4
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Understanding face processing in autism spectrum disorder: insights from cognitive neuroscience
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“These changes in oxytocin signaling can influence neural circuits involved in social behavior and emotional regulation, thereby contributing to the social difficulties commonly observed in individuals with ASD (Maud et al. 2018).”
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Metadata
- Authors
- Maud, C., Ryan, J., McIntosh, J. E., & Olsson, C. A.
- Affiliations
- Deakin University (AU)
- Royal Children's Hospital (AU)
- Corresponding author
- Maud, Catherine
- Venue
- BMC Psychiatry
- Published
- 2018-05-29
- Volume
- 18
- Issue
- 1
- Pages
- 154-154
- ISSN
- 1471-244X (ISSN-L)
- PMC
- PMC5975530
- OpenAlex
- W2805059767
- Cited by
- 151
- References
- 68
- Citations by year
- 2026: 19 · 2025: 17 · 2024: 15 · 2023: 20 · 2022: 19 · 2021: 24 · 2020: 22 · 2019: 9 · 2018: 5
- FWCI
- 2.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Monash University Research Portal (Monash University) (submittedVersion, other-oa)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- 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 gene, oxytocin receptor, DNA methylation, epigenetics, oxytocin, social behavior, emotional functioning, callous-unemotional traits, autism spectrum disorder, anorexia nervosa, emotion regulation, perinatal stress, postpartum depression, social anxiety, mood disorders
- MeSH terms
- Cognition, Emotions, Humans, Synaptic Transmission, Oxytocin, Social Behavior, Receptors, Oxytocin, DNA Methylation, Gene Expression Profiling, Epigenomics
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