Associations between childhood maltreatment and DNA methylation of the oxytocin receptor gene in immune cells of mother–newborn dyads
Open accessAbstract
The neuropeptide oxytocin (OXT) and its receptor (OXTR) modulate interpersonal relationships, particularly mother–child interactions. DNA methylation (DNAm) changes of the OXTR gene were observed in individuals who experienced Childhood Maltreatment (CM). A modulatory role of single nucleotide polymorphisms (SNP) within OXTR in association with CM on the regulation of OXTR was also postulated. Whether these CM-induced epigenetic alterations are biologically inherited by the offspring remains unknown. We thus investigated possible intergenerational effects of maternal CM exposure on DNAm and OXTR gene expression, additionally accounting for the possible influence of three SNP: rs53576 and rs2254298 ( OXTR gene), and rs2740210 ( OXT gene). We used the Childhood Trauma Questionnaire to classify mothers into individuals with (CM+) or without CM (CM−). Maternal peripheral immune cells were isolated from venous blood ( N = 117) and fetal immune cells from the umbilical cord ( N = 113) after parturition. DNA methylation was assessed using MassARRAY. Taqman assays were performed for genotyping and gene expression analyses. Among mothers, CM was not associated with OXTR mean methylation or gene expression. However, four CpG sites showed different methylation levels in CM− compared to CM+. In mothers, the OXTR rs53576 and OXT rs2740210 allelic variations interacted with CM load on the OXTR mean methylation. Maternal and newborns’ mean methylation of OXTR were positively associated within CM− dyads, but not in CM+ dyads. We show gene×environment interactions on the epigenetic regulation of the oxytocinergic signaling and show the intergenerational comparability of the OXTR DNAm might be altered in infants of CM+ mothers.
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The 22 publications come from 19 independent studies.
“These publications come from 19 independent studies, as in some cases the same study has been used to investigate different genes [87,88,89,90,91].”
From Biological Embedding of Early-Life Adversity and a Scoping Review of the Evidence for Intergenerational Epigenetic Transmission of Stress and Trauma in Humans (2023) · cites this paper as [89]
The Methods section (Study participants) describes this paper’s mother–newborn cohort, and the References list an earlier paper on other genes. Our copy does not establish that the two publications used the same study, or address the citing document’s count of 22 publications from 19 independent studies (searched for the count and cohort reuse). (LLM, conf=0.70)
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- Authors
- Ramo-Fernández, L., Gumpp, A. M., Boeck, C., Krause, S., Bach, A. M., Waller, C., Kolassa, I.-T., & Karabatsiakis, A.
- Affiliations
- Universität Ulm (DE)
- University Hospital Ulm (DE)
- Paracelsus Medizinische Privatuniversität (DE)
- Universität Innsbruck (AT)
- Corresponding author
- Karabatsiakis, Alexander
- ORCID
- Venue
- Translational Psychiatry
- Published
- 2021-09-01
- Volume
- 11
- Issue
- 1
- Pages
- 449-449
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC8410844
- OpenAlex
- W3196692381
- Cited by
- 30
- References
- 76
- Citations by year
- 2026: 10 · 2025: 3 · 2024: 4 · 2023: 8 · 2022: 4 · 2021: 1
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
- OPen Access Repositorium der Universität Ulm (OPARU) (Ulm University) (submittedVersion, other-oa)
- Universität Ulm, Kommunikations- und Informationszentrum (kiz) (cc-by)
- Funders
- Konrad-Adenauer-Stiftung
- Carl-Zeiss-Stiftung
- Bundesministerium für Bildung und Forschung (01KR1304A)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- child abuse, oxytocin receptor gene, DNA methylation, epigenetics, intergenerational transmission, mother-newborn dyads, umbilical cord blood, maternal immune cells, single nucleotide polymorphisms, oxytocin, CpG sites, mother-child interaction
- MeSH terms
- Child, Child Abuse, Female, Humans, Mothers, Oxytocin, Receptors, Oxytocin, DNA Methylation, Epigenesis, Genetic
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