Oxytocin receptor DNA methylation and alterations of brain volumes in maltreated children
Open accessAbstract
Although oxytocin (OXT) plays an important role in secure attachment formation with a primary caregiver, which is impaired in many children with childhood maltreatment (CM), epigenetic regulation in response to CM is a key factor in brain development during childhood. To address this issue, we first investigated differences in salivary DNA methylation of the oxytocin receptor (OXTR) between CM and Non-CM groups of Japanese children (CM: n = 44; Non-CM: n = 41) and its impact on brain structures in subgroup analysis using brain imaging and full clinical data (CM: n = 24; Non-CM: n = 31). As a result, we observed that the CM group showed higher CpG 5,6 methylation than did the Non-CM group and confirmed negative correlations of gray matter volume (GMV) in the left orbitofrontal cortex (OFC) with CpG 5,6 methylation. In addition, the CM group showed significantly lower GMV in the left OFC than did the Non-CM group. Furthermore, as a result of examining the relationship between GMV in the left OFC and psychiatric symptoms in CM, we observed a negative association with insecure attachment style and also confirmed the mediation effect of left-OFC GMV reduction on the relationship between OXTR methylation and insecure attachment style. These results suggest that any modulation of the oxytocin signaling pathway induced by OXTR hypermethylation at CpG 5,6 leads to atypical development of the left OFC, resulting in distorted attachment formation in children with CM.
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Children experiencing childhood abuse or neglect have hypermethylation of the Oxtr MT2 region in the orbital frontal cortex.
“Similar results are seen in humans, as children experiencing childhood abuse or neglect have hypermethylation of the Oxtr MT2 region in the orbital frontal cortex (OFC) [69].”
From The Neurobiology of Love and Pair Bonding from Human and Animal Perspectives (2023) · cites this paper as [69]
The Results (page unavailable) report higher OXTR CpG 5,6 methylation in maltreated children, and the Methods identify the tested region as MT2. But methylation was measured in saliva, not in the orbitofrontal cortex; the Results report a correlation between salivary methylation and left-OFC gray-matter volume. The claim conflates the measurement site with the brain region examined by imaging. (LLM, conf=0.91)
Experimental — accuracy not yet measuredThere are other candidate genes with at least some data in childhood trauma and epigenetic alterations, such as COMT, IL-6, and OXTR.
“There are other candidate genes with at least some data in childhood trauma and epigenetic alterations, such as COMT, IL-6 (188), and OXTR (189).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [189]
In a recent study, there was hypermethylation at OXTR CpG sites in children who had experienced childhood trauma.
“there was hypermethylation at OXTR CpG sites in children who had experienced childhood trauma”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [189]
OXTR hypermethylation has been associated with decreased grey matter volumes in the orbitofrontal cortex (OFC).
“hypermethylation has been associated with decreased grey matter volumes in the orbitofrontal cortex (OFC)”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [189]
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Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma
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“Facial attractiveness is additionally evaluated by a network of cortical regions, including the lateral OFC, ventromedial PFC (vmPFC), and the anterior IC (aIC), with the degree of activity in these regions correlating with perceived facial attractiveness, which is then translated into a romantic interest [104,105].”
ResultInfluential
- Authors
- Fujisawa, T. X., Nishitani, S., Takiguchi, S., Shimada, K., Smith, A. K., & Tomoda, A.
- Affiliations
- University of Fukui (JP)
- Emory University (US)
- University of Fukui Hospital (JP)
- Corresponding author
- Tomoda, Akemi
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2019-05-09
- Volume
- 44
- Issue
- 12
- Pages
- 2045-2053
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC6898679
- OpenAlex
- W2944121801
- Cited by
- 85
- References
- 70
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 13 · 2023: 20 · 2022: 8 · 2021: 17 · 2020: 8 · 2019: 1
- FWCI
- 9.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- MEXT | Japan Society for the Promotion of Science (15K01753, 15K21026, 15H03106, 15K12720)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- oxytocin receptor, DNA methylation, child abuse, epigenetics, brain development, gray matter volume, orbitofrontal cortex, insecure attachment, salivary DNA, mediating effect, psychiatric symptoms
- MeSH terms
- Adolescent, Adult, Brain, Child, Child Abuse, Female, Humans, Japan, Magnetic Resonance Imaging, Male, Prefrontal Cortex, Receptors, Oxytocin, DNA Methylation, Epigenesis, Genetic, Asian People, Young Adult, Gray Matter
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