Association between the oxytocin receptor gene and amygdalar volume in healthy adults
Abstract
Background Recent studies have suggested that oxytocin affects social cognition and behavior mediated by the oxytocin receptor (OXTR) in amygdala in humans as well as in experimental animals. Genetic studies have revealed a link between the OXTR gene and the susceptibility to autism spectrum disorders (ASD), especially in the social dysfunctional feature of ASD.Methods We examined the relationship between amygdala volume measured with manual tracing methodology and seven single nucleotide polymorphisms and one haplotype-block in OXTR, which were previously reported to be associated with ASD, in 208 socially intact Japanese adults with no neuropsychiatric history or current diagnosis.Results The rs2254298A allele of OXTR was significantly associated with larger bilateral amygdala volume. The rs2254298A allele effect on amygdala volume varied in proportion to the dose of this allele. The larger the number of rs2254298A alleles an individual had, the larger their amygdala volume. Such an association was not observed with hippocampal volume or with global brain volumes, including whole gray, white matter, and cerebrospinal-fluid space. Furthermore, two three-single nucleotide polymorphism haplotypes, including rs2254298G allele, showed significant associations with the smaller bilateral amygdala volume.Conclusions The present results suggest that OXTR might be associated with the susceptibility to ASD, especially in its aspects of social interaction and communication mediated by a modulation of amygdala development, one of the most distributed brain regions with high density of OXTR. Furthermore, amygdala volume measured with magnetic resonance imaging could be a useful intermediate phenotype to uncover the complex link between OXTR and social dysfunction in ASD.
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Other studies report links between OXTR and ASD endophenotypes, such as structural differences in social-cognition brain regions.
“and others have reported associations with endophenotypes of ASD (20, 82, 83), including structural variability in brain regions relevant to social cognition (80, 84).”
From Variation in the Oxytocin Receptor Gene Predicts Brain Region–Specific Expression and Social Attachment (2016) · cites this paper as [83]
Participants with an A allele for SNP rs2254298 had greater amygdala volumes compared to those homozygous for the G allele in adolescent girls and adult men and women.
“Participants with an A allele for SNP rs2254298 also had greater amygdala volumes compared to those homogyzous for the G allele in adolescent girls (Furman et al., 2011) and adult men and women (Inoue et al., 2010).”
From Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior (2016) · cites this paper as Inoue et al., 2010
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- Authors
- Inoue, H., Yamasue, H., Tochigi, M., Abe, O., Liu, X., Kawamura, Y., Takei, K., Suga, M., Yamada, H., Rogers, M. A., Aoki, S., Sasaki, T., & Kasai, K.
- Affiliations
- The University of Tokyo (JP)
- Japan Science and Technology Agency (JP)
- Corresponding author
- Yamasue, Hidenori
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 68
- Issue
- 11
- Pages
- 1066-1072
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W1983037600
- Cited by
- 164
- References
- 63
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 8 · 2022: 4 · 2021: 4 · 2020: 10 · 2019: 11 · 2018: 9 · 2017: 12 · 2016: 14 · 2015: 14 · 2014: 14 · 2013: 17 · 2012: 25
- FWCI
- 24.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Health, Labour, and Welfare
- JSPS/MEXT (20023009, 21249064, 08105853)
- Topics
- Social Sciences › Psychology › Social Psychology › 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 receptor gene, oxytocin receptor, amygdala volume, autism spectrum disorder, single nucleotide polymorphisms, rs2254298, haplotypes, genetic susceptibility, social dysfunction, endophenotypes, amygdala development, healthy adults
- MeSH terms
- Adult, Age Factors, Alleles, Amygdala, Analysis of Variance, Female, Gene Frequency, Genotype, Haplotypes, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Receptors, Oxytocin, Polymorphism, Single Nucleotide, Genetic Association Studies
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