title: 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.
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Inoue
authors.forename: Hidenori
authors.initials: H
authors.lastname: Yamasue
authors.forename: Mamoru
authors.initials: M
authors.lastname: Tochigi
authors.forename: Osamu
authors.initials: O
authors.lastname: Abe
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Liu
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Kunio
authors.initials: K
authors.lastname: Takei
authors.forename: Motomu
authors.initials: M
authors.lastname: Suga
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Yamada
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rogers
authors.forename: Shigeki
authors.initials: S
authors.lastname: Aoki
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sasaki
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Kasai
mesh_terms: D000328:Adult; D000367:Age Factors; D000483:Alleles; D000679:Amygdala / Q000033:anatomy & histology*; D000704:Analysis of Variance; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D018045:Receptors, Oxytocin / Q000235:genetics*
chemical_list: D018045:Receptors, Oxytocin