Association Between the Oxytocin Receptor Gene and Amygdalar Volume in Healthy Adults

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• 作者：Hideyuki Inoue ; Hidenori Yamasue ; Mamoru Tochigi ; Osamu Abe ; Xiaoxi Liu ; Yoshiya Kawamura ; Kunio Takei ; Motomu Suga ; Haruyasu Yamada ; Mark A. Rogers ; Shigeki Aoki ; Tsukasa Sasaki ; Kiyoto Kasai
• 关键词：Amygdala ; autism ; MRI ; OXTR ; oxytocin ; social dysfunction
• 刊名：Biological Psychiatry
• 出版年：2010
• 出版时间：1 December 2010
• 年：2010
• 卷：68
• 期：11
• 页码：1066-1072
• 全文大小：684 K

文摘

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.