Association Between the Oxytocin Receptor Gene and Amygdalar Volume in Healthy Adults
Association Between the Oxytocin Receptor Gene and Amygdalar Volume in Healthy Adults
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DOI：
10.1016/j.biopsych.2010.07.019
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发表时间：
2010-12-01
影响因子：
10.6
通讯作者：
Kasai, Kiyoto
中科院分区：
文献类型：
--
作者：
Inoue, Hideyuki;Yamasue, Hidenori;Kasai, Kiyoto
背景：近年来的研究表明，催产素通过人类和实验动物杏仁核中的催产素受体（OXTR）介导社会认知和行为。遗传学研究揭示了OXTR基因与自闭症谱系障碍（ASD）易感性之间的联系，特别是在ASD的社会功能障碍特征中。方法：我们在208名没有神经精神病史或当前诊断的社会完整的日本成年人中，研究了用手工追踪方法测量的杏仁核体积与OXTR中七个单核苷酸多态性和一个单倍型块之间的关系，这些基因先前被报道与ASD相关。结果：OXTR的rs2254298A等位基因与双侧杏仁核体积增大显著相关。rs2254298A等位基因对杏仁核体积的影响与该等位基因的剂量成正比。个体的rs2254298A等位基因数量越多，其杏仁核体积越大。海马体体积或整个脑体积（包括整个灰质、白质和脑脊液空间）未观察到这种关联。此外，包括rs2254298G等位基因在内的两种三单核苷酸多态性单倍型与双侧杏仁核体积减小有显著相关。结论：目前的研究结果表明，OXTR可能与ASD易感性有关，特别是在杏仁核发育调节的社会互动和沟通方面，杏仁核是OXTR密度最大的大脑区域之一。此外，磁共振成像测量的杏仁核体积可能是一种有用的中间表型，可以揭示OXTR与ASD社交功能障碍之间的复杂联系。
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.