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自闭症样特质的神经关联以及催产素受体基因中的一个常见等位基因

Neural correlate of autistic-like traits and a common allele in the oxytocin receptor gene.

作者信息

Saito Yuki, Suga Motomu, Tochigi Mamoru, Abe Osamu, Yahata Noriaki, Kawakubo Yuki, Liu Xiaoxi, Kawamura Yoshiya, Sasaki Tsukasa, Kasai Kiyoto, Yamasue Hidenori

机构信息

Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, Department of Radiology, Nihon University School of Medicine, 30-1 Oyaguchi kami-cho, Itabashi-ku, Tokyo 173-8610, Japan, Global Center of Excellence (COE) Program, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Child Psychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Health Service Center, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, and Japan Science and Technology Agency, CREST, 5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.

Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, Department of Radiology, Nihon University School of Medicine, 30-1 Oyaguchi kami-cho, Itabashi-ku, Tokyo 173-8610, Japan, Global Center of Excellence (COE) Program, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Child Psychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Health Service Center, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, and Japan Science and Technology Agency, CREST, 5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, Department of Radiology, Nihon University School of Medicine, 30-1 Oyaguchi kami-cho, Itabashi-ku, Tokyo 173-8610, Japan, Global Center of Excellence (COE) Program, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Child Psychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan, Health Service Center, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan, and Japan Science and Technology Agency, CREST, 5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.

出版信息

Soc Cogn Affect Neurosci. 2014 Oct;9(10):1443-50. doi: 10.1093/scan/nst136. Epub 2013 Aug 14.

Abstract

Sub-clinical autistic-like traits (ALTs) are continuously distributed in the general population and genetically linked to autism. Although identifying the neurogenetic backgrounds of ALTs might enhance our ability to identify those of autism, they are largely unstudied. Here, we have examined the neuroanatomical basis of ALTs and their association with the oxytocin receptor gene (OXTR) rs2254298A, a known risk allele for autism in Asian populations which has also been implicated in limbic-paralimbic brain structures. First, we extracted a four-factor structure of ALTs, as measured using the Autism-Spectrum Quotient, including 'prosociality', 'communication', 'details/patterns' and 'imagination' in 135 neurotypical adults (79 men, 56 women) to reduce the genetic heterogeneity of ALTs. Then, in the same population, voxel-based morphometry revealed that lower 'prosociality', which indicates strong ALTs, was significantly correlated to smaller regional grey matter volume in the right insula in males. Males with lower 'prosociality' also had less interregional structural coupling between the right insula and the ventral anterior cingulate cortex. Furthermore, males with OXTR rs2254298A had significantly smaller grey matter volume in the right insula. These results show that decreased volume of the insula is a neuroanatomical correlate of ALTs and a potential intermediate phenotype linking ALTs with OXTR in male subjects.

摘要

亚临床自闭症样特质(ALTs)在普通人群中呈连续分布,且与自闭症存在遗传关联。尽管确定ALTs的神经遗传学背景可能会增强我们识别自闭症神经遗传学背景的能力,但目前对其研究甚少。在此,我们研究了ALTs的神经解剖学基础及其与催产素受体基因(OXTR)rs2254298A的关联,该基因是亚洲人群中已知的自闭症风险等位基因,也与边缘-旁边缘脑结构有关。首先,我们在135名神经典型成年人(79名男性,56名女性)中提取了使用自闭症谱系商测量的ALTs的四因素结构,包括“亲社会行为”、“沟通”、“细节/模式”和“想象力”,以减少ALTs的遗传异质性。然后,在同一人群中,基于体素的形态学测量显示,较低的“亲社会行为”(表明存在强烈的ALTs)与男性右侧岛叶较小的区域灰质体积显著相关。“亲社会行为”较低的男性在右侧岛叶和腹侧前扣带回皮质之间的区域间结构耦合也较少。此外,携带OXTR rs2254298A的男性右侧岛叶灰质体积明显较小。这些结果表明,岛叶体积减小是ALTs的神经解剖学相关因素,也是男性受试者中连接ALTs与OXTR的潜在中间表型。

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