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DISC1 半胱氨酸等位基因携带者中信息传递效率较低:基于弥散磁共振成像的脑网络研究。

Less efficient information transfer in Cys-allele carriers of DISC1: a brain network study based on diffusion MRI.

机构信息

LIAMA Center for Computational Medicine, National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China.

出版信息

Cereb Cortex. 2013 Jul;23(7):1715-23. doi: 10.1093/cercor/bhs167. Epub 2012 Jun 12.

Abstract

Previous neuroimaging studies of brain networks have revealed less efficient information transfer in patients with schizophrenia. However, the underlying genetic basis remains largely unexplored. In this study, we investigated the brain anatomical networks of 278 healthy volunteers with different genotypes in the common missense variant (Ser704Cys) of the Disrupted-in-Schizophrenia-1 (DISC1) gene, which is one of the main susceptibility genes of schizophrenia and other psychiatric disorders. The anatomical brain network for each individual was constructed using fiber tractography technique based on diffusion magnetic resonance imaging (dMRI). The properties of this network were then calculated using graph theory. This revealed that Cys-allele carriers showed significantly lower global efficiency of their brain networks than Ser homozygotes, thereby supporting our hypothesis that genetic variation in DISC1 may relate to the risk of schizophrenia by affecting the efficiency of brain network. Additional dMRI analyses were also performed at different levels, with a convergent trend towards decreased white matter integrity being consistently observed in Cys-allele carriers. Together these findings not only provide new clues for understanding DISC1 function, but also suggest that network analyses based on graph theory combined with neuroimaging techniques may reveal structural disruptions related to genetic risk in the brains of healthy individuals.

摘要

先前有关大脑网络的神经影像学研究表明,精神分裂症患者的信息传递效率较低。然而,其潜在的遗传基础在很大程度上仍未得到探索。在这项研究中,我们调查了 278 名具有不同基因型的健康志愿者的大脑解剖网络,这些志愿者均携带有精神分裂症和其他精神障碍的主要易感基因之一——Disrupted-in-Schizophrenia-1(DISC1)基因的常见错义变异(Ser704Cys)。基于弥散磁共振成像(dMRI)的纤维束追踪技术,为每位个体构建大脑解剖网络。然后使用图论计算该网络的性质。结果表明,Cys 等位基因携带者的大脑网络全局效率明显低于 Ser 纯合子,这支持了我们的假设,即 DISC1 的遗传变异可能通过影响大脑网络的效率与精神分裂症的风险相关。还在不同水平上进行了额外的 dMRI 分析,一致观察到 Cys 等位基因携带者的白质完整性降低。这些发现不仅为理解 DISC1 功能提供了新的线索,还表明基于图论的网络分析结合神经影像学技术可能会揭示与健康个体的遗传风险相关的结构破坏。

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