Wang Fei, Jiang Tianzi, Sun Zhiguo, Teng Siew-Leng, Luo Xingguang, Zhu Zhongjun, Zang Yufeng, Zhang Handi, Yue Weihua, Qu Mei, Lu Tianlan, Hong Nan, Huang Haiyan, Blumberg Hilary P, Zhang Dai
National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, China.
J Psychiatry Neurosci. 2009 May;34(3):181-6.
Neuregulin1 (NRG1) influences the development of white matter connectivity and is implicated in genetic susceptibility to schizophrenia. The cingulum bundle is a white matter structure implicated in schizophrenia. Its anterior component is especially implicated, as it provides reciprocal connections between brain regions with prominent involvement in the disorder. Abnormalities in the structural integrity of the anterior cingulum in patients with schizophrenia have been reported previously. The present study investigated the potential contribution of NRG1 variation to anterior cingulum abnormalities in participants with schizophrenia.
We studied 31 men with schizophrenia and 36 healthy men using diffusion tensor imaging to investigate the association between fractional anisotropy in the anterior cingulum and a single-nucleotide polymorphism (SNP8NRG221533: rs35753505) of NRG1.
Consistent with previous reports, fractional anisotropy was significantly reduced in the anterior cingulum in the schizophrenia group. Moreover, the results revealed a significant group (schizophrenia, control) by genotype (C/C, T carriers, including CT and TT) interaction between genetic variation in NRG1 and diagnosis of schizophrenia, such that the patients with the T allele for SNP8NRG221533 had significantly decreased anterior cingulum fractional anisotropy compared with patients homozygous for the C allele and healthy controls who were T carriers.
Limitations of our study included the small sample size of the TT subgroup and our use of only fractional anisotropy as an index of myelin integrity. In addition, the use of diffusion tensor imaging acquisition methods limited our ability to study other brain regions that may be involved in schizophrenia.
Our results suggest that NRG1 variation may play a role in the pathophysiology of anterior cingulum abnormalities in patients with schizophrenia.
神经调节蛋白1(NRG1)影响白质连接的发育,并与精神分裂症的遗传易感性有关。扣带束是一种与精神分裂症有关的白质结构。其前部成分尤其相关,因为它在大脑区域之间提供相互连接,而这些区域在该疾病中显著受累。先前已有报道精神分裂症患者前扣带的结构完整性存在异常。本研究调查了NRG1变异对精神分裂症患者前扣带异常的潜在影响。
我们对31名男性精神分裂症患者和36名健康男性进行了研究,使用扩散张量成像来研究前扣带各向异性分数与NRG1的单核苷酸多态性(SNP8NRG221533:rs35753505)之间的关联。
与先前报道一致,精神分裂症组前扣带的各向异性分数显著降低。此外,结果显示NRG1基因变异与精神分裂症诊断之间存在显著的组(精神分裂症组、对照组)×基因型(C/C、T携带者,包括CT和TT)交互作用,即SNP8NRG221533的T等位基因患者与C等位基因纯合患者及T携带者的健康对照相比,前扣带各向异性分数显著降低。
我们研究的局限性包括TT亚组样本量小,且仅使用各向异性分数作为髓鞘完整性指标。此外,扩散张量成像采集方法的使用限制了我们研究可能参与精神分裂症的其他脑区的能力。
我们的结果表明,NRG1变异可能在精神分裂症患者前扣带异常的病理生理学中起作用。