Li Zezhi, Liu Lihua, Lin Wei, Zhou Yongjie, Zhang Guangya, Du Xiangdong, Li Yi, Tang Wei, Zhang Xiangyang
Department of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Psychiatry, Qingdao Mental Health Center, Qingdao, China.
Schizophr Res. 2020 Jan;215:134-139. doi: 10.1016/j.schres.2019.10.060. Epub 2019 Nov 18.
Cognitive deficit is a fundamental trait of schizophrenia, but its mecwhanisms remain unknown. The neuregulin 3 (NRG3) gene, involving in neuronal function, has been considered to be associated with schizophrenia and cognition. However, no study has investigated the effects of NRG3 polymorphism on cognitive deficits in a large sample of the patients with schizophrenia.
A total of 1112 schizophrenia patients and 423 controls were recruited and genotyped with NRG3 rs10748842. Among them, 864 patients and 403 controls were assessed for cognition through the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). SHEsis was applied and followed by logistic regression analysis. The models of analyses of covariance (ANCOVA) were constructed to examine the effects of NRG3 rs10748842 on cognitive deficits.
No differences in NRG3 rs10748842 allele and genotype were found between patients and controls (both p > 0.05). With the exception of Visuospatial/construction, the other RBANS scores were significantly lower in patients compared to controls after adjusting for gender and education (all p < 0.001). Interestingly, we found that NRG3 rs10748842 was associated with cognitive deficit in schizophrenia, showing that patients carrying C allele had lower attention and total scores than those with TT genotype (both p < 0.05).
NRG3 rs10748842 may not confer susceptibility to schizophrenia, but may be more closely associated with cognitive deficit, especially attention performance in chronic schizophrenia.
认知缺陷是精神分裂症的一个基本特征,但其机制尚不清楚。神经调节蛋白3(NRG3)基因参与神经元功能,被认为与精神分裂症和认知有关。然而,尚无研究在大量精神分裂症患者样本中调查NRG3基因多态性对认知缺陷的影响。
共招募了1112例精神分裂症患者和423名对照,并对NRG3 rs10748842进行基因分型。其中,864例患者和403名对照通过可重复神经心理状态评估量表(RBANS)进行认知评估。应用SHEsis并随后进行逻辑回归分析。构建协方差分析(ANCOVA)模型以检查NRG3 rs10748842对认知缺陷的影响。
患者与对照之间在NRG3 rs10748842等位基因和基因型上未发现差异(均p>0.05)。除视觉空间/结构外,在调整性别和教育程度后,患者的其他RBANS评分显著低于对照(均p<0.001)。有趣的是,我们发现NRG3 rs10748842与精神分裂症的认知缺陷相关,表明携带C等位基因的患者的注意力和总分低于TT基因型患者(均p<0.05)。
NRG3 rs10748842可能不会赋予精神分裂症易感性,但可能与认知缺陷,特别是慢性精神分裂症的注意力表现更密切相关。