Cai Suping, Lv Yahui, Huang Kexin, Zhang Wei, Wang Qiang, Huang Liyu, Wang Jijun
School of Life Sciences and Technology, Xidian University, Xi'an, China.
The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
Front Neurosci. 2020 Apr 21;14:351. doi: 10.3389/fnins.2020.00351. eCollection 2020.
The frontal-striatum-thalamus pathway is important in the glutamic neural circuit. The hypofunction of GRIN1 and GRIA2 subunits from glutamic receptors has been hypothesized as the primary process in the etiology of schizophrenia. Identified gene polymorphism involved in the pathogenesis of schizophrenia may uncover relevant mechanism pathways.
We selected two loci of rs11146020 and rs3813296 distributed in GRIN1 and GRIA2 genes and tested their main and interaction effects on causality connections and structural characteristics in the frontal-striatum-thalamus pathway in 55 Han Chinese first-episode negative schizophrenia patients.
We found that: (1) rs11146020 has a significant main effect on the causality connections between the bilateral dorsolateral prefrontal cortex, and rs3813296 mainly influences those of the descending pathway from the prefrontal cortex to the striatum; (2) interaction effect of rs11146020 and rs3813296 on causality connections are located in the ascending pathway from the pallidum to the dorsolateral prefrontal cortex; and (3) the two loci have effects on the volumes of several regions of this pathway.
Our results suggested there is modulation on glutamic frontal-striatum-thalamus pathway by rs11146020 and rs3813296 gene polymorphism. Patients with different genotypes have different neuroimaging characteristics, which indirectly reminded clinicians those patients should receive different clinical interventions.
额叶-纹状体-丘脑通路在谷氨酸能神经回路中很重要。谷氨酸受体的GRIN1和GRIA2亚基功能减退被认为是精神分裂症病因的主要过程。已确定的参与精神分裂症发病机制的基因多态性可能揭示相关的机制途径。
我们选择了分布在GRIN1和GRIA2基因中的rs11146020和rs3813296两个位点，并在55例汉族首发阴性精神分裂症患者中测试了它们对额叶-纹状体-丘脑通路中因果联系和结构特征的主要及交互作用。
我们发现：（1）rs11146020对双侧背外侧前额叶皮质之间的因果联系有显著的主要影响，rs3813296主要影响从前额叶皮质到纹状体的下行通路的因果联系；（2）rs11146020和rs3813296对因果联系的交互作用位于从苍白球到背外侧前额叶皮质的上行通路中；（3）这两个位点对该通路几个区域的体积有影响。
我们的结果表明rs11146020和rs3813296基因多态性对谷氨酸能额叶-纹状体-丘脑通路有调节作用。不同基因型的患者有不同的神经影像学特征，这间接提醒临床医生这些患者应接受不同的临床干预。
