Ingason A, Giegling I, Hartmann A M, Genius J, Konte B, Friedl M, Ripke S, Sullivan P F, St Clair D, Collier D A, O'Donovan M C, Mirnics K, Rujescu D
Department of Psychiatry, University of Halle-Wittenberg, Halle, Germany.
Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany.
Transl Psychiatry. 2015 Oct 13;5(10):e656. doi: 10.1038/tp.2015.151.
Antagonists of the N-methyl-D-aspartate (NMDA)-type glutamate receptor induce psychosis in healthy individuals and exacerbate schizophrenia symptoms in patients. In this study we have produced an animal model of NMDA receptor hypofunction by chronically treating rats with low doses of the NMDA receptor antagonist MK-801. Subsequently, we performed an expression study and identified 20 genes showing altered expression in the brain of these rats compared with untreated animals. We then explored whether the human orthologs of these genes are associated with schizophrenia in the largest schizophrenia genome-wide association study published to date, and found evidence for association for 4 out of the 20 genes: SF3B1, FOXP1, DLG2 and VGLL4. Interestingly, three of these genes, FOXP1, SF3B1 and DLG2, have previously been implicated in neurodevelopmental disorders.
N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体拮抗剂可在健康个体中诱发精神病，并加重患者的精神分裂症症状。在本研究中，我们通过用低剂量的NMDA受体拮抗剂MK-801长期治疗大鼠，建立了NMDA受体功能减退的动物模型。随后，我们进行了一项表达研究，鉴定出20个基因，与未治疗的动物相比，这些基因在这些大鼠大脑中的表达发生了改变。然后，在迄今为止发表的最大规模的精神分裂症全基因组关联研究中，我们探究了这些基因的人类直系同源基因是否与精神分裂症相关，结果发现这20个基因中有4个基因存在关联证据：SF3B1、FOXP1、DLG2和VGLL4。有趣的是，其中三个基因，即FOXP1、SF3B1和DLG2，此前已被认为与神经发育障碍有关。
