| 1 | Psychiatr. Genet. 2001 Jun 11: 79-83 |
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| PMID | 11525421 |
| Title | Mutation screening of the metabotropic glutamate receptor mGluR4 (GRM4) gene in patients with schizophrenia. |
| Abstract | Disturbances in glutamate function have been implicated in the pathophysiology of精神分裂症。We searched for mutations in the exons of the metabotropic glutamate receptor mGluR4 (GRM4) gene on human chromosome 6p21.3 and evaluated associations between these polymorphisms with精神分裂症in Japanese patients. Nine nuclear variants of 450G > T, 1455T > C, 2202A > G, 2389G > A (Val797 > Ile797), 2890A > G, 3601C > T, 3639C > T, IVS4-36G > A, and IVS5 + 29(CCGGG)1-2, were found. The Val797Ile variant, although found in both the patient and control groups, was rare and the only variant that causes a non-synonymous amino acid change. There was no statistically significant association between any mGluR4 gene polymorphism and精神分裂症。因此，这项研究没有提供MGLUR4基因对的证据精神分裂症在日本人中。 |
| SCZ Keywords | 精神分裂症, schizophrenic |
| 2 | Am. J. Hum. Genet. 2005 Dec 77: 918-36 |
| PMID | 16380905 |
| Title | 双相情感障碍和精神分裂症：Ashkenazi犹太人案例三重奏中的64个候选基因的440个单核苷酸多态性筛查。 |
| Abstract | Bipolar,精神分裂症, and schizoaffective disorders are common, highly heritable psychiatric disorders, for which familial coaggregation, as well as epidemiological and genetic evidence, suggests overlapping etiologies. No definitive susceptibility genes have yet been identified for any of these disorders. Genetic heterogeneity, combined with phenotypic imprecision and poor marker coverage, has contributed to the difficulty in defining risk variants. We focused on families of Ashkenazi Jewish descent, to reduce genetic heterogeneity, and, as a precursor to genomewide association studies, we undertook a single-nucleotide polymorphism (SNP) genotyping screen of 64 candidate genes (440 SNPs) chosen on the basis of previous linkage or of association and/or biological relevance. We genotyped an average of 6.9 SNPs per gene, with an average density of 1 SNP per 11.9 kb in 323 bipolar I disorder and 274精神分裂症or schizoaffective Ashkenazi case-parent trios. Using single-SNP and haplotype-based transmission/disequilibrium tests, we ranked genes on the basis of strength of association (P<.01). Six genes (DAO, GRM3,GRM4、GRIN2B IL2RB, TUBA8)达到这一标准bipolar I disorder; only DAO has been previously associated with bipolar disorder. Six genes (RGS4, SCA1,GRM4, DPYSL2, NOS1, and GRID1) met this criterion for精神分裂症or schizoaffective disorder; five replicate previous associations, and one, GRID1, shows a novel association with精神分裂症。In addition, six genes (DPYSL2, DTNBP1, G30/G72, GRID1,GRM4, and NOS1) showed overlapping suggestive evidence of association in both disorders. These results may help to prioritize candidate genes for future study from among the many suspected/proposed for精神分裂症and bipolar disorders. They provide further support for shared genetic susceptibility between these two disorders that involve glutamate-signaling pathways. |
| SCZ Keywords | 精神分裂症, schizophrenic |
| 3 | Schizophr Bull 2007 11月33日：1343-53 |
| PMID | 17329232 |
| Title | EIF2B和少突胶质细胞的生存：在躁郁症和精神分裂症中自然和养育相遇？ |
| Abstract | Bipolar disorder and精神分裂症共享常见的染色体敏感性基因座和许多促进风险的基因。少突胶质细胞的丧失和低司启示都是两种疾病共同的。许多环境危险因素，包括饥荒，病毒感染以及产前或儿童期压力，也可能容易精神分裂症or bipolar disorder. In cells, related stressors (starvation, viruses, cytokines, oxidative, and endoplasmic reticulum stress) activate a series of eIF2-alpha kinases, which arrest protein synthesis via the eventual inhibition, by phosphorylated eIF2-alpha, of the translation initiation factor eIF2B. Growth factors increase protein synthesis via eIF2B activation and counterbalance this system. The control of protein synthesis by eIF2-alpha kinases is also engaged by long-term potentiation and repressed by long-term depression, mediated by N-methyl-D-aspartate (NMDA) and metabotropic glutamate receptors. Many genes reportedly associated with both精神分裂症为蛋白质和双相情感障碍代码within or associated with this network. These include NMDA (GRIN1, GRIN2A, GRIN2B) and metabotropic (GRM3,GRM4) glutamate receptors, growth factors (BDNF, NRG1), and many of their downstream signaling components or accomplices (AKT1, DAO, DAOA, DISC1, DTNBP1, DPYSL2, IMPA2, NCAM1, NOS1, NOS1AP, PIK3C3, PIP5K2A, PDLIM5, RGS4, YWHAH). They also include multiple gene products related to the control of the stress-responsive eIF2-alpha kinases (IL1B, IL1RN, MTHFR, TNF, ND4, NDUFV2, XBP1). Oligodendrocytes are particularly sensitive to defects in the eIF2B complex, mutations in which are responsible for vanishing white matter disease. The convergence of natural and genetic risk factors on this area in bipolar disorder and精神分裂症在这些条件下，可能有助于解释该细胞类型的明显脆弱性。这种融合也可能有助于调和与自然和养育在这些精神疾病的病因中的重要性有关的某些论点。两者都可能影响与压力相关的常见信号通路，该信号通路决定了少突胶质细胞活力和突触可塑性。 |
| SCZ Keywords | 精神分裂症, schizophrenic |
| 4 | Psychiatry Clin. Neurosci. 2007 Feb 61: 3-19 |
| PMID | 17239033 |
| Title | Molecular genetics of bipolar disorder and depression. |
| Abstract | In this review, all papers relevant to the molecular genetics of bipolar disorder published from 2004 to the present (mid 2006) are reviewed, and major results on depression are summarized. Several candidate genes for精神分裂症may also be associated with bipolar disorder: G72, DISC1, NRG1, RGS4, NCAM1, DAO, GRM3,GRM4，grin2b，mlc1，syngr1和slc12a6。其中，与G72的关联可能最强大。然而，与躁郁症相关的G72单倍型和多态性与彼此不一致。位置候选方法显示躁郁症与TRPM2（21q22.3），GPR50（XQ28），Citron（12Q24），CHMP1.5（18P11.2），GCHI（14Q222-24），MLC1（22Q13），GABRA5，GCHI（14Q222-24），GCHI（14Q222-24），GABRA5（GABRA5）之间存在关联。（15Q11-Q13），BCR（22Q11），CUX2，FLJ32356（12Q23-Q24）和NAPG（18P11）。侧重于与躯体症状的情绪障碍合并的研究表明，线粒体DNA（mtDNA）3644突变和POLG突变作用。从基因表达分析中，发现PDLIM5，生长抑素和MTDNA 3243突变与躁郁症有关。尽管随后的研究不支持以前的大多数积极发现，但DRD1和IMPA2与后续研究有关。据报道，昼夜节律途径，BMAL1，永恒和周期3中的几个候选基因与双相情感障碍有关。链接研究显示了许多新的链接基因座。 In depression, the previously reported positive finding of a gene-environmental interaction between HTTLPR (insertion/deletion polymorphism in the promoter of a serotonin transporter) and stress was not replicated. Although the role of the TPH2 mutation in depression had drawn attention previously, this has not been replicated either. Pharmacogenetic studies show a relationship between antidepressant response and HTR2A or FKBP5. New technologies for comprehensive genomic analysis have already been applied. HTTLPR and BDNF promoter polymorphisms are now found to be more complex than previously thought, and previous papers on these polymorphisms should be treated with caution. Finally, this report addresses some possible causes for the lack of replication in this field. |
| SCZ Keywords | 精神分裂症, schizophrenic |
| 5 | Psychiatry Res 2009 May 167: 88-96 |
| PMID | 19351574 |
| Title | III组代谢型谷氨酸受体基因，GRM4和GRM7与精神分裂症的结合研究。 |
| Abstract | 基于以下假设：谷氨酸能功能障碍参与精神分裂症, we have been conducting systematic studies on the association between glutamate receptor genes and精神分裂症。Here we report association studies of精神分裂症with polymorphisms in group III metabotropic glutamate receptor genes,GRM4和grm7。我们选择了分布在整个基因区域的8和43个常见SNPGRM4(>111 kb) and GRM7 (>900 kb), respectively. We scanned significant associations with精神分裂症使用100对日语对照对。我们在GRM7中确定了两个相邻的SNP（RS12491620和RS1450099）精神分裂症surviving the FDR correction. We then performed additional typing of the two SNPs using the expanded sample set (404 cases and 420 controls) and confirmed the significant association with the disease. We conclude that at least one susceptibility locus for精神分裂症位于或附近的GRM7中，而GRM4不太可能成为主要的易感基因精神分裂症in the Japanese population. |
| SCZ Keywords | 精神分裂症, schizophrenic |
| 6 | Pharmacogenet。基因组学2011年4月21日：206-16 |
| PMID | 20859245 |
| Title | Glutamatergic gene variants impact the clinical profile of efficacy and side effects of haloperidol. |
| Abstract | The glutamatergic system may be relevant to the pathophysiology of psychosis and to the effects of antipsychotic treatments. 我们研究了一组62个SNP，位于编码谷氨酸能受体亚基的基因中（GAD1，Gria1，Gria3，Gria4，Gria4，Grid2，Grik1，Grik1，Grik1，Grik2，Grik2，Grik3，Grik3，Grik4，Grin2b，Grm1，Grm1和Grm1和Grm1和Grm1和Grm1和Grm1和Grm1和Grm1和Grm1和GRM4), and the transporter of glycine (SLC6A5), as modulators of the effects of haloperidol. We studied a sample of 101 acutely ill psychotic patients. We then validated our result in two independent samples from Slovenia (n=71 and n=118) of精神分裂症接受抗精神病药治疗的患者。我们都研究了基线和第3、7、14、21和28天的抗精神病药作用（正和负综合征量表）和运动副作用（锥体外症状评级量表）。SLC6A5变体（RS22988826）与快速相关运动开始时运动副作用的上升（反复的方差分析度量，p = 0.0002），然后进行随后的适应性，可能取决于氟哌啶醇的剂量下降滴定。注意到运动障碍症状的特定作用。单倍型分析加强了SLC6A5：C-A-C单倍型（RS1443548，RS883377，RS1945771）的相关性与跨层外症状较高的评级量表分数有关（总体p = 0.01，单倍型P = 0.000001）。我们成功地在来自斯洛文尼亚的两个独立样本中复制了这一发现。 该结果进一步强调了谷氨酸能系统在调节氟哌啶醇处理的影响方面的相关性，尤其是在运动副作用方面。 |
| SCZ Keywords | 精神分裂症, schizophrenic |