Further evidence for a functional role of the glutamate receptor gene GRM3 in schizophrenia
Further evidence for a functional role of the glutamate receptor gene GRM3 in schizophrenia
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DOI：
10.1016/j.euroneuro.2008.05.007
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发表时间：
2008-10-01
影响因子：
5.6
通讯作者：
Maier, Wolfgang
中科院分区：
文献类型：
--
作者：
Moessner, Rainald;Schuhmacher, Anna;Maier, Wolfgang
近年来，越来越多的证据表明谷氨酸在精神分裂症的发病机制和病理生理中起着重要作用。在这方面特别重要的是代谢性谷氨酸受体（GRM）。因此，最近发表的一项关于氨基酸类似物LY2140023的试验表明，与奥氮平治疗相比，LY2140023通过激活谷氨酸受体GRM3/GRM2发挥作用，改善了阳性和阴性症状。已经描述了GRM3的功能变体，它调节突触谷氨酸水平。我们在大量患者和对照样本中评估了这种功能变异rs6465084是否与精神分裂症有关。我们发现精神分裂症患者A等位基因（p=0.027）和AA基因型（p=0.024）的频率增加。此外，在精神分裂症内表型的评估中，AA基因型患者在数字符号测试中表现不佳，这是一种注意力测量（p=0.008）。我们的研究结果为谷氨酸受体GRM3在精神分裂症中的潜在重要性提供了进一步的证据，并表明新型抗精神病药LY2140023实际上可能针对精神分裂症的致病途径。(C) 2008 Elsevier B.V.和ECNP。版权所有。
In recent years, evidence has been accumulating indicating a major role of glutamate in the pathogenesis and pathophysiology of schizophrenia. Of particular importance in this regard are the metabotropic glutamate receptors (GRM). Thus, a recently published trial of the amino acid analogue LY2140023, which exerts its effects through the activation of the glutamate receptors GRM3/GRM2, showed an improvement of positive and negative symptoms comparable to treatment with olanzapine. A functional variant of GRM3 has been described which modulates synaptic glutamate levels. We assessed whether this functional variant rs6465084 is related to schizophrenia in a large sample of patients and controls. We found an increased frequency of the A allele (p=0.027) and the AA genotype (p=0.024) in schizophrenia patients. Moreover, in an assessment of schizophrenia endophenotypes, patients of the AA genotype performed poorly in the digit symbol test, a measure of attention (p=0.008). Our results provide further evidence for the potential importance of the glutamate receptor GRM3 in schizophrenia, and indicate that the novel antipsychotic LY2140023 may actually be targeting a pathogenic pathway of schizophrenia. (C) 2008 Elsevier B.V. and ECNP. All rights reserved.