Institute of Mental Health/Woodbridge Hospital, 10 Buangkok View, Singapore 539747, Singapore.
Neurosci Biobehav Rev. 2010 May;34(6):958-77. doi: 10.1016/j.neubiorev.2010.01.002. Epub 2010 Jan 7.
Schizophrenia (SZ) and bipolar disorder (BD) are debilitating neurobehavioural disorders likely influenced by genetic and non-genetic factors and which can be seen as complex disorders of synaptic neurotransmission. The glutamatergic and GABAergic neurotransmission systems have been implicated in both diseases and we have reviewed extensive literature over a decade for evidence to support the association of glutamate and GABA genes in SZ and BD. Candidate-gene based population and family association studies have implicated some ionotrophic glutamate receptor genes (GRIN1, GRIN2A, GRIN2B and GRIK3), metabotropic glutamate receptor genes (such as GRM3), the G72/G30 locus and GABAergic genes (e.g. GAD1 and GABRB2) in both illnesses to varying degrees, but further replication studies are needed to validate these results. There is at present no consensus on specific single nucleotide polymorphisms or haplotypes associated with the particular candidate gene loci in these illnesses. The genetic architecture of glutamate systems in bipolar disorder need to be better studied in view of recent data suggesting an overlap in the genetic aetiology of SZ and BD. There is a pressing need to integrate research platforms in genomics, epistatic models, proteomics, metabolomics, neuroimaging technology and translational studies in order to allow a more integrated understanding of glutamate and GABAergic signalling processes and aberrations in SZ and BD as well as their relationships with clinical presentations and treatment progress over time.
精神分裂症（SZ）和双相情感障碍（BD）是使人衰弱的神经行为障碍，可能受遗传和非遗传因素的影响，可被视为突触神经传递的复杂障碍。谷氨酸能和 GABA 能神经传递系统与这两种疾病都有关联，我们在过去十年中查阅了大量文献，以寻找支持 SZ 和 BD 中谷氨酸和 GABA 基因关联的证据。基于候选基因的人群和家族关联研究表明，一些离子型谷氨酸受体基因（GRIN1、GRIN2A、GRIN2B 和 GRIK3）、代谢型谷氨酸受体基因（如 GRM3）、G72/G30 基因座和 GABA 能基因（如 GAD1 和 GABRB2）在这两种疾病中都有不同程度的关联，但需要进一步的复制研究来验证这些结果。目前，在这些疾病中，没有关于特定候选基因座的特定单核苷酸多态性或单倍型的共识。鉴于最近的数据表明 SZ 和 BD 的遗传病因存在重叠，需要更好地研究谷氨酸系统在双相情感障碍中的遗传结构。有迫切需要整合基因组学、上位模型、蛋白质组学、代谢组学、神经影像学技术和转化研究的研究平台，以便更全面地了解 SZ 和 BD 中的谷氨酸和 GABA 能信号传递过程及其异常，以及它们与临床表现和治疗进展随时间的关系。
