Psychiatry CEDD, New Frontiers Science Park, GlaxoSmithKline, Harlow, Essex, UK.
Mol Psychiatry. 2009 Dec;14(12):1083-94. doi: 10.1038/mp.2009.18. Epub 2009 Mar 3.
Schizophrenia is a severe psychiatric disorder with a world-wide prevalence of 1%. The pathophysiology of the illness is not understood, but is thought to have a strong genetic component with some environmental influences on aetiology. To gain further insight into disease mechanism, we used microarray technology to determine the expression of over 30 000 mRNA transcripts in post-mortem tissue from a brain region associated with the pathophysiology of the disease (Brodmann area 10: anterior prefrontal cortex) in 28 schizophrenic and 23 control patients. We then compared our study (Charing Cross Hospital prospective collection) with that of an independent prefrontal cortex dataset from the Harvard Brain Bank. We report the first direct comparison between two independent studies. A total of 51 gene expression changes have been identified that are common between the schizophrenia cohorts, and 49 show the same direction of disease-associated regulation. In particular, changes were observed in gene sets associated with synaptic vesicle recycling, transmitter release and cytoskeletal dynamics. This strongly suggests multiple, small but synergistic changes in gene expression that affect nerve terminal function.
精神分裂症是一种严重的精神疾病，全球发病率为 1%。该病的病理生理学尚不清楚，但据认为具有很强的遗传成分，病因也受到一些环境因素的影响。为了进一步深入了解疾病机制，我们使用微阵列技术来确定 28 名精神分裂症患者和 23 名对照患者死后组织中超过 30000 个 mRNA 转录本的表达，这些组织取自与疾病病理生理学相关的脑区（布罗德曼区 10：额前皮质）。然后，我们将我们的研究（查令十字医院前瞻性收集）与哈佛脑库的独立前额皮质数据集进行了比较。我们报告了两个独立研究之间的首次直接比较。共确定了 51 个在精神分裂症队列中共同存在的基因表达变化，其中 49 个表现出与疾病相关的相同调节方向。特别是，观察到与突触小泡回收、递质释放和细胞骨架动力学相关的基因集发生了变化。这强烈表明影响神经末梢功能的基因表达存在多种小但协同的变化。
