Arion Dominique, Unger Travis, Lewis David A, Levitt Pat, Mirnics Károly
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Biol Psychiatry. 2007 Oct 1;62(7):711-21. doi: 10.1016/j.biopsych.2006.12.021. Epub 2007 Jun 13.
Schizophrenia is characterized by complex gene expression changes. The transcriptome alterations in the prefrontal cortex have been the subject of several recent postmortem studies that yielded both convergent and divergent findings.
To increase measurement precision, we used a custom-designed DNA microarray platform with long oligonucleotides and multiple probes with replicates. The platform was designed to assess the expression of > 1800 genes specifically chosen because of their hypothesized roles in the pathophysiology of schizophrenia. The gene expression differences in dorsolateral prefrontal cortex samples from 14 matched pairs of schizophrenia and control subjects were analyzed with two technical replicates and four data mining approaches.
In addition to replicating many expression changes in synaptic, oligodendrocyte, and signal transduction genes, we uncovered and validated a robust immune/chaperone transcript upregulation in the schizophrenia samples.
We speculate that the overexpression of SERPINA3, IFITM1, IFITM2, IFITM3, CHI3L1, MT2A, CD14, HSPB1, HSPA1B, and HSPA1A in schizophrenia subjects represents a long-lasting and correlated signature of an early environmental insult during development that actively contributes to the pathophysiology of prefrontal dysfunction.
精神分裂症的特征是复杂的基因表达变化。前额叶皮质中的转录组改变一直是最近几项尸检研究的主题，这些研究得出了一些趋同和分歧的结果。
为了提高测量精度，我们使用了一个定制设计的DNA微阵列平台，该平台具有长寡核苷酸和多个带有重复序列的探针。该平台旨在评估超过1800个因假设在精神分裂症病理生理学中起作用而特别挑选的基因的表达。对来自14对匹配的精神分裂症患者和对照受试者的背外侧前额叶皮质样本中的基因表达差异进行了分析，采用了两个技术重复和四种数据挖掘方法。
除了复制突触、少突胶质细胞和信号转导基因中的许多表达变化外，我们还发现并验证了精神分裂症样本中一种强大的免疫/伴侣转录上调。
我们推测，精神分裂症患者中SERPINA3、IFITM1、IFITM2、IFITM3、CHI3L1、MT2A、CD14、HSPB1、HSPA1B和HSPA1A的过表达代表了发育过程中早期环境损伤的一种持久且相关的特征，这一特征积极促成了前额叶功能障碍的病理生理学。
