Schizophrenia (Sz) probably occurs after genetically susceptible individuals encounter a deleterious environmental factor that triggers epigenetic mechanisms to change CNS gene expression. To determine if omnibus changes in CNS gene expression are present in Sz, we compared mRNA levels in the frontal pole (Brodmann’s area (BA) 10), the dorsolateral prefrontal cortex (BA 9) and cingulate cortex (BA 33) from 15 subjects with Sz and 15 controls using the Affymetrix™ Human Exon 1.0 ST Array. Differences in mRNA levels (±≥20%; p < 0.01) were identified (JMP Genomics 5.1) and used to predict pathways and gene x gene interactions that would be affected by the changes in gene expression using Ingenuity Pathway Analysis. There was significant variation in mRNA levels with diagnoses for 566 genes in BA 10, 65 genes in BA 9 and 40 genes in BA 33. In Sz, there was an over-representation of genes with changed expression involved in inflammation and development in BA 10, cell morphology in BA 9 and amino acid metabolism and small molecule biochemistry in BA 33. Using 94 genes with altered levels of expression in BA 10 from subjects with Sz, it was possible to construct an interactome of proven direct gene x gene interactions that was enriched for genes in inflammatory, developmental, oestrogen, serotonergic, cholinergic and NRG1 regulated pathways. Our data shows complex, regionally specific changes in cortical gene expression in Sz that are predicted to affect homeostasis between biochemical pathways already proposed to be important in the pathophysiology of the disorder.

精神分裂症（Sz）可能发生在遗传易感个体遇到有害的环境因素后，该环境因素触发表观遗传机制来改变CNS基因表达。为了确定Sz中是否存在CNS基因表达的综合变化，我们比较了15名受试者的额叶（Brodmann's Area（BA）10），背外侧前额叶皮层（BA 9）和扣带回皮层（BA 33）的mRNA水平。使用Affymetrix™Human Exon 1.0 ST阵列的Sz和15个控件。mRNA水平差异（±≥20％；p <0.01）（JMP Genomics 5.1）被确定，并被用于预测路径和基因x基因相互作用，这些影响将通过使用Ingenuity Pathway Analysis受到基因表达变化的影响。在诊断为BA 10中的566个基因，BA 9中的65个基因和BA 33中的40个基因的情况下，mRNA水平存在显着差异。在Sz中，BA 10中涉及炎症和发育的表达变化的基因过分表达，BA 9中的细胞形态以及BA 33中的氨基酸代谢和小分子生物化学。使用94个Sz受试者在BA 10中表达水平发生变化的基因，可以构建一个经过验证的直接基因x基因相互作用的相互作用基因组。富含炎症，发育，雌激素，血清素能，胆碱能和NRG1调控途径中的基因。我们的数据显示，