Development of a diagnostic test of bipolar disorder using gene expression analysis

我们之前报道过神经元特异性突变Polg1（线粒体DNA聚合酶）转基因（Tg）小鼠表现出双相情感障碍（BD）样表型。我们寻找BD患者死后脑与对照组、Tg小鼠死后脑与野生型小鼠脑之间的差异表达基因。基因本体论分析显示，BD患者与小鼠模型基因表达谱的改变有16类重叠。在Tg小鼠的大脑中，有33个基因在额叶皮层和海马体中显示出与野生型小鼠相似的变化。在33个基因中，SFPQ和PPIF在BD患者死后大脑中的表达与对照组相比存在差异。这些基因和其他候选基因被用于双相情感障碍患者和对照组淋巴母细胞样细胞的基因表达分析。使用17个基因，将第一批样本分为患者和对照组。利用该判别函数对第二样本集进行分类。第二个样本的鉴别性接近显著性（p=0.05）。这些发现表明，基因表达分析可能有助于双相情感障碍的诊断。

We previously reported that neuron-specific mutant Polg1 (mitochondrial DNA polymerase) transgenic (Tg) mice exhibited bipolar disorder (BD)-like phenotypes. We searched for the genes differentially expressed between post-mortem brains of BD patients and control subjects, and between the brains of Tg and wild-type mice. Gene ontology analysis showed that 16 categories overlapped in the altered gene expression profiles of BD patients and the mouse model. In the brains of Tg mice, 33 genes showed similar changes in the frontal cortex and hippocampus compared to wild-type mice. Among the 33 genes, SFPQ and PPIF were differentially expressed in post-mortem brains of BD patients compared to control subjects. These genes and other candidate genes were used for the gene expression analysis in lymphoblastoid cells obtained from patients with bipolar disorder and control subjects. Using 17 genes, the first sample were classified into patients and controls. Using this discriminate function, the second sample set was classified. Discrimination of the second sample was close to significance (p=0.05). These findings suggest that gene expression analysis may be useful for the diagnosis of bipolar disorder.