Gene exression data from Gene Expression Omnibus - GSE46449

"There are currently no biological tests that differentiate patients with bipolar disorder (BPD) from healthy controls. While there is evidence that peripheral gene expression differences between patients and controls can be utilized as biomarkers for psychiatric illness, it is unclear whether current use or residual effects of antipsychotic and mood stabilizer medication drives much of the differential transcription. We therefore tested whether expression changes in first-episode, never-medicated bipolar patients, can contribute to a biological classifier that is less influenced by medication and could potentially form a practicable biomarker assay for BPD.<br>We employed microarray technology to measure global leukocyte gene expression in first-episode (n=3) and currently medicated BPD patients (n=26), and matched healthy controls (n=25). Following an initial feature selection of the microarray data, we developed a cross-validated 10-gene model that was able to correctly predict the diagnostic group of the training sample (26 medicated patients and 12 controls), with 89% sensitivity and 75% specificity (p&lt;0.001). The 10-gene predictor was further explored via testing on an independent test cohort consisting of three pairs of monozygotic twins discordant for BPD, plus the original enrichment sample cohort (the three never-medicated BPD patients and 13 matched control subjects), and a sample of experimental replicates (n=34). 83% of the independent test sample was correctly predicted, with a sensitivity of 67% and specificity of 100% (although this result did not reach statistical significance). Additionally, 88% of sample diagnostic classes were classified correctly for both the enrichment (p=0.015) and the replicate samples (p&lt;0.001)."<br>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE46449

目前尚无能够区分双相情感障碍（bipolar disorder, BPD）患者与健康对照者的生物学检测手段。尽管有证据表明，患者与健康对照之间的外周基因表达差异可作为精神疾病的生物标志物，但目前尚不清楚抗精神病药物与心境稳定剂的当前使用或残留效应在多大程度上驱动了差异转录。因此，我们测试了首次发作、从未接受过药物治疗的双相障碍患者的基因表达变化，是否有助于构建受药物影响更小的生物学分类器，并有望成为双相障碍（BPD）实用的生物标志物检测方法。<br>我们采用微阵列（microarray）技术，对首次发作且未接受药物治疗的双相障碍患者（n=3）、当前正在接受药物治疗的双相障碍患者（n=26）以及匹配的健康对照者（n=25）的全血白细胞基因表达进行了检测。在对微阵列数据进行初步特征筛选后，我们构建了一个经交叉验证的10基因模型，该模型能够正确预测训练样本（26名药物治疗患者与12名对照）的诊断分组，敏感性达89%，特异性达75%（p<0.001）。该10基因预测模型进一步通过独立测试队列进行了验证，该测试队列包括3对双相障碍表型不一致的同卵双胞胎、原始富集样本队列（3名未接受药物治疗的双相障碍患者与13名匹配对照受试者）以及34份实验重复样本。该独立测试样本的83%被正确预测，敏感性为67%，特异性为100%（尽管该结果未达到统计学显著性）。此外，富集样本（p=0.015）与重复样本（p<0.001）的样本诊断分类准确率均达到88%。<br>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE46449