Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Mol Psychiatry. 2011 Jan;16(1):37-58. doi: 10.1038/mp.2009.117. Epub 2009 Nov 24.
There are to date no objective clinical laboratory blood tests for psychotic disease states. We provide proof of principle for a convergent functional genomics (CFG) approach to help identify and prioritize blood biomarkers for two key psychotic symptoms, one sensory (hallucinations) and one cognitive (delusions). We used gene expression profiling in whole blood samples from patients with schizophrenia and related disorders, with phenotypic information collected at the time of blood draw, then cross-matched the data with other human and animal model lines of evidence. Topping our list of candidate blood biomarkers for hallucinations, we have four genes decreased in expression in high hallucinations states (Fn1, Rhobtb3, Aldh1l1, Mpp3), and three genes increased in high hallucinations states (Arhgef9, Phlda1, S100a6). All of these genes have prior evidence of differential expression in schizophrenia patients. At the top of our list of candidate blood biomarkers for delusions, we have 15 genes decreased in expression in high delusions states (such as Drd2, Apoe, Scamp1, Fn1, Idh1, Aldh1l1), and 16 genes increased in high delusions states (such as Nrg1, Egr1, Pvalb, Dctn1, Nmt1, Tob2). Twenty-five of these genes have prior evidence of differential expression in schizophrenia patients. Predictive scores, based on panels of top candidate biomarkers, show good sensitivity and negative predictive value for detecting high psychosis states in the original cohort as well as in three additional cohorts. These results have implications for the development of objective laboratory tests to measure illness severity and response to treatment in devastating disorders such as schizophrenia.
迄今为止，还没有用于精神疾病状态的客观临床实验室血液检测。我们提供了一个收敛性功能基因组学（CFG）方法的原理证明，以帮助识别和优先考虑两种关键精神症状的血液生物标志物，一种是感觉（幻觉），另一种是认知（妄想）。我们使用全血样本中的基因表达谱对精神分裂症和相关障碍患者进行了研究，并在采血时收集了表型信息，然后将数据与其他人类和动物模型的证据进行交叉匹配。在我们的候选血液生物标志物列表中，有四个基因在高幻觉状态下表达降低（Fn1、Rhobtb3、Aldh1l1、Mpp3），三个基因在高幻觉状态下表达增加（Arhgef9、Phlda1、S100a6）。所有这些基因都有先前在精神分裂症患者中差异表达的证据。在我们的候选血液生物标志物列表中，有 15 个基因在高妄想状态下表达降低（如 Drd2、Apoe、Scamp1、Fn1、Idh1、Aldh1l1），16 个基因在高妄想状态下表达增加（如 Nrg1、Egr1、Pvalb、Dctn1、Nmt1、Tob2）。其中 25 个基因有先前在精神分裂症患者中差异表达的证据。基于顶级候选生物标志物的预测评分，在原始队列以及另外三个队列中，对检测高精神病状态具有良好的敏感性和阴性预测值。这些结果对开发客观的实验室测试具有重要意义，可用于衡量精神分裂症等毁灭性疾病的严重程度和治疗反应。
