Section of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, United States.
Eur Neuropsychopharmacol. 2017 Oct;27(10):1054-1063. doi: 10.1016/j.euroneuro.2017.07.002. Epub 2017 Jul 18.
Schizophrenia (SCZ) is a severe psychiatric disorder with a genetic susceptibility. Alterations in neurochemical signaling, as well as changes in brain structure and function, manifest during the course of SCZ and are likely causative of the symptoms shown by affected individuals. However, little is known about the timing of these changes, particularly in the pre-morbid and prodromal phases of SCZ. Here, we performed a gene-based and pathway-based meta-analysis of 5 microarray datasets from human induced pluripotent stem cells (hiPSCs)-derived neurons and post-mortem brain tissue from SCZ and healthy controls (HC), with the underlying assumption they might represent the neurobiological make-up of SCZ in the pre-morbid and chronic stages of illness, respectively. Thus, we identified 1 microarray expression profiling dataset of hiPSCs-derived neurons (GSE25673) and performed a systematic search of microarray expression profiling datasets from SCZ post-mortem brain publicly available on the Gene Expression Omnibus (GEO) repository. We selected 4 different SCZ post-mortem brain microarray expression profiling datasets (GSE17612, GSE21935, GSE12649, and GSE21338) according to specific inclusion and exclusion criteria. We downloaded raw data and performed quality controls, differential expression analysis, and gene-based, as well as pathway-based meta-analysis. Neuronal pentraxin 2 (NPTX2) gene was consistently down-regulated across all datasets, with highly significant association in the meta-analysis (FDR<1.0E-04). These results highlight the heuristic value of microarray meta-analysis and suggest a role of NPTX2 as a disease biomarker, provided that it achieves biological validation in future studies examining whether this down-regulation has predictive value with respect to the developmental trajectory of SCZ.
精神分裂症（SCZ）是一种具有遗传易感性的严重精神障碍。神经化学信号的改变，以及大脑结构和功能的变化，在 SCZ 的过程中表现出来，很可能是受影响个体表现出的症状的原因。然而，人们对这些变化的时间知之甚少，特别是在 SCZ 的前病期和前驱期。在这里，我们对来自人类诱导多能干细胞（hiPSC）衍生神经元和 SCZ 及健康对照（HC）死后脑组织的 5 个微阵列数据集进行了基于基因和基于途径的荟萃分析，假设它们分别代表了 SCZ 在疾病前病期和慢性期的神经生物学构成。因此，我们确定了一个来自 hiPSC 衍生神经元的微阵列表达谱数据集（GSE25673），并对 GEO 存储库中公开的来自 SCZ 死后脑组织的微阵列表达谱数据集进行了系统搜索。我们根据特定的纳入和排除标准选择了 4 个不同的 SCZ 死后脑组织微阵列表达谱数据集（GSE17612、GSE21935、GSE12649 和 GSE21338）。我们下载了原始数据并进行了质量控制、差异表达分析以及基于基因和途径的荟萃分析。神经五聚素 2（NPTX2）基因在所有数据集均下调，荟萃分析具有高度显著相关性（FDR<1.0E-04）。这些结果突出了微阵列荟萃分析的启发价值，并表明 NPTX2 作为疾病生物标志物的作用，前提是它在未来研究中通过检查这种下调是否对 SCZ 的发育轨迹具有预测价值来实现生物学验证。
