de Baumont Angelica, Maschietto Mariana, Lima Leandro, Carraro Dirce Maria, Olivieri Eloisa Helena, Fiorini Alex, Barreta Luiz André Nardin, Palha Joana Almeida, Belmonte-de-Abreu Paulo, Moreira Filho Carlos Alberto, Brentani Helena
Institute of Psychiatry - University of Sao Paulo, Medical School (FMUSP), São Paulo (SP), Brazil.
Institute of Psychiatry - University of Sao Paulo, Medical School (FMUSP), São Paulo (SP), Brazil; Laboratory of Genomics and Molecular Biology/CIPE - AC Camargo Hospital Cancer Center, Sao Paulo (SP), Brazil.
Schizophr Res. 2015 Feb;161(2-3):215-21. doi: 10.1016/j.schres.2014.10.055. Epub 2014 Dec 6.
Schizophrenia (SZ) and bipolar disorder (BD) are severe psychiatric conditions with a neurodevelopmental component. Genetic findings indicate the existence of an overlap in genetic susceptibility across the disorders. Also, image studies provide evidence for a shared neurobiological basis, contributing to a dimensional diagnostic approach. This study aimed to identify the molecular mechanisms that differentiate SZ and BD patients from health controls but also that distinguish both from health individuals. Comparison of gene expression profiling in post-mortem brains of both disorders and health controls (30 cases), followed by a further comparison between 29 BD and 29 SZ revealed 28 differentially expressed genes. These genes were used in co-expression analysesthat revealed the pairs CCR1/SERPINA1, CCR5/HCST, C1QA/CD68, CCR5/S100A11 and SERPINA1/TLR1 as presenting the most significant difference in co-expression between SZ and BD. Next, a protein-protein interaction (PPI) network using the 28 differentially expressed genes as seeds revealed CASP4, TYROBP, CCR1, SERPINA1, CCR5 and C1QA as having a central role in the diseases manifestation. Both co-expression and network topological analyses pointed to genes related to microglia functions. Based on this data, we suggest that differences between SZ and BP are due to genes involved with response to stimulus, defense response, immune system process and response to stress biological processes, all having a role in the communication of environmental factors to the cells and associated to microglia.
精神分裂症（SZ）和双相情感障碍（BD）是具有神经发育成分的严重精神疾病。遗传学研究结果表明，这些疾病在遗传易感性方面存在重叠。此外，影像学研究为共同的神经生物学基础提供了证据，有助于采用维度诊断方法。本研究旨在确定区分SZ和BD患者与健康对照者，以及区分这两种疾病与健康个体的分子机制。对这两种疾病和健康对照者（30例）的死后大脑进行基因表达谱比较，随后对29例BD患者和29例SZ患者进行进一步比较，发现了28个差异表达基因。这些基因用于共表达分析，结果显示CCR1/SERPINA1、CCR5/HCST、C1QA/CD68、CCR5/S100A11和SERPINA1/TLR1这几对基因在SZ和BD的共表达中差异最为显著。接下来，以这28个差异表达基因作为种子构建蛋白质-蛋白质相互作用（PPI）网络，结果显示CASP4、TYROBP、CCR1、SERPINA1、CCR5和C1QA在疾病表现中起核心作用。共表达分析和网络拓扑分析均指向与小胶质细胞功能相关的基因。基于这些数据，我们认为SZ和BP之间的差异是由于与刺激反应、防御反应、免疫系统过程和应激生物过程反应相关的基因所致，所有这些基因在环境因素与细胞的通讯中发挥作用，并与小胶质细胞相关。
