Innate immune response is differentially dysregulated between bipolar disease and schizophrenia
Innate immune response is differentially dysregulated between bipolar disease and schizophrenia
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DOI：
10.1016/j.schres.2014.10.055
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发表时间：
2015-02-01
影响因子：
4.5
通讯作者：
Brentani, Helena
中科院分区：
文献类型：
--
作者：
de Baumont, Angelica;Maschietto, Mariana;Brentani, Helena
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，存在着重叠的遗传易感性的疾病。此外，图像研究提供了证据，共享的神经生物学基础，有助于三维诊断方法。本研究旨在确定区分SZ和BD患者与健康对照的分子机制，以及区分两者与健康个体的分子机制。比较疾病和健康对照（30例）的死后大脑中的基因表达谱，然后进一步比较29 BD和29 SZ，发现28个差异表达基因。这些基因用于共表达分析，显示CCR 1/SERPINA 1、CCR 5/HCST、C1 QA/CD 68、CCR 5/S100 A11和SERPINA 1/TLR 1对在SZ和BD之间的共表达中呈现最显著的差异。接下来，使用28个差异表达基因作为种子的蛋白质-蛋白质相互作用（PPI）网络揭示CASP 4、TYROBP、CCR 1、SERPINA 1、CCR 5和C1 QA在疾病表现中具有核心作用。共表达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之间的差异是由于涉及对刺激的反应、防御反应、免疫系统过程和对应激生物过程的反应的基因，所有这些基因都在环境因素与细胞的通信中起作用，并且与小胶质细胞相关。(C)2014爱思唯尔有限公司版权所有。
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. (C) 2014 Elsevier B.V. All rights reserved.