PTSD Blood Transcriptome Mega-Analysis: Shared Inflammatory Pathways across Biological Sex and Modes of Trauma
PTSD Blood Transcriptome Mega-Analysis: Shared Inflammatory Pathways across Biological Sex and Modes of Trauma
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DOI：
10.1038/npp.2017.220
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发表时间：
2018-02-01
影响因子：
7.6
通讯作者：
Glatt, Stephen J.
中科院分区：
文献类型：
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作者：
Breen, Michael S.;Tylee, Daniel S.;Glatt, Stephen J.
在创伤后应激障碍(PTSD)的发生和发展过程中，外周血的转录组范围的筛查表明广泛的免疫失调。然而，关于生物性行为和创伤事件的类型是否影响创伤后应激障碍的共同或不同的生物学途径，人们知之甚少。我们对涵盖229例创伤后应激障碍和311例对照个体的7种创伤类型的5项独立的创伤后应激障碍血液转录组研究进行了联合分析，以综合现有的数据。按创伤类型进行的分析显示，创伤后应激障碍基因表达特征清楚地区分了与人际(IP)相关的创伤和与战斗相关的创伤。共表达网络分析整合了所有数据，并确定了创伤后应激障碍中跨性别和创伤模式的不同基因表达扰动，包括一个伤口愈合模块在战斗创伤中下调，一个IL-12介导的信号模块在IP相关创伤中上调，以及两个与脂代谢和丝裂原激活蛋白激酶活性相关的模块在IP相关创伤中上调。值得注意的是，在创伤后应激障碍的性别和创伤模式中，转录失调的高度共享也被观察到汇聚在共同的信号级联上，包括细胞因子、先天免疫和I型干扰素途径。综上所述，这些发现为创伤后应激障碍的免疫失调提供了一个广阔的视角，并展示了分子收敛和特异性的炎症途径，这可能为该疾病的机制和诊断生物标志物提供信息。
Transcriptome-wide screens of peripheral blood during the onset and development of posttraumatic stress disorder (PTSD) indicate widespread immune dysregulation. However, little is known as to whether biological sex and the type of traumatic event influence shared or distinct biological pathways in PTSD. We performed a combined analysis of five independent PTSD blood transcriptome studies covering seven types of trauma in 229 PTSD and 311 comparison individuals to synthesize the extant data. Analyses by trauma type revealed a clear pattern of PTSD gene expression signatures distinguishing interpersonal (IP)-related traumas from combat-related traumas. Co-expression network analyses integrated all data and identified distinct gene expression perturbations across sex and modes of trauma in PTSD, including one wound-healing module downregulated in men exposed to combat traumas, one IL-12-mediated signaling module upregulated in men exposed to IP-related traumas, and two modules associated with lipid metabolism and mitogen-activated protein kinase activity upregulated in women exposed to IP-related traumas. Remarkably, a high degree of sharing of transcriptional dysregulation across sex and modes of trauma in PTSD was also observed converging on common signaling cascades, including cytokine, innate immune, and type I interferon pathways. Collectively, these findings provide a broad view of immune dysregulation in PTSD and demonstrate inflammatory pathways of molecular convergence and specificity, which may inform mechanisms and diagnostic biomarkers for the disorder.