Blood-based gene-expression biomarkers of post-traumatic stress disorder among deployed marines: A pilot study.
Blood-based gene-expression biomarkers of post-traumatic stress disorder among deployed marines: A pilot study.
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DOI：
10.1016/j.psyneuen.2014.09.024
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发表时间：
2015-01
影响因子：
3.7
通讯作者：
Tsuang, Ming T.
中科院分区：
文献类型：
--
作者：
Tylee, Daniel S.;Chandler, Sharon D.;Nievergelt, Caroline M.;Liu, Xiaohua;Pazol, Joel;Woelk, Christopher H.;Lohr, James B.;Kremen, William S.;Baker, Dewleen G.;Glatt, Stephen J.;Tsuang, Ming T.
关键词：
创伤后应激障碍（PTSD）的病因可能涉及众多基因和环境因素的相互作用。同样，外周血中的基因表达水平同时受到基因和环境的影响，许多基因的表达水平在外周血和脑组织之间表现出良好的对应性。在这种背景下，这项试点研究试图检验以下假设：1）患有和不患有创伤后应激障碍的海军陆战队员外周血中基因子集的创伤后表达水平会有所不同； 2) 基于易于评估的外周血细胞中的基因表达，可以开发高危个体中 PTSD 的诊断生物标志物组； 3）基于单个外显子表达的诊断面板将超过基于全长基因转录本表达的模型的准确性。 50 名美国海军陆战队员（25 名 PTSD 病例和 25 名非 PTSD 对照受试者）从部署到伊拉克或阿富汗战区返回后，通过微阵列测定了他们外周血样本的基因表达水平。原始样本被划分为训练和测试子集，用于构建支持向量机分类器。仅基于两个全长转录本（GSTM1 和 GSTM2）的表达，外周血生物标记物组在测试子集中就实现了 80% 的预测准确度。基于 20 个外显子的生物标记物组在测试子集中的准确度提高了 90%。尽管需要进一步完善和复制这些生物标志物谱，但这些初步结果为血液 mRNA 表达在创伤暴露个体中诊断 PTSD 的效用提供了原理证明。
The etiology of post-traumatic stress disorder (PTSD) likely involves the interaction of numerous genes and environmental factors. Similarly, gene-expression levels in peripheral blood are influenced by both genes and environment, and expression levels of many genes show good correspondence between peripheral blood and brain tissues. In that context, this pilot study sought to test the following hypotheses: 1) post-trauma expression levels of a gene subset in peripheral blood would differ between Marines with and without PTSD; 2) a diagnostic biomarker panel of PTSD among high-risk individuals could be developed based on gene expression in readily assessable peripheral blood cells; and 3) a diagnostic panel based on expression of individual exons would surpass the accuracy of a model based on expression of full-length gene transcripts. Gene-expression levels in peripheral blood samples from 50 U.S. Marines (25 PTSD cases and 25 non-PTSD comparison subjects) were determined by microarray following their return from deployment to war-zones in Iraq or Afghanistan. The original sample was carved into training and test subsets for construction of support vector machine classifiers. The panel of peripheral blood biomarkers achieved 80% prediction accuracy in the test subset based on the expression of just two full-length transcripts (GSTM1 and GSTM2). A biomarker panel based on 20 exons attained an improved 90% accuracy in the test subset. Though further refinement and replication of these biomarker profiles are required, these preliminary results provide proof-of-principle for the diagnostic utility of blood-based mRNA-expression in PTSD among trauma-exposed individuals.
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