Using Next-Generation Sequencing Transcriptomics to Determine Markers of Post-traumatic Symptoms - preliminary findings from a post-deployment cohort

Post-traumatic stress disorder is a concerning psycho behavioral disorder thought to emerge from the complex interaction between genetic and environmental factors. For soldiers exposed to combat, the risk of developing this disorder is two-fold and diagnosis is often late, when much sequela has set in. To be able to identify and diagnose in advance those at “risk” of developing PTSD, would greatly taper the gap between late sequelae and treatment. Therefore, this study sought to test the hypothesis that the transcriptome can be used to track the development of PTSD in this unique and susceptible cohort of individuals. Gene expression levels in peripheral blood samples from 85 Canadian infantry soldiers (n = 58 subjects negative for PTSD symptoms and n = 27 subjects with PTSD symptoms) were determined by RNA sequencing technology following their return from deployment to Afghanistan. Count-based gene expression quantification, normalization and differential analysis (with thorough correction for confounders) revealed significant differences in two genes, LRP8 and GOLM1 . These preliminary results provide a proof-of-principle for the diagnostic utility of blood-based gene expression profiles for tracking symptoms of post-traumatic stress disorder in soldiers returning from tour. It is also the first to report transcriptome-wide expression profiles alongside a post-traumatic symptom checklist. Peripheral blood samples from 85 Canadian infantry soldiers (n = 58 subjects negative for PTSD symptoms and n = 27 subjects with PTSD symptoms)

创伤后应激障碍（Post-traumatic stress disorder, PTSD）是一种备受关注的心理行为障碍，被认为由遗传与环境因素间的复杂交互作用诱发。对于经历过作战的士兵而言，罹患该障碍的风险翻倍，且诊断往往滞后，彼时诸多后遗症已然形成。若能提前识别并诊断出存在PTSD发病“风险”的个体，将大幅缩短晚期后遗症形成与启动治疗之间的时间差。因此，本研究旨在验证这一假说：转录组（transcriptome）可用于追踪这一独特且易感的个体队列中PTSD的发生发展。本研究的研究对象为85名加拿大步兵士兵（其中58名无PTSD症状，27名存在PTSD症状），在从阿富汗部署归国后，采集其外周血样本，通过RNA测序（RNA sequencing）技术检测基因表达水平。基于计数的基因表达定量、标准化及差异分析（针对混杂因素进行了全面校正）结果显示，LRP8与GOLM1这两个基因存在显著表达差异。本初步研究结果为基于血液基因表达谱诊断追踪退伍士兵创伤后应激障碍症状提供了原理验证。本研究亦是首个将全转录组表达谱与创伤后症状检查表结合进行报道的研究。85名加拿大步兵士兵（其中58名无PTSD症状，27名存在PTSD症状）的外周血样本。