Yang Ruoting, Kannan Swapna, Gautam Aarti, Powell Teresa M, LeardMann Cynthia A, Hoke Allison V, Dimitrov George I, Jett Marti, Donoho Carrie J, Rull Rudolph P, Hammamieh Rasha
Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Army Resilience Directorate, HQDA DCS G-1, Arlington, VA 22201, USA.
Int J Mol Sci. 2025 May 28;26(11):5195. doi: 10.3390/ijms26115195.
Post-traumatic stress disorder (PTSD) is a complex, debilitating condition prevalent among military personnel exposed to traumatic events, necessitating biomarkers for early detection and intervention. Using data from the Millennium Cohort Study, the largest and longest-running military health study initiated in 2001, our objective was to identify specific microRNA (miRNA) expression patterns associated with distinct PTSD symptom trajectories among service members and veterans and assess their potential for predicting resilience and symptom severity. We analyzed 1052 serum samples obtained from the Department of Defense Serum Repository and linked with survey data collected at baseline and across three follow-up waves (2001-2011), using miRNA sequencing and statistical modeling. Our analysis identified five PTSD trajectories-resilient, pre-existing, new-onset moderate, new-onset severe, and adaptive-and revealed significant dysregulation of three key miRNAs (miR-182-5p, miR-9-5p, miR-204-5p) in participants with PTSD compared to resilient individuals. These miRNAs, which inhibit brain-derived neurotrophic factor (BDNF) and target pathways like NFκB, Notch, and TGF-alpha, were associated with neuronal plasticity, inflammation, and tissue repair, reflecting PTSD pathophysiology. These findings suggest that miRNA profiles could serve as biomarkers for early identification of PTSD risk and resilience, guiding targeted interventions to improve long-term health outcomes for military personnel.
创伤后应激障碍（PTSD）是一种复杂且使人衰弱的病症，在经历创伤事件的军事人员中普遍存在，因此需要生物标志物用于早期检测和干预。利用千年队列研究的数据（这是2001年启动的规模最大、持续时间最长的军事健康研究），我们的目标是确定与现役军人和退伍军人中不同PTSD症状轨迹相关的特定微小RNA（miRNA）表达模式，并评估它们预测恢复力和症状严重程度的潜力。我们分析了从国防部血清库获得的1052份血清样本，并将其与基线时以及三个随访期（2001 - 2011年）收集的调查数据相关联，采用miRNA测序和统计建模方法。我们的分析确定了五种PTSD轨迹——恢复力强型、既往存在型、新发中度型、新发重度型和适应型——并揭示与恢复力强的个体相比，PTSD患者中三种关键miRNA（miR - 182 - 5p、miR - 9 - 5p、miR - 204 - 5p）存在显著失调。这些miRNA抑制脑源性神经营养因子（BDNF）并靶向NFκB、Notch和TGF - α等通路，与神经元可塑性、炎症和组织修复相关，反映了PTSD的病理生理学。这些发现表明，miRNA谱可作为早期识别PTSD风险和恢复力的生物标志物，指导针对性干预，以改善军事人员的长期健康结局。
