Mann Frank D, Waszczuk Monika A, Clouston Sean A P, Bromet Evelyn J, Marx Brian P, Shabalin Andrey A, Docherty Anna R, Kuan Pei-Fen, Carr Melissa A, Yang Xiaohua, Luft Benjamin J, Kotov Roman
Program in Public Health and Department of Family, Population, and Preventive Medicine, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA.
Department of Medicine, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA.
Mol Psychiatry. 2025 Sep 19. doi: 10.1038/s41380-025-03235-2.
Posttraumatic stress disorder (PTSD) is persistent over time, thus identifying risk factors for chronic PTSD is crucial for clinical research. Trauma exposure severity and polygenic liability are two established predictors of PTSD onset and severity, but their contributions to the long-term course of PTSD remain largely unknown. In this prospective longitudinal cohort study, we tested whether severity of trauma exposure and polygenic risk for symptoms of PTSD independently predict long-term trajectories of PTSD symptoms. Data included 49,402 observations, spanning July 2002 to December 2022, from n = 5687 World Trade Center responders who had predominately European ancestry (baseline mean age = 37.74, SD = 8.19, range = 16-75; 92.89% male). First, the best-fitting model of 20-year PTSD trajectories was determined. Next, a polygenic risk score and a sum score of traumatic exposures were included as predictors of individual differences in intercepts (initial levels) and slopes (rates of change), adjusting for demographic covariates. The polygenic risk score significantly predicted rates of change in PTSD symptoms, independent of the intercept, such that higher polygenic risk was associated with more rapid increases in the years after trauma and a steeper arch-shaped trajectory. Exposure severity predicted initial levels and rates of change in symptoms, with more pronounced effects on initial levels. These findings indicate that polygenic liability and exposure severity predict the long-term prognosis of PTSD and have the potential to inform future clinical studies in trauma-exposed populations.
创伤后应激障碍（PTSD）会随着时间持续存在，因此识别慢性PTSD的风险因素对临床研究至关重要。创伤暴露严重程度和多基因易感性是PTSD发病和严重程度的两个既定预测因素，但它们对PTSD长期病程的影响在很大程度上仍不清楚。在这项前瞻性纵向队列研究中，我们测试了创伤暴露严重程度和PTSD症状的多基因风险是否能独立预测PTSD症状的长期轨迹。数据包括2002年7月至2022年12月期间对n = 5687名世界贸易中心应急响应者的49402次观察结果，这些应急响应者主要为欧洲血统（基线平均年龄 = 37.74，标准差 = 8.19，范围 = 16 - 75岁；92.89%为男性）。首先，确定了20年PTSD轨迹的最佳拟合模型。接下来，将多基因风险评分和创伤暴露总分作为个体差异在截距（初始水平）和斜率（变化率）方面的预测因素，并对人口统计学协变量进行了调整。多基因风险评分显著预测了PTSD症状的变化率，独立于截距，即更高的多基因风险与创伤后几年症状更快增加以及更陡峭的拱形轨迹相关。暴露严重程度预测了症状的初始水平和变化率，对初始水平的影响更为明显。这些发现表明，多基因易感性和暴露严重程度可预测PTSD的长期预后，并有可能为未来针对创伤暴露人群的临床研究提供信息。
