Waszczuk Monika A, Docherty Anna R, Shabalin Andrey A, Miao Jiaju, Yang Xiaohua, Kuan Pei-Fen, Bromet Evelyn, Kotov Roman, Luft Benjamin J
Department of Psychiatry, Stony Brook University, Stony Brook, NY, USA.
Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA.
Psychol Med. 2020 Oct 23:1-9. doi: 10.1017/S0033291720003839.
Genetics hold promise of predicting long-term post-traumatic stress disorder (PTSD) outcomes following trauma. The aim of the current study was to test whether six hypothesized polygenic risk scores (PRSs) developed to capture genetic vulnerability to psychiatric conditions prospectively predict PTSD onset, severity, and 18-year course after trauma exposure.
Participants were 1490 responders to the World Trade Center (WTC) disaster (mean age at 9/11 = 38.81 years, s.d. = 8.20; 93.5% male; 23.8% lifetime WTC-related PTSD diagnosis). Prospective longitudinal data on WTC-related PTSD symptoms were obtained from electronic medical records and modelled as PTSD trajectories using growth mixture model analysis. Independent regression models tested whether six hypothesized psychiatric PRSs (PTSD-PRS, Re-experiencing-PRS, Generalized Anxiety-PRS, Schizophrenia-PRS, Depression-PRS, and Neuroticism-PRS) are predictive of WTC-PTSD outcomes: lifetime diagnoses, average symptom severity, and 18-year symptom trajectory. All analyses were adjusted for population stratification, 9/11 exposure severity, and multiple testing.
Depression-PRS predicted PTSD diagnostic status (OR 1.37, CI 1.17-1.61, adjusted p = 0.001). All PRSs, except PTSD-PRS, significantly predicted average PTSD symptoms (β = 0.06-0.10, adjusted p < 0.05). Re-experiencing-PRS, Generalized Anxiety-PRS and Schizophrenia-PRS predicted the high severity PTSD trajectory class (ORs 1.21-1.28, adjusted p < 0.05). Finally, PRSs prediction was independent of 9/11 exposure severity and jointly accounted for 3.7 times more variance in PTSD symptoms than the exposure severity.
Psychiatric PRSs prospectively predicted WTC-related PTSD lifetime diagnosis, average symptom severity, and 18-year trajectory in responders to 9/11 disaster. Jointly, PRSs were more predictive of subsequent PTSD than the exposure severity. In the future, PRSs may help identify at-risk responders who might benefit from targeted prevention approaches.
遗传学有望预测创伤后长期创伤后应激障碍(PTSD)的结局。本研究的目的是测试为捕捉对精神疾病的遗传易感性而开发的六个假设的多基因风险评分(PRSs)是否能前瞻性地预测创伤暴露后的PTSD发病、严重程度和18年病程。
参与者为1490名世界贸易中心(WTC)灾难的幸存者(9·11事件时的平均年龄 = 38.81岁,标准差 = 8.20;93.5%为男性;23.8%有与WTC相关的终身PTSD诊断)。从电子病历中获取与WTC相关的PTSD症状的前瞻性纵向数据,并使用生长混合模型分析将其建模为PTSD轨迹。独立回归模型测试六个假设的精神PRSs(PTSD-PRS、重新体验-PRS、广泛性焦虑-PRS、精神分裂症-PRS、抑郁症-PRS和神经质-PRS)是否能预测WTC-PTSD结局:终身诊断、平均症状严重程度和18年症状轨迹。所有分析均针对人群分层、9·11暴露严重程度和多重检验进行了调整。
抑郁症-PRS预测了PTSD诊断状态(比值比1.37,置信区间1.17 - 1.61,校正p = 0.001)。除PTSD-PRS外,所有PRSs均显著预测了平均PTSD症状(β = 0.06 - 0.10,校正p < 0.05)。重新体验-PRS、广泛性焦虑-PRS和精神分裂症-PRS预测了高严重程度PTSD轨迹类别(比值比1.21 - 1.28,校正p < 0.05)。最后,PRSs的预测独立于9·11暴露严重程度,并且在PTSD症状中共同解释的方差比暴露严重程度多3.7倍。
精神PRSs前瞻性地预测了9·11灾难幸存者中与WTC相关的PTSD终身诊断、平均症状严重程度和18年病程。联合起来,PRSs对后续PTSD的预测比暴露严重程度更强。未来,PRSs可能有助于识别可能从针对性预防方法中受益的高危幸存者。