Polygenic risk for mental disorders as predictors of posttraumatic stress disorder after mild traumatic brain injury.
Polygenic risk for mental disorders as predictors of posttraumatic stress disorder after mild traumatic brain injury.
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DOI：
10.1038/s41398-023-02313-9
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发表时间：
2023-01-25
影响因子：
6.8
通讯作者：
TRACK TBI Investigators
中科院分区：
文献类型：
--
作者：
Stein, Murray J.;Jain, Sonia S.;Parodi, Livia A.;Choi, Karmel;Maihofer, Adam J.;Nelson, Lindsay;Mukherjee, Pratik;Sun, Xiaoying T.;He, Feng;Okonkwo, David;Giacino, Joseph;Korley, Frederick R.;Vassar, Mary;Robertson, Claudia;McCrea, Michael;Temkin, Nancy;Markowitz, Amy;Diaz-Arrastia, Ramon R.;Rosand, Jonathan K.;Manley, Geoffrey;TRACK TBI Investigators
许多患有轻度创伤性脑损伤（mTBI）的患者都有心理健康问题的风险，如创伤后应激障碍（PTSD）。本研究的目的是确定创伤后应激障碍（或相关精神健康障碍或特征，包括重度抑郁症[MDD]和神经质[NEU]）的多基因风险是否与mTBI后创伤后应激障碍的可能性增加相关。我们使用了来自TRACK-TBI（n = 714）的欧洲血统mTBI患者的数据，TRACK-TBI是一项针对1级创伤中心患者的前瞻性纵向研究。116例mTBI患者（16.3%）在伤后6个月时可能患有PTSD（PCL-5评分≥33）。我们使用最近GWAS研究PTSD、MDD和NEU的汇总统计数据，为样本中的个体生成多基因风险评分（PRS）。一个多变量模型，包括年龄，性别，受伤前的精神障碍史，和受伤的原因解释7%的方差在PTSD的结果;增加PTSD-PRS（和五个祖先的主成分）显着增加方差解释到11%。PTSD-PRS最高五分位数的PTSD调整后的几率比PTSD-PRS最低五分位数高近4倍（aOR = 3.71，95%CI 1.80-7.65）。没有证据表明PTSD-PRS和既往精神障碍史之间存在统计学显著的相互作用，表明PTSD-PRS在有和无损伤前精神疾病的患者中具有相似的预测效用。当添加到模型中时，MDD-PRS和NEU-PRS均与PTSD结局无显著相关性。这些发现表明，在mTBI的背景下，PTSD的风险部分受到遗传的影响。他们还提出了一种可能性，即如果使用（可能与其他非遗传预测因子一起使用），个人的PRS可能具有临床可操作性，以表明需要加强随访和早期干预;这种精准医学方法需要进行前瞻性研究。
Many patients with mild traumatic brain injury (mTBI) are at risk for mental health problems such as posttraumatic stress disorder (PTSD). The objective of this study was to determine whether the polygenic risk for PTSD (or for related mental health disorders or traits including major depressive disorder [MDD] and neuroticism [NEU]) was associated with an increased likelihood of PTSD in the aftermath of mTBI. We used data from individuals of European ancestry with mTBI enrolled in TRACK-TBI (n = 714), a prospective longitudinal study of level 1 trauma center patients. One hundred and sixteen mTBI patients (16.3%) had probable PTSD (PCL-5 score ≥33) at 6 months post-injury. We used summary statistics from recent GWAS studies of PTSD, MDD, and NEU to generate polygenic risk scores (PRS) for individuals in our sample. A multivariable model that included age, sex, pre-injury history of mental disorder, and cause of injury explained 7% of the variance in the PTSD outcome; the addition of the PTSD-PRS (and five ancestral principal components) significantly increased the variance explained to 11%. The adjusted odds of PTSD in the uppermost PTSD-PRS quintile was nearly four times higher (aOR = 3.71, 95% CI 1.80–7.65) than in the lowest PTSD-PRS quintile. There was no evidence of a statistically significant interaction between PTSD-PRS and prior history of mental disorder, indicating that PTSD-PRS had similar predictive utility among those with and without pre-injury psychiatric illness. When added to the model, neither MDD-PRS nor NEU-PRS were significantly associated with the PTSD outcome. These findings show that the risk for PTSD in the context of mTBI is, in part, genetically influenced. They also raise the possibility that an individual’s PRS could be clinically actionable if used—possibly with other non-genetic predictors—to signal the need for enhanced follow-up and early intervention; this precision medicine approach needs to be prospectively studied.
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