Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
School of Public Health, University of California, San Diego, La Jolla, CA, USA.
Transl Psychiatry. 2023 Jan 25;13(1):24. doi: 10.1038/s41398-023-02313-9.
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.
许多轻度创伤性脑损伤 (mTBI) 患者存在心理健康问题的风险，例如创伤后应激障碍 (PTSD)。本研究的目的是确定 PTSD 的多基因风险（或与相关心理健康障碍或特征相关，包括重度抑郁症 [MDD] 和神经质 [NEU]）是否与 mTBI 后 PTSD 的可能性增加有关。我们使用了来自欧洲血统的 mTBI 患者的数据，这些患者参加了 TRACK-TBI（n=714），这是一项针对一级创伤中心患者的前瞻性纵向研究。16.3%（116 名）mTBI 患者在受伤后 6 个月时患有 PTSD（PCL-5 评分≥33）。我们使用了 PTSD、MDD 和 NEU 的最新 GWAS 研究的汇总统计数据，为我们样本中的个体生成了多基因风险评分（PRS）。一个包含年龄、性别、受伤前精神障碍史和损伤原因的多变量模型解释了 PTSD 结果的 7%的方差；加入 PTSD-PRS（和五个祖先主要成分）可将解释的方差显著增加到 11%。在 PTSD-PRS 最高五分位数的 PTSD 调整后的优势比（aOR=3.71，95%CI 1.80-7.65）几乎是最低五分位数的四倍。在 PTSD-PRS 和先前精神障碍史之间没有观察到统计学上显著的交互作用，这表明 PTSD-PRS 在有和没有受伤前精神疾病的个体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 结果无关。这些发现表明，mTBI 背景下的 PTSD 风险在一定程度上受遗传影响。它们还提出了这样一种可能性，即个体的 PRS 如果用于（可能与其他非遗传预测因素一起）提示需要增强随访和早期干预，则可能具有临床可操作性；这种精准医疗方法需要前瞻性研究。
