Major depression has been recognized as the most commonly diagnosed psychiatric complication of mild traumatic brain injury (mTBI). Moreover, major depression is associated with poor outcomes following mTBI; however, the underlying biological mechanisms of this are largely unknown. Recently, genomic and epigenetic factors have been increasingly implicated in the recovery following TBI. This study leveraged DNA methylation within the major depression pathway, along with demographic and behavior measures (features used in the clinical model) to predict post-concussive symptom burden and quality of life four-month post-injury in a cohort of 110 pediatric mTBI patients and 87 age-matched healthy controls. The results demonstrated that including DNA methylation markers in the major depression pathway improved the prediction accuracy for quality of life but not persistent post-concussive symptom burden. Specifically, the prediction accuracy (i.e., the correlation between the predicted value and observed value) of quality of life was improved from 0.59 (p = 1.20 × 10–3) (clinical model) to 0.71 (p = 3.89 × 10–5); the identified cytosine-phosphate-guanine sites were mainly in the open sea regions and the mapped genes were related to TBI in several molecular studies. Moreover, depression symptoms were a strong predictor (with large weights) for both post-concussive symptom burden and pediatric quality of life. This study emphasized that both molecular and behavioral manifestations of depression symptoms played a prominent role in predicting the recovery process following pediatric mTBI, suggesting the urgent need to further study TBI-caused depression symptoms for better recovery outcome.

中文翻译：

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重度抑郁通路下的 DNA 甲基化可预测儿科轻度创伤性脑损伤后 4 个月的儿科生活质量

重度抑郁症已被公认为轻度创伤性脑损伤 (mTBI) 最常诊断的精神并发症。此外，重度抑郁症与 mTBI 后的不良预后相关；然而，其潜在的生物学机制在很大程度上是未知的。最近，基因组和表观遗传因素越来越多地参与 TBI 后的恢复。本研究利用重度抑郁通路中的 DNA 甲基化，以及人口统计和行为测量（临床模型中使用的特征）来预测一组 110 名儿童 mTBI 患者的脑震荡后症状负担和受伤后四个月的生活质量和 87 名年龄匹配的健康对照。结果表明，在重度抑郁症通路中加入 DNA 甲基化标志物可以提高生活质量的预测准确性，但不会改善持续的脑震荡后症状负担。具体来说，生活质量的预测准确度（即预测值与观察值之间的相关性）从0.59（p = 1.20 × 10-3）（临床模型）提高到0.71（p = 3.89 × 10-5） ; 确定的胞嘧啶-磷酸-鸟嘌呤位点主要位于公海区域，并且在多项分子研究中，映射的基因与 TBI 相关。此外，抑郁症状是脑震荡后症状负担和儿科生活质量的强预测因子（权重较大）。