Department of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, USA.
Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, Emory University, 55 Park Place NE, 18th Floor, Atlanta, GA, 30303, USA.
Clin Epigenetics. 2021 Jul 12;13(1):140. doi: 10.1186/s13148-021-01128-z.
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) (clinical model) to 0.71 (p = 3.89 × 10); 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.
重度抑郁症已被确认为轻度创伤性脑损伤（mTBI）最常见的诊断性精神并发症。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尚不清楚。最近，基因组和表观遗传因素越来越多地被认为与 TBI 后的恢复有关。
本研究利用重度抑郁症途径中的 DNA 甲基化，以及人口统计学和行为测量（用于临床模型的特征），预测了 110 名儿科 mTBI 患者和 87 名年龄匹配的健康对照组在损伤后四个月的脑震荡后症状负担和生活质量。结果表明，在重度抑郁症途径中加入 DNA 甲基化标志物可以提高生活质量的预测准确性，但不能提高持续性脑震荡后症状负担的预测准确性。具体来说，生活质量的预测准确性（即预测值与观察值之间的相关性）从 0.59（p=1.20×10）（临床模型）提高到 0.71（p=3.89×10）；鉴定的胞嘧啶-磷酸-鸟嘌呤位点主要位于开放海域，映射的基因与几项分子研究中的 TBI 有关。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（具有较大权重）。
本研究强调，抑郁症状的分子和行为表现都在预测儿科 mTBI 后的恢复过程中起着突出作用，这表明迫切需要进一步研究 TBI 引起的抑郁症状，以获得更好的恢复结果。
