Emotion Regulation Circuitries in Youth with Mild Traumatic Brain Injury.

摘要 精神病发病率是轻度成人中最常见且具有社交障碍的后果之一 创伤性脑损伤（mTBI），但在青少年中的研究很少。根据 mTBI 国际合作 mTBI 中精神疾病发病率的预后和预测仍然是一个挑战。脑震荡后症状有 高度非特异性并且与精神症状显着重叠。事实上，抑郁、焦虑、情绪不稳定， 受伤后易怒是很常见的。然而，mTBI 的病理生理机制与 TBI 后精神症状的后续发作仍不清楚。这种关系是最重要的 在大脑发育研究中的重要性，其中大脑损伤有可能挖掘正常的 参与情绪调节的神经回路的发育。额颞叶边缘不平衡 系统已被提议作为儿科精神病患者情绪失调的神经机制 失调。然而，尚无研究探讨额颞叶边缘病变与癫痫发作之间的关系。 TBI 后精神症状。拟议研究的合理性是额颞叶异常 患有 mTBI 的青少年的边缘区域可能代表了情绪脆弱性的结构基础 调节电路，可能导致 TBI 后精神疾病发病风险增加。的目标 该应用程序是使用多模态神经成像技术来表征大脑结构和功能 受伤后 1 周 200 名青少年的情绪调节回路。五项临床评估将定义 1 年 每个参与者的抑郁症状、焦虑、情绪不稳定和易怒的轨迹。根据现有 文献和我们的初步发现，我们的总体假设是，急性损伤可以通过神经影像学量化 对大脑结构和功能的测量早于 TBI 后精神症状的发生和进程 青少年受伤后长达一年的前瞻性特征。具体来说，该提案旨在 1）检查是否 额颞叶边缘区域 mTBI 相关病变可预测 TBI 后精神症状的严重程度 3 受伤几周后。该提案还旨在 2) 确定预测 1 年的人口和临床风险因素 TBI 后精神症状的轨迹。这种方法是创新的，因为没有研究检查 mTBI 是否 情绪调节回路的相关损伤与 TBI 后精神症状的急性发作有关 患有 mTBI 的青少年。确定 TBI 后精神症状的 1 年轨迹也是创新的 并将允许检查神经影像学测量和临床风险因素的结合使用是否可以有所帮助 预测 mTBI 后 1 年内的这些症状。最后，通过收集青年子样本的第二次扫描 (n=100) mTBI 后 6 个月，我们将检查 6 个月时的神经影像学测量值是否高于神经影像学测量值 受伤时的测量，可以帮助预测 TBI 后精神症状的一年轨迹。这个贡献是 预计意义重大，因为该战略有可能识别出处于危险中的青少年子集。 发生 TBI 后精神疾病的人可能会从早期干预策略中受益。

ABSTRACT Psychiatric morbidity is one of the most common and socially disabling consequences in adults with mild traumatic brain injury (mTBI), yet poorly studied in youth. According to the International Collaboration in mTBI Prognosis, prediction of psychiatric morbidity in mTBI remains a challenge. Post-concussion symptoms are highly aspecific and significantly overlap with psychiatric symptoms. In fact, depression, anxiety, mood lability, and irritability are common after injury. Yet, a clear link between pathophysiologic mechanisms of mTBI and the subsequent onset of post-TBI psychiatric symptoms remains unclear. This relationship is of utmost importance in the study of developing brains, where brain lesions have the potential to mine the normative development of neural circuitries involved in emotional regulation. An imbalance in fronto-temporo-limbic systems has been proposed as a neural mechanism of emotional dysregulation in pediatric psychiatric disorders. Yet, no study has examined the relationship between fronto-temporo-limbic lesions and the onset of post-TBI psychiatric symptoms. The rational for the proposed research is that abnormalities in fronto-temporo- limbic regions in youth with mTBI might represent the structural basis for the vulnerability of emotional regulation circuitries, possibly leading to a heightened risk for post-TBI psychiatric morbidity. The objective of this application is to use multimodal neuroimaging techniques to characterize the brain structure and functioning of emotional regulation circuitries in 200 youth 1 week after injury. Five clinical assessments will define 1-year trajectories of depressive symptoms, anxiety, mood lability and irritability in each participant. Based on the extant literature and our preliminary findings, our overall hypothesis is that acute injury quantifiable with neuroimaging measures of brain structure and functioning predates the onset and course of post-TBI psychiatric symptoms in youth prospectively characterized for up to 1 year after injury. Specifically, this proposal aims to 1) examine if mTBI-related lesions in fronto-temporo-limbic regions predict the severity of post-TBI psychiatric symptoms 3 weeks after injury. This proposal also aims to 2) identify demographic and clinical risk factors predicting 1-year trajectories of post-TBI psychiatric symptoms. This approach is innovative because no study examined if mTBI- related lesions in emotional regulation circuitries relate to the acute onset of post-TBI psychiatric symptoms in youth with mTBI. The identification of 1-year trajectories of post-TBI psychiatric symptoms is also innovative and will allow to examine if the combined use of neuroimaging measures and clinical risk factors can help predict these symptoms up to 1-year after mTBI. Finally, by collecting a second scan in a subsample of youth (n=100) 6 months after mTBI, we will examine if neuroimaging measures at 6-month, more than neuroimaging measures at-injury, can help predict 1-year trajectories of post-TBI psychiatric symptoms. This contribution is anticipated to be significant because this strategy has the potential to identify a subset of youth at-risk for developing post-TBI psychiatric morbidity, who might benefit from early intervention strategies.