Emotion Regulation Circuitries in Youth with Mild Traumatic Brain Injury.

摘要 精神障碍是成人轻症患者最常见和社会残疾的后果之一。 创伤性脑损伤(MTBI)，但在年轻人中研究很少。根据mTBI中的国际合作 预测mTBI患者的精神并发症的预后仍然是一个挑战。脑震荡后的症状是 高度无特异性，并与精神症状显著重叠。事实上，抑郁、焦虑、情绪不稳定， 和易怒在受伤后是很常见的。然而，mTBI的病理生理机制与 随后出现的脑外伤后精神症状仍不清楚。这一关系是至关重要的 在大脑发育研究中的重要性，其中大脑病变有可能挖掘正常的 参与情绪调节的神经回路的发展。额颞部边缘不平衡 系统被认为是儿科精神病患者情绪失调的神经机制 精神错乱。然而，还没有研究检验额 脑外伤后的精神症状。提出这项研究的理由是额颞部的异常- 青少年mTBI的边缘区域可能是情绪易感性的结构基础 调节回路，可能导致创伤性脑损伤后精神疾病的高风险。的目标是 这项应用是使用多模式神经成像技术来表征大脑的结构和功能 200名青年伤后1周的情绪调节回路。五项临床评估将确定一年 每个参与者的抑郁症状、焦虑、情绪不稳定和易怒的轨迹。基于现有的 文献和我们的初步发现，我们的总体假设是急性损伤可以用神经成像来量化 脑结构和功能的测量早于脑外伤后精神症状的出现和病程 青壮年受伤后的预期特征为长达1年。具体地说，这项提案旨在1)审查 额颞部边缘MTBI相关病变可预测脑外伤后精神症状的严重程度3 受伤后几周。这项建议还旨在2)确定人口统计学和临床风险因素，预测1年 脑外伤后精神症状的轨迹。这种方法是创新的，因为没有研究检查mTBI- 情绪调节回路的相关损害与颅脑损伤后精神症状的急性发作有关 患有mTBI的年轻人。对脑外伤后精神症状1年轨迹的识别也是创新的 并将允许检查神经成像测量和临床风险因素的联合使用是否有帮助 这些症状可预测到mTBI后1年。最后，通过在青年样本中收集第二次扫描 (n=100)mTBI后6个月，我们将检查是否在6个月时进行神经成像测量，超过神经成像 损伤时的测量，可以帮助预测脑外伤后精神症状的1年轨迹。这一贡献是 预计将具有重大意义，因为该战略有可能确定高危青年的子集 发展脑外伤后精神疾病，谁可能受益于早期干预策略。

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.