Endophenotypes of Persistent Post-Concussive Symptoms in Adolescents: CARE4Kids

青少年持续性脑震荡后症状的内表型：CARE4Kids

• 批准号: 10203603
• 负责人: CHRISTOPHER C GIZA
• 金额: $ 178.59万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-08 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10203603
• 关键词: Accident and Emergency department; Acute; Adolescent; Age; Algorithms; Anxiety; Area Under Curve; Behavioral; Biochemical; Biological; Biological Markers; Blood; Blood flow; Brain Concussion; Brain Injuries; Cardiovascular system; Centers for Disease Control and Prevention (U.S.); Childhood Injury; Chronic; Clinic; Clinical; Common Data Element; Detection; Development; Diagnostic; Dysautonomias; Early identification; Functional disorder; Future; Goals; Gold; Guidelines; Image; Immune; Impairment; Individual; Inflammation; Injury; Lesion; Lipids; Longitudinal cohort study; Measures; Medical; Mental Depression; Migraine; Monitor; Multivariate Analysis; National Institute of Neurological Disorders and Stroke; Nature; Neurobiology; Neurologic; Neurologic Symptoms; Neuropsychology; Neurotransmitters; Outcome; Pain; Phase; Phenotype; Physiological; Physiology; Post-Concussion Syndrome; Prevention; Prevention strategy; Primary Health Care; Public Health; Radiology Specialty; Recovery; Research; Research Project Grants; Resolution; Resources; Sampling; Science; Site; Symptoms; Techniques; Testing; Time; Traumatic Brain Injury; Validation; Youth; base; biological adaptation to stress; biomarker development; blood-based biomarker; cell injury; clinical biomarkers; clinical phenotype; cognitive performance; cohort; common symptom; disability; endophenotype; experience; functional disability; imaging biomarker; improved; mild traumatic brain injury; multidisciplinary; multimodality; neurobehavioral; neuroimaging; novel therapeutics; prediction algorithm; preventive intervention; prognostic; prognostic tool; programs; prospective; recruit; research clinical testing; risk stratification; sex; symptom cluster; trait

PROJECT SUMMARY/ABSTRACT – Research Project Concussion or mild traumatic brain injury (mTBI) is the most common type of acquired brain injury in children and adolescents. While the majority of youth with concussion recover within 2-4 weeks, a substantial subset (15-30%) take longer to recover and develop persistent post-concussive symptoms (PPCS). This group experiences worse function, more pain and seeks a greater amount of medical assessments and treatments. Prolonged impairments in early and middle adolescents (EMA) can result in changes in developmental trajectory and long-term disability. There is no single agreed upon definition for PPCS and predictive algorithms are largely based on nonspecific subjective clinical symptoms. Furthermore, there are currently no good preventive strategies or targeted treatments. It is a major public health challenge to develop objective biological markers that better predict PPCS, which will provide the opportunity for improved prognostication, potential preventive interventions and new therapeutics based on underlying biological mechanisms. It is the central goal of this CARE4Kids Center Without Walls to discover objective autonomic, imaging and blood-based biomarkers that, when integrated with neuropsychological and neurological signs and symptoms, will optimally predict PPCS in EMA. Once identified, these biomarkers and clinical measures will then be validated in a more generalized group and developed into an improved predictive algorithm for PPCS. The linkage of objective biological measures to different clinical phenotypes (termed endophenotypes in this application) will provide a mechanistic understanding of different types of PPCS. It is hypothesized that endophenotypes may share pathobiology with migraine, dysautonomia, anxiety, depression or other symptoms commonly seen in those with PPCS. By understanding the underlying neurobiology of PPCS, it will become possible to develop mechanism- based prevention or treatment measures.

项目概要/摘要-研究项目 脑震荡或轻度创伤性脑损伤（mTBI）是儿童获得性脑损伤最常见的类型 和青少年。虽然大多数患有脑震荡的年轻人在2-4周内恢复， （15-30%）需要更长的时间才能恢复并出现持续的脑震荡后症状（PPCS）。这群 经历更差的功能，更多的疼痛，并寻求更多的医疗评估和治疗。 早期和中期青少年（EMA）的长期损伤可导致发育轨迹的变化 长期残疾。PPCS没有单一的商定定义，预测算法主要是 基于非特异性主观临床症状。此外，目前还没有很好的预防措施。 策略或有针对性的治疗。开发客观的生物标志物是一项重大的公共卫生挑战 更好地预测PPCS，这将为改进预测提供机会， 基于潜在生物学机制的干预和新疗法。这是我们的中心目标 CARE 4Kids Center Without Walls发现客观自主，成像和基于血液的生物标志物 当与神经心理学和神经学体征和症状相结合时， 预测EMA中的PPCS。一旦确定，这些生物标志物和临床措施将在一个更广泛的领域进行验证。 广义群，并发展成为PPCS的改进预测算法。目标联系 对不同临床表型（在本申请中称为内表型）的生物学测量将提供 对不同类型PPCS的机械理解。据推测，内表型可能共享 病理生物学与偏头痛，自主神经功能障碍，焦虑，抑郁或其他症状常见于那些 PPCS。通过了解PPCS的潜在神经生物学，将有可能开发机制- 预防或治疗措施。