Tramatic Stress After Pediatric Injury: Neurobiological Influences

描述（由申请人提供）：创伤性损伤是一个主要的儿科公共卫生问题。每年，超过800万17岁以下的儿童遭受某种身体伤害，近50万儿童遭受脑外伤（TBI）。包括创伤性损伤在内的各种病因的创伤性应激（TS）与神经生物学应激反应系统以及大脑结构和功能的无数变化有关。TBI和TS有重叠的症状，可能改变相似脑核心区域的结构和功能，并激活内分泌应激反应系统。我们的初步研究表明，在创伤性脑损伤或颅外损伤的青少年中，多种应激系统的显著失调在损伤后持续数年。尽管儿童外伤后TBI和TS的发生率很高或同时发生，但对应激反应系统的创伤后变化知之甚少。采用纵向前瞻性队列设计，我们将研究8-15岁的儿童和青少年在机动车碰撞中发生严重的颅脑和/或颅外损伤后住院的创伤后第一年应激系统的变化。我们将检查来自每个应激系统的生物标志物如下：下丘脑-垂体-肾上腺轴，唾液皮质醇；去甲肾上腺素能系统、唾液1-淀粉酶、心率和心率变异性；以及前额叶边缘回路，测量灰质核、前额叶皮层和相关通路的体积或完整性。目的1研究创伤性损伤对脑外伤或颅外损伤后第一年三种应激反应性神经生物系统生物标志物的影响。目的2研究这些应激反应系统的生物标志物在多大程度上介导损伤特征与受TBI和/或TS影响的纵向认知、神经行为和心理健康结果之间的关系。这种跨学科和纵向的创伤性损伤研究方法研究了多个应激反应系统和大脑变化对TBI和TS人群常见的关键结果的共同影响。这些结果包括注意力效率降低、记忆功能障碍、抑制性控制障碍、躯体抱怨、过度觉醒、焦虑和抑郁。这个新颖的研究项目有潜力推进儿科损伤患者的科学探究和临床护理。更好地了解导致创伤性损伤后慢性发病率的神经生物学机制对于设计有针对性的干预措施以降低发病率和促进康复至关重要。

DESCRIPTION (provided by applicant): Traumatic injury is a major pediatric public health concern. Annually, over 8 million children under the age of 17 years sustain some physical injury and nearly half a million children sustain traumatic injury to the brain (TBI). Traumatic stress (TS) from a variety of etiologies, including traumatic injury, has been linked to myriad changes in the neurobiological stress response systems and to brain structure and function. TBI and TS have overlapping symptoms, may alter the structure and function of similar core brain regions, and activate endocrine stress response systems. Our preliminary studies suggested significant dysregulation of multiple stress systems in youth with either TBI or extracranial injury that persisted years after injury. Despite the high occurrence and co-occurrence of TBI and TS following pediatric injury, little is known about post-traumatic changes in stress-responsive systems. Using a longitudinal, prospective cohort design, we will examine post- traumatic changes to stress systems during the first year following traumatic injury in children and adolescents ages 8-15 who are hospitalized following significant traumatic brain and/or extracranial injuries sustained in motor vehicle collisions. We will examine biomarkers from each stress system as follows: the hypothalamic- pituitary-adrenal axis, salivary cortisol; the noradrenergic system, salivary 1-amylase, heart rate, and heart rate variability; and prefrontal-limbic circuitry, measures of volume or integrity of gray matter nuclei, prefrontal cortex, and related pathways. Aim 1 investigates the impact of traumatic injury on the biomarkers of the three stress-responsive neurobiological systems during the first year after TBI or extracranial injury. Aim 2 examines the degree to which biomarkers of these stress-responsive systems mediate the relation of injury characteristics to longitudinal cognitive, neurobehavioral, and psychological health outcomes affected by TBI and/or TS. This interdisciplinary and longitudinal approach to the study of traumatic injury examines the joint influences of changes in multiple stress-response systems and the brain on key outcomes that are common to TBI and TS populations. These outcomes include reduced attentional efficiency, memory dysfunction, inhibitory dyscontrol, somatic complaints, hyperarousal, anxiety, and depression. This novel program of research has the potential to advance both scientific inquiry and clinical care of pediatric injury patients. Better understanding of the neurobiological mechanisms contributing to chronic morbidity following traumatic injuries is essential to design targeted interventions to reduce morbidity and enhance recovery.