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。每年有800多万17岁以下的儿童遭受某种程度的身体伤害，近50万儿童遭受脑外伤。创伤性应激（Traumatic stress，TS）是由多种病因引起的，包括创伤性损伤（traumatic injury），它与神经生物学应激反应系统以及脑结构和功能的大量变化有关。TBI和TS有重叠的症状，可能会改变类似的核心脑区域的结构和功能，并激活内分泌应激反应系统。我们的初步研究表明，无论是创伤性脑损伤还是颅外损伤，在受伤后持续数年的青年中，多个应激系统存在显著的失调。尽管儿童创伤后TBI和TS的发生率很高，但对创伤后应激反应系统的变化知之甚少。采用纵向、前瞻性队列设计，我们将检查8-15岁儿童和青少年创伤后第一年内应激系统的创伤后变化，这些儿童和青少年因机动车碰撞造成的严重创伤性脑和/或颅外损伤而住院。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;和前额边缘系统电路，测量灰质核的体积或完整性，前额皮质和相关通路。目的1探讨创伤性脑损伤（TBI）或颅外损伤后第一年内对三种应激反应神经生物学系统生物标志物的影响。目的2检查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的关系。这种跨学科和纵向的方法来研究创伤性损伤，检查了多种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联合影响。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、躯体主诉、过度觉醒、焦虑和抑郁。这项新的研究计划有可能促进儿科损伤患者的科学探究和临床护理。更好地了解创伤后慢性发病率的神经生物学机制是设计有针对性的干预措施，以减少发病率和促进恢复至关重要。

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.