Prediction of Alcohol Use Disorder and PTSD After Trauma in Adolescents

青少年创伤后酒精使用障碍和创伤后应激障碍 (PTSD) 的预测

• 批准号: 10367692
• 负责人: CHARLES B NEMEROFF
• 金额: $ 94.79万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-05 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10367692
• 关键词: Acceleration; Accident and Emergency department; Acoustics; Acute; Address; Adolescence; Adolescent; Adult; Age; Aging; Alcohol dependence; Anti-Inflammatory Agents; Autonomic nervous system; Biological; Biological Markers; Blood; Brain; Cessation of life; Child; Clinic; Clinics and Hospitals; Cognitive; Collection; Cross-Sectional Studies; DNA Methylation; DSM-V; Data; Data Set; Development; Diagnosis; Disease; Early Intervention; Electrocardiogram; Electromyography; Emotional; Enrollment; Epigenetic Process; Exhibits; Exposure to; Family Study; Galvanic Skin Response; Genetic Risk; Genomics; Heart Rate; Heritability; Hospitals; Individual; Inflammation; Inflammatory; Inflammatory Response; Injury; Interferon Type II; Longitudinal Studies; Machine Learning; Measurement; Measures; Medical; Medical center; Modeling; Neuraxis; Neurobiology; Outcome; Pathogenesis; Pathway interactions; Patients; Phenotype; Physiological; Post-Traumatic Stress Disorders; Prospective Studies; Psychophysiology; RNA; Reflex action; Research; Risk; Risk Factors; Role; Sampling; Site; Startle Reaction; Statistical Models; Stress; TNF gene; Techniques; Texas; Time; Tissues; Trauma; Twin Studies; Universities; Untranslated RNA; Validation; Work; alcohol risk; alcohol use disorder; austin; base; biosignature; cohort; comorbidity; cytokine; design; disorder risk; drinking onset; early onset; epidemiology study; epigenomics; follow-up; genomic predictors; heart rate variability; high risk; indexing; molecular marker; novel; polygenic risk score; post-trauma; predictive marker; predictive modeling; predictive tools; prospective; response; sexual violence; socioeconomics; statistics; tool; transcriptomics; trauma centers; trauma exposure

PROJECT SUMMARY Acute trauma, defined by the DSM-5 criterion A for the diagnosis of post-traumatic stress disorder (PTSD) as exposure to actual or threatened death, serious injury or sexual violence, is associated with an increase in the development of both Alcohol Use Disorder (AUD) and PTSD. It is well established that patients with PTSD have a markedly increased risk for AUD. Furthermore, understanding risk for AUD during development, particularly in adolescents is critical, as early onset drinking is one of the highest risk factors for lifetime alcohol addiction. This current proposal seeks to further explore the relationship of AUD and PTSD in adolescents exposed to acute trauma by focusing on biological predictors of AUD and/or PTSD development. In brief, 500 adolescents will be studied in the immediate aftermath of trauma in emergency departments, hospital clinics or psychiatric settings in Austin, Texas (Dell Children’s Medical Center) and Galveston, Texas (University of Texas Medical Branch (UTMB) affiliated hospitals). Using emerging statistical techniques and machine learning-based analytics, we will identify predictive: 1. Genomic and epigenomic, 2. Inflammatory, and 3. Psychophysiological biomarkers of risk for AUD and PTSD. Although several risk factors have been identified in adults for the development of these two disorders, relatively little data is available in adolescents. Family and twin studies have provided estimates of genetic risk for AUD and PTSD of 50% and 30-40%, respectively. We will utilize the latest AUD and PTSD polygenic risk factor scores for these disorders, together with epigenomic analysis. Previous work has implicated alterations in inflammatory response in both AUD and PTSD and we will assess this in the immediate aftermath of the trauma. Finally, measures of autonomic nervous system (including skin conductance response [SCR], heart rate and heart rate variability [HRV] via electrocardiography [ECG]) and central nervous system (acoustic startle response assessed via electromyography [EMG]) reactivity will be assessed immediately after post-trauma medical clearance. Using state of the art statistical modeling, we will identify biological predictors of AUD and PTSD and their interrelationship. These data will be used to develop novel tools to predict which adolescents exposed to trauma will likely develop AUD and/or PTSD, allowing for early intervention at this critical time in development.

项目摘要 急性创伤，根据DSM-5创伤后应激障碍（PTSD）诊断标准A定义为： 暴露于实际或威胁的死亡、严重伤害或性暴力， 酒精使用障碍（AUD）和PTSD的发展。创伤后应激障碍患者 患AUD的风险显著增加。此外，了解开发过程中AUD的风险， 特别是在青少年中是至关重要的，因为早发性饮酒是终生饮酒的最高风险因素之一。 成瘾本研究旨在进一步探讨青少年AUD与PTSD的关系 通过关注AUD和/或PTSD发展的生物学预测因素，暴露于急性创伤。简而言之， 青少年将在急诊室、医院诊所或其他医疗机构接受创伤后立即进行研究。 德克萨斯州奥斯汀（戴尔儿童医疗中心）和德克萨斯州加尔维斯顿（德克萨斯大学）的精神病机构 德克萨斯州医疗分支（UTMB）附属医院）。利用新兴的统计技术和机器 基于学习的分析，我们将确定预测：1.基因组学和表观基因组学，2。炎症，3。 AUD和PTSD风险的心理生理学生物标志物尽管已经确定了几个风险因素， 在成年人中，这两种疾病的发展，在青少年中的数据相对较少。家庭和 双胞胎研究估计AUD和PTSD的遗传风险分别为50%和30- 40%。我们 将利用这些疾病的最新AUD和PTSD多基因风险因素评分，以及表观基因组 分析.以前的研究表明，AUD和PTSD的炎症反应发生了改变，我们认为， 将在创伤发生后立即评估这一点。最后，自主神经系统的测量 （包括通过心电图的皮肤电导反应[SCR]、心率和心率变异性[HRV] [心电图]）和中枢神经系统（通过肌电图[EMG]评估的声音惊吓反应） 将在创伤后体检合格后立即评估反应性。使用最先进的统计技术 模型，我们将确定AUD和PTSD的生物学预测因子及其相互关系。这些数据将 用于开发新的工具，以预测哪些青少年暴露于创伤可能会发展AUD和/或 创伤后应激障碍，允许在这个发展的关键时刻进行早期干预。