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，由DSM-5标准A定义，用于诊断创伤后应激障碍（PTSD） 暴露于实际或受到威胁的死亡，严重伤害或性暴力，与增加有关 饮酒障碍（AUD）和PTSD的发展。众所周知，患有PTSD的患者 AUD的风险显着增加。此外，了解开发过程中AUD的风险， 特别是在青少年中至关重要，因为早期饮酒是终生酒精的最高风险因素之一 瘾。当前的建议旨在进一步探索青少年的AUD和PTSD的关系 通过关注AUD和/或PTSD开发的生物学预测因子，暴露于急性创伤。简而言之，500 青少年将在急诊室，医院诊所或 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（大学 德克萨斯州医疗部（UTMB）会员医院）。使用新兴统计技术和机器 基于学习的分析，我们将确定预测性：1。基因组和表观基因组学，2。炎症和3。 AUD和PTSD风险的心理生理生物标志物。尽管已经确定了几个风险因素 在成年人开发这两种疾病中，青少年的数据相对较少。家庭和 双胞胎研究提供了对AUD和PTSD遗传风险和PTSD的估计分别为50％和30-40％。我们 将利用这些疾病的最新AUD和PTSD多基因风险因素分数以及表观基因组学 分析。以前的工作已经在AUD和PTSD中实施了炎症反应的改变，我们 将在创伤后立即评估这一点。最后，自主神经系统的度量 （包括皮肤电导响应[SCR]，心率和心率变异性[HRV]通过心电图学 [ECG]）和中枢神经系统（通过肌电图评估[EMG]评估的声学惊吓反应） 在创伤后医疗清除后，将立即评估反应性。使用最先进的统计数据 建模，我们将确定AUD和PTSD及其相互关系的生物学预测因子。这些数据将是 用于开发新颖的工具来预测哪些接触创伤的青少年可能会发展AUD和/或 PTSD，允许在开发的关键时期进行早期干预。