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.

项目总结