Cardiac Electrical Instability in Posttraumatic Stress Disorder: A Twin Study

创伤后应激障碍中的心脏电不稳定：一项双胞胎研究

• 批准号: 9915968
• 负责人: Amit Jasvant Shah
• 金额: $ 7.8万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9915968
• 关键词: 3-Dimensional; Acute; Algorithms; Ambulatory Monitoring; Arrhythmia; Autonomic Dysfunction; Award; Behavior Therapy; Cardiac; Cardiac Electrophysiologic Techniques; Charge; Chronic; Clinical; Clinical Management; Coronary heart disease; Custom; Data; Dizygotic Twins; EKG QRS Complex; Electrocardiogram; Electrophysiology (science); Emotional Stress; Evaluation; Exposure to; Frequencies; Functional disorder; Future; Genetic; Genetic study; High Prevalence; Hour; Individual; International; Investigation; Laboratories; Lead; Link; Machine Learning; Measures; Mentored Patient-Oriented Research Career Development Award; Mentors; Methods; Modeling; Monitor; Monozygotic twins; Morphology; Pathway interactions; Phenotype; Physiological; Post-Traumatic Stress Disorders; Prevalence; Psyche structure; Psychological Stress; Publications; Publishing; Reaction; Research; Resolution; Risk; Risk Factors; Risk stratification; Role; Sampling; Seminal; Stress; Symptoms; Tachyarrhythmias; Testing; Trauma; Twin Multiple Birth; Twin Studies; Ventricular; Ventricular Arrhythmia; Veterans; Viola; Visit; War; Work; acute stress; base; biomedical informatics; cardiovascular risk factor; cohort; design; experience; heart disease risk; heart rate variability; high risk; improved; insight; interest; male; method development; mortality risk; novel; post-traumatic symptoms; programs; recruit; signal processing; sudden cardiac death; traumatic event; traumatic stress; vector

PROJECT SUMMARY/ABSTRACT Posttraumatic stress disorder (PTSD) is a chronic disabling psychiatric condition characterized by a persistent maladaptive reaction to the exposure to severe psychological stress, including trauma re-experiencing, hypervigilance, and hyperarousal. Our group has conducted seminal work to establish PTSD as a risk factor for coronary heart disease and autonomic dysfunction. A major concern, based on these findings, is that PTSD could increases the risk of ventricular arrhythmia and sudden cardiac death (SCD) through autonomic dysregulation. This has important clinical implications on management of cardiovascular risk in PTSD. Two important metrics that are potentially useful for risk stratification are T-wave alternans (TWA) and Morphological Beat Variability (MVB). We have found in preliminary investigations that TWA may be linked to acute stress and PTSD, but additional study is needed. In this R03 application, we seek to collaborate with Dr. Gari Clifford in Biomedical Informatics to create a custom program that measures TWA and MVB with state-of- the-art signal processing in a recently recruited cohort of male veteran twins with high-resolution ECG data. We will also study for genetic influences with twin modeling and the effects of acute stress with laboratory- based trauma reminder challenges. Our aims are to 1) Examine the relationship of PTSD with MVB and TWA a) over 24 hours, and b) during trauma recall challenge; 2) Evaluate the potential role for familial and genetic factors by comparing the within-pair difference in MVB and TWA between monozygotic and dizygotic twin pairs discordant for PTSD. We hypothesize that MVB and TWA will be higher, on average, during a 24 hour period, and will increase during trauma recall challenge in PTSD subjects compared to those without PTSD. In addition, we hypothesize that the relationship of PTSD with MVB and TWA will be stronger within DZ pairs than MZ pairs, implying that there is a common genetic pathway linking PTSD and SCD risk. The development of methods to measure these factors, as well as the study of these important mechanisms, will accelerate Dr. Shah’s progress towards research independence, and help to establish him as an expert in the field of mental stress and SCD.

项目总结/摘要 创伤后应激障碍（PTSD）是一种慢性致残性精神疾病，其特征是持续的 对暴露于严重心理压力的适应不良反应，包括创伤再体验， 过度警觉和过度觉醒我们的小组已经进行了开创性的工作，以确定创伤后应激障碍是一个危险因素 治疗冠心病和植物神经功能紊乱基于这些发现，一个主要的担忧是， 创伤后应激障碍可增加室性心律失常和心源性猝死（SCD）的风险， 自主神经失调这对心血管风险的管理具有重要的临床意义， 创伤后应激障碍对风险分层潜在有用的两个重要指标是T波交替（TWA）和 形态搏动变异性（MVB）。我们在初步调查中发现，环球航空公司可能与 急性应激和创伤后应激障碍，但需要进一步的研究。在R 03申请中，我们寻求与Dr. Gari Clifford在生物医学信息学中创建了一个自定义程序，该程序可以测量TWA和MVB， 最先进的信号处理在最近招募的一组男性退伍军人双胞胎与高分辨率心电图数据。 我们还将研究双胞胎模型的遗传影响和实验室急性应激的影响- 基于创伤提醒的挑战本研究的目的是：1）探讨创伤后应激障碍与MVB和TWA的关系 a）超过24小时，和B）在创伤回忆挑战期间; 2）评估家族和遗传因素的潜在作用 通过比较同卵双生子和异卵双生子MVB和TWA的对内差异，分析影响因素 与创伤后应激障碍不一致我们假设在24小时内，平均而言，MVB和TWA会更高， 并且与没有PTSD的受试者相比，在PTSD受试者的创伤回忆挑战期间将增加。在 此外，我们假设PTSD与MVB和TWA的关系在DZ对中比在DZ对中更强。 MZ对，这意味着有一个共同的遗传途径连接PTSD和SCD风险。的发展 测量这些因素的方法，以及对这些重要机制的研究，将加速博士。 沙阿的进步走向研究的独立性，并帮助建立他作为一个专家在该领域的精神 应力和SCD。