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.

项目概要/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 对严重心理压力的适应不良反应，包括重新经历创伤， 我们的小组开展了开创性工作，将创伤后应激障碍 (PTSD) 确定为危险因素。 基于这些发现，对于冠心病和自主神经功能障碍来说，一个主要问题是。 PTSD 可能通过以下方式增加室性心律失常和心源性猝死 (SCD) 的风险 自主神经失调对心血管风险的管理具有重要的临床意义。 PTSD 可能对风险分层有用的两个重要指标是 T 波交替 (TWA) 和 我们在初步调查中发现 TWA 可能与形态心跳变异性 (MVB) 有关。 急性压力和创伤后应激障碍（PTSD），但需要进行更多研究，在此 R03 应用中，我们寻求与 Dr. 合作。 生物医学信息学领域的 Gari Clifford 创建了一个自定义程序，用于测量 TWA 和 MVB 的现状 对最近招募的一组男性退伍军人双胞胎进行最先进的信号处理，并提供高分辨率心电图数据。 我们还将通过双胞胎模型研究遗传影响，并通过实验室研究急性压力的影响 我们的目标是 1) 检查 PTSD 与 MVB 和 TWA 的关系。 a) 超过 24 小时，以及 b) 在创伤回忆挑战期间 2) 评估家族和遗传的潜在作用； 通过比较同卵双胞胎和异卵双胞胎之间 MVB 和 TWA 的配对内差异来影响因素 我们勇敢地说，在 24 小时内，MVB 和 TWA 会更高， 与没有 PTSD 的受试者相比，PTSD 受试者在创伤回忆挑战期间会增加。 此外，我们发现 PTSD 与 MVB 和 TWA 的关系在 DZ 对内比 MZ 配对，意味着有一个共同的遗传途径将 PTSD 和 SCD 风险联系起来。 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的研究。 沙阿在研究独立方面取得的进展，并帮助他成为心理领域的专家 压力和 SCD。