CSR&D Research Career Scientist Award

我的研究重点是那些被诊断为创伤后应激障碍(PTSD)的退伍军人，这是一场战争- 相关疾病。我是最早记录个人之间的敌意、暴力和愤怒的人之一(无论是男人还是 女性)患有创伤后应激障碍。我也是第一批观察到创伤后应激障碍患者自我报告和 被诊断出有更多的身体健康问题，包括心血管疾病。这项工作导致了 在理解行为和心理生理机制方面的几个重大贡献 增加创伤后应激障碍患者健康不良的风险，包括创伤后应激障碍患者 较高的动态心率和血压，较低的压力感受器敏感性，以及较低的心率变异性。我 已经表明患有创伤后应激障碍的人睡眠时间和睡眠效率降低，这可能导致 降低动态心率变异性水平，这些影响发生在那些 发展成创伤后应激障碍。我已经研究了一些机制，这些机制可以解释流行率上升与 患有创伤后应激障碍的吸烟者对尼古丁的依赖程度更高。我评估了尼古丁和吸烟行为对 患有和不患有创伤后应激障碍的吸烟者的脉冲前抑制和声学惊厥。我的研究表明 患有创伤后应激障碍的吸烟者对创伤线索的反应有更高的渴望和负面影响，吸烟 香烟加不加尼古丁都能减轻症状，但改善效果是短暂的，而且这种情绪 对创伤刺激的反应与吸烟复发的时间较短有关。我开发了一种新的移动健康 干预措施在减少创伤后应激障碍和其他疾病患者中的吸烟方面显示出巨大的希望 精神障碍。我与我的同事们合作，证明全球定位监测可能是 最终在干预吸烟者方面是有用的。我目前正在扩大对移动保健方法的评估 在美国国立卫生研究院资助的精神分裂症吸烟者治疗发展基金和功绩审查资助的 无家可归吸烟者的随机临床试验。我和我的指导者有几个正在审查的拨款申请 将这项工作扩展到同时改变两个行为目标(例如，戒酒和吸烟； 戒烟和增加体力活动；戒烟和大麻)。这其中的每一个 这些方法可能会帮助退伍军人解决关键的健康问题。因为我在创伤后应激障碍机制和 开发注册表的经验，我被邀请领导VA VISN 6心理遗传学实验室 2006年在疾病研究、教育和临床中心任职，自成立以来我一直担任这一职务 VISN 6 MIRECC目前的登记已经收集了近4000名回国退伍军人的DNA和RNA。我的 团队和我已经发表了一项关于创伤后应激障碍病例和非病例的全基因组关联研究(Gwas)，以及 评估了创伤后应激障碍的几个候选基因。我还代表MIRECC参加了国家创伤后应激障碍遗传学 和MIRECC样本已被收录在一个非常大规模的国际地球科学联合会手稿中 (总共超过21,000个样本)和一份甲基化手稿。在收集、提取和生成数据之后 在过去的10年里，我们目前很高兴能评估MIRECC中的甲基化和基因表达 采样以及参与与该联盟相关的荟萃分析。我最近被批准了 作为退伍军人百万计划(MVP)的Durham VAMC现场PI，这将导致额外的 MIRECC Genetics Core和MVP相关项目之间富有成效的合作，重点是创伤后应激障碍和 滥用药物。我将继续我关于创伤后应激障碍和并发症的研究计划。

My research focus is on Veterans who have been diagnosed with posttraumatic stress disorder (PTSD), a war- related illness. I was among the first to document hostility, violence and anger among individuals (both men and women) with PTSD. I was also among the first researchers to observe that individuals with PTSD self-report and are diagnosed with more physical health problems, including cardiovascular disorders. This work has led to several significant contributions in understanding the behavioral and psychophysiological mechanisms that may contribute to increased risk of poor health among persons with PTSD, including that individuals with PTSD have higher ambulatory heart rate and blood pressure, lower baroreceptor sensitivity, and lower heart rate variability. I have shown that individuals with PTSD have reduced sleep duration and sleep efficiency, which may lead to reduced levels of ambulatory heart rate variability, and that these effects occur early in the trajectory of those who develop PTSD. I have investigated mechanisms that may explain the association between increased prevalence and higher nicotine dependence in smokers with PTSD. I evaluated the effect of nicotine and smoking behavior on prepulse inhibition as well as acoustic startle among smokers with and without PTSD. My research has shown that smokers with PTSD experience higher craving and negative affect in response to trauma cues, that smoking cigarettes with or without nicotine reduces symptoms, but the ameliorative effect is short lived, and that emotional reactivity to trauma stimuli is related to a shorter time to smoking relapse. I have developed a novel mobile health intervention that has shown tremendous promise toward reducing smoking among those with PTSD and other psychiatric disorders. I have worked with my colleagues to demonstrate that global positioning monitoring may be ultimately useful in intervening with smokers. I am currently expanding the evaluation of mobile health approaches in a NIH-funded treatment development grant for smokers with schizophrenia and a merit review-funded randomized clinical trial in homeless smokers. My mentees and I have several grant applications under review to extend this work to changing two behavioral targets simultaneously (e.g., quitting alcohol and smoking cigarettes; quitting smoking and increasing physical activity; and quitting smoking tobacco and marijuana). Each of these approaches may help Veterans with key health problems. Because of my expertise in PTSD mechanisms and experience with developing registries, I was invited to lead the Genetics Laboratory of the VA VISN 6 Mental Illness Research, Education, and Clinical Center in 2006, and I have served in that role since the inception of the VISN 6 MIRECC. The current registry has collected DNA and RNA among nearly 4,000 returning Veterans. My team and I have published a genome-wide association study (GWAS) with PTSD cases and non-cases, and evaluated several candidate genes in PTSD. I have also represented the MIRECC in the national PTSD Genetics Consortium, and the MIRECC samples have been included in a very large scale Consortium GWAS manuscript (more than 21,000 total samples) and a methylation manuscript. After collecting, extracting, and generating data over the past 10 years, we are currently excited to evaluate methylation and gene expression in the MIRECC sample as well as participate in the meta-analyses associated with the Consortium. I have recently been approved to serve as the Durham VAMC site PI for the VA Million Veteran Project (MVP), and this should lead to additional productive collaborations between the MIRECC Genetics Core and MVP-related projects focused on PTSD and substance abuse. I will continue my research program on PTSD and co-morbid conditions.