CSR&D Research Career Scientist Award

我的研究重点是那些被诊断患有创伤后应激障碍（PTSD）的退伍军人

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.