Biological Mechanisms of Stress Disorders Co-Morbid with HIV in African American Women

 描述(由申请人提供)：在感染之前和之后，艾滋病毒感染者的创伤暴露程度都很高。据报道，在3000万艾滋病毒携带者(PLWH)中，创伤后应激障碍(PTSD)的发病率约为5%-15%。创伤后应激障碍是一种严重衰弱的、与压力相关的精神疾病，与侵入性和恐惧的记忆以及闪回、创伤事件的噩梦有关(S饰)，并对日常生活造成严重损害。PTSD带来的挑战在PLWH中被放大，因为PTSD导致对抗逆转录病毒(ART)药物的依从性差，增加了病毒学失败的几率。创伤后应激障碍还会增加性行为风险，增加传播的风险。在过去的二十年里，创伤后应激障碍的神经生物学一直是一个密集的研究主题；然而，在艾滋病毒的背景下，对创伤后应激障碍的神经生物学的了解很少。有两个系统被反复证明是导致创伤后应激障碍症状的原因，这两个系统是作为惊吓反应基础的神经回路和控制身体对压力的反应的内分泌轴。因此，目前的应用将检验核心假设，即艾滋病毒加剧了女性创伤后应激障碍的症状，并增强了潜在的神经生物学相关性。研究创伤和创伤后应激障碍与艾滋病毒的相互作用的一个限制是，在PLWH内暴露于创伤的可能性很高，这使得很难确定用于严格实验分析的对照组。为了解决之前的限制，目前的工作将比较PLWH和艾滋病毒高危人群之间类似水平的创伤暴露的影响。这项研究选择的人群将从美国国立卫生研究院资助的女性机构间艾滋病毒研究(WIHS)的亚特兰大站点招募，该研究从NIH资助的Grady Trauma Project(GTP)的重叠招募人群中招募人员。近10年来，GTP一直在研究创伤暴露对以非裔美国人为主的人群的影响，并将拟议的工作重点放在PLWH最危险的人群之一，南部非洲裔美国女性。目前的项目利用这两项既定研究中的专门知识，并协同结合各自的专门知识领域，在尽可能短的时间内使所产生的工作产生最大影响。在拟议的项目中，我们将研究恐惧消退作为创伤相关症状的中间表型的临床、生理和神经内分泌相关性。我们将使用维度方法进行症状分析(目标1)、创新生物行为评估(目标2)和尖端生物分子技术(目标3)，以更好地了解创伤后应激障碍与艾滋病毒共病的病理生理学。确定创伤过程和艾滋病毒感染之间相互作用的生物学相关性有可能在药物和行为干预方面带来更好的治疗方法，最终导致改善抗逆转录病毒治疗的依从性，减少危险行为，并提高生活质量。

 DESCRIPTION (provided by applicant): Trauma exposure is high in HIV-infected individuals both prior and subsequent to infection. The incidence of post-traumatic stress disorder (PTSD) has been reported to be between approximately 5% - 15% among the 30 million people living with HIV (PLWH). PTSD is a severely debilitating, stress-related psychiatric illness associated with intrusive and fearful memories as well as flashbacks, and nightmares of the traumatic event(s) for much of the victims' lives, and significant impairment in routine daily activities. Th challenges presented by PTSD are magnified in PLWH because PTSD leads to poor adherence to antiretroviral (ART) medications, increasing the odds of virologic failure. PTSD also increases sexual risk behaviors, increasing the risk of transmission. The neurobiology of PTSD has been a topic of intense study over the past two decades; however, there is minimal understanding of the neurobiology of PTSD within the context of HIV. Two systems that have been repeatedly documented to drive PTSD symptoms are the neural circuitry that underlies the startle response and the endocrine axis that controls the body's response to stress. Therefore, the current application will test the central hypothesis that HIV exacerbates PTSD symptoms and augments underlying neurobiological correlates of PTSD in women. One limitation to studying the interaction of trauma and PTSD with HIV is the high likelihood of trauma exposure within PLWH, making it difficult to identify a control group for rigorous experimental analysis. In order to address this previous limitation, the current work will compare the impact of similar levels of trauma exposure between PLWH and individuals at high risk for HIV. The population selected for this study will be recruited from the Atlanta site of the NIH-funded Women's Interagency HIV Study (WIHS) which recruits from a population with overlapping recruitment for the NIH-funded Grady Trauma Project (GTP). The GTP has studied the impact of trauma exposure in a predominantly African American population for nearly 10 years focusing the proposed work on one of the most at-risk populations of PLWH, southern African-American women. The current project leverages the expertise in these two established studies and synergistically combines their individual areas of expertise positioning the generated body of work for maximum impact in the shortest amount of time possible. In the proposed project, we will examine the clinical, physiological, and neuroendocrine correlates of fear extinction as an intermediate phenotype of trauma-related symptoms. We will use dimensional approaches to symptom analyses (Aim 1), innovative biobehavioral assessments (Aim 2), and cutting-edge biomolecular techniques (Aim 3) in order to better understand the pathophysiology of PTSD co-morbid with HIV. The identification of the biological correlates of interactions among trauma processes and HIV infection has the potential to lead to better treatment approaches in terms of both pharmacological and behavioral interventions ultimately leading to improved ART adherence, reduced risk behaviors, and an enriched quality of life.