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

 描述（由申请人提供）：创伤暴露是高艾滋病毒感染的个人之前和之后的感染。据报道，在3000万艾滋病毒感染者（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，与侵入性和恐惧性记忆以及闪回和创伤事件的噩梦有关，对大多数受害者的生活，以及日常日常活动的显著损害。PTSD带来的挑战在PLWH中被放大，因为PTSD导致抗逆转录病毒（ART）药物依从性差，增加了病毒学失败的几率。PTSD也会增加性风险行为，增加传播的风险。PTSD的神经生物学在过去的二十年里一直是一个深入研究的主题;然而，在HIV的背景下，对PTSD的神经生物学的了解很少。有两个系统被反复证明是导致PTSD症状的原因，一个是作为惊吓反应基础的神经回路，另一个是控制身体对压力反应的内分泌轴。因此，本申请将检验HIV加重PTSD症状并增强女性PTSD的潜在神经生物学相关性的中心假设。研究创伤和PTSD与HIV相互作用的一个限制是PLWH中创伤暴露的可能性很高，因此很难确定一个对照组进行严格的实验分析。为了解决这一问题，目前的工作将比较类似程度的创伤暴露对艾滋病毒感染者和艾滋病毒高危人群的影响。本研究选择的人群将从NIH资助的妇女机构间HIV研究（WIHS）的亚特兰大站点招募，该研究从NIH资助的Grady创伤项目（GTP）的重叠招募人群中招募。GTP研究了近10年来主要是非洲裔美国人人群中创伤暴露的影响，重点是PLWH风险最高的人群之一，即南部非洲裔美国妇女。目前的项目利用了这两项既定研究的专门知识，并协同结合了各自的专业领域，使所产生的工作在尽可能短的时间内产生最大的影响。在拟议的项目中，我们将研究恐惧消退的临床，生理和神经内分泌相关性，作为创伤相关症状的中间表型。我们将使用维度方法进行症状分析（目标1），创新的生物行为评估（目标2）和尖端的生物分子技术（目标3），以更好地了解PTSD与HIV共病的病理生理学。创伤过程和HIV感染之间相互作用的生物学相关性的识别有可能导致更好的治疗方法，在药理学和行为干预方面，最终导致改善ART依从性，减少风险行为，并丰富生活质量。

 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.