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

非裔美国女性应激障碍与艾滋病毒共存的生物学机制

基本信息

批准号：
9975221
负责人：
Tanja Jovanovic
金额：
$ 35.14万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-12 至 2022-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9975221
关键词：
Address Adherence Adult African American Anti-Retroviral Agents Area Behavior Therapy Biological Biology Brain Chronic Clinical Control Groups DNA Dimensions Discrimination Disease Progression Doctor of Medicine Doctor of Philosophy Economic Burden Endocrine Extinction (Psychology)Failure Fright Functional disorder Funding Geographic Locations Glucocorticoid Receptor Goals HIV HIV Infections High Prevalence Impairment Incidence Individual Infection Inflammation Knowledge Lead Learning Life Measures Memory Mental disorders Methods Molecular Multiple Trauma Neurobiology Neurosecretory Systems Nightmare Participant Pathology Pharmaceutical Preparations Pharmacology Phenotype Physiological Population Populations at Risk Positioning Attribute Post-Traumatic Stress Disorders Process Psychophysiology Quality of life Recording of previous events Regulation Reporting Research Risk Risk Behaviors Sampling Site Startle Reaction Stress Symptoms System Techniques Testing Therapeutic Intervention Time Trauma United States National Institutes of Health Urban Population Woman Women’s Interagency HIV Study Work biobehavior cognitive process comorbidity conditioned fear conditioning design effective intervention experimental analysis high risk immune function improved innovation neural circuit neuropathology neurophysiology neuropsychiatric disorder public health relevance receptor function recruit relating to nervous system response sexual risk behavior stress disorder transmission process trauma exposure traumatic event treatment adherence virology

项目摘要

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.

描述（由申请人提供）： HIV 感染者在感染前和感染后遭受创伤的情况均较高据报道，在 3000 万人中，创伤后应激障碍 (PTSD) 的发病率约为 5% - 15%。 HIV 感染者 (PLWH) 是一种严重使人衰弱、与压力相关的精神疾病，与侵入性和恐惧性记忆以及创伤事件的闪回和噩梦有关。创伤后应激障碍 (PTSD) 会影响感染者的生活，并严重损害患者的日常活动，因为创伤后应激障碍 (PTSD) 会导致抗逆转录病毒 (ART) 药物的依从性较差，从而增加病毒学失败的几率，从而增加性风险行为。过去二十年来，PTSD 的神经生物学一直是研究的热点；然而，人们对 HIV 背景下的 PTSD 神经生物学了解甚少。 PTSD 症状是惊吓反应背后的神经回路和控制身体对压力的反应的内分泌轴，因此，当前的应用将测试 HIV 加剧 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。研究创伤和创伤后应激障碍 (PTSD) 与 HIV 之间的相互作用的一个原因是 PLWH 中创伤暴露的可能性很高，因此很难确定对照组进行严格的实验分析。为了解决先前的局限性，当前的工作将比较类似的影响。艾滋病毒感染者和艾滋病毒高危人群之间的创伤暴露水平。本研究选择的人群将从 NIH 资助的妇女机构间艾滋病毒研究 (WIHS) 的亚特兰大站点招募，该研究从与 NIH 重叠招募的人群中招募。资助的格雷迪创伤项目 (GTP) 近 10 年来一直在研究创伤暴露对主要非裔美国人的影响，拟议的工作重点关注感染者风险最高的人群之一——南部地区。当前的项目利用了这两项既定研究的专业知识，并协同结合了她们各自的专业领域，以在尽可能短的时间内产生最大的影响。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）、创新的生物行为评估（目标 2）和尖端技术。生物分子技术（目标 3），以更好地了解与 HIV 共存的 PTSD 的病理生理学，识别创伤过程和 HIV 感染之间相互作用的生物学相关性，有可能在药理学和治疗方面带来更好的治疗方法。行为干预最终可以提高 ART 依从性、减少危险行为并提高生活质量。