Effects of Stress and Stress Hormones on Cognition in HIV-Infected Women

描述(申请人提供)：在联合抗逆转录病毒治疗的时代，认知缺陷在艾滋病毒患者中仍然普遍存在，抑制了对拯救生命的坚持 治疗和降低生活质量。感染艾滋病毒的妇女报告暴露在急性和慢性压力源中的比率很高，例如儿童早期创伤的高流行率，以及成年后艾滋病毒疾病管理方面的挑战。这些应激源可能导致深刻和持续的负面生理和心理后果，包括认知缺陷和脑功能障碍。该项目的主要目标是开发一个独立的学术研究计划，解决压力和压力荷尔蒙在艾滋病毒女性认知功能障碍中的作用，最终目标是设计一种降低压力和改善认知的干预措施。这项为期四年的培训和研究计划包括：1)应用流行病学和生物统计学方法分析来自艾滋病毒和艾滋病毒妇女的大型、纵向、多地点队列的认知数据，以研究与艾滋病毒状况有关的功能障碍，特别是在患有创伤后应激障碍(PTSD)的妇女中；以及2)进行药理学挑战研究，以更好地了解压力和相关认知功能障碍的机制，然后利用新获得的知识设计干预措施，以增强艾滋病毒妇女的认知功能。培训将包括在流行病学、生物统计学、药理学挑战研究和艾滋病毒背景下的干预科学方面的课程作业、指导和实践经验。提出了两项研究。第一项研究将在女性机构间艾滋病毒研究(WIHS)中描述艾滋病毒与艾滋病毒之间的压力和认知之间的关系-女性机构间艾滋病毒研究(WIHS)是美国最大的针对高危女性的前瞻性多中心队列研究，也是正在进行的关于女性艾滋病毒疾病进展的最长时间的研究。基于对大约1000名HIV女性和未感染对照的数据的初步结果，我们将检验这样一种假设，即感知压力和PTSD症状严重程度与HIV女性的认知障碍更密切相关，并且HIV相关的应激易感性在涉及前额叶皮质的任务中最为明显。第二项研究是在HIV女性中进行的氢化可的松挑战研究，比较有PTSD诊断的(n=15)和没有PTSD诊断的(n=15)，以确定前者在使用氢化可的松后是否表现出比后者更大的额叶前任务障碍。这两项研究的结果将为设计后续的机制和治疗研究(R01)以改善艾滋病毒妇女的认知提供基础，并提交赠款提案以资助这一调查路线。

DESCRIPTION (provided by applicant): Cognitive deficits remain prevalent among HIV+ individuals in the era of combination antiretroviral therapies, inhibiting adherence to life-saving treatments and lowering quality of life. HIV-infected women report high rates of exposure to acute and chronic stressors such as those resulting from the high prevalence of early childhood trauma as well as challenges related to HIV disease management in adulthood. These stressors can lead to profound and sustained negative physiological and psychological consequences including cognitive deficits and brain dysfunction. The primary goal of this project is to develop an independent scholarly program of research that addresses the role of stress and stress hormones on cognitive dysfunction among HIV+ women, with the ultimate objective of designing an intervention that lowers stress and improves cognition. This four- year program of training and research includes: 1) application of epidemiological and biostatistical methods to analysis of cognitive data from a large, longitudinal, multi-site cohort of HIV+ and HIV- women to study dysfunction associated with HIV status, especially among women with post-traumatic stress disorder (PTSD); and 2) conducting a pharmacological challenge study to better understand the mechanisms underlying stress and related cognitive dysfunction, and then using newly acquired knowledge to design an intervention to enhance cognitive function among HIV+ women. Training will include coursework, mentoring, and practical experience in advanced methods in epidemiology, biostatistics, pharmacological challenge studies, and intervention science in the context of HIV. Two studies are proposed. The first will characterize relationships between stress and cognition in HIV+ vs. HIV- women in the Women's Interagency HIV Study (WIHS), the largest prospective multicenter cohort study of at-risk women in the U.S. and the longest ongoing study of HIV disease progression in women. Based on preliminary results from data on ~1000 HIV+ women and uninfected controls, we will test the hypothesis that perceived stress and PTSD symptom severity are more strongly related to cognitive impairment in HIV+ than HIV- women, and that HIV-associated vulnerability to stress is most evident on tasks involving the prefrontal cortex. The second study is a hydrocortisone challenge study among HIV+ women contrasting those with (n=15) and without (n=15) a PTSD diagnosis to determine whether the former group shows greater prefrontal task impairment than the latter following hydrocortisone administration. Results of these two studies will provide a foundation for designing subsequent mechanistic and treatment studies (R01s) to improve cognition among HIV+ women, and submission of grant proposals to fund this line of inquiry.