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

压力和压力激素对艾滋病毒感染女性认知的影响

• 批准号: 8531356
• 负责人: Leah Helane Rubin
• 金额: $ 16.25万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-15 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8531356
• 关键词: Acute; Address; Adherence; Adrenal Glands; Adult; Applications Grants; Area; Attention; Attenuated; Behavioral inhibition; Biometry; Biostatistical Methods; Brain; Brain region; Characteristics; Child Sexual Abuse; Chronic; Chronic stress; Cognition; Cognitive; Cognitive deficits; Cohort Studies; Data; Diagnosis; Disease; Disease Management; Disease Progression; Enrollment; Epidemiologic Methods; Epidemiology; Exposure to; Family; Foundations; Functional disorder; Funding; Future; Glucocorticoid Receptor; Glucocorticoids; Goals; HIV; High Prevalence; Hippocampus (Brain); Hormonal; Hormones; Hydrocortisone; Hypothalamic structure; Impaired cognition; Impairment; Individual; Intervention; Intervention Studies; Interview; Knowledge; Lactation; Lead; Life; Link; Longitudinal Studies; Measures; Mediating; Mediator of activation protein; Memory; Mentors; Methods; Morbidity - disease rate; Nerve Degeneration; Neurobiology; Neurocognitive; Neurosecretory Systems; Oxytocin; Participant; Pathway interactions; Patient Self-Report; Performance; Personal Satisfaction; Physiological; Pituitary Gland; Placebos; Post-Traumatic Stress Disorders; Prefrontal Cortex; Pregnancy; Process; Psyche structure; Public Health; Quality of life; Recording of previous events; Reporting; Research; Research Training; Risk; Role; Sampling; Science; Severities; Site; Stress; Structure; Symptoms; Testing; Trail Making Test; Training; Training Programs; Trauma; Treatment Cost; Woman; antiretroviral therapy; base; behavior measurement; biological adaptation to stress; clinical Diagnosis; cognitive function; cohort; density; design; early childhood; effective therapy; experience; flexibility; hypothalamic-pituitary-adrenal axis; improved; men; mortality; pediatric trauma; post-traumatic stress; programs; prospective; psychologic; response; stress management; stressor; therapy design; treatment adherence

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.

描述（由申请人提供）：在联合抗逆转录病毒疗法时代，认知缺陷在 HIV+ 个体中仍然普遍存在，抑制了对挽救生命的坚持 治疗和降低生活质量。感染艾滋病毒的妇女报告说，她们遭受急性和慢性压力源的比例很高，例如由于幼儿时期创伤的高发率以及与成年期艾滋病毒疾病管理相关的挑战而造成的压力。这些压力源可能导致深远且持续的负面生理和心理后果，包括认知缺陷和大脑功能障碍。该项目的主要目标是开发一个独立的学术研究计划，研究压力和压力激素对艾滋病毒阳性女性认知功能障碍的作用，最终目标是设计一种减轻压力和改善认知的干预措施。这个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来分析来自大型、纵向、多地点的 HIV+ 和 HIV- 女性队列的认知数据，以研究与 HIV 状态相关的功能障碍，特别是患有创伤后应激障碍（PTSD）的女性； 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，以增强艾滋病毒阳性女性的认知功能。培训将包括艾滋病毒背景下流行病学、生物统计学、药理学挑战研究和干预科学先进方法的课程作业、指导和实践经验。提出了两项​​研究。第一个研究将描述女性机构间艾滋病毒研究 (WIHS) 中 HIV+ 与 HIV- 女性的压力和认知之间的关系，WIHS 是美国最大的针对高危女性的前瞻性多中心队列研究，也是持续时间最长的女性 HIV 疾病进展研究。基于约 1000 名 HIV 阳性女性和未感染对照者的数据的初步结果，我们将检验这一假设：与 HIV 阴性女性相比，HIV 阳性女性感知到的压力和 PTSD 症状严重程度与认知障碍的相关性更强，并且与 HIV 相关的压力脆弱性在涉及前额皮质的任务中最为明显。第二项研究是一项针对 HIV+ 女性的氢化可的松挑战研究，对比那些患有 PTSD 诊断的女性 (n=15) 和没有 (n=15) PTSD 诊断的女性，以确定在给予氢化可的松后，前一组是否比后者表现出更大的前额任务损伤。这两项研究的结果将为设计后续机制和治疗研究（R01s）奠定基础，以改善艾滋病毒阳性女性的认知，并提交拨款提案来资助这一研究。