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: 8668166
• 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/8668166
• 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）：在抗逆转录病毒疗法的时代，艾滋病毒+个体中的认知缺陷仍然普遍存在，抑制了遵守生命的遵守 治疗和降低生活质量。艾滋病毒感染的妇女报告说，急性压力和慢性压力的暴露率很高，例如由于幼儿创伤的高流行而导致的，以及成年后与HIV疾病管理有关的挑战。这些压力源会导致深远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。该项目的主要目的是制定独立的学术研究计划，该计划解决压力和压力激素对艾滋病毒+妇女认知功能障碍的作用，其最终目标是设计一种降低压力并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）将流行病学和生物统计学方法应用于分析来自大型，纵向的，多部位的HIV+和HIV妇女的认知数据，以研究与HIV状况相关的功能障碍，尤其是在具有创伤后压力障碍的女性中（PTSD）； 2）进行一项药理挑战研究，以更好地了解压力和相关认知功能障碍的基础机制，然后使用新获得的知识来设计干预措施，以增强HIV+女性的认知功能。培训将包括课程工作，指导和在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领域的高级方法方面的实践经验。提出了两项​​研究。第一个将表征艾滋病毒+与艾滋病毒妇女在妇女间艾滋病毒研究（WIHS）中的压力与认知之间的关系，这是美国高危妇女的最大前瞻性多中心队列研究，也是妇女正在进行的艾滋病毒疾病进展最长的研究。基于关于约1000名HIV+女性和未感染的对照的数据的初步结果，我们将检验以下假设：与HIV妇女相比，感知到的压力和PTSD症状严重程度与HIV+的认知障碍更密切相关，并且HIV相关的脆弱性是对涉及预先属于cortex的任务的最明显的压力。第二项研究是在HIV+女性中进行的氢化可的松挑战研究对比（n = 15）和没有（n = 15）的PTSD诊断，以确定前者是否表现出比氢化可的松给药后后者更大的前额叶任务障碍。这两项研究的结果将为设计随后的机械和治疗研究（R01）提供基础，以改善艾滋病毒+妇女的认知，并提交赠款建议以资助这一调查渠道。