Examining a Biopsychosocial Model of Neurocognitive Health for HIV-positive Sexual Minority Men

项目摘要/摘要 自艾滋病高峰期以来，神经认知障碍(NCI)对HIV+人群的影响不成比例 艾滋病危机。尽管现代抗逆转录病毒疗法大大延长了寿命，但总体而言 艾滋病毒相关神经认知障碍(HAND)的流行率三十年来一直保持稳定。有性 少数族裔男性(SMM)在美国所有艾滋病毒诊断病例中占大多数 流行病。然而，很少有研究探讨SMM可能相应地被过度代表的概念 在受非传染性疾病影响的高比例艾滋病毒感染者中。此外，对手部病因学的理解是 目前有限，这阻碍了经验支持的预防和治疗的发展 手中的策略。研究表明，HIV感染的慢性炎症作用将HIV+ NCI风险较高的个人，但尽管普遍易患神经炎，约有一半 的艾滋病毒携带者在一生中表现出标准的认知功能，这表明个人水平 背景因素是认知风险和弹性的基础。慢性压力也与 神经炎症，通过促炎细胞因子的增加。建立在符号学理论和 少数族裔压力，这项调查基于一种新的假设，即社会结构性共同因素(例如， 贫困、创伤)与少数民族压力(即与个人心理压力相关的慢性心理压力 性别认同)，以减少认知储备(即，神经元对损伤的弹性)。此外，我们 假设慢性高水平的炎性细胞因子代表潜在的致病机制 少数族裔压力通过这一途径对认知健康产生负面影响。因此，该项目侧重于三个目标： (1)为了检验这一假设，NCI风险会随着心理压力(即少数民族压力)的增加而增加 艾滋病毒+SMM报告的社会结构综合因素(例如，低教育、无家可归)；(2)审查 少数群体压力和社会结构共同脆弱性对非传染性疾病风险的交互影响；以及(3)评估 促炎细胞因子(如IL-6)升高在两种疾病之间假说关联中的中介作用 少数族裔压力与NCI风险。建议的项目将嵌入一项更大的研究(R01MH114735，PI： Rendina)，在此称为父项目，该项目正在积极招募250名艾滋病毒+SMM来审查 少数民族和艾滋病毒相关压力对心理、行为和免疫健康结果的作用。这个 提议的项目将在母项目现有的神经认知测试单元上增加一项评估，以允许 以更细微地了解艾滋病毒+SMM的认知健康概况。研究和培训 指导这项提议的计划是精心制定的，以优化我正在进行的博士培训经历 并促进我作为一名未来独立研究科学家的发展。

PROJECT SUMMARY/ABSTRACT Neurocognitive impairment (NCI) has disproportionately impacted the HIV+ population since the height of the AIDS crisis. Though modern antiretroviral therapy has afforded vast improvements in longevity, the overall prevalence of HIV-associated neurocognitive disorders (HAND) has remained stable for three decades. Sexual minority men (SMM) have comprised the majority of all HIV diagnoses in the U.S. for the duration of the epidemic. However, few studies have explored the notion that SMM may be correspondingly overrepresented in the high proportion of HIV+ individuals impacted by NCI. Moreover, understanding of HAND etiology is currently limited, which has hindered the development of empirically supported prevention and treatment strategies for HAND. Research suggests that the chronic inflammatory action of HIV infection places HIV+ individuals at a higher risk for NCI, but despite common vulnerability to neuroinflammation, approximately half of HIV+ individuals exhibit normative cognitive function across the lifespan, suggesting that individual-level contextual factors underlie cognitive risk and resiliency. Chronic stress has also been associated with neuroinflammation, via increases in pro-inflammatory cytokines. Building upon theories of syndemics and minority stress, this investigation is based on a novel hypothesis that socio-structural syndemic factors (e.g., poverty, trauma) additively interact with minority stress (i.e., chronic psychological stress related to one’s sexual identity) to diminish cognitive reserve (i.e., neuronal resilience against injury). Furthermore, we hypothesize that chronically high levels of inflammatory cytokines represent a potential causative mechanism through which minority stress negatively impacts cognitive health. As such, the project focuses on three aims: (1) to test the hypothesis the NCI risk will increase with the number of psychological (i.e., minority stress) and socio-structural syndemic (e.g., low education, homelessness) factors reported by HIV+SMM; (2) examine the interactive impact of minority stress and socio-structural syndemic vulnerabilities on NCI risk; and (3) assess the mediating role of elevated pro-inflammatory cytokines (e.g., IL-6) in the hypothesized association between minority stress and NCI risk. The proposed project will be embedded into a larger study (R01MH114735, PI: Rendina), referred to herein as the parent project, which is actively enrolling 250 HIV+ SMM to examine the role of minority and HIV-related stress on psychological, behavioral, and immunological health outcomes. The proposed project will add one assessment to the parent project’s existing neurocognitive test battery to allow for a more nuanced understanding of the cognitive health profile of HIV+ SMM. The research and training plans guiding this proposal have been carefully crafted to optimize my ongoing doctoral training experiences and foster my development as a future independent research scientist.