Psycho-neuro-immune Mechanisms Linking Stigma and Discrimination to Carotid Plaque Formation in Persons living with HIV

将耻辱和歧视与艾滋病毒感染者颈动脉斑块形成联系起来的心理神经免疫机制

• 批准号: 10762603
• 负责人: Roger Christopher McIntosh
• 金额: $ 70.89万
• 依托单位: UNIVERSITY OF MIAMI CORAL GABLES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10762603
• 关键词: Adult; Age; Amygdaloid structure; Anterior; Anti-Inflammatory Agents; Anti-Retroviral Agents; Area; Area Under Curve; Atherosclerosis; Autonomic Pathways; Brain; Brain region; Carotid Artery Plaques; Case Series; Cellular Phone; Chronic; Complex; Detection; Discrimination; Ecological momentary assessment; Ethnic Origin; Functional Magnetic Resonance Imaging; Future; Gender; Genes; Genetic Transcription; HIV; HIV Infections; Health; Heart failure; Immune; Individual; Inflammation; Inflammatory; Insula of Reil; Interdisciplinary Study; Interleukin-6; Intervention; Knowledge; Lead; Link; Lymphocyte; Lymphoid Tissue; Measures; Mediating; Mediation; Mediator; Methods; Modeling; Morphology; Neuroimmune; Neuroimmunomodulation; Outcome Study; Participant; Pathway interactions; Patient Self-Report; Peripheral Blood Mononuclear Cell; Persons; Phenotype; Procedures; Process; Prospective Studies; Race; Recording of previous events; Regimen; Research; Resolution; Role; Salivary; Sex Orientation; Stigmatization; Stress; System; Testing; Time; Viral Load result; afferent nerve; aged; atherosclerosis risk; biobehavior; blood oxygen level dependent; calcification; cardiovascular disorder risk; cardiovascular health; cholinergic; cohort; coronary plaque; cytokine; design; ethnic minority; experience; follow-up; gender minority; heart rate variability; immune function; indexing; innovation; intersectionality; marginalization; monocyte; mortality; multidisciplinary; neural; perceived discrimination; peripheral blood; portability; psychosocial; racial minority; response; sexual minority; social; social relationships; social stigma; time use; ultrasound

Abstract: Persons living with HIV experience constant stigma and discrimination. The project objective is to model the impact of the psychosocial experiences of stigma/discrimination on the complex interactions between multiple systems (neural, immune, and autonomic) that give rise to atherosclerotic processes in the context of treated chronic HIV-infection. This project assembles a multi-disciplinary team that will decipher the complexity of these interactions within a cohort of 150 racially, ethnically, and sexually diverse persons living with HIV (PWH) between the ages of 35-55 years that have stable anti-retroviral regimens and detectable viral loads without history of heart failure. The study aims to test two separate psycho-neuro-immune mediation models for experiences of social rejection and discrimination on carotid plaque formation measured through high resolution ultrasound. In the first model, using an interactive functional magnetic resonance imaging (fMRI) paradigm, change from pre- to post-task peripheral blood monocyte activation and expression of IL-6 will be tested as a mediator of the association between activation of threat-sensitive brain regions to social rejection and carotid plaque formation. In the second model, 7-day salivary IL-6 expression will be tested as mediator for the association of 7-day ecological momentary assessments (EMA) of everyday experiences of discrimination with carotid plaque formation. The reliability of these models of putative psycho-neuro-immune mechanisms in predicting carotid plaque burden will be assessed at baseline and 3-month follow-up. The study further aims to evaluate the potential mitigating role of the acetyl-cholinergic anti-inflammatory pathway on carotid plaque formation by testing whether an index of vagal-mediated heart rate variability (HRV) moderates of the associations of neural activation to rejection/discrimination (Aim 1) and naturalistic rejection/discrimination experiences (Aim 2) with change in proinflammatory cytokine expression. The long-term objectives of this study are two-fold. First, to elucidate the relationships amongst these biobehavioral determinants of carotid plaque formation in PWH, who are traditionally stigmatized and discriminated due to intersectionality of their race, ethnicity, gender, health, and sexual orientation status. The second long-term objective is to evaluate whether vagal-mediated HRV has a mitigating effect and thus serve as a target for future biobehavioral interventions for atherosclerotic CVD in PWH that have traditionally been socially marginalized, stigmatized and discriminated.

翻译后摘要：艾滋病毒感染者经历不断的耻辱和歧视。项目目标是 模拟羞辱/歧视的心理社会经验对以下因素之间复杂相互作用的影响： 多个系统（神经，免疫和自主神经）在动脉粥样硬化的背景下引起动脉粥样硬化过程， 治疗慢性HIV感染。这个项目汇集了一个多学科的团队，将破译的复杂性， 在一个由150名不同种族、民族和性别的艾滋病毒感染者（PWH）组成的队列中， 年龄在35-55岁之间，具有稳定的抗逆转录病毒治疗方案和可检测的病毒载量， 心力衰竭史。该研究旨在测试两种不同的心理-神经-免疫调解模型， 高分辨率测量颈动脉斑块形成的社会排斥和歧视经历 超声.在第一个模型中，使用交互式功能磁共振成像（fMRI）范例， 从任务前到任务后的外周血单核细胞活化和IL-6表达的变化将被测试为 威胁敏感脑区对社会排斥反应的激活与颈动脉 斑块形成在第二个模型中，将测试7天唾液IL-6表达作为免疫调节剂。 对每天遭受歧视的经历进行为期7天的生态瞬时评估， 颈动脉斑块形成。这些假定的心理神经免疫机制模型的可靠性， 将在基线和3个月随访时评估预测颈动脉斑块负荷。该研究还旨在 评价乙酰胆碱能抗炎通路对颈动脉斑块的潜在缓解作用 通过测试迷走神经介导的心率变异性（HRV）指数是否调节了 神经激活与拒绝/歧视（目标1）和自然主义拒绝/歧视的关联 经验（目的2）与促炎细胞因子表达的变化。本研究的长期目标 是双重的。首先，阐明颈动脉斑块的这些生物行为决定因素之间的关系 威尔斯亲王医院的儿童，由于种族的交叉性，传统上受到污名化和歧视， 种族、性别、健康和性取向状况。第二个长期目标是评估 迷走神经介导的HRV具有缓解作用，因此可作为未来生物行为干预的目标， 动脉粥样硬化性心血管疾病在PWH传统上被社会边缘化，污名化和歧视。