Inflammation, Social Networks, and Depression in Rural Uganda

乌干达农村地区的炎症、社交网络和抑郁症

• 批准号: 10155766
• 负责人: ALEXANDER C TSAI
• 金额: $ 35.91万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-13 至 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10155766
• 关键词: Adult; Africa South of the Sahara; Anti-Inflammatory Agents; Biological; Biological Markers; Budgets; Buffers; C-reactive protein; Caring; Catabolism; Chronic; Clinical Data; Cohort Studies; Communicable Diseases; Data; Disease; Early treatment; Freezing; Future; HIV; HIV antiretroviral; Health; Incidence; Individual; Inflammation; Inflammation Mediators; Inflammatory; Injury; Interleukin-6; Interleukins; Intervention; Investigation; Link; Literature; Major Depressive Disorder; Measures; Mediating; Mediation; Mental Depression; Mental Health; Methods; Mission; Network-based; Outcome; Participant; Pathogenesis; Pathway interactions; Perception; Personal Satisfaction; Plasma; Play; Population; Prevalence; Process; Production; Public Health; Recovery; Research; Resources; Role; Rural; Sampling; Severities; Social Interaction; Social Network; Specimen; Structural Models; Structure; Surveys; TNF gene; Testing; Time; Tryptophan; Tryptophan 2,3 Dioxygenase; Uganda; United States National Institutes of Health; Universities; antiretroviral therapy; biobehavior; biopsychosocial factor; cohort; cytokine; depressive symptoms; design; food insecurity; inflammatory marker; innovation; insight; interest; member; network architecture; novel; psychosocial stressors; rural area; social; social factors; social stigma; theories; treatment response; treatment strategy; years lived with disability

PROJECT SUMMARY Major depressive disorder is one of the top 5 contributors to years lived with disability among adults in sub- Saharan Africa. Numerous studies have suggested a link between social networks and depression, but none have measured actual changes in social network structure in relation to depression or have examined the potential mediating role of inflammation. This is an important gap in the literature because negative social interactions increase production of pro-inflammatory cytokines, and inflammation is believed to play an important role in depression pathogenesis. Our scientific objective is to estimate the causal effect of social networks on depression and to assess the extent to which inflammation causally mediates this effect. The cytokine theory of depression is consistent with our strong preliminary data from rural Uganda showing that: elevated C-reactive protein and interleukin-6 values correlate strongly with depression; reversals in tryptophan catabolism, mediated by the activity of indoleamine 2,3-dioxygenase-1, explain improvements in depression symptom severity over the course of early HIV antiretroviral treatment; and social networks provide a moderating, or “buffering,” effect against the adverse mental health impacts of food insecurity. The proposed study will leverage the resources of an ongoing, whole-population social network cohort study in Mbarara and a long-term partnership with Mbarara University that is presently focused on characterizing the contributions of social networks and HIV stigma to HIV care cascade outcomes. The sample of opportunity includes 3 waves of existing survey data and biological specimens from this whole-population sample; the plasma samples are currently in -80C storage. During the three-year study we propose here, we will test our currently held 3 years of frozen plasma samples for inflammatory markers of interest, and collect an additional 3 years of survey and biomarker data (total N=1,776, T=6). We will accomplish two specific aims: (1) Estimate the causal effect of social networks on depression symptom severity; and (2) assess the extent to which inflammatory activity mediates the causal effect of social networks on depression. Our expected contribution is detailed mechanistic insight into the causal pathways linking social networks, inflammation, & major depressive disorder. Our key innovation is that we will apply state-of-the-art methods of causal inference to whole-population social network cohort data in rural Uganda to identify the causal effect of social networks on depression & the causal mediation effects of inflammation. This contribution will have significant public health impact by providing novel data linking social network structure to depression and therefore inform future social network-based interventions; investigation of inflammatory mediators will inform the use of anti-inflammatory depression treatment strategies or of inflammatory testing to predict depression treatment response.

项目概要 重度抑郁症是亚健康成年人残疾寿命的 5 大诱因之一。 撒哈拉非洲。许多研究表明社交网络与抑郁症之间存在联系，但没有一项研究表明社交网络与抑郁症之间存在联系。 测量了与抑郁症相关的社交网络结构的实际变化，或者研究了 炎症的潜在介导作用。这是文献中的一个重要空白，因为消极的社会 相互作用会增加促炎细胞因子的产生，而炎症被认为发挥着重要作用 在抑郁症发病机制中发挥重要作用。我们的科学目标是估计社会影响的因果影响 抑郁症网络并评估炎症介导这种影响的程度。这 抑郁症的细胞因子理论与我们来自乌干达农村地区的强有力的初步数据一致，表明： C反应蛋白和白细胞介素6值升高与抑郁症密切相关；色氨酸的逆转 由吲哚胺 2,3-双加氧酶-1 活性介导的分解代谢解释了抑郁症的改善 早期艾滋病毒抗逆转录病毒治疗过程中症状的严重程度；和社交网络提供了 缓和或“缓冲”作用，以应对粮食不安全对心理健康的不利影响。拟议的 研究将利用姆巴拉拉正在进行的全民社交网络队列研究的资源 与姆巴拉拉大学建立了长期合作伙伴关系，目前重点关注以下方面的贡献： 社交网络和艾滋病毒耻辱对艾滋病毒护理的级联结果。机会样本包括 3 波 来自整个人口样本的现有调查数据和生物标本；血浆样本是 目前在-80C储存。在我们在这里提出的三年研究期间，我们将测试我们目前举行的三年 冷冻血浆样本的感兴趣的炎症标记物，并收集另外 3 年的调查和 生物标志物数据（总计 N=1,776，T=6）。我们将实现两个具体目标：（1）估计因果效应 关于抑郁症状严重程度的社交网络； (2) 评估炎症活动的程度 介导社交网络对抑郁症的因果影响。我们的预期贡献是详细的机制 深入了解社交网络、炎症和重度抑郁症之间的因果关系。我们的钥匙 创新在于我们将最先进的因果推理方法应用于全民社交网络 乌干达农村地区的队列数据以确定社交网络对抑郁症的因果影响及其因果关系 炎症的中介作用。这一贡献将通过提供新颖的方式对公共卫生产生重大影响 将社交网络结构与抑郁症联系起来的数据，从而为未来基于社交网络的 干预措施；炎症介质的研究将为抗炎抑郁症的使用提供信息 治疗策略或炎症测试来预测抑郁症治疗反应。