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: 10513831
• 负责人: ALEXANDER C TSAI
• 金额: $ 34.21万
• 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 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10513831
• 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; Parameter Estimation; Participant; Pathogenesis; Pathway interactions; Perception; Personal Satisfaction; Plasma; Play; Population; Prevalence; Process; Production; Public Health; Recovery; Research; Resource-limited setting; 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; improved; 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.

项目摘要 重度抑郁症是导致亚健康成年人残疾年数的前5大因素之一， 撒哈拉非洲。许多研究表明，社交网络和抑郁症之间存在联系，但没有一个 已经测量了与抑郁症有关的社会网络结构的实际变化，或者已经检查了 炎症的潜在介导作用。这是文献中的一个重要空白， 相互作用增加促炎细胞因子的产生，并且认为炎症在炎症中起作用。 在抑郁症发病机制中起重要作用。我们的科学目标是估计社会的因果效应 网络上的抑郁症，并评估炎症因果介导这种影响的程度。的 抑郁症的细胞因子理论与我们来自乌干达农村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; 由吲哚胺2，3-双加氧酶-1的活性介导的钙拮抗剂，解释了抑郁症的改善 在早期艾滋病毒抗逆转录病毒治疗过程中， 减轻或“缓冲”粮食不安全对心理健康的不利影响。拟议 这项研究将利用正在姆巴拉拉进行的全人群社交网络队列研究的资源， 与姆巴拉拉大学的长期合作伙伴关系，目前的重点是描述 社交网络和艾滋病毒污名化对艾滋病毒护理的级联结果。机会的样本包括三波 现有的调查数据和生物标本从这个整个人口样本;血浆样本是 目前在-80 ℃储存。在我们这里提出的三年研究期间，我们将测试我们目前持有的三年 冷冻血浆样本用于感兴趣的炎症标志物，并收集额外的3年调查， 生物标志物数据（总N= 1，776，T=6）。我们将实现两个具体目标：（1）估计因果效应， 社交网络对抑郁症症状严重程度的影响;以及（2）评估炎症活动 介导了社交网络对抑郁症的因果影响。我们预期的贡献是详细的机制 深入了解联系社交网络、炎症和重度抑郁症的因果途径。我们的关键 创新之处在于，我们将把最先进因果推理方法应用于整个人群的社会网络 乌干达农村的队列数据，以确定社交网络对抑郁症的因果影响， 炎症的调节作用。这一贡献将通过提供新颖的方法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;炎症介质的调查将告知抗炎抑郁症的使用 治疗策略或炎症测试来预测抑郁症的治疗反应。