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.

项目总结 严重抑郁障碍是导致亚健康成年人残疾寿命的前五大因素之一。 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这两者之间存在联系 衡量了与抑郁相关的社交网络结构的实际变化，或检查了 炎症的潜在中介作用。这是文学中的一个重要缺口，因为负面的社会 相互作用会增加促炎细胞因子的产生，而炎症被认为在 在抑郁症发病机制中起重要作用。我们的科学目标是评估社会的因果关系 并评估炎症在多大程度上对这种影响进行因果调节。这个 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反应蛋白和白介素6的升高与抑郁症密切相关；色氨酸的逆转 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的症状严重程度；和社会网络提供 缓解或“缓冲”粮食不安全对心理健康的不利影响。建议数 研究将利用姆巴拉拉正在进行的全人口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，目前侧重于描述 社会网络和艾滋病毒污名对艾滋病毒护理的连锁结果。机会的样本包括3波 现有的调查数据和来自该全人群样本的生物样本；血浆样本为 目前在零下80C的存储中。在我们提出的为期三年的研究中，我们将测试我们目前持有的三年 冰冻血浆样本的感兴趣的炎症标志物，并收集另外3年的调查和 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 社会网络对抑郁症状严重程度的影响；以及(2)评估炎症活动的程度 调节社会网络对抑郁的因果效应。我们的预期贡献是详细的机械性的 洞察社会网络、炎症和严重抑郁障碍之间的因果关系。我们的钥匙 创新之处在于，我们将把最先进的因果推理方法应用于全种群社会网络 乌干达农村地区确定社会网络对抑郁的因果影响的队列数据 炎症的调节作用。这一贡献将通过提供新的 将社交网络结构与抑郁联系起来的数据，并因此告知未来基于社交网络的 干预；对炎症介质的研究将告知抗炎抑制的使用 治疗策略或炎性试验以预测抑郁症治疗反应。