Effects of simvastatin on innate and adaptive immunity in major depressive disorder with comorbid obesity: An ancillary study to the randomized controlled SIMCODE trial

辛伐他汀对合并肥胖的重度抑郁症先天免疫和适应性免疫的影响:随机对照 SIMCODE 试验的辅助研究

基本信息

项目摘要

Major depressive disorder (MDD) and obesity are among the most common disorders in the general population and are associated with substantial disease burden and health care costs. Depression and obesity often co-occur and the presence of one increases the risk for developing the other.Converging lines of evidence from epidemiological and clinical studies as well as animal models have implicated inflammation and immune dysfunction in the pathogenesis of both depression and obesity, indicating a putative shared pathobiology. Intriguingly, evidence for an antidepressant effects of statins has emerged from animal models, epidemiological studies, and several small RCTs. These may - at least in part - be due to their pleiotropic effects on the immune system.We have recently received funding for a multicenter trial to test the efficacy of simvastatin as an add-on to escitalopram for patients with comorbid depression and obesity in a double blind, randomized controlled trial. Here, we are now applying for funding to conduct an ancillary study to explore the potential effects of this therapy on immune function in these patients. We propose to test the effects on read-outs of innate immunity (monocyte phenotype, metabolic function, and transcriptional profiles), adaptive immunity (T cell phenotype, metabolic function, and antiviral T cell responses) as well as systemic markers of inflammation (CRP, IL-6, TNF). This study will provide novel insights into the putative mechanisms of statins in depression and help to elucidate the cause effect relationship between markers of immune function and depression severity in patients with comorbid MDD and obesity.
严重抑郁障碍(MDD)和肥胖是普通人群中最常见的疾病之一,与巨大的疾病负担和医疗费用有关。抑郁症和肥胖症经常并存,其中一种的存在增加了患另一种抑郁症的风险。来自流行病学和临床研究以及动物模型的一系列证据表明,炎症和免疫功能障碍与抑郁症和肥胖症的发病机制有关,这表明可能存在共同的病理生物学。有趣的是,他汀类药物抗抑郁作用的证据已经从动物模型、流行病学研究和几个小型随机对照试验中出现。这些可能--至少部分是由于它们对免疫系统的多效性作用。我们最近获得了一项多中心试验的资金,在一项双盲随机对照试验中测试辛伐他汀作为依西妥普兰附件治疗抑郁症和肥胖症患者的疗效。在这里,我们现在正在申请资金进行一项辅助研究,以探索这种疗法对这些患者免疫功能的潜在影响。我们建议测试对先天免疫(单核细胞表型、代谢功能和转录谱)、获得性免疫(T细胞表型、代谢功能和抗病毒T细胞反应)以及全身炎症标记物(CRP、IL-6、TNF)读出的影响。这项研究将为他汀类药物在抑郁症中的作用机制提供新的见解,并有助于阐明MDD和肥胖症患者的免疫功能指标与抑郁严重程度之间的因果关系。

项目成果

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Professor Dr. Manuel A. Friese其他文献

Professor Dr. Manuel A. Friese的其他文献

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{{ truncateString('Professor Dr. Manuel A. Friese', 18)}}的其他基金

Targeting the neurovascular niche in COVID-19
针对 COVID-19 中的神经血管生态位
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    458698659
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    2021
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    --
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    Research Grants
Control of mitochondrial function in neurons by microRNAs during inflammation-induced neurodegeneration
炎症诱导的神经变性过程中 microRNA 对神经元线粒体功能的控制
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    389362063
  • 财政年份:
    2017
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    --
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    Priority Programmes
T cell diversity and plasticity during pregnancy and their contribution to multiple sclerosis disease activity
妊娠期间 T 细胞的多样性和可塑性及其对多发性硬化症活动的贡献
  • 批准号:
    269118981
  • 财政年份:
    2015
  • 资助金额:
    --
  • 项目类别:
    Clinical Research Units
Charakterisierung der CD8+-T-Zellen in der Pathogenese der Multiplen Sklerose
CD8 T 细胞在多发性硬化症发病机制中的表征
  • 批准号:
    73397672
  • 财政年份:
    2008
  • 资助金额:
    --
  • 项目类别:
    Independent Junior Research Groups
Funktionelle Bedeutung CD8-positiver-T-Zellen sowie mikrobieller Faktoren in der Pathogenese der Multiplen Sklerose
CD8阳性T细胞和微生物因子在多发性硬化症发病机制中的功能意义
  • 批准号:
    5426395
  • 财政年份:
    2003
  • 资助金额:
    --
  • 项目类别:
    Research Fellowships
Profiling neurodegeneration of sensory systems in multiple sclerosis
多发性硬化症中感觉系统的神经变性分析
  • 批准号:
    513877247
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Decoding IL-17A-mediated influences on stroke recovery
解码 IL-17A 介导的中风恢复影响
  • 批准号:
    428778375
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
    Research Units
Functional genetics of sex differences in autoimmunity
自身免疫性别差异的功能遗传学
  • 批准号:
    453860947
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
    Research Units
The miR-92a–Cpeb3 network in inflammation-induced neurodegeneration
炎症诱导的神经变性中的 miR-92aâCpeb3 网络
  • 批准号:
    511556502
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
    Research Grants
Proteinopathy in inflammatory neurodegeneration
炎症性神经变性中的蛋白质病
  • 批准号:
    321760974
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
    Research Grants

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A bioluminescent-based imaging probe for noninvasive longitudinal monitoring of CoQ10 uptake in vivo
基于生物发光的成像探针,用于体内 CoQ10 摄取的无创纵向监测
  • 批准号:
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用于治疗胰腺炎的降胆固醇药物:验证具有临床意义的新型治疗靶点和方法
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以前列腺癌为模型的强化降胆固醇干预和抗肿瘤免疫
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    10802975
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The MUltidimenSional phenotyping In Critical care (MUSIC) Consortium: A pathway to precision medicine at the bedside
重症监护 (MUSIC) 多维度表型分析联盟:床边精准医疗的途径
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Evolution and resolution of ARDS molecular phenotypes
ARDS 分子表型的进化和解析
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The role of alpha-aminoadipic acid (2-AAA) in residual CVD risk in T2D
α-氨基己二酸 (2-AAA) 在 T2D 残余 CVD 风险中的作用
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Dysregulated cholesterol homeostasis, caused by lysosomal/autophagy dysfunction, mediates pancreatitis
由溶酶体/自噬功能障碍引起的胆固醇稳态失调可介导胰腺炎
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Biomarkers and subphenotypes predictive of clinical outcomes in patients with COVID-19 related acute respiratory distress syndrome
预测 COVID-19 相关急性呼吸窘迫综合征患者临床结果的生物标志物和亚表型
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Vulnerabilities of MMR-deficient glioblastoma
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Cocaine self-administration and cholesterol metabolism
可卡因自我给药和胆固醇代谢
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