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

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。

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.