Reconsidering the reasons for heightened inflammation in major depressive disorder
Reconsidering the reasons for heightened inflammation in major depressive disorder
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DOI：
10.1016/j.jad.2020.12.109
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发表时间：
2021-01-07
影响因子：
6.6
通讯作者：
Powell, Timothy R.
中科院分区：
文献类型：
--
作者：
Palmos, Alish B.;Chung, Raymond;Powell, Timothy R.
背景：循环中促炎性标志物的增加与重性抑郁症（MDD）反复相关。然而，目前尚不清楚炎症是否代表MDD的因果机制，或者这种关联是否受到混杂因素如体重指数（BMI）的影响：为了更好地了解这种复杂的关系，我们在人群队列中生成MDD和BMI的多基因风险评分（PRS），并试图隔离这些潜在的风险因素对成年炎症的影响。收集外周血样本作为南东伦敦社区健康研究的一部分，在该研究中，我们使用基于多重ELISA的技术生成MDD和BMI的个性化PRS并量化炎症标志物。我们进行了线性回归，以探讨抑郁症和BMI炎症标记物levels.Results的PRS的影响：出35炎症标记物，我们发现了一个名义上的影响抑郁症的PRS对白细胞介素-10。我们还发现BMI对9种炎症标志物有显著的积极影响，其中两种受影响最大的标志物白细胞介素-6（IL-6）和C反应蛋白（CRP）也可以通过BMI PRS进行名义预测。局限性：本研究采用了中等样本量的横断面设计。我们的研究结果表明，可能没有共同的遗传机制导致MDD和更高的炎症标志物水平。然而，BMI和成人CRP和IL-6水平之间可能存在共同的遗传病因。因此，BMI的多基因风险评分可能是成年期炎症水平升高的有用指标。
Background: Increased circulating pro-inflammatory markers have repeatedly been associated with major depressive disorder (MDD). However, it remains unclear whether inflammation represents a causal mechanism for MDD, or whether the association is influenced by confounding factors such as body mass index (BMI).Methods: To better understand this complex relationship, we generated polygenic risk scores (PRS) for MDD and BMI in a population cohort and attempted to isolate the impact these potential risk factors have on adulthood inflammation. Peripheral blood samples were collected as part of the South East London Community Health study, where we generated individualized PRS for MDD and BMI and quantified inflammatory markers using multiplex ELISA-based technology. We performed linear regressions to investigate the effects of PRS for MDD and BMI on inflammatory marker levels.Results: Out of 35 inflammatory markers, we found a nominal effect of PRS for MDD on interleukin-10. We also found a significant positive effect of BMI on nine inflammatory markers, of which the two most strongly affected markers, interleukin-6 (IL-6) and C-reactive protein (CRP), were also nominally predicted by BMI PRS.Limitations: The study utilized a cross-sectional design with a moderately sized sample.Conclusions: Our findings suggest there may not be a shared genetic mechanism contributing to MDD and higher inflammatory marker levels. However, there may be shared genetic etiology between BMI and adulthood levels of CRP and IL-6. Therefore, polygenic risk scores for BMI may represent a useful indicator for heightened levels of inflammation in adulthood.