Genetic Contributions of Inflammation to Depression.
Genetic Contributions of Inflammation to Depression.
复制标题
DOI：
10.1038/npp.2016.169
复制
发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
本文通过对2000年至2016年期间发表的所有论文进行系统综述，描述了免疫基因遗传变异和mRNA表达对抑郁症风险、严重程度和抗抑郁治疗反应的影响。我们的研究结果主要基于病例对照研究，表明常见的遗传变异和基因表达途径参与免疫激活和抑郁症。复制最多且最相关的遗传变异包括白细胞介素（IL）-1β、IL-6、IL-10、单核细胞趋化蛋白-1、肿瘤坏死因子-α、C-反应蛋白和磷脂酶A2基因的多态性。此外，增加的血液细胞因子mRNA表达（特别是IL-1β）确定患者不太可能对常规抗抑郁药有反应。然而，即使是最重复的发现也存在不一致的结果，不仅在研究之间，而且在遗传变异的免疫效应和对抑郁症的影响之间。我们发现的证据表明，这些不一致的结果可以解释，至少部分，由抑郁症免疫表型的异质性，环境影响和基因×环境的相互作用，以及复杂的接口的遗传变异与基因表达。事实上，一些最有力的发现已经在用干扰素-α治疗的背景下发展成抑郁症的患者中获得，干扰素-α是一种广泛使用的在炎症背景下模拟抑郁症的模型。通过GWAS和转录组学，进一步的“组学”方法最终将揭示免疫基因之间的相互作用，它们的表达和环境的影响，在抑郁症的发病机制。
This paper describes the effects of immune genes genetic variants and mRNA expression on depression's risk, severity, and response to antidepressant treatment, through a systematic review on all papers published between 2000 and 2016. Our results, based largely on case–control studies, suggest that common genetic variants and gene-expression pathways are involved in both immune activation and depression. The most replicated and relevant genetic variants include polymorphisms in the genes for interleukin (IL)-1β, IL-6, IL-10, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, C-reactive protein, and phospholipase A2. Moreover, increased blood cytokines mRNA expression (especially of IL-1β) identifies patients that are less likely to respond to conventional antidepressants. However, even for the most replicated findings there are inconsistent results, not only between studies, but also between the immune effects of the genetic variants and the resulting effects on depression. We find evidence that these discrepant findings may be explained, at least in part, by the heterogeneity of the depression immunophenotype, by environmental influences and gene × environment interactions, and by the complex interfacing of genetic variants with gene expression. Indeed, some of the most robust findings have been obtained in patients developing depression in the context of treatment with interferon-alpha, a widely used model to mimic depression in the context of inflammation. Further ‘omics' approaches, through GWAS and transcriptomics, will finally shed light on the interaction between immune genes, their expression, and the influence of the environment, in the pathogenesis of depression.
登录
查看更多内容
炎症激活与忧郁症主要抑郁症的住院患者的单核细胞中糖皮质激素受体α/β表达比降低有关。
影响因子：
6.8
作者：
Carvalho LA;Bergink V;Sumaski L;Wijkhuijs J;Hoogendijk WJ;Birkenhager TK;Drexhage HA
通讯作者：
Drexhage HA
影响因子：
6.8
作者：
Ancelin ML;Farré A;Carrière I;Ritchie K;Chaudieu I;Ryan J
通讯作者：
Ryan J
影响因子：
11
作者：
Bosker, F. J.;Hartman, C. A.;Nolen, W. A.
通讯作者：
Nolen, W. A.
影响因子：
3.3
作者：
Clerici, Mario;Arosio, Beatrice;Altamura, A. Carlo
通讯作者：
Altamura, A. Carlo
影响因子：
6.6
作者：
Chocano-Bedoya PO;Mirzaei F;O'Reilly EJ;Lucas M;Okereke OI;Hu FB;Rimm EB;Ascherio A
通讯作者：
Ascherio A