Replicable and Coupled Changes in Innate and Adaptive Immune Gene Expression in Two Case-Control Studies of Blood Microarrays in Major Depressive Disorder.
Replicable and Coupled Changes in Innate and Adaptive Immune Gene Expression in Two Case-Control Studies of Blood Microarrays in Major Depressive Disorder.
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DOI：
10.1016/j.biopsych.2017.01.021
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发表时间：
2018-01-01
影响因子：
10.6
通讯作者：
Bullmore ET
中科院分区：
文献类型：
--
作者：
Leday GGR;Vértes PE;Richardson S;Greene JR;Regan T;Khan S;Henderson R;Freeman TC;Pariante CM;Harrison NA;MRC Immunopsychiatry Consortium;Perry VH;Drevets WC;Wittenberg GM;Bullmore ET
外周炎症通常与重度抑郁症（MDD）相关，抑郁症的免疫学生物标志物仍然是研究的焦点。我们使用了来自两项独立的MDD病例对照研究的全血微阵列数据：葛兰素史克高血压病特异性靶点识别计划[GSK-HiTDiP]研究（113名患者和57名健康对照受试者）和Janssen-Brain Resource Company研究（94名患者和100名对照受试者）。全基因组差异基因表达分析（18，863个探针）导致每个研究中每个基因的p值。贝叶斯方法确定了最大的p值阈值（q = 0.025）与两项研究中差异表达的基因数量的两倍相比，偶然的病例对照差异的数量。两项研究中共有165个基因差异表达，倍数变化方向一致。MDD中过度表达的90个基因（或UP基因）显著富集了对感染的免疫应答，集中在与先天免疫相关的基因共表达网络的模块中，并包括在单核细胞、单核细胞衍生的树突状细胞和中性粒细胞中具有相关表达的基因簇。相比之下，MDD中75个低表达基因（或DOWN基因）与适应性免疫反应相关，包括在T细胞、自然杀伤细胞和成红细胞中表达相关的基因簇。与此一致，UP基因过表达的MDD患者也有DOWN基因表达不足（两项研究中相关性> 0.70）。MDD可复制地与外周先天免疫系统的促炎激活相关，再加上适应性免疫系统的相对失活，表明转录生物标志物对抑郁症患者免疫分层的潜力。
Peripheral inflammation is often associated with major depressive disorder (MDD), and immunological biomarkers of depression remain a focus of investigation. We used microarray data on whole blood from two independent case-control studies of MDD: the GlaxoSmithKline–High-Throughput Disease-specific target Identification Program [GSK-HiTDiP] study (113 patients and 57 healthy control subjects) and the Janssen–Brain Resource Company study (94 patients and 100 control subjects). Genome-wide differential gene expression analysis (18,863 probes) resulted in a p value for each gene in each study. A Bayesian method identified the largest p-value threshold (q = .025) associated with twice the number of genes differentially expressed in both studies compared with the number of coincidental case-control differences expected by chance. A total of 165 genes were differentially expressed in both studies with concordant direction of fold change. The 90 genes overexpressed (or UP genes) in MDD were significantly enriched for immune response to infection, were concentrated in a module of the gene coexpression network associated with innate immunity, and included clusters of genes with correlated expression in monocytes, monocyte-derived dendritic cells, and neutrophils. In contrast, the 75 genes underexpressed (or DOWN genes) in MDD were associated with the adaptive immune response and included clusters of genes with correlated expression in T cells, natural killer cells, and erythroblasts. Consistently, the MDD patients with overexpression of UP genes also had underexpression of DOWN genes (correlation > .70 in both studies). MDD was replicably associated with proinflammatory activation of the peripheral innate immune system, coupled with relative inactivation of the adaptive immune system, indicating the potential of transcriptional biomarkers for immunological stratification of patients with depression.
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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：
25.8
作者：
Miller AH;Raison CL
通讯作者：
Raison CL
DOI：
10.1016/j.bbi.2015.06.001
发表时间：
2015-10
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Haapakoski R;Mathieu J;Ebmeier KP;Alenius H;Kivimäki M
通讯作者：
Kivimäki M
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
10.6
作者：
Miller, Andrew H.;Maletic, Vladimir;Raison, Charles L.
通讯作者：
Raison, Charles L.