Replicable and Coupled Changes in Innate and Adaptive Immune Gene Expression in Two Case-Control Studies of Blood Microarrays in Major Depressive Disorder

被引:161
作者
Leday, Gwenael G. R. [1 ]
Vertes, Petra E. [2 ]
Richardson, Sylvia [1 ]
Greene, Jonathan R. [9 ]
Regan, Tim [4 ]
Khan, Shahid [5 ]
Henderson, Robbie [5 ]
Freeman, Tom C. [4 ]
Pariante, Carmine M. [6 ]
Harrison, Neil A. [7 ]
Perry, V. Hugh [8 ]
Drevets, Wayne C. [10 ]
Wittenberg, Gayle M. [10 ]
Bullmore, Edward T. [2 ,3 ,5 ]
机构
[1] Univ Cambridge, Med Res Council, Biostat Unit, Cambridge, England
[2] Univ Cambridge, Dept Psychiat, Herchel Smith Bldg Brain & Mind Sci,Cambridge Bio, Cambridge CB2 0SZ, England
[3] Cambridge Shire & Peterborough Natl Hlth Serv Fdn, Cambridge, England
[4] Univ Edinburgh, Roslin Inst, Edinburgh, Midlothian, Scotland
[5] GlaxoSmithKline Res & Dev Ltd, ImmunoPsychiat, Stevenage, Herts, England
[6] Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England
[7] Univ Sussex, Brighton & Sussex Med Sch, Brighton, E Sussex, England
[8] Univ Southampton, Ctr Biol Sci, Southampton, Hants, England
[9] Rancho BioSci, San Diego, CA USA
[10] Janssen Res & Dev, Titusville, NJ USA
基金
英国生物技术与生命科学研究理事会; 英国医学研究理事会;
关键词
Affymetrix; Bayesian; Biomarker; Inflammation; Systems; Transcriptome; C-REACTIVE PROTEIN; INFLAMMATION; ALPHA; VISUALIZATION; INTERLEUKIN-6; METAANALYSIS; ASSOCIATION; ACTIVATION; CHILDHOOD; CYTOKINES;
D O I
10.1016/j.biopsych.2017.01.021
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
BACKGROUND: Peripheral inflammation is often associated with major depressive disorder (MDD), and immunological biomarkers of depression remain a focus of investigation. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
引用
收藏
页码:70 / 80
页数:11
相关论文
共 51 条
[1]  
[Anonymous], 2019, topGO: enrichment analysis for gene ontology
[2]   Gene Ontology: tool for the unification of biology [J].
Ashburner, M ;
Ball, CA ;
Blake, JA ;
Botstein, D ;
Butler, H ;
Cherry, JM ;
Davis, AP ;
Dolinski, K ;
Dwight, SS ;
Eppig, JT ;
Harris, MA ;
Hill, DP ;
Issel-Tarver, L ;
Kasarskis, A ;
Lewis, S ;
Matese, JC ;
Richardson, JE ;
Ringwald, M ;
Rubin, GM ;
Sherlock, G .
NATURE GENETICS, 2000, 25 (01) :25-29
[3]   PENETRATION OF INTERLEUKIN-6 ACROSS THE MURINE BLOOD-BRAIN-BARRIER [J].
BANKS, WA ;
KASTIN, AJ ;
GUTIERREZ, EG .
NEUROSCIENCE LETTERS, 1994, 179 (1-2) :53-56
[4]   Statistical tools for synthesizing lists of differentially expressed features in related experiments [J].
Blangiardo, Marta ;
Richardson, Sylvia .
GENOME BIOLOGY, 2007, 8 (04)
[5]   sdef: an R package to synthesize lists of significant features in related experiments [J].
Blangiardo, Marta ;
Cassese, Alberto ;
Richardson, Sylvia .
BMC BIOINFORMATICS, 2010, 11
[6]   Immune suppression and immune activation in depression [J].
Blume, Joshua ;
Douglas, Steven D. ;
Evans, Dwight L. .
BRAIN BEHAVIOR AND IMMUNITY, 2011, 25 (02) :221-229
[7]   Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-α and ribavirin treatment [J].
Bull, S. J. ;
Huezo-Diaz, P. ;
Binder, E. B. ;
Cubells, J. F. ;
Ranjith, G. ;
Maddock, C. ;
Miyazaki, C. ;
Alexander, N. ;
Hotopf, M. ;
Cleare, A. J. ;
Norris, S. ;
Cassidy, E. ;
Aitchison, K. J. ;
Miller, A. H. ;
Pariante, C. M. .
MOLECULAR PSYCHIATRY, 2009, 14 (12) :1095-1104
[8]   Inflammatory activation is associated with a reduced glucocorticoid receptor alpha/beta expression ratio in monocytes of inpatients with melancholic major depressive disorder [J].
Carvalho, L. A. ;
Bergink, V. ;
Sumaski, L. ;
Wijkhuijs, J. ;
Hoogendijk, W. J. ;
Birkenhager, T. K. ;
Drexhage, H. A. .
TRANSLATIONAL PSYCHIATRY, 2014, 4 :e344-e344
[9]   Childhood maltreatment predicts adult inflammation in a life-course study [J].
Danese, Andrea ;
Pariante, Carmine M. ;
Caspi, Avshalom ;
Taylor, Alan ;
Poulton, Richie .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (04) :1319-1324
[10]   From inflammation to sickness and depression: when the immune system subjugates the brain [J].
Dantzer, Robert ;
O'Connor, Jason C. ;
Freund, Gregory G. ;
Johnson, Rodney W. ;
Kelley, Keith W. .
NATURE REVIEWS NEUROSCIENCE, 2008, 9 (01) :46-57