Elsevier

Biological Psychiatry

Volume 83, Issue 1, 1 January 2018, Pages 70-80
Biological Psychiatry

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

https://doi.org/10.1016/j.biopsych.2017.01.021Get rights and content
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Abstract

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.

Keywords

Affymetrix
Bayesian
Biomarker
Inflammation
Systems
Transcriptome

Cited by (0)

Immunopsychiatry Consortium: Edward Bullmore, Petra Vertes, Rudolf Cardinal (University of Cambridge); Sylvia Richardson, Gwenael Leday (Medical Research Council Biostatistics Unit); Tom Freeman, Tim Regan, David Hume, Zhaozong Wu (University of Edinburgh); Carmine Pariante, Annamaria Cattaneo, Patricia Zunszain, Alessandra Borsini, Robert Stewart, David Chandran (King’s College London); Livia Carvalho, Joshua Bell, Luis Souza-Teodoro (University College London); Hugh Perry (University of Southampton); Neil Harrison (University of Sussex); Wayne Drevets, Gayle Wittenberg, Declan Jones (Janssen Research & Development); Edward Bullmore, Shahid Khan, Annie Stylianou, Robbie Henderson (GlaxoSmithKline).

GGRL and PEV contributed equally to this work.

GMW and ETB contributed equally to this work.