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Biol Psychiatry. 2018 Jan 1;83(1):70-80. doi: 10.1016/j.biopsych.2017.01.021. Epub 2017 Jul 6.

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

Author information

1
Medical Research Council Biostatistics Unit, Cambridge, United Kingdom.
2
Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
3
Rancho BioSciences, San Diego, California.
4
Roslin Institute, University of Edinburgh, Edinburgh, United Kingdom.
5
ImmunoPsychiatry, GlaxoSmithKline Research & Development, Stevenage, United Kingdom.
6
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
7
Brighton and Sussex Medical School, University of Sussex, Brighton, United Kingdom.
8
Centre for Biological Sciences, University of Southampton, Southampton, United Kingdom.
9
Janssen Research & Development, Titusville, New Jersey.
10
Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Cambridgeshire and Peterborough National Health Service Foundation Trust, Cambridge, United Kingdom; ImmunoPsychiatry, GlaxoSmithKline Research & Development, Stevenage, United Kingdom. Electronic address: etb23@cam.ac.uk.

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

PMID:
28688579
PMCID:
PMC5720346
DOI:
10.1016/j.biopsych.2017.01.021
[Indexed for MEDLINE]
Free PMC Article

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