Replicable and coupled changes in innate and adaptive immune gene expression in two case-control studies of blood microarrays in major depressive disorder

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: GSK-HiTDiP, 113 patients and 57 healthy controls; and Janssen-BRC, 94 patients and 100 controls. 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 = 0.025) associated with twice the number of genes differentially expressed in both studies compared to the number of coincidental case-control differences expected by chance. Results. 165 genes were differentially expressed in both studies with concordant direction of fold change. The 90 genes over-expressed (UP) in MDD were significantly enriched for immune response to infection; concentrated in a module of the gene co-expression 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 under-expressed (DOWN) in MDD were associated with the adaptive immune response; and included clusters of genes with correlated expression in T cells, NK cells and erythroblasts. Consistently, the MDD patients with over-expression of UP genes also had under-expression of DOWN genes (correlation > 0.7 in both studies). Conclusions. Major depressive disorder was replicably associated with pro-inflammatory 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 depressed patients.

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