Table 6 Studies examining alterations in the expression levels of genes associated with depression using transcriptomics techniques.

From: Gene expression studies in Depression development and treatment: an overview of the underlying molecular mechanisms and biological processes to identify biomarkers

Citation

Sample

Methods

Main findings

Tissue

Leday et al. 2017115

GSK-HiTDiP: 113 MDD patients57 healthy control Janssen–BRC: 94 MDD patients 100 healthy control

Microarray

A total of 165 genes were differentially expressed in both studies with concordant direction of fold change. The 90 genes overexpressed in MDD were significantly enriched for immune response to infection, were 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. The 75 genes downregulated 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.

Peripheral blood

Malki et al. 2014116

11 MDD patients 15 healthy controls

Microarray

Out of a total of 15 genes, VAMP-2 is significantly downregulated in MDD patients when compared with controls.

Postmortem prefrontal cortex

Mostafavi et al. 2014117

467 patients with rDD 459 healthy controls

HTSeq

Significant association was observed between MDD and the expression of genes involved in IFN α/β signalling pathway.

Peripheral blood

Jansen et al. 2016118

882 current MDD 635 remitted MDD 331 healthy controls

Microarray

Genes associated with MDD were enriched for IL-6 signalling and NK cell pathways. Thirteen gene expression clusters with specific clusters enriched for genes involved in NK cell activation (downregulated in current MDD,) and IL-6 pathways (upregulated in current MDD) were identified.

Peripheral blood

Yamagata et al. 2017119

23 MDD patients: 10 depressed state 13 remitted state 30 healthy controls

Microarray

SLC35A3, HIST1H2AL, YEATS4, ERLIN2 and PLPP5 were downregulated in patients with MDD when compared with controls.

Leukocytes

Duric et al. 2013126

21 MDD patients 18 healthy controls

Microarray

Downregulation of several pre- and post-synaptic genes in MDD subjects when compared with controls. Decreases in expression of MAP1A, MAP1B, MAP2 and MAPT genes and of AMPA receptors genes, specifically GLUR1 and GLUR3 subunits observed in both the DG and CA1 of subjects with MDD when compared with controls.

Postmortem brain tissues

Fan et al. 2014120

91 MDD patients 46 healthy control

Microarray

26 miRNAs were identified with significantly different expression levels in MDD patients compared with controls. Of these, 21 miRNAs were upregulated, and 5 others were downregulated in MDD patients compared with controls. With the exception of miRNA-338, the expressions of the other 9 miRNAs conformed to microarray assay results, among which 5 miRNAs (miRNA-26b, miRNA-1972, miRNA-4485, miRNA-4498 and miRNA-4743) were upregulated with a significant difference in MDD patients compared with controls.

PBMC

Hennings et al. 2015127

24 male MDD patients: 12 responders 12 non-responders 142 unipolar depressed patients:80 responders 62 non-responders

Microarray

127 transcripts were significantly associated with treatment response. Lower expression of retinoid-related orphan receptor alpha (RORa), germinal center expressed transcript 2 (GCET2) and chitinase 3-like protein 2 (CHI3L2) on admission were associated with beneficial treatment response. In addition, leukocyte-specific protein 1 (LSP1) significantly decreased after 5 weeks of treatment in responders.

Peripheral blood

Woo et al. 2018121

38 Korean patients with MDD 14 healthy individuals

Microarray

CD58, CXCL8, EGF, TARP, TNFSF4, ZNF583 and ZNF587. CXCL8, EGF, and TNFSF4 genes were downregulated in MDD patients, whereas the other genes were upregulated in MDD patients.

Peripheral blood

Watanabe et al. 2015122

Pilot study: 25 drug-naive MDD patients 25 healthy controls Subsequent replication study: 20 drug-naive MDD patients 18 healthy controls

custom-made PCR array plates

Among 40 candidate genes, the expression levels of seven genes (PDGFC, SLC6A4, PDLIM5, ARHGAP24, PRNP, HDAC5 and IL-1R2) significantly differed between MDD and control samples in the pilot study.Ultimately, five genes (PDGFC, SLC6A4, ARHGAP24, PRNP and HDAC5) whose expression best differentiated between MDD patients and controls were selected for a multi-assay diagnostic test.

Peripheral blood

Hepgul et al. 2016128

20 MDD patients with chronic HCV infection due to commence combination antiviral therapy with IFN-α and ribavirin for at least 24 weeks 38 healthy controls

Microarray

506 genes were modulated only in patients who developed depression and 70 genes were modulated only in patients who did not develop depression. Pathway analysis of 506 genes modulated only in patients who developed depression were identified 65 pathways, including those related to inflammation (IL-1, IL-6 and IL-8 signalling, GR signalling, triggering receptor expressed on myeloid cells 1 signalling and NF-κB signalling), neuroplasticity (extracellular signal-regulated kinase 5 (ERK5) signalling and axonal guidance signalling), and oxidative stress (NRF2-mediated oxidative stress response, p53 signalling and production of nitric oxide and reactive oxygen species in macrophages).

Peripheral blood

Eyre et al. 2016123

35 MDD patients: 24 remitters 11 non-remitters randomized to methylphenidate and citalopram, citalopram and placebo or methylphenidate and placebo

RNA expression profiling assays

18 genes had higher expression levels in the group of early remitters versus non-remitters.

PBMC

Ju et al. 2019129

211 MDD patients treated with escitalopram 112 healthy controls

Array-Based Gene Expression Analysis

Increased mRNA expression of CHN2 and JAK2 in the non-responders group.

Peripheral blood

  1. MDD major depressive disorder, PCR polymerase chain reaction, HCV hepatitis C virus, rDD recurrent major depression.