Brain differential gene expression and blood cross-validation of a molecular signature of patients with major depressive disorder.

Introduction: The agreement between clinicians diagnosing major depressive disorder (MDD) is poor. The objective of this study was to identify a reproducible and robust gene expression marker capable of differentiating MDD from healthy control (HC) subjects.

Materials and methods: Brain and blood gene expression datasets were searched, which included subjects with MDD and HC. The largest database including different areas of brain samples (GSE80655) was used to identify an initial gene expression marker. Tests of robustness and reproducibility were then implemented in 13 brain and 7 blood independent datasets. Correlations between expression in brain and blood samples were also examined. Finally, an enrichment analysis to explore the marker biological meaning was completed.

Results: Twenty-eight genes were differentially expressed in GSE80655, of which 23 were critical to differentiate MDD from HC. The accuracy obtained using the 23 genes was 0.77 and 0.8, before and after the forward selection model, respectively. The gene marker's robustness and reproducibility were between the range of 0.46 and 0.63 in the other brain datasets and between 0.45 and 0.78 for the blood datasets. Brain and blood expression tended to correlate in some samples. Thirteen of the 23 genes were related to stress and immune response.

Conclusion: A 23 gene expression marker was able to distinguish subjects with MDD from HC, with adequate reproducibility and low robustness in the independent databases investigated. This gene set was similarly expressed in the brain and blood and involved genes related to stress and immune response.