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Biol Psychiatry. 2015 Feb 1;77(3):256-265. doi: 10.1016/j.biopsych.2014.05.015. Epub 2014 Jun 2.

Coordinated messenger RNA/microRNA changes in fibroblasts of patients with major depression.

Author information

1
Department of Psychiatry, Vanderbilt University, Nashville, Tennessee.
2
Department of Psychiatry, Vanderbilt University, Nashville, Tennessee; Institute for Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest.
3
Department of Psychiatry, Vanderbilt University, Nashville, Tennessee; Department of Psychiatry, University of Szeged, Szeged.
4
Department of Psychiatry, Kútvölgyi Clinical Centre, Semmelweis University, Budapest, Hungary.
5
Department of Psychiatry, Vanderbilt University, Nashville, Tennessee; Vanderbilt Kennedy Center for Research on Human Development (ZK, KM), Vanderbilt University, Nashville, Tennessee.
6
Department of Psychiatry, University of Alabama, Birmingham, Alabama.
7
Department of Psychiatry, Vanderbilt University, Nashville, Tennessee; Department of Psychiatry, University of Szeged, Szeged; Vanderbilt Kennedy Center for Research on Human Development (ZK, KM), Vanderbilt University, Nashville, Tennessee.. Electronic address: karoly.mirnics@vanderbilt.edu.

Abstract

BACKGROUND:

Peripheral biomarkers for major psychiatric disorders have been an elusive target for the last half a century. Dermal fibroblasts are a simple, relevant, and much underutilized model for studying molecular processes of patients with affective disorders, as they share considerable similarity of signal transduction with neuronal tissue.

METHODS:

Cultured dermal fibroblast samples from patients with major depressive disorder (MDD) and matched control subjects (n = 16 pairs, 32 samples) were assayed for genome-wide messenger RNA (mRNA) expression using microarrays. In addition, a simultaneous quantitative polymerase chain reaction-based assessment of >1000 microRNA (miRNA) species was performed. Finally, to test the relationship between the mRNA-miRNA expression changes, the two datasets were correlated with each other.

RESULTS:

Our data revealed that MDD fibroblasts, when compared with matched control subjects, showed a strong mRNA gene expression pattern change in multiple molecular pathways, including cell-to-cell communication, innate/adaptive immunity, and cell proliferation. Furthermore, the same patient fibroblasts showed altered expression of a distinct panel of 38 miRNAs, which putatively targeted many of the differentially expressed mRNAs. The miRNA-mRNA expression changes appeared to be functionally connected, as the majority of the miRNA and mRNA changes were in the opposite direction.

CONCLUSIONS:

Our data suggest that combined miRNA-mRNA assessments are informative about the disease process and that analyses of dermal fibroblasts might lead to the discovery of promising peripheral biomarkers of MDD that could be potentially used to aid the diagnosis and allow mechanistic testing of disturbed molecular pathways.

KEYWORDS:

Biomarker; DNA microarray; Gene expression; Human fibroblasts; Major depression; miRNA

PMID:
25016317
PMCID:
PMC4254393
DOI:
10.1016/j.biopsych.2014.05.015
[Indexed for MEDLINE]
Free PMC Article

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