Differential expression of microRNA in peripheral blood mononuclear cells as specific biomarker for major depressive disorder patients

J Psychiatr Res. 2014 Dec:59:45-52. doi: 10.1016/j.jpsychires.2014.08.007. Epub 2014 Aug 24.

Abstract

Currently, diagnosis and treatment of major depressive disorder (MDD) are based on the patients' description of symptoms, mental status examinations, and clinical behavioral observations, which increases the chance of misdiagnosis. There is a serious need to find a practical biomarker for the proper diagnosis of MDD. This study aimed to explore the possibility of microRNA (miRNA) in peripheral blood mononuclear cells (PBMCs) as specific blood-based biomarker for MDD patients. By using an Affymetrix array that covers 723 human miRNAs, we identified 26 miRNAs with significant changes in expression in PBMCs of MDD patients. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis in a larger cohort of 81 MDD patients and 46 healthy controls confirmed that the expression levels of 5 miRNAs (miRNA-26b, miRNA-1972, miRNA-4485, miRNA-4498, and miRNA-4743) were up-regulated. By receiver operating characteristic (ROC) curve analysis, the combining area under the ROC curve (AUC) of these five miRNAs was 0.636 [95% confidence interval (CI): 0.58-0.90]. MiRNA target gene prediction and functional annotation analysis showed that there was a significant enrichment in several pathways associated with nervous system and brain functions, supporting the hypothesis that differentially-regulated miRNAs may be involved in mechanism underlying development of MDD. We conclude that altered expression of miRNAs in PMBCs might be involved in multiple stages of MDD pathogenesis, and thus might be able to serve as specific biomarker for diagnosis of MDD.

Keywords: Functional annotation analysis; Major depressive disorder; MicroRNA; Microarray analysis; Peripheral blood mononuclear cells; Target gene prediction.

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood
  • Depressive Disorder, Major / metabolism*
  • Depressive Disorder, Major / pathology*
  • Female
  • Gene Expression Profiling
  • Humans
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • MicroRNAs / blood*
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Psychiatric Status Rating Scales
  • ROC Curve
  • Up-Regulation / physiology*
  • Young Adult

Substances

  • Biomarkers
  • MicroRNAs