Decreased miR-15b-5p/miR-155-5p levels and increased miR-134-5p/miR-652-3p levels among BD patients under lithium treatment

J Affect Disord. 2022 Nov 15:317:6-14. doi: 10.1016/j.jad.2022.08.034. Epub 2022 Aug 23.

Abstract

Background: There is an increasing interest about the role of miRNAs in the pathogenesis of bipolar disorder (BD). In this study, we aimed to examine the role of miRNAs as potential diagnostic and clinical biomarkers in BD.

Methods: Fifteen miRNAs in plasmas obtained from BD patients (n = 66) and from the healthy control group (n = 66) were analyzed by a qPCR test. Clinical variables including lithium treatment response were assessed with various test batteries. The correlation of the miRNA levels with the clinical variables and scale scores was examined. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the DIANA-miRPath v.3.0 software to identify the possible target genes.

Results: The miR-132, miR-134, miR-152, miR-607, miR-633, and miR-652 levels were significantly increased, whereas the miR-15b and miR-155 levels were found to be significantly decreased in the patient group compared to the controls. The miR-15b-5p and miR-155-5p levels and increases in the miR-134-5p and miR-652-3p levels were calculated to have 83.3 % sensitivity and 78.8 % specificity in determining the risk of BD. miR-155-5p was associated with the disease burden and severity. Fatty acid biosynthesis and metabolism, viral carcinogenesis, the EBV infection, and extracellular matrix and adhesion pathways were highlighted as target pathways.

Conclusion: We can conclude that miRNAs may play a role in the pathophysiology of BD through various biological pathways and that miRNAs may be used as a screening test to distinguish bipolar patients from healthy controls. Our findings will provide a basis for long-term follow-up studies with larger samples.

Keywords: Biomarker; Bipolar disorder; Circadian rhythm; Lithium response; MicroRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Bipolar Disorder* / diagnosis
  • Bipolar Disorder* / drug therapy
  • Bipolar Disorder* / genetics
  • Fatty Acids
  • Gene Expression Profiling
  • Humans
  • Lithium / therapeutic use
  • Lithium Compounds / pharmacology
  • Lithium Compounds / therapeutic use
  • MicroRNAs* / genetics

Substances

  • Biomarkers
  • Fatty Acids
  • Lithium Compounds
  • MIRN134 microRNA, human
  • MIRN152 microRNA, human
  • MIRN155 microRNA, human
  • MIRN633 microRNA, human
  • MIRN652 microRNA, human
  • MicroRNAs
  • Lithium