Relationship between circulating mitochondrial DNA and microRNA in patients with major depression

Area of Science:

• Biomarkers for Affective Disorders
• Molecular Mechanisms of Depression
• Mitochondrial Biology and Stress Response

Background:

• MicroRNAs (miRNAs) and circulating cell-free mitochondrial DNA (ccf-mtDNA) are potential biomarkers for affective disorders.
• Stress-induced diffusion of mitochondrial miRNAs and mtDNA into the cytoplasm is a known phenomenon.
• This study investigates the hypothesis that nuclear-derived miRNAs contribute to mitochondrial damage and mtDNA fragmentation in major depressive disorder (MDD).

Purpose of the Study:

• To analyze plasma miRNA levels and ccf-mtDNA copy number in patients with depression.
• To identify correlations between miRNAs and ccf-mtDNA, and associated genes/pathways.
• To evaluate the relationship between miRNA-ccf-mtDNA correlations and antidepressant treatment outcomes.

Main Methods:

• Comprehensive analysis of plasma miRNA expression and ccf-mtDNA quantification in 69 depressed patients.
• Random assignment of patients to selective serotonin reuptake inhibitors (SSRI) or mirtazapine treatment.
• Four-week evaluation of therapeutic efficacy correlated with miRNA and ccf-mtDNA levels.

Main Results:

• Five miRNAs showed a significant positive correlation with ccf-mtDNA copy number.
• These miRNAs are implicated in thyroid hormone synthesis, Hippo signaling, water reabsorption, and lysine degradation.
• miR-6068 and miR-4708-3p were significantly associated with SSRI and mirtazapine treatment outcomes, respectively.

Conclusions:

• Specific miRNA expression levels correlate with ccf-mtDNA copy number in untreated depressed patients.
• These miRNAs are linked to the outcomes of antidepressant treatments (SSRI and mirtazapine).
• Findings may elucidate novel pathological mechanisms underlying depression.