Downregulated mitochondria-encoded long non-coding RNAs in mood disorders

Abstract

Background: Mitochondrial genome-encoded long non-coding RNAs (mt-LncRNAs) that play roles in regulation of energy metabolism and mitochondrial function, both crucial in mood disorder pathogenesis, yet remain poorly explored despite growing interest. This study examines their expression levels in individuals with major depressive disorder (MDD), bipolar disorder (BD), siblings of individuals with BD (SIB), and healthy controls (HC).

Methods: Blood samples from 153 participants (31 MDD, 40 BD, 39 SIB, 43 HC) were analyzed for 10 mt-LncRNAs via RT-qPCR. Samples from a subgroup of 15 remitted MDD (MDD_REM) patients following 8-week treatment were included for exploratory analysis. A composite score for all LncRNAs, global factor, was derived using principal component analysis. All comparisons were adjusted for age, sex, smoking, BMI, and multiple comparisons.

Results: Global scores showed overall downregulation in MDD, BD, and SIB compared to HCs, with BD exhibiting the lowest levels (p < 0.01). All mt-LncRNAs were downregulated in BD and SIB, while 8 (excluding ASncmtRNA-2 and 7S RNA) were downregulated in MDD (p < 0.05). Mt-LncRNA levels were lower in BD than in SIB and MDD (p < 0.05), with 6 also lower in SIB compared to MDD (p < 0.05). Exploratory analysis revealed a significant increase in 8 mt-LncRNAs (excluding LIPCAR and 7S RNA) in MDD_REM compared to baseline MDD (p < 0.05).

Conclusion: Findings show a significant mt-LncRNA downregulation in mood disorders and suggest genetic transmission as well as a capacity to change with treatment. Further research is needed to explore the genetics and modifiability of mt-LncRNAs in mood disorders.

Keywords: Bipolar disorder; Major depressive disorder; Mitochondrial genome-encoded long non-coding RNAs; Mood disorders.