Downregulated mitochondria-encoded long non-coding RNAs in mood disorders
1Koç University Research Center for Translational Medicine, İstanbul, Türkiye.
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Summary
Mitochondrial long non-coding RNAs (mt-LncRNAs) are downregulated in major depressive disorder (MDD) and bipolar disorder (BD). Their expression levels may be genetically influenced and can change with MDD treatment.
Area of Science:
- Genetics and Molecular Biology
- Neuroscience
- Biochemistry
Background:
- Mitochondrial genome-encoded long non-coding RNAs (mt-LncRNAs) are implicated in energy metabolism and mitochondrial function, processes vital to mood disorder pathogenesis.
- Despite growing interest, the role of mt-LncRNAs in mood disorders remains underexplored.
Purpose of the Study:
- To investigate the expression levels of 10 specific mt-LncRNAs in individuals diagnosed with major depressive disorder (MDD), bipolar disorder (BD), siblings of individuals with BD (SIB), and healthy controls (HC).
- To explore potential changes in mt-LncRNA expression following treatment in a subgroup of MDD patients.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) was used to analyze 10 mt-LncRNAs in blood samples from 153 participants (31 MDD, 40 BD, 39 SIB, 43 HC).
- Principal component analysis was employed to derive a global factor score for all analyzed mt-LncRNAs.
- Exploratory analysis included samples from 15 remitted MDD patients (MDD_REM) after 8 weeks of treatment. Statistical analyses were adjusted for age, sex, smoking, BMI, and multiple comparisons.
Main Results:
- A significant global downregulation of mt-LncRNAs was observed in MDD, BD, and SIB groups compared to HCs, with BD showing the most pronounced reduction.
- Specific mt-LncRNAs were downregulated across all patient groups, with BD and SIB exhibiting lower levels than MDD.
- Exploratory analysis indicated a significant upregulation of 8 mt-LncRNAs in MDD_REM patients compared to their baseline MDD levels.
Conclusions:
- The study demonstrates significant downregulation of mt-LncRNAs in individuals with mood disorders.
- Findings suggest both a potential genetic component in mt-LncRNA expression and a capacity for these molecules to be modified by treatment.
- Further investigation into the genetic underpinnings and therapeutic modifiability of mt-LncRNAs in mood disorders is warranted.