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

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.