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

İbrahim Fettahoğlu1, İzel Cemre Akşahin2, Buket Yeşiloğlu2

  • 1Koç University Research Center for Translational Medicine, İstanbul, Türkiye.

Journal of Affective Disorders
|June 14, 2025
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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 indicate genetic links and change with treatment for MDD.

Keywords:
Bipolar disorderMajor depressive disorderMitochondrial genome-encoded long non-coding RNAsMood disorders

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Area of Science:

  • Mitochondrial genomics
  • Non-coding RNA biology
  • Neuropsychiatry

Background:

  • Mitochondrial genome-encoded long non-coding RNAs (mt-LncRNAs) are implicated in energy metabolism and mitochondrial function, processes vital for mood regulation.
  • 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) and bipolar disorder (BD).
  • To compare mt-LncRNA expression in patients, their siblings (SIB), and healthy controls (HC).
  • To explore potential changes in mt-LncRNA expression following treatment in a subgroup of MDD patients.

Main Methods:

  • Quantitative reverse transcription PCR (RT-qPCR) was used to analyze blood samples from 153 participants across MDD, BD, SIB, and HC groups.
  • Principal component analysis was employed to derive a composite global factor score for all analyzed mt-LncRNAs.
  • Statistical analyses were adjusted for covariates including age, sex, smoking status, and body mass index (BMI).

Main Results:

  • A significant overall downregulation of mt-LncRNAs was observed in MDD, BD, and SIB groups compared to HCs, with BD showing the most pronounced decrease.
  • Specific mt-LncRNAs were downregulated across all patient groups, with variations in the number of affected RNAs depending on the disorder.
  • Exploratory analysis indicated a significant upregulation of several mt-LncRNAs in remitted MDD patients compared to their baseline levels.

Conclusions:

  • The study demonstrates a significant downregulation of mt-LncRNAs in individuals with mood disorders.
  • These findings suggest a potential role for genetic transmission and treatment-induced modifiability of mt-LncRNAs in the context of mood disorders.
  • Further investigation into the genetic underpinnings and therapeutic potential of mt-LncRNAs in mood disorders is warranted.