Mitochondrial DNA oxidation, methylation, and copy number alterations in major and bipolar depression

Deniz Ceylan; Bilge Karacicek; Kemal Ugur Tufekci; Izel Cemre Aksahin; Sevin Hun Senol; Sermin Genc

doi:10.3389/fpsyt.2023.1304660

Mitochondrial DNA oxidation, methylation, and copy number alterations in major and bipolar depression

Front Psychiatry. 2023 Dec 14:14:1304660. doi: 10.3389/fpsyt.2023.1304660. eCollection 2023.

Authors

Deniz Ceylan^{1

2}, Bilge Karacicek³, Kemal Ugur Tufekci^{4

5}, Izel Cemre Aksahin^{1

6}, Sevin Hun Senol², Sermin Genc³

Affiliations

¹ Affective Laboratory, Koç University Research Center for Translational Medicine, Istanbul, Türkiye.
² Department of Psychiatry, Koç University Hospital, Istanbul, Türkiye.
³ Izmir Biomedicine and Genome Center, Genç Lab, Izmir, Türkiye.
⁴ Brain and Neuroscience Research and Application Center, Izmir Demokrasi University, Izmir, Türkiye.
⁵ Vocational School of Health Services, Izmir Democracy University, Izmir, Türkiye.
⁶ Graduate School of Health Sciences, Koç University, Istanbul, Türkiye.

Abstract

Background: Mood disorders are common disabling psychiatric disorders caused by both genetic and environmental factors. Mitochondrial DNA (mtDNA) modifications and epigenetics are promising areas of research in depression since mitochondrial dysfunction has been associated with depression. In this study we aimed to investigate the mtDNA changes in depressive disorder (MDD) and bipolar disorder (BD).

Methods: Displacement loop methylation (D-loop-met), relative mtDNA copy number (mtDNA-cn) and mtDNA oxidation (mtDNA-oxi) were investigated in DNA samples of individuals with MDD (n = 34), BD (n = 23), and healthy controls (HC; n = 40) using the Real-Time Polymerase Chain Reaction (RT-PCR). Blood samples were obtained from a subset of individuals with MDD (n = 15) during a depressive episode (baseline) and after remission (8th week).

Results: The study groups exhibited significant differences in D-loop-met (p = 0.020), while relative mtDNA-cn and mtDNA-oxi showed comparable results. During the remission phase (8th week), there were lower levels of relative mtDNA-cn (Z = -2.783, p = 0.005) and D-loop-met (Z = -3.180, p = 0.001) compared to the acute MDD baseline, with no significant change in mtDNA-oxi levels (Z = -1.193, p = 0.233).

Conclusion: Our findings indicate significantly increased D-loop methylation in MDD compared to BD and HCs, suggesting distinct mtDNA modifications in these conditions. Moreover, the observed alterations in relative mtDNA-cn and D-loop-met during remission suggest a potential role of mtDNA alterations in the pathophysiology of MDD. Future studies may provide valuable insights into the dynamics of mtDNA modifications in both disorders and their response to treatment.

Keywords: depression; epigenetics; methylation; mitochondrial copy number; mtDNA; oxidation.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by TUSEB (TUSEB 20131-DC) and a BAGEP award by the Science Academy of Turkey. The publication was supported by Koç University.