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Circulating Cell-Free Mitochondrial DNA - a Novel Marker of Mitochondrial Stress Associated With Suicidality and Major Depressive Disorder
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
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2018 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 83, no 9, suppl. 1, p. S25-S26, article id 62Article in journal, Meeting abstract (Other academic)
Abstract [en]

Background: Mitochondrial DNA copy number (mtDNA-cn), which represents the number of mitochondrial genomes per cell, can be quantified in peripheral blood mononuclear cells (PBMC) and is thought to reflect variations in mitochondrial biogenesis. Additionally, mtDNA may be released at low levels into the circulation from mitochondria under cellular stress, resulting in circulating cell-free mtDNA (ccf-mtDNA) detectable in plasma. The source or physiological significance of ccf-mtDNA in psychiatric illness is unknown but may reflect cell damage, cell death, or bioenergetic compromise. Methods: We enrolled suicide attempters (across diagnoses), non-suicidal subjects with Major Depressive Disorder (MDD), and healthy controls (all medication-free) in two independent cohorts (n=110 & n=74). MtDNA was quantified in cell-free plasma and in PBMCs. Results: Ccf-mtDNA was elevated in suicide attempters and in non-suicidal MDD subjects, compared to healthy controls. These group effects were very large (Cohen’s d ranging from 0.9 to 4.0, all p<0.00001). Ccf-mtDNA and cellular PBMC mtDNA-cn were not significantly correlated with each other (r=0.02, p=0.87), suggesting they reflect different processes. Ccf-mtDNA correlated with post-dexamethasone cortisol (r=0.5, p<0.001), suggesting that HPA-axis hyperactivity may be associated with cellular damage and release of ccf-mtDNA into the blood. Ccf-mtDNA also directly correlated with the antioxidant enzyme glutathione peroxidase (r=0.32, p=0.001), possibly reflecting a compensatory attempt to upregulate antioxidant defence mechanisms due to cellular stress. Conclusions: Ccf-mtDNA may represent a novel marker of cellular stress, which is increased in certain psychiatric conditions. These results call for replication in larger cohorts and in longitudinal studies.

Place, publisher, year, edition, pages
Elsevier, 2018. Vol. 83, no 9, suppl. 1, p. S25-S26, article id 62
Keywords [en]
mtDNA Copy Number, Major Depressive Disorder (MDD), Suicide Attempts, Circulating Cell-Free DNA, Antioxidant Enzymes
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:mau:diva-5056DOI: 10.1016/j.biopsych.2018.02.079ISI: 000432466300063Local ID: 26550OAI: oai:DiVA.org:mau-5056DiVA, id: diva2:1401891
Conference
73rd Annual Scientific Convention and Meeting, New York City, USA (May 10-12, 2018)
Available from: 2020-02-28 Created: 2020-02-28 Last updated: 2021-01-15Bibliographically approved

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Ohlsson, LarsLjunggren, Lennart

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