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Neuropsychopharmacology. 2018 Jun;43(7):1557-1564. doi: 10.1038/s41386-017-0001-9. Epub 2018 Jan 30.

Circulating cell-free mitochondrial DNA, but not leukocyte mitochondrial DNA copy number, is elevated in major depressive disorder.

Author information

1
Faculty of Medicine, Department of Clinical Sciences, Psychiatry, Lund University, Lund, Sweden. daniel.lindqvist@med.lu.se.
2
Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA. daniel.lindqvist@med.lu.se.
3
Psychiatric Clinic, Lund, Division of Psychiatry, Lund, Sweden. daniel.lindqvist@med.lu.se.
4
Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA.
5
Division of Behavioral Medicine, Department of Psychiatry, Columbia University Medical Center, New York, NY, USA.
6
Department of Neurology and Columbia Translational Neuroscience Initiative, Columbia University Medical Center, New York, NY, USA.
7
Columbia Aging Center, Columbia University Medical Center, New York, NY, USA.
8
Department of Biomedical Science, Malmö University, Malmö, Sweden.
9
Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
10
Faculty of Medicine, Department of Clinical Sciences, Psychiatry, Lund University, Lund, Sweden.
11
Psychiatric Clinic, Lund, Division of Psychiatry, Lund, Sweden.
12
Department of Psychology, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
13
Department of Biochemistry and Biophysics, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA.
14
Department of OB/GYN and Reproductive Sciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA.

Abstract

Major depressive disorder (MDD) has been linked to mitochondrial defects, which could manifest in mitochondrial DNA (mtDNA) polymorphisms or mutations. Additionally, copy number of mtDNA (mtDNA-cn) can be quantified in peripheral blood mononuclear cells (PBMC)s, indirectly reflecting cellular energetics, or in the circulating cell-free mtDNA (ccf-mtDNA) levels, which may reflect a fraction of the mitochondrial genome released during cellular stress. Few studies have examined ccf-mtDNA in MDD, and no studies have tested its relationship with intracellular mtDNA-cn or with antidepressant treatment response. Here, mtDNA levels were quantified in parallel from: (i) PBMCs and (ii) cell-free plasma of 50 unmedicated MDD subjects and 55 controls, in parallel with PBMC telomere length (TL) and antioxidant enzyme glutathione peroxidase (GpX) activity. MtDNA measures were repeated in 19 MDD subjects after 8 weeks of open-label SSRI treatment. In analyses adjusted for age, sex, BMI, and smoking, MDD subjects had significantly elevated levels of ccf-mtDNA (F = 20.6, p = 0.00002). PBMC mtDNA-cn did not differ between groups (p > 0.4). In preliminary analyses, we found that changes in ccf-mtDNA with SSRI treatment differed between SSRI responders and non-responders (F = 6.47, p = 0.02), with the non-responders showing an increase in ccf-mtDNA and responders not changing. Baseline ccf-mtDNA was positively correlated with GpX (r = 0.32, p = 0.001), and PBMC mtDNA correlated positively with PBMC TL (r = 0.38, p = 0.0001). These data suggest that plasma ccf-mtDNA and PBMC mtDNA-cn reflect different cellular processes and that the former may be more reflective of certain aspects of MDD pathophysiology and of the response to SSRI antidepressants.

PMID:
29453441
PMCID:
PMC5983469
DOI:
10.1038/s41386-017-0001-9
[Indexed for MEDLINE]
Free PMC Article

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