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

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

Lindqvist, Daniel (författare): Lund University,Lunds universitet,Psykiatri, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Enheten för klinisk suicidforskning,Forskargrupper vid Lunds universitet,Psychiatry (Lund),Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Unit for clinical suicide research,Lund University Research Groups,University of California, San Francisco,Skåne University Hospital

Wolkowitz, Owen M. (författare): Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA

Picard, Martin (författare): Division of Behavioral Medicine, Department of Psychiatry, Columbia University Medical Center, New York, NY, USA; Department of Neurology and Columbia Translational Neuroscience Initiative, Columbia University Medical Center, New York, NY, USA; Columbia Aging Center, Columbia University Medical Center, New York, NY, USA

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Ohlsson, Lars (författare): Malmö University,Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV)

Bersani, Francesco S. (författare): Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA; Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy

Fernström, Johan (författare): Lund University,Lunds universitet,Psykiatri, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Enheten för klinisk suicidforskning,Forskargrupper vid Lunds universitet,Psychiatry (Lund),Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Unit for clinical suicide research,Lund University Research Groups,Skåne University Hospital

Westrin, Åsa (författare): Lund University,Lunds universitet,Psykiatri, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Enheten för klinisk suicidforskning,Forskargrupper vid Lunds universitet,Psychiatry (Lund),Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Unit for clinical suicide research,Lund University Research Groups,Skåne University Hospital

Hough, Christina M. (författare): Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA; Department of Psychology, University of California, Los Angeles (UCLA), Los Angeles, CA, USA

Lin, Jue (författare): Department of Biochemistry and Biophysics, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA

Reus, Victor I. (författare): Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA

Epel, Elissa S. (författare): Department of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA

Mellon, Synthia H. (författare): Department of OB/GYN and Reproductive Sciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA

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2018-01-30
2018
Engelska.
Ingår i: Neuropsychopharmacology. - : Nature Publishing Group. - 0893-133X .- 1740-634X. ; 43:7, s. 1557-1564

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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.

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Av författaren/redakt...: Lindqvist, Danie ...; Wolkowitz, Owen ...; Picard, Martin; Ohlsson, Lars; Bersani, Frances ...; Fernström, Johan; visa fler...; Westrin, Åsa; Hough, Christina ...; Lin, Jue; Reus, Victor I.; Epel, Elissa S.; Mellon, Synthia ...; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Psykiatri

Artiklar i publikationen: Neuropsychopharm ...

Av lärosätet: Malmö universitet; Lunds universitet

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

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