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Circulating cell-free mitochondrial DNA, but not leukocyte mitochondrial DNA copy number, is elevated in major depressive disorder
Open accessAbstract
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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“Assessing the presence of extracellular mitochondria or their fragments by measuring ccf-mtDNA levels could allow on-flight direct estimation of cellular stress to take preventive measures of cumulative damage196,199–206.”
From Key points for the development of antioxidant cocktails to prevent cellular stress and damage caused by reactive oxygen species (ROS) during manned space missions (2021) · cites this paper as [206]
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Cites
Hamilton, M. (1960) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.23.1.56 · Cited by 32,817
Circulating mitochondrial DAMPs cause inflammatory responses to injury
Zhang, Q., Raoof, M., Chen, Y., Sumi, Y., Sursal, T., Junger, W., Brohi, K., Itagaki, K., & Hauser, C. J. (2010) · Nature · doi:10.1038/nature08780 · Cited by 3,812
Structured Clinical Interview for DSM-IV Axis I Disorders
Spitzer, R. L., First, M. B., & Gibbon, M. (1997) · Medical Entomology and Zoology · Cited by 3,582
Telomere measurement by quantitative PCR
Cawthon, R. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.10.e47 · Cited by 3,550
Jahr, S., Hentze, H., Englisch, S., Hardt, D., Fackelmayer, F. O., Hesch, R. D., & Knippers, R. (2001) · PubMed · Cited by 2,169
Telomere dysfunction induces metabolic and mitochondrial compromise
Sahin, E., Colla, S., Liesa, M., Moslehi, J., Müller, F. L., Guo, M., Cooper, M., Kotton, D., Fabian, A. J., Walkey, C., et al. (2011) · Nature · doi:10.1038/nature09787 · Cited by 1,319 · cited 2×
“Mitochondrial integrity and bioenergetics are also related to nuclear DNA senescence, due to a direct link between telomere shortening, repression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and diminished mitochondrial biogenesis in certain tissues [28].”
BackgroundLubos, E., Loscalzo, J., & Handy, D. E. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2010.3586 · Cited by 1,280
Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype
Wiley, C. D., Velarde, M. C., Lecot, P., Liu, S., Sarnoski, E. A., Freund, A., Shirakawa, K., Lim, H. W., Davis, S. S., Ramanathan, A., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.11.011 · Cited by 1,275 · cited 1×
“Beyond energy production, mitochondria generate other signaling molecules that influence cellular and physiological functions, [8, 9] including cellular senescence [10] and production of free radicals [11].”
BackgroundNumber matters: control of mammalian mitochondrial DNA copy number
Montier, L., Deng, J., & Bai, Y. (2009) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/s1673-8527(08)60099-5 · Cited by 532
Impaired mitochondrial function in psychiatric disorders
Manji, H. K., Kato, T., Prospero, N. A. D., Ness, S. L., Beal, M. F., Krams, M., & Chen, G. (2012) · Nature reviews. Neuroscience · doi:10.1038/nrn3229 · Cited by 493
The rise of mitochondria in medicine
Picard, M. A., Wallace, D. C., & Burelle, Y. (2016) · Mitochondrion · doi:10.1016/j.mito.2016.07.003 · Cited by 475
Self-citationOxidative stress, inflammation and treatment response in major depression
Lindqvist, D., Dhabhar, F. S., James, S. J., Hough, C. M., Jain, F. A., Bersani, F. S., Reus, V. I., Verhoeven, J. E., Epel, E. S., Mahan, L., et al. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.11.031 · Cited by 473
Self-citationNakahira, K., Kyung, S.-Y., Rogers, A. J., Gazourian, L., Youn, S., Massaro, A. F., Quintana, C., Osorio, J. C., Wang, Z., Zhao, Y., et al. (2013) · PLoS Medicine · doi:10.1371/journal.pmed.1001577 · Cited by 445
Lin, J., Epel, E., Cheon, J., Kroenke, C., Sinclair, E., Bigos, M., Wolkowitz, O., Mellon, S., & Blackburn, E. (2010) · Journal of Immunological Methods · doi:10.1016/j.jim.2009.09.012 · Cited by 426
Self-citationMitochondrial allostatic load puts the 'gluc' back in glucocorticoids
Picard, M., Juster, R.-P., & McEwen, B. S. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.22 · Cited by 405
Self-citationSignal Transduction by Mitochondrial Oxidants
Finkel, T. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r111.271999 · Cited by 390
MITOCHONDRIAL DNA IS RELEASED BY SHOCK AND ACTIVATES NEUTROPHILS VIA P38 MAP KINASE
Zhang, Q., Itagaki, K., & Hauser, C. J. (2010) · Shock · doi:10.1097/shk.0b013e3181cd8c08 · Cited by 361
Gardner, A., & Boles, R. G. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.07.030 · Cited by 333
Picard, M., McManus, M. J., Gray, J. D., Nasca, C., Moffat, C., Kopinski, P. K., Seifert, E. L., McEwen, B. S., & Wallace, D. C. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1515733112 · Cited by 293
Self-citationNuclear and mitochondrial DNA repair: similar pathways?
Larsen, N. B., Rasmussen, M., & Rasmussen, L. J. (2005) · Mitochondrion · doi:10.1016/j.mito.2005.02.002 · Cited by 289
Lindqvist, D., Epel, E. S., Mellon, S. H., Penninx, B. W., Révész, D., Verhoeven, J. E., Reus, V. I., Lin, J., Mahan, L., Hough, C. M., et al. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.05.007 · Cited by 285
Self-citationMolecular Signatures of Major Depression
Cai, N., Chang, S., Li, Y., Li, Q., Hu, J., Liang, J., Song, L., Kretzschmar, W. W., Gan, X., Nicod, J., et al. (2015) · Current Biology · doi:10.1016/j.cub.2015.03.008 · Cited by 274
Tyrka, A. R., Parade, S. H., Price, L. H., Kao, H.-T., Porton, B., Philip, N. S., Welch, E. S., & Carpenter, L. L. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.12.025 · Cited by 259
The role of mitochondria in health and disease
Johannsen, D. L., & Ravussin, É. (2009) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2009.09.002 · Cited by 243
Suomalainen, A., Majander, A. S., Haltia, M., Somer, H., Lönnqvist, J. K., Savontaus, M. L., & Peltonen, L. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115856 · Cited by 242
Lü, B., Kwan, K., Levine, Y. A., Olofsson, P. S., Yang, H., Li, J., Joshi, S., Wang, H., Andersson, U., Chavan, S. S., et al. (2014) · Molecular Medicine · doi:10.2119/molmed.2013.00117 · Cited by 209
Quantitative Analysis of Circulating Mitochondrial DNA in Plasma
Chiu, R. W. K., Chan, L. Y. S., Lam, N. Y. L., Tsui, N. B. Y., Ng, E. K., Rainer, T. H., & Lo, Y. M. D. (2003) · Clinical Chemistry · doi:10.1373/49.5.719 · Cited by 209
A mitochondrial bioenergetic basis of depression
Klinedinst, N. J., & Regenold, W. T. (2014) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-014-9584-6 · Cited by 161
Tyrka, A. R., Carpenter, L. L., Kao, H.-T., Porton, B., Philip, N. S., Ridout, S. J., Ridout, K. K., & Price, L. H. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.04.002 · Cited by 125
Wolkowitz, O. M., Mellon, S. H., Epel, E. S., Lin, J., Reus, V. I., Rosser, R., Burke, H., Compagnone, M., Nelson, J. C., Dhabhar, F. S., et al. (2011) · Molecular Psychiatry · doi:10.1038/mp.2010.133 · Cited by 125
Self-citationMitochondrial Dysfunction Induced by Sertraline, an Antidepressant Agent
Li, Y., Couch, L., Higuchi, M., Fang, J.-L., & Guo, L. (2012) · Toxicological Sciences · doi:10.1093/toxsci/kfs100 · Cited by 120 · cited 1×
“, via inhibition of mitochondrial enzyme complexes [50], and uncoupling of oxidative phosphorylation [51].”
BackgroundKageyama, Y., Kasahara, T., Kato, M., Sakai, S., Deguchi, Y., Tani, M., Kuroda, K., Hattori, K., Yoshida, S., Goto, Y., et al. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.06.001 · Cited by 116
Anti‐inflammatory, antiapoptotic, and antioxidant activity of fluoxetine
Caiaffo, V., de Oliveira, B. D. R., de Sá, F. B., & Evêncio‐Neto, J. (2016) · Pharmacology Research & Perspectives · doi:10.1002/prp2.231 · Cited by 112
Lindqvist, D., Fernström, J., Grudet, C., Ljunggren, L., Träskman-Bendz, L., Ohlsson, L., & Westrin, Å. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.236 · Cited by 111
Self-citationAnderson, G. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.04.022 · Cited by 111
Kim, J., Kim, H. K., Ko, J., Bang, H., & Lee, D. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067227 · Cited by 109
Chang, C., Jou, S., Lin, T., Lai, T., & Liu, C. (2015) · PLoS ONE · doi:10.1371/journal.pone.0125855 · Cited by 106
Increased circulating mitochondrial DNA after myocardial infarction
Bliksøen, M., Mariero, L. H., Ohm, I. K., Haugen, F., Yndestad, A., Solheim, S., Seljeflot, I., Ranheim, T., Andersen, G. Ø., Aukrust, P., et al. (2012) · International Journal of Cardiology · doi:10.1016/j.ijcard.2012.04.047 · Cited by 104
Number matters： control of mammalian mitochondrial DNA copy number
Laura, L., Clay, Montier, Janice, Deng, Yidong, & Bai (2009) · Acta Scientiarum Naturalium Universitatis Sunyatseni · Cited by 103
Mitochondrial DNA copy number is reduced in male combat veterans with PTSD
Bersani, F. S., Morley, C., Lindqvist, D., Epel, E. S., Picard, M. A., Yehuda, R., Flory, J. D., Bierer, L. M., Makotkine, I., Amara, D. A., et al. (2015) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2015.06.012 · Cited by 93
Self-citationCirculating cell-free mitochondrial DNA as a novel cancer biomarker: opportunities and challenges
Yu, M. (2012) · Mitochondrial DNA · doi:10.3109/19401736.2012.696625 · Cited by 89
Verhoeven, J. E., Révész, D., Picard, M. A., Epel, E. S., Wolkowitz, O. M., Matthews, K. A., Penninx, B. W. J. H., & Puterman, E. M. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.48 · Cited by 87
Self-citationLeukocyte mitochondrial DNA (mtDNA) content is associated with depression in old women
Kim, M.-Y., Lee, J., Kang, H., Kim, E., & Lee, D. (2010) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2010.11.019 · Cited by 85
Fluoxetine affects antioxidant system and promotes apoptotic signaling in Wistar rat liver
Djordjevic, J., Djordjevic, A., Adzic, M., Elaković, I., Matić, G., & Radojcic, M. B. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2011.03.003 · Cited by 78
Abdel-Razaq, W., Kendall, D. A., & Bates, T. E. (2010) · Neurochemical Research · doi:10.1007/s11064-010-0331-z · Cited by 74
Chang, C., Jou, S., Lin, T., & Liu, C. (2014) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12163 · Cited by 72
Glutathione peroxidase 1 protects mitochondria against hypoxia/reoxygenation damage in mouse hearts
Thu, V. T., Kim, H. K., Ha, S. H., Yoo, J. Y., Park, W. S., Kim, N., Oh, G. T., & Han, J. (2010) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-010-0811-7 · Cited by 65
Aberrant telomere length and mitochondrial DNA copy number in suicide completers
Otsuka, I., Izumi, T., Boku, S., Kimura, A., Zhang, Y., Mouri, K., Okazaki, S., Shiroiwa, K., Takahashi, M., Ueno, Y., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-03599-8 · Cited by 63
Antidepressant Action on Mitochondrial Dysfunction in Psychiatric Disorders
Adzic, M., Brkic, Z., Bulajic, S., Mitic, M., & Radojcic, M. B. (2016) · Drug Development Research · doi:10.1002/ddr.21332 · Cited by 60
Leukocyte mitochondrial DNA copy number in bipolar disorder
SOUSA, R. T. D., Uno, M., Zanetti, M. V., Oba‐Shinjo, S. M., Busatto, G. F., Gattaz, W. F., Marie, S. K. N., & Machado‐Vieira, R. (2013) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2013.09.002 · Cited by 57
Hé, Y., Tang, J., Li, Z., Li, H., Liao, Y., Tang, Y., Tan, L., Chen, J., Xia, K., & Chen, X. (2014) · PLoS ONE · doi:10.1371/journal.pone.0096869 · Cited by 56
Nortriptyline delays disease onset in models of chronic neurodegeneration
Wang, H., Guan, Y., Wang, X., Smith, K., Cormier, K., Zhu, S., Stavrovskaya, I. G., Huo, C., Ferrante, R. J., Kristal, B. S., et al. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05663.x · Cited by 53
Liu, J., Zou, Y., Tang, Y., Xi, M., Xie, L., Zhang, Q., & Gong, J. (2015) · Journal of Diabetes Investigation · doi:10.1111/jdi.12366 · Cited by 50
The Amount of Mitochondrial DNA in Blood Reflects the Course of a Depressive Episode
Nicod, J., Wagner, S., Vonberg, F. W., Bhomra, A., Schlicht, K. F., Tadić, A., Mott, R., Lieb, K., & Jonathan Flint, C. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.12.019 · Cited by 28
Calcium-dependent mitochondrial extrusion in ciliated protozoa
Bisharyan, Y., & Clark, T. G. (2011) · Mitochondrion · doi:10.1016/j.mito.2011.08.001 · Cited by 25
Impact of Intravenous Ascorbic Acid Infusion on Novel Biomarkers in Patients with Severe Sepsis
Natarajan, R. (2014) · Journal of Pulmonary & Respiratory Medicine · doi:10.4172/2161-105x.1000214 · Cited by 22
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Metadata
- Authors
- Lindqvist, D., Wolkowitz, O. M., Picard, M., Ohlsson, L., Bersani, F. S., Fernström, J., Westrin, Å., Hough, C. M., Lin, J., Reus, V. I., Epel, E. S., & Mellon, S. H.
- Affiliations
- University of California, San Francisco (US)
- Columbia University Irving Medical Center (US)
- Malmö University (SE)
- Lund University (SE)
- University of California, Los Angeles (US)
- Corresponding author
- Lindqvist, Daniel
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2018-01-30
- Volume
- 43
- Issue
- 7
- Pages
- 1557-1564
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC5983469
- OpenAlex
- W2789855059
- Cited by
- 188
- References
- 56
- Citations by year
- 2026: 15 · 2025: 18 · 2024: 26 · 2023: 27 · 2022: 23 · 2021: 27 · 2020: 26 · 2019: 20 · 2018: 5
- FWCI
- 6.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuropsychopharmacology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Lund University Publications (Lund University) (submittedVersion)
- Malmö University Publications (Malmö University) (submittedVersion)
- Funders
- Vetenskapsrådet (2015-00387)
- Svenska Läkaresällskapet
- University of California, San Francisco
- National Institute of Mental Health (MH083784, R01MH083784)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- major depressive disorder, circulating cell-free mitochondrial DNA, mitochondrial DNA copy number, peripheral blood mononuclear cells, telomere length, glutathione peroxidase, oxidative stress, antidepressant non-responders, mitochondrial dysfunction
- MeSH terms
- Cell-Free Nucleic Acids, Adult, Major Depressive Disorder, Depressive Disorder, Major, DNA, Mitochondrial, Female, Glutathione Peroxidase, Humans, Leukocytes, Mononuclear, Male, Case-Control Studies, Treatment Outcome, Selective Serotonin Reuptake Inhibitors, Young Adult, DNA Copy Number Variations, Telomere Homeostasis
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