The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Figures
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
Cited by
Sorted by citations
Molecular pathways of major depressive disorder converge on the synapse
Fries, G. R., Saldana, V. A., Finnstein, J., & Rein, T. (2023) · Molecular Psychiatry · doi:10.1038/s41380-022-01806-1 · Cited by 504
Todkar, K., Chikhi, L., Desjardins, V., El-Mortada, F., Pépin, G., & Germain, M. (2021) · Nature Communications · doi:10.1038/s41467-021-21984-w · Cited by 382
Han, L. K. M., Dinga, R., Hahn, T., Ching, C. R. K., Eyler, L. T., Aftanas, L. I., Aghajani, M., Aleman, A., Baune, B. T., Berger, K., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0754-0 · Cited by 351
Mitochondria: It is all about energy
Casanova, A., Wevers, A., Ledesma, S. N., & Pruimboom, L. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1114231 · Cited by 350
Mitochondrial transfer/transplantation: an emerging therapeutic approach for multiple diseases
Liu, Z., Sun, Y., Qi, Z., Cao, L., & Ding, S. (2022) · Cell & Bioscience · doi:10.1186/s13578-022-00805-7 · Cited by 236
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
