CoChat
Sign Up
Cited by 188Mitochondrial Function and PathologyTreatment of Major DepressionTryptophan and brain disorders

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 access
Lindqvist, Daniel, Wolkowitz, Owen M., Picard, Martin, Ohlsson, Lars, Bersani, Francesco S., Fernström, Johan, Westrin, Åsa, Hough, Christina M., Lin, Jue, Reus, Victor I., Epel, Elissa S., Mellon, Synthia H.·2018·Neuropsychopharmacology
DOI 10.1038/s41386-017-0001-9PMC PMC5983469
Open this paper in CoChat — free accountOpen PDF

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.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41386-017-0001-9

Cites

56 of 56 references verified0 citation errors · 0 not checkable

Statistics

Figures

Fig. 1 Circulating cell-free mitochondrial DNA (Ccf-mtDNA) and peripheral blood mononuclear cell (PBMC) mtDNA copy number in MDD subjects and controls. Data were log-transformed. Error bars indicate ±1 SD
Fig. 1 Circulating cell-free mitochondrial DNA (Ccf-mtDNA) and peripheral blood mononuclear cell (PBMC) mtDNA copy number in MDD subjects and controls. Data were log-transformed. Error bars indicate ±1 SDCC BY · PubMed Central
Fig. 2 Change in circulating cell-free mitochondrial DNA (ccf-mtDNA) (mean + SEM) between baseline and week 8 in SSRI responders and non-responders. Data were log-transformed
Fig. 2 Change in circulating cell-free mitochondrial DNA (ccf-mtDNA) (mean + SEM) between baseline and week 8 in SSRI responders and non-responders. Data were log-transformedCC BY · PubMed Central
Fig. 3 Circulating cell-free mitochondrial DNA (ccf mtDNA) (log-transformed) plotted against glutathione peroxidase activity (GpX) (z-scores) in MDD subjects and healthy controls. Pearson’s r = 0.32, p = 0.001
Fig. 3 Circulating cell-free mitochondrial DNA (ccf mtDNA) (log-transformed) plotted against glutathione peroxidase activity (GpX) (z-scores) in MDD subjects and healthy controls. Pearson’s r = 0.32, p = 0.001CC BY · PubMed Central
Fig. 4 Peripheral blood mononuclear cell (PBMC) telomere length plotted against PBMC mitochondrial DNA-copy number (mtDN-cn) (log-transformed) in MDD subjects and healthy controls. Pearson’s r = 0.28, p = 0.005
Fig. 4 Peripheral blood mononuclear cell (PBMC) telomere length plotted against PBMC mitochondrial DNA-copy number (mtDN-cn) (log-transformed) in MDD subjects and healthy controls. Pearson’s r = 0.28, p = 0.005CC BY · PubMed Central

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.

A few free checks a day · papers already verified open instantly · results are public

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?

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

Show all 56 references

Cited by

Sorted by citations

Items 101–188 of 188

Related

See all

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
Publisher
Springer Science and Business Media LLC
Published
2018-01-30
Volume
43
Issue
7
Pages
1557-1564
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/s41386-017-0001-9
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
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