Evidence map›Paper›PMID 29453441›Full record

Trial reportNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2018

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

Daniel Lindqvist, Owen M Wolkowitz, Martin Picard, Lars Ohlsson, Francesco S Bersani, Johan Fernström, Åsa Westrin, Christina M Hough, Jue Lin, Victor I Reus and 2 more

Open access · hybridAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed, 8 pooled it
7.4field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

117 citing papers in PubMed, 8 syntheses or guidelines pooled it, 189 citations in OpenAlex.

  1. Pooled it
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  9. Trial
  10. Trial
  11. Article
  12. Review
  13. Article
  14. Review
  15. Premature aging in serious mental illness.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Review
  16. Review
  17. Review
  18. Review
  19. Cell-Free DNA and Mitochondria in Parkinson's Disease.International journal of molecular sciences · 2025
    Review
  20. Review

57 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 3 countries.

Daniel LindqvistFaculty of Medicine, Department of Clinical Sciences, Psychiatry, Lund University, Lund, Sweden. daniel.lindqvist@med.lu.se.
Owen M WolkowitzDepartment of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA.
Martin PicardDivision of Behavioral Medicine, Department of Psychiatry, Columbia University Medical Center, New York, NY, USA.
Lars OhlssonDepartment of Biomedical Science, Malmö University, Malmö, Sweden.
Francesco S BersaniDepartment of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA.
Johan FernströmFaculty of Medicine, Department of Clinical Sciences, Psychiatry, Lund University, Lund, Sweden.
Åsa WestrinFaculty of Medicine, Department of Clinical Sciences, Psychiatry, Lund University, Lund, Sweden.
Christina M HoughDepartment of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA.
Jue LinDepartment of Biochemistry and Biophysics, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA.
Victor I ReusDepartment of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA.
Elissa S EpelDepartment of Psychiatry, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA.
Synthia H MellonDepartment of OB/GYN and Reproductive Sciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA.
University of California, San Francisco · USLund University · SEColumbia University Irving Medical Center · USMalmö University · SESapienza University of Rome · ITUniversity of California, Los Angeles · US

Funding

Cell Aging in Major DepressionR01MH083784 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI EPEL, ELISSA S., MELLON, SYNTHIA H · 2010 to 2020
$6.7M
NIMH NIH HHS R01 MH083784
6 · The paper itself

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.

Indexed as

AdultCase-Control StudiesCell-Free Nucleic AcidsDNA Copy Number VariationsDNA, MitochondrialFemaleGlutathione PeroxidaseHumansLeukocytes, MononuclearMajor Depressive DisorderMaleSelective Serotonin Reuptake InhibitorsTelomere HomeostasisTreatment OutcomeYoung AdultCell-Free Nucleic AcidsDNA, MitochondrialGlutathione PeroxidaseSelective Serotonin Reuptake Inhibitors

Identifiers

PMID29453441
PMCPMC5983469
OpenAlexW2789855059

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.