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Plasma circulating cell-free mitochondrial DNA in depressive disorders

Fernström, Johan LU ; Ohlsson, Lars ; Asp, Marie LU ; Lavant, Eva ; Holck, Amanda LU ; Grudet, Cécile LU orcid ; Westrin, Åsa LU and Lindqvist, Daniel LU (2021) In PLoS ONE 16(11 November).
Abstract

Plasma circulating cell-free mitochondrial DNA (ccf-mtDNA) is an immunogenic molecule and a novel biomarker of psychiatric disorders. Some previous studies reported increased levels of ccf-mtDNA in unmedicated depression and recent suicide attempters, while other studies found unchanged or decreased ccf-mtDNA levels in depression. Inconsistent findings across studies may be explained by small sample sizes and between-study variations in somatic and psychiatric co-morbidity or medication status. Methods We measured plasma ccf-mtDNA in a cohort of 281 patients with depressive disorders and 49 healthy controls. Ninety-three percent of all patients were treated with one or several psychotropic medications. Thirty-six percent had a... (More)

Plasma circulating cell-free mitochondrial DNA (ccf-mtDNA) is an immunogenic molecule and a novel biomarker of psychiatric disorders. Some previous studies reported increased levels of ccf-mtDNA in unmedicated depression and recent suicide attempters, while other studies found unchanged or decreased ccf-mtDNA levels in depression. Inconsistent findings across studies may be explained by small sample sizes and between-study variations in somatic and psychiatric co-morbidity or medication status. Methods We measured plasma ccf-mtDNA in a cohort of 281 patients with depressive disorders and 49 healthy controls. Ninety-three percent of all patients were treated with one or several psychotropic medications. Thirty-six percent had a personality disorder, 13% bipolar disorder. All analyses involving ccf-mtDNA were a priori adjusted for age and sex. Results Mean levels in ccf-mtDNA were significantly different between patients with a current depressive episode (n = 236), remitted depressive episode (n = 45) and healthy controls (n = 49) (f = 8.3, p<0.001). Post-hoc tests revealed that both patients with current (p<0.001) and remitted (p = 0.002) depression had lower ccf-mtDNA compared to controls. Within the depressed group there was a positive correlation between ccf-mtDNA and “inflammatory depression symptoms” (r = 0.15, p = 0.02). We also found that treatment with mood stabilizers lamotrigine, valproic acid or lithium was associated with lower ccf-mtDNA (f = 8.1, p = 0.005). Discussion Decreased plasma ccf-mtDNA in difficult-to-treat depression may be partly explained by concurrent psychotropic medications and co-morbidity. Our findings suggest that ccf-mtDNA may be differentially regulated in different subtypes of depression, and this hypothesis should be pursued in future studies.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
16
issue
11 November
article number
e0259591
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:34735532
  • scopus:85118663333
ISSN
1932-6203
DOI
10.1371/journal.pone.0259591
language
English
LU publication?
yes
additional info
Publisher Copyright: Copyright: © 2021 Fernström et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
id
1a0914e5-7332-4b85-9e7a-8e49cabe9fd5
date added to LUP
2021-11-25 11:15:24
date last changed
2021-11-26 03:00:05
@article{1a0914e5-7332-4b85-9e7a-8e49cabe9fd5,
  abstract     = {<p>Plasma circulating cell-free mitochondrial DNA (ccf-mtDNA) is an immunogenic molecule and a novel biomarker of psychiatric disorders. Some previous studies reported increased levels of ccf-mtDNA in unmedicated depression and recent suicide attempters, while other studies found unchanged or decreased ccf-mtDNA levels in depression. Inconsistent findings across studies may be explained by small sample sizes and between-study variations in somatic and psychiatric co-morbidity or medication status. Methods We measured plasma ccf-mtDNA in a cohort of 281 patients with depressive disorders and 49 healthy controls. Ninety-three percent of all patients were treated with one or several psychotropic medications. Thirty-six percent had a personality disorder, 13% bipolar disorder. All analyses involving ccf-mtDNA were a priori adjusted for age and sex. Results Mean levels in ccf-mtDNA were significantly different between patients with a current depressive episode (n = 236), remitted depressive episode (n = 45) and healthy controls (n = 49) (f = 8.3, p&lt;0.001). Post-hoc tests revealed that both patients with current (p&lt;0.001) and remitted (p = 0.002) depression had lower ccf-mtDNA compared to controls. Within the depressed group there was a positive correlation between ccf-mtDNA and “inflammatory depression symptoms” (r = 0.15, p = 0.02). We also found that treatment with mood stabilizers lamotrigine, valproic acid or lithium was associated with lower ccf-mtDNA (f = 8.1, p = 0.005). Discussion Decreased plasma ccf-mtDNA in difficult-to-treat depression may be partly explained by concurrent psychotropic medications and co-morbidity. Our findings suggest that ccf-mtDNA may be differentially regulated in different subtypes of depression, and this hypothesis should be pursued in future studies.</p>},
  author       = {Fernström, Johan and Ohlsson, Lars and Asp, Marie and Lavant, Eva and Holck, Amanda and Grudet, Cécile and Westrin, Åsa and Lindqvist, Daniel},
  issn         = {1932-6203},
  language     = {eng},
  number       = {11 November},
  publisher    = {Public Library of Science (PLoS)},
  series       = {PLoS ONE},
  title        = {Plasma circulating cell-free mitochondrial DNA in depressive disorders},
  url          = {http://dx.doi.org/10.1371/journal.pone.0259591},
  doi          = {10.1371/journal.pone.0259591},
  volume       = {16},
  year         = {2021},
}