Increased blood lactate levels during exercise and mitochondrial DNA alterations converge on mitochondrial dysfunction in schizophrenia.
Comorbidity
Lactate
Mitochondria
Mitochondrial DNA
Schizophrenia
Journal
Schizophrenia research
ISSN: 1573-2509
Titre abrégé: Schizophr Res
Pays: Netherlands
ID NLM: 8804207
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
23
07
2019
revised:
13
03
2020
accepted:
29
03
2020
pubmed:
25
4
2020
medline:
22
6
2021
entrez:
25
4
2020
Statut:
ppublish
Résumé
Mitochondrial dysfunction and an elevation of lactate are observed in patients with schizophrenia (SZ). However, it is unknown whether mitochondrial dysfunction is associated with the presence of mitochondrial DNA (mtDNA) alterations and comorbid clinical conditions. We aimed to identify systemic mitochondrial abnormalities in blood samples of patients with SZ that may have a high impact on the brain due to its high bioenergetic requirements. Case/control study between 57 patients with SZ and 33 healthy controls (HCs). We measured lactate levels at baseline, during 15 min of exercise (at 5, 10 and 15 min) and at rest. We also evaluated the presence of clinical conditions associated with mitochondrial disorders (CAMDs), measured the neutrophil to lymphocyte ratio (NLR, a subclinical inflammatory marker), and analyzed mtDNA variation and copy number. Linear models adjusting for covariates showed that patients with SZ exhibited higher elevation of lactate than HCs during exercise but not at baseline or at rest. In accordance, patients showed higher number of CAMDs and lower mtDNA copy number. Interestingly, CAMDs correlated with both lactate levels and mtDNA copy number, which in turn correlated with the NLR. Finally, we identified 13 putative pathogenic variants in the mtDNA of 11 participants with SZ not present in HCs, together with a lactate elevation during exercise that was significantly higher in these 11 carriers than in the noncarriers. These results are consistent with systemic mitochondrial malfunctioning in SZ and pinpoint lactate metabolism and mtDNA as targets for potential therapeutic treatments.
Sections du résumé
BACKGROUND
Mitochondrial dysfunction and an elevation of lactate are observed in patients with schizophrenia (SZ). However, it is unknown whether mitochondrial dysfunction is associated with the presence of mitochondrial DNA (mtDNA) alterations and comorbid clinical conditions. We aimed to identify systemic mitochondrial abnormalities in blood samples of patients with SZ that may have a high impact on the brain due to its high bioenergetic requirements.
METHODS
Case/control study between 57 patients with SZ and 33 healthy controls (HCs). We measured lactate levels at baseline, during 15 min of exercise (at 5, 10 and 15 min) and at rest. We also evaluated the presence of clinical conditions associated with mitochondrial disorders (CAMDs), measured the neutrophil to lymphocyte ratio (NLR, a subclinical inflammatory marker), and analyzed mtDNA variation and copy number.
RESULTS
Linear models adjusting for covariates showed that patients with SZ exhibited higher elevation of lactate than HCs during exercise but not at baseline or at rest. In accordance, patients showed higher number of CAMDs and lower mtDNA copy number. Interestingly, CAMDs correlated with both lactate levels and mtDNA copy number, which in turn correlated with the NLR. Finally, we identified 13 putative pathogenic variants in the mtDNA of 11 participants with SZ not present in HCs, together with a lactate elevation during exercise that was significantly higher in these 11 carriers than in the noncarriers.
CONCLUSIONS
These results are consistent with systemic mitochondrial malfunctioning in SZ and pinpoint lactate metabolism and mtDNA as targets for potential therapeutic treatments.
Identifiants
pubmed: 32327316
pii: S0920-9964(20)30181-X
doi: 10.1016/j.schres.2020.03.070
pii:
doi:
Substances chimiques
DNA, Mitochondrial
0
Lactates
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
61-68Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors have no conflicts of interest to report, financial or otherwise.