Author, as appears in the article.: Valiente-Pallejà A; Torrell H; Alonso Y; Vilella E; Muntané G; Martorell L
Department: Medicina i Cirurgia
URV's Author/s: Martorell Bonet, Lourdes / Muntané Medina, Gerard / Valiente Pallejà, Alba / Vilella Cuadrada, Elisabet
Keywords: Variants Stress test Schizophrenia Prioritization Mtdna Mitochondrial dna Mitochondria Metabolism Lactate Illness Heteroplasmy Diagnosis Complex i Comorbidity mitochondrial dna mitochondria lactate comorbidity
Abstract: © 2020 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.
Thematic Areas: Saúde coletiva Química Psychology Psychiatry and mental health Psychiatry Psicología Odontología Medicina ii Medicina i Interdisciplinar General medicine Farmacia Ensino Engenharias iv Educação física Ciencias sociales Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Biotecnología Biological psychiatry Biodiversidade Antropologia / arqueologia Administração pública e de empresas, ciências contábeis e turismo
licence for use: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 09209964
Author's mail: alba.valiente@urv.cat elisabet.vilella@urv.cat gerard.muntane@urv.cat lourdes.martorell@urv.cat
Author identifier: 0000-0002-1887-5919 0000-0003-4999-2197
Record's date: 2024-06-08
Papper version: info:eu-repo/semantics/acceptedVersion
Link to the original source: https://www.sciencedirect.com/science/article/abs/pii/S092099642030181X
Papper original source: Schizophrenia Research. 220 61-68
APA: Valiente-Pallejà A; Torrell H; Alonso Y; Vilella E; Muntané G; Martorell L (2020). Increased blood lactate levels during exercise and mitochondrial DNA alterations converge on mitochondrial dysfunction in schizophrenia. Schizophrenia Research, 220(), 61-68. DOI: 10.1016/j.schres.2020.03.070
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Article's DOI: 10.1016/j.schres.2020.03.070
Entity: Universitat Rovira i Virgili
Journal publication year: 2020
Publication Type: Journal Publications