Articles producció científica> Medicina i Cirurgia

Increased blood lactate levels during exercise and mitochondrial DNA alterations converge on mitochondrial dysfunction in schizophrenia

  • Dades identificatives

    Identificador: imarina:6248038
    Autors:
    Valiente-Pallejà ATorrell HAlonso YVilella EMuntané GMartorell L
    Resum:
    © 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.
  • Altres:

    Autor segons l'article: Valiente-Pallejà A; Torrell H; Alonso Y; Vilella E; Muntané G; Martorell L
    Departament: Medicina i Cirurgia
    Autor/s de la URV: Martorell Bonet, Lourdes / Muntané Medina, Gerard / Valiente Pallejà, Alba / Vilella Cuadrada, Elisabet
    Paraules clau: Variants Stress test Schizophrenia Prioritization Mtdna Mitochondrial dna Mitochondria Metabolism Lactate Illness Heteroplasmy Diagnosis Complex i Comorbidity mitochondrial dna mitochondria lactate comorbidity
    Resum: © 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.
    Àrees temàtiques: 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
    Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 09209964
    Adreça de correu electrònic de l'autor: alba.valiente@urv.cat elisabet.vilella@urv.cat gerard.muntane@urv.cat lourdes.martorell@urv.cat
    Identificador de l'autor: 0000-0002-1887-5919 0000-0003-4999-2197
    Data d'alta del registre: 2024-06-08
    Versió de l'article dipositat: info:eu-repo/semantics/acceptedVersion
    Enllaç font original: https://www.sciencedirect.com/science/article/abs/pii/S092099642030181X
    Referència a l'article segons font original: Schizophrenia Research. 220 61-68
    Referència de l'ítem segons les normes 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
    URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    DOI de l'article: 10.1016/j.schres.2020.03.070
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2020
    Tipus de publicació: Journal Publications
  • Paraules clau:

    Biological Psychiatry,Psychiatry,Psychiatry and Mental Health
    Variants
    Stress test
    Schizophrenia
    Prioritization
    Mtdna
    Mitochondrial dna
    Mitochondria
    Metabolism
    Lactate
    Illness
    Heteroplasmy
    Diagnosis
    Complex i
    Comorbidity
    mitochondrial dna
    mitochondria
    lactate
    comorbidity
    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
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