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Mitochondrial DNA copy number is associated with psychosis severity and anti-psychotic treatment

Mitochondrial pathology has been implicated in the pathogenesis of psychotic disorders. A few studies have proposed reduced leukocyte mitochondrial DNA (mtDNA) copy number in schizophrenia and bipolar disorder type I, compared to healthy controls. However, it is unknown if mtDNA copy number alterati...

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Autores principales: Kumar, Parvin, Efstathopoulos, Paschalis, Millischer, Vincent, Olsson, Eric, Wei, Ya Bin, Brüstle, Oliver, Schalling, Martin, Villaescusa, J. Carlos, Ösby, Urban, Lavebratt, Catharina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109159/
https://www.ncbi.nlm.nih.gov/pubmed/30143692
http://dx.doi.org/10.1038/s41598-018-31122-0
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author Kumar, Parvin
Efstathopoulos, Paschalis
Millischer, Vincent
Olsson, Eric
Wei, Ya Bin
Brüstle, Oliver
Schalling, Martin
Villaescusa, J. Carlos
Ösby, Urban
Lavebratt, Catharina
author_facet Kumar, Parvin
Efstathopoulos, Paschalis
Millischer, Vincent
Olsson, Eric
Wei, Ya Bin
Brüstle, Oliver
Schalling, Martin
Villaescusa, J. Carlos
Ösby, Urban
Lavebratt, Catharina
author_sort Kumar, Parvin
collection PubMed
description Mitochondrial pathology has been implicated in the pathogenesis of psychotic disorders. A few studies have proposed reduced leukocyte mitochondrial DNA (mtDNA) copy number in schizophrenia and bipolar disorder type I, compared to healthy controls. However, it is unknown if mtDNA copy number alteration is driven by psychosis, comorbidity or treatment. Whole blood mtDNA copy number was determined in 594 psychosis patients and corrected for platelet to leukocyte count ratio (mtDNAcn(res)). The dependence of mtDNAcn(res) on clinical profile, metabolic comorbidity and antipsychotic drug exposure was assessed. mtDNAcn(res) was reduced with age (β = −0.210, p < 0.001), use of clozapine (β = −0.110,p = 0.012) and risperidone (β = −0.109,p = 0.014), dependent on prescribed dosage (p = 0.006 and p = 0.026, respectively), and the proportion of life on treatment (p = 0.006). Clozapine (p = 0.0005) and risperidone (p = 0.0126) had a reducing effect on the mtDNA copy number also in stem cell-derived human neurons in vitro at therapeutic plasma levels. For patients not on these drugs, psychosis severity had an effect (β = −0.129, p = 0.017), similar to age (β = −0.159, p = 0.003) and LDL (β = −0.119, p = 0.029) on whole blood mtDNAcn(res). Further research is required to determine if mtDNAcn(res) reflects any psychosis-intrinsic mitochondrial changes.
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spelling pubmed-61091592018-08-31 Mitochondrial DNA copy number is associated with psychosis severity and anti-psychotic treatment Kumar, Parvin Efstathopoulos, Paschalis Millischer, Vincent Olsson, Eric Wei, Ya Bin Brüstle, Oliver Schalling, Martin Villaescusa, J. Carlos Ösby, Urban Lavebratt, Catharina Sci Rep Article Mitochondrial pathology has been implicated in the pathogenesis of psychotic disorders. A few studies have proposed reduced leukocyte mitochondrial DNA (mtDNA) copy number in schizophrenia and bipolar disorder type I, compared to healthy controls. However, it is unknown if mtDNA copy number alteration is driven by psychosis, comorbidity or treatment. Whole blood mtDNA copy number was determined in 594 psychosis patients and corrected for platelet to leukocyte count ratio (mtDNAcn(res)). The dependence of mtDNAcn(res) on clinical profile, metabolic comorbidity and antipsychotic drug exposure was assessed. mtDNAcn(res) was reduced with age (β = −0.210, p < 0.001), use of clozapine (β = −0.110,p = 0.012) and risperidone (β = −0.109,p = 0.014), dependent on prescribed dosage (p = 0.006 and p = 0.026, respectively), and the proportion of life on treatment (p = 0.006). Clozapine (p = 0.0005) and risperidone (p = 0.0126) had a reducing effect on the mtDNA copy number also in stem cell-derived human neurons in vitro at therapeutic plasma levels. For patients not on these drugs, psychosis severity had an effect (β = −0.129, p = 0.017), similar to age (β = −0.159, p = 0.003) and LDL (β = −0.119, p = 0.029) on whole blood mtDNAcn(res). Further research is required to determine if mtDNAcn(res) reflects any psychosis-intrinsic mitochondrial changes. Nature Publishing Group UK 2018-08-24 /pmc/articles/PMC6109159/ /pubmed/30143692 http://dx.doi.org/10.1038/s41598-018-31122-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kumar, Parvin
Efstathopoulos, Paschalis
Millischer, Vincent
Olsson, Eric
Wei, Ya Bin
Brüstle, Oliver
Schalling, Martin
Villaescusa, J. Carlos
Ösby, Urban
Lavebratt, Catharina
Mitochondrial DNA copy number is associated with psychosis severity and anti-psychotic treatment
title Mitochondrial DNA copy number is associated with psychosis severity and anti-psychotic treatment
title_full Mitochondrial DNA copy number is associated with psychosis severity and anti-psychotic treatment
title_fullStr Mitochondrial DNA copy number is associated with psychosis severity and anti-psychotic treatment
title_full_unstemmed Mitochondrial DNA copy number is associated with psychosis severity and anti-psychotic treatment
title_short Mitochondrial DNA copy number is associated with psychosis severity and anti-psychotic treatment
title_sort mitochondrial dna copy number is associated with psychosis severity and anti-psychotic treatment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109159/
https://www.ncbi.nlm.nih.gov/pubmed/30143692
http://dx.doi.org/10.1038/s41598-018-31122-0
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