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

Parvin Kumar1,2, Paschalis Efstathopoulos3,4, Vincent Millischer3,4

  • 1Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. parvin.kumar@ki.se.

Scientific Reports
|August 26, 2018
PubMed

Insights

Mitochondrial DNA copy number is reduced in psychosis patients, influenced by age and antipsychotic medications like clozapine and risperidone. Psychosis severity also impacts mitochondrial DNA copy number in patients not on these specific drugs.

Area of Science:

  • Neuroscience
  • Genetics
  • Psychiatry

Background:

  • Mitochondrial dysfunction is increasingly linked to psychotic disorders.
  • Previous studies suggest reduced leukocyte mitochondrial DNA (mtDNA) copy number in schizophrenia and bipolar disorder.
  • It remains unclear whether these alterations are caused by psychosis itself, comorbidities, or treatments.

Purpose of the Study:

  • To investigate the relationship between whole blood mtDNA copy number and clinical factors in psychosis patients.
  • To assess the impact of antipsychotic drug exposure, metabolic comorbidities, and psychosis severity on mtDNA copy number.
  • To explore potential in vitro effects of antipsychotics on mtDNA levels in neurons.

Main Methods:

  • Whole blood mtDNA copy number was measured in 594 psychosis patients and corrected for platelet-to-leukocyte ratio (mtDNAcnres).
  • Statistical analyses were performed to determine the association of mtDNAcnres with age, clinical profile, metabolic comorbidity, and antipsychotic drug exposure (clozapine, risperidone).
  • In vitro experiments using stem cell-derived human neurons assessed the effect of clozapine and risperidone on mtDNA copy number at therapeutic plasma levels.

Main Results:

  • Reduced mtDNAcnres was associated with older age, clozapine use, and risperidone use, with effects dependent on dosage and duration of treatment.
  • In vitro, clozapine and risperidone demonstrated a reducing effect on mtDNA copy number in human neurons at therapeutic levels.
  • In patients not on clozapine or risperidone, psychosis severity, age, and LDL cholesterol levels were significantly associated with reduced mtDNAcnres.

Conclusions:

  • Antipsychotic medications, particularly clozapine and risperidone, and their dosage/duration, significantly reduce mtDNA copy number in psychosis patients.
  • Psychosis severity, age, and metabolic factors also influence mtDNA copy number, independent of these specific drug treatments.
  • Further research is needed to ascertain if observed mtDNAcnres reductions reflect psychosis-intrinsic mitochondrial changes or are primarily treatment-related effects.

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