Investigation of mitochondrial DNA copy number in patients with major depressive disorder

Psychiatry Res. 2019 Dec;282:112616. doi: 10.1016/j.psychres.2019.112616. Epub 2019 Oct 14.

Abstract

Mitochondrial dysfunction is implicated in the pathophysiology of major depressive disorder (MDD). This dysfunction can be indirectly assessed using the mitochondrial DNA (mtDNA) copy number. A total of 118 patients with MDD and 116 age- and sex-matched control subjects were recruited for this study, and mtDNA copy numbers were measured in peripheral blood cells. This study also examined the potential variables that might impact mtDNA copy number in MDD, including age and clinical features. Additionally, epigenetic control of mtDNA copy number was examined by assessing DNA methylation ratios in the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) promoter in nuclear DNA and the displacement loop (D-loop) region of mtDNA. The present results showed that patients with MDD had a higher mtDNA copy number and a decreased DNA methylation status in the PGC1α promoter. mtDNA copy numbers were negatively associated with an age, psychomotor agitation, and somatic symptoms in MDD. These results suggest that the alterations in mitochondrial function and epigenetic change of PGC1α may be relevant to the pathophysiology of MDD.

Keywords: Displacement loop; Major depressive disorder; Methylation; Mitochondria; Peroxisome-proliferator-activated receptor γ co-activator-1α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • DNA Copy Number Variations
  • DNA Methylation / genetics
  • DNA, Mitochondrial / genetics*
  • Depressive Disorder, Major / genetics*
  • Depressive Disorder, Major / physiopathology*
  • Epigenesis, Genetic / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism*
  • Young Adult

Substances

  • DNA, Mitochondrial
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha