title: Leukocyte mitochondrial DNA copy number in bipolar disorder.
abstract: BACKGROUND
  Evidence supports the role for mitochondrial impairment in the pathophysiology of bipolar disorder (BD). BD has been associated with decreased mitochondrial electron transport chain activity and increased oxidative stress. Also, mitochondrial DNA (mtDNA) encodes mitochondrial electron transport chain proteins and has been associated with altered oxidative stress. Preclinical studies showed that lithium treatment increased mtDNA content, but no study has directly assessed mtDNA content in subjects with BD in vivo. Also, the effects of lithium treatment on mtDNA content have never been evaluated in humans.
  
  
  METHODS
  Leukocyte mtDNA content using real time-PCR was evaluated in subjects with BD (n=23) in a depressive episode (≥18 in the 21-item Hamilton Depression Rating Scale) before and after 6-week lithium treatment versus healthy controls (n=24).
  
  
  RESULTS
  mtDNA content showed no significant difference between subjects with BD at baseline and controls (p=0.46); also no difference was observed when comparing before and after lithium treatment. A trend for decreased mtDNA content was specifically observed in BD type I compared to controls and BD type II (p=0.05). Importantly, endpoint mtDNA copy number was significantly correlated with age.
  
  
  CONCLUSIONS
  In BD subjects who were younger, unmedicated and had a shorter duration of illness, no change was observed in mtDNA copy number. More studies with larger samples are warranted to evaluate mtDNA content changes in BD and its potential role as a treatment target, especially in BD type I and its association with aging.
authors.affiliation: Laboratory of Neuroscience, LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Brazil.
authors.forename: Rafael T
authors.initials: RT
authors.lastname: de Sousa
authors.forename: Miyuki
authors.initials: M
authors.lastname: Uno
authors.forename: Marcus V
authors.initials: MV
authors.lastname: Zanetti
authors.forename: Sueli M O
authors.initials: SM
authors.lastname: Shinjo
authors.forename: Geraldo F
authors.initials: GF
authors.lastname: Busatto
authors.forename: Wagner F
authors.initials: WF
authors.lastname: Gattaz
authors.forename: Sueli K N
authors.initials: SK
authors.lastname: Marie
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Machado-Vieira
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000097:blood* / Q000235:genetics*; D016022:Case-Control Studies; D056915:DNA Copy Number Variations / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial
keywords: 21-item Hamilton Depression Scale; Antidepressant; BD; Bipolar disorder; CGI; Clinical Global Impression; Depression; ETC; HAM-D; HBb; Hemoglobin Beta; Lithium; Mitochondria; SCID; Structured Clinical Interview for Axis I DSM-IV-TR Disorders; Treatment; YMRS; Young Mania Rating Scale; electron transport chain; mitochondrial DNA; mtDNA