title: Mitochondria DNA change and oxidative damage in clinically stable patients with major depressive disorder.
abstract: BACKGROUND
  To compare alterations of mitochondria DNA (mtDNA) copy number, single nucleotide polymorphisms (SNPs), and oxidative damage of mtDNA in clinically stable patients with major depressive disorder (MDD).
  
  
  METHODS
  Patients met DSM-IV diagnostic criteria for MDD were recruited from the psychiatric outpatient clinic at Changhua Christian Hospital, Taiwan. They were clinically stable and their medications had not changed for at least the preceding two months. Exclusion criteria were substance-induced psychotic disorder, eating disorder, anxiety disorder or illicit substance abuse. Comparison subjects did not have any major psychiatric disorder and they were medically healthy. Peripheral blood leukocytes were analyzed to compare copy number, SNPs and oxidative damage of mtDNA between the two groups.
  
  
  RESULTS
  40 MDD patients and 70 comparison subjects were collected. The median age of the subjects was 42 years and 38 years in MDD and comparison groups, respectively. Leukocyte mtDNA copy number of MDD patients was significantly lower than that of the comparison group (p = 0.037). MDD patients had significantly higher mitochondrial oxidative damage than the comparison group (6.44 vs. 3.90, p<0.001). After generalized linear model adjusted for age, sex, smoking, family history, and psychotropic use, mtDNA copy number was still significantly lower in the MDD group (p<0.001). MtDNA oxidative damage was positively correlated with age (p<0.001) and MDD (p<0.001). Antipsychotic use was negatively associated with mtDNA copy number (p = 0.036).
  
  
  CONCLUSIONS
  The study is cross-sectional with no longitudinal follow up. The cohort is clinically stable and generalizability of our result to other cohort should be considered.
  
  
  CONCLUSIONS
  Our study suggests that oxidative stress and mitochondria may play a role in the pathophysiology of MDD. More large-scale studies are warranted to assess the interplay between oxidative stress, mitochondria dysfunction and MDD.
authors.affiliation: The Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Psychiatry, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Cheng-Chen
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Department of Psychiatry, Taichung Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Taichung, Taiwan; Department of Medicine, Buddhist Tzu Chi University, Hualien, Taiwan; Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Shaw-Hwa
authors.initials: SH
authors.lastname: Jou
authors.affiliation: Vascular and Genomic Research Center, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Ta-Tsung
authors.initials: TT
authors.lastname: Lin
authors.affiliation: The Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Psychiatry, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Te-Jen
authors.initials: TJ
authors.lastname: Lai
authors.affiliation: Vascular and Genomic Research Center, Changhua Christian Hospital, Changhua, Taiwan; Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Chin-San
authors.initials: CS
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D056915:DNA Copy Number Variations / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D018628:Gene Dosage / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial