Mitochondria DNA change and oxidative damage in clinically stable patients with major depressive disorder.

Cheng-Chen Chang,Chin-San Liu,Te-Jen Lai,Shaw-Hwa Jou,Ta-Tsung Lin,Yidong Bai

doi:10.1371/journal.pone.0125855

Abstract

BackgroundTo 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).MethodsPatients 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.Results40 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).LimitationsThe 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.ConclusionsOur 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.

Highlights

Mitochondria play an important role in energy metabolism [1,2]
After generalized linear model adjusted for age, sex, smoking, family history, and psychotropic use, mitochondrial DNA (mtDNA) copy number was still significantly lower in the major depressive disorder (MDD) group (p
Our study suggests that oxidative stress and mitochondria may play a role in the pathophysiology of MDD

Summary

Introduction

Mitochondria play an important role in energy metabolism [1,2]. It is well known that mitochondrial oxidative phosphorylation system generates free radicals and the electron transport chain itself is vulnerable to damage by free radicals [3]. Human mitochondrial DNA (mtDNA) is prone to oxidative injury because mtDNA is not protected by histones and mitochondria generate reactive oxygen species (ROS) during ATP synthesis [4]. Mitochondrial dysfunction results from alterations in biochemical cascade and the damage to the electron transport chain has been suggested to be an important factor in the pathogenesis of a range of psychiatric disorders, such as major depressive disorder (MDD) [5]. Kato et al proposed mitochondrial dysfunction hypothesis involving the 10398A and 5178C genotypes in the pathophysiology of BD [10,11], whether 10398A and 5178C mtDNA polymorphisms play a role in MDD is unknown. 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

Results

Conclusion