ROS-Induced DNA Damage Associates with Abundance of Mitochondrial DNA in White Blood Cells of the Untreated Schizophrenic Patients.

I V Chestkov,G P Kostyuk,E S Ershova,N Yu Kolesina,V L Izhevskaya,T V Lezheiko,S I Kutsev,O A Dolgikh,V G Golimbet,N N Veiko,S V Kostyuk,E M Jestkova

doi:10.1155/2018/8587475

Abstract

Objective The aim of this study was (1) to examine the leukocyte mtDNA copy number (CN) in unmedicated (SZ (m−)) and medicated (SZ (m+)) male patients with paranoid schizophrenia (SZ) in comparison with the healthy male controls (HC) and (2) to compare the leukocyte mtDNA CN with the content of an oxidation marker 8-oxodG in lymphocytes of the SZ (m−) patients. Methods We evaluated leukocyte mtDNA CN of 110 subjects with SZ in comparison with 60 male HC by the method qPCR (ratio mtDNA/nDNA (gene B2M) was detected). SZ patients were divided into two subgroups. The patients of the subgroups SZ (m+) (N = 55) were treated with standard antipsychotic medications in the hospital. The patients of the subgroup SZ (m−) (N = 55) were not treated before venous blood was sampled. To evaluate oxidative DNA damage, we quantified the levels of 8-oxodG in lymphocytes (flow cytometry) of SZ (m−) patients (N = 55) and HC (N = 30). Results The leukocyte mtDNA CN showed no significant difference in SZ (m+) patients and HC. The mtDNA CN in the unmedicated subgroup SZ (m−) was significantly higher than that in the SZ (m+) subgroup or in HC group. The level of 8-oxodG in the subgroup SZ (m−) was significantly higher than that in HC group. Conclusion The leukocytes of the unmedicated SZ male patients with acute psychosis contain more mtDNA than the leukocytes of the male SZ patients treated with antipsychotic medications or the healthy controls. MtDNA content positively correlates with the level of 8-oxodG in the unmedicated SZ patients.

Highlights

1% of the world’s population suffer from schizophrenia (SZ)
Some authors show lower mtDNA copy number in brain tissues and peripheral lymphocytes of schizophrenia patients compared with healthy controls (HC) [4,5,6,7]
In 12 patients of 55 (21.8%) from SZ (m−) group and only in 1 patients of 55 (1.7%) from SZ (m+) group, a considerable increase in mtDNA copy number (CN) compared to the HC was found (Figure 1)

Summary

Introduction

1% of the world’s population suffer from schizophrenia (SZ). Schizophrenia is a highly heritable neuropsychiatric disorder of complex genetic etiology. Mitochondrion (mt) is a cellular organelle involved in the regulation of a variety of complex cellular processes. MtDNA copy number (CN) variation has been suggested as a sensitive index of cellular oxidative stress, inflammation, and mitochondrial dysfunction [1, 2]. The accumulating morphological, genetic, and imaging data delineates mitochondrial multifaceted dysfunction as a pathological factor in schizophrenia [3]. Several studies have evaluated the influence of schizophrenia on mtDNA copy number. Some authors show lower mtDNA copy number in brain tissues and peripheral lymphocytes of schizophrenia patients compared with healthy controls (HC) [4,5,6,7].

Methods

Results

Conclusion