title: Quantification of cell-free DNA in blood plasma and DNA damage degree in lymphocytes to evaluate dysregulation of apoptosis in schizophrenia patients.
abstract: Oxidative DNA damage has been proposed as one of the causes of schizophrenia (SZ), and post mortem data indicate a dysregulation of apoptosis in SZ patients. To evaluate apoptosis in vivo we quantified the concentration of plasma cell-free DNA (cfDNA index, determined using fluorescence), the levels of 8-oxodG in cfDNA (immunoassay) and lymphocytes (FL1-8-oxodG index, flow cytometry) of male patients with acute psychotic disorders: paranoid SZ (total N = 58), schizophreniform (N = 11) and alcohol-induced (N = 14) psychotic disorder, and 30 healthy males. CfDNA in SZ (N = 58) does not change compared with controls. In SZ patients. Elevated levels of 8-oxodG were found in cfDNA (N = 58) and lymphocytes (n = 45). The main sources of cfDNA are dying cells with oxidized DNA. Thus, the cfDNA/FL1-8-oxodG ratio shows the level of apoptosis in damaged cells. Two subgroups were identified among the SZ patients (n = 45). For SZ-1 (31%) and SZ-2 (69%) median values of cfDNA/FL1-8-oxodG index are related as 1:6 (p < 0.0000001). For the patients with other psychotic disorders and healthy controls, cfDNA/FL1-8-oxodG values were within the range of the values in SZ-2. Thus, apoptosis is impaired in approximately one-third of SZ patients. This leads to an increase in the number of cells with damaged DNA in the patient's body tissues and may be a contributing cause of acute psychotic disorder.
authors.affiliation: Research Centre for Medical Genetics (RCMG), Moscow, 115478, Russia; V. A. Negovsky Research Institute of General Reanimatology, Moscow, 107031, Russia.
authors.forename: E S
authors.initials: ES
authors.lastname: Ershova
authors.affiliation: Psychiatric Hospital № 14 of Moscow City Health Department, Moscow, 115447, Russia.
authors.forename: E M
authors.initials: EM
authors.lastname: Jestkova
authors.affiliation: Research Centre for Medical Genetics (RCMG), Moscow, 115478, Russia.
authors.forename: I V
authors.initials: IV
authors.lastname: Chestkov
authors.affiliation: Research Centre for Medical Genetics (RCMG), Moscow, 115478, Russia. Electronic address: med-gen@mail.ru.
authors.forename: L N
authors.initials: LN
authors.lastname: Porokhovnik
authors.affiliation: Research Centre for Medical Genetics (RCMG), Moscow, 115478, Russia.
authors.forename: V L
authors.initials: VL
authors.lastname: Izevskaya
authors.affiliation: Research Centre for Medical Genetics (RCMG), Moscow, 115478, Russia.
authors.forename: S I
authors.initials: SI
authors.lastname: Kutsev
authors.affiliation: Research Centre for Medical Genetics (RCMG), Moscow, 115478, Russia; V. A. Negovsky Research Institute of General Reanimatology, Moscow, 107031, Russia.
authors.forename: N N
authors.initials: NN
authors.lastname: Veiko
authors.affiliation: Research Centre for Medical Genetics (RCMG), Moscow, 115478, Russia.
authors.forename: G
authors.initials: G
authors.lastname: Shmarina
authors.affiliation: Research Centre for Medical Genetics (RCMG), Moscow, 115478, Russia.
authors.forename: O
authors.initials: O
authors.lastname: Dolgikh
authors.affiliation: Research Centre for Medical Genetics (RCMG), Moscow, 115478, Russia; V. A. Negovsky Research Institute of General Reanimatology, Moscow, 107031, Russia.
authors.forename: S V
authors.initials: SV
authors.lastname: Kostyuk
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D020751:Alcohol-Induced Disorders / Q000097:blood / Q000473:pathology; D017209:Apoptosis; D004247:DNA / Q000097:blood*; D004249:DNA Damage; D003848:Deoxyguanine Nucleotides / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology*; D008297:Male; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000097:blood / Q000473:pathology; D011714:Pyrans; D012559:Schizophrenia; D012563:Schizophrenia, Paranoid / Q000097:blood* / Q000473:pathology*; D018709:Statistics, Nonparametric
chemical_list: D003848:Deoxyguanine Nucleotides; D011714:Pyrans; C078206:8-oxodeoxyguanosine triphosphate; C079963:1,5-bis(3,4-dimethoxyphenyl)tetrahydropyran; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine
keywords: 8-oxodG; Cell-free DNA; Lymphocytes; Oxidized DNA; Schizophrenia; cfDNA