8-hydroxy-2--deoxyguanosine and Psychotic-Disorders

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.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Alcohol-Induced Disorders; Apoptosis; Deoxyguanine Nucleotides; Deoxyguanosine; DNA; DNA Damage; Female; Flow Cytometry; Humans; Lymphocytes; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Pyrans; Schizophrenia; Schizophrenia, Paranoid; Statistics, Nonparametric

Oxidative stress has been reported to play a role in the psychopathology of schizophrenia, though only a few studies have investigated the relationship between early-onset schizophrenia and oxidative stress. The aim of the present study is to evaluate the level of oxidative stress and the presence of DNA damage in first-episode psychosis (FEP) in adolescents.. This study was conducted in the Department of Child Psychiatry of the Dicle University Hospital. It included 20 adolescent patients (age 11-17 years) with psychosis (acute psychosis, schizophreniform disorder, or schizophrenia) according to DSM-IV criteria who had received no previous psychiatric therapy (patient group) and 20 age/gender-matched healthy adolescents (control group). Structured psychiatric interviews [Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version (K-SADS-PL) and Positive and Negative Symptom Scale (PANSS)] were conducted on the patients, and the Clinical Global Impressions (CGI) scale was used to evaluate the severity of disease. Glutathione peroxidase (GPx), superoxide dismutase (SOD), coenzyme Q (CoQ), and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were determined using the ELISA method and commercial ELISA kits.. The mean age was 14.5 ± 1.6 years in the FEP group (male-to-female ratio: 8/12) and 14.4 ± 1.5 years in the control group (male-to-female ratio: 8/12). There were no differences between the patient and control groups in terms of SOD, GPx, or 8-OHdG values (p > 0.05).. This study on DNA damage and oxidative stress in FEP in adolescents had a small sample size, and our data suggest that oxidative stress is associated with a chronic disease course rather than being an early sign of early-onset schizophrenia.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Child; Deoxyguanosine; Diagnostic and Statistical Manual of Mental Disorders; DNA Damage; Enzyme-Linked Immunosorbent Assay; Female; Glutathione Peroxidase; Humans; Interview, Psychological; Male; Oxidative Stress; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Superoxide Dismutase; Ubiquinone

Psychosocial stress alters the hypothalamic-pituitary-adrenal axis (HPA-axis). Increasing evidence shows a link between these alterations and oxidant elevation. Oxidative stress is implicated in the stress response and in the pathogenesis of neurologic and psychiatric diseases. NADPH oxidases (NOXs) are a major source of reactive oxygen species (ROS) in the central nervous system. Here, we investigated the contributory role of NOX2-derived ROS to the development of neuroendocrine alterations in a rat model of chronic psychosocial stress, the social isolation.. Significant elevations in the hypothalamic levels of corticotropin-releasing factor and plasmatic adrenocorticotropic hormone were observed from 4 weeks of social isolation. Increased levels of peripheral markers of the HPA-axis (plasmatic and salivary corticosterone) were observed at a later time point of social isolation (7 weeks). Alteration in the exploratory activity of isolated rats followed the same time course. Increased expression of markers of oxidative stress (8-hydroxy-2-deoxyguanosine [8OhdG] and nitrotyrosine) and NOX2 mRNA was early detectable in the hypothalamus of isolated rats (after 2 weeks), but later (after 7 weeks) in the adrenal gland. A 3-week treatment with the antioxidant/NOX inhibitor apocynin stopped the progression of isolation-induced alterations of the HPA-axis. Rats with a loss-of-function mutation in the NOX2 subunit p47(phox) were totally protected from the alterations of the neuroendocrine profile, behavior, and increased NOX2 mRNA expression induced by social isolation.. We demonstrate that psychosocial stress induces early elevation of NOX2-derived oxidative stress in the hypothalamus and consequent alterations of the HPA-axis, leading ultimately to an altered behavior.. Pharmacological targeting of NOX2 might be of crucial importance for the treatment of psychosocial stress-induced psychosis.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acetophenones; Adrenal Glands; Adrenocorticotropic Hormone; Animals; Antioxidants; Biomarkers; Corticosterone; Deoxyguanosine; Female; Hypothalamo-Hypophyseal System; Hypothalamus; Male; Mutation; NADPH Oxidases; Neurosecretory Systems; Oxidative Stress; Pituitary-Adrenal System; Psychosocial Deprivation; Psychotic Disorders; Rats; Rats, Wistar; Restraint, Physical; Saliva; Social Isolation; Stress, Psychological; Tyrosine