title: Increased systemic oxidatively generated DNA and RNA damage in schizophrenia.
abstract: Schizophrenia is associated with a substantially increased somatic morbidity and mortality, which may partly be caused by accelerated cellular aging. Oxidative stress is an established mediator of aging and a suggested aetiological mechanism in both schizophrenia and age-related medical disorders such as cardiovascular disease, type 2 diabetes and dementia. We determined the urinary excretion of markers of systemic Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA) oxidation, 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-7,8-dihydroguanosine, respectively, in 40 schizophrenia patients and 40 age- and sex-matched controls, using ultra-performance liquid chromatography with tandem mass spectrometry. Measures of psychopathology, perceived stress and cortisol secretion were collected. Patients were re-examined after four months. We found a 20% increase in the median excretion of both markers in schizophrenia patients vs. healthy controls (P=0.003 and <0.001, respectively). This difference persisted after the adjustment for multiple demographical, lifestyle and metabolic factors. In patients, the marker excretion was not influenced by medication load, and was not driven by symptom severity, perceived stress or cortisol secretion, neither at baseline nor in relation to changes at follow-up. We conclude that schizophrenia is associated with increased systemic nucleic acid damage from oxidation, which could constitute a molecular link between schizophrenia and its associated signs of accelerated aging.
authors: Psychiatric Centre Copenhagen, University Hospital of Copenhagen, Denmark; Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark. Electronic address: anders.01.joergensen@regionh.dk.
authors: Anders
authors: A
authors: Jorgensen
authors: Kasper
authors: K
authors: Broedbaek
authors: Anders
authors: A
authors: Fink-Jensen
authors: Ulla
authors: U
authors: Knorr
authors: Mia
authors: M
authors: Greisen Soendergaard
authors: Trine
authors: T
authors: Henriksen
authors: Allan
authors: A
authors: Weimann
authors: Peter
authors: P
authors: Jepsen
authors: Jens
authors: J
authors: Lykkesfeldt
authors: Henrik Enghusen
authors: HE
authors: Poulsen
authors: Martin
authors: M
authors: Balslev Jorgensen
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004249:DNA Damage / Q000502:physiology*; D003849:Deoxyguanosine / Q000378:metabolism; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives / Q000652:urine; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D012313:RNA / Q000378:metabolism*; D012189:Retrospective Studies; D012463:Saliva / Q000378:metabolism; D012559:Schizophrenia / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D055815:Young Adult
chemical_list: D006151:Guanosine; C046215:8-hydroxyguanosine; D008315:Malondialdehyde; D012313:RNA; D003849:Deoxyguanosine; D006854:Hydrocortisone
keywords: 8-oxoGuo; 8-oxodG; Cortisol; Oxidative stress; Perceived stress; Schizophrenia