Increased systemic oxidatively generated DNA and RNA damage in schizophrenia

TY - JOUR

T1 - Increased systemic oxidatively generated DNA and RNA damage in schizophrenia

AU - Jørgensen, Anders

AU - Brødbæk, Kasper

AU - Fink-Jensen, Anders

AU - Knorr, Ulla

AU - Greisen Søndergaard, Mia

AU - Henriksen, Trine

AU - Weimann, Allan

AU - Jepsen, Peter

AU - Lykkesfeldt, Jens

AU - Poulsen, Henrik Enghusen

AU - Jørgensen, Martin Balslev

PY - 2013/10/30

Y1 - 2013/10/30

N2 - 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.

AB - 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.

KW - Faculty of Health and Medical Sciences

KW - Schizophrenia

KW - Oxidative stress

KW - 8-oxodG

KW - 8-oxoGuo

KW - Perceived stress

KW - Cortisol

U2 - 10.1016/j.psychres.2013.01.033

DO - 10.1016/j.psychres.2013.01.033

M3 - Journal article

C2 - 23465294

SN - 0165-1781

VL - 209

SP - 417

EP - 423

JO - Psychiatry Research

JF - Psychiatry Research

IS - 3

ER -