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 -
