TY - JOUR

T1 - Systemic oxidatively generated DNA/RNA damage in clinical depression

T2 - associations to symptom severity and response to electroconvulsive therapy

AU - Jorgensen, Anders

AU - Krogh, Jesper

AU - Miskowiak, Kamilla

AU - Bolwig, Tom G

AU - Kessing, Lars V

AU - Fink-Jensen, Anders

AU - Nordentoft, Merete

AU - Henriksen, Trine

AU - Weimann, Allan

AU - Poulsen, Henrik E

AU - Jorgensen, Martin B

N1 - Copyright © 2013 Elsevier B.V. All rights reserved.

PY - 2013

Y1 - 2013

N2 - BACKGROUND: Depression has been associated with increased oxidative stress and hypothesized to accelerate aging. Nucleic acid damage from oxidation is a critical part of the aging process, and a suggested early event in age-related somatic morbidities that are also prevalent in depression, such as dementia and type 2 diabetes. We hypothesized that increased severity of depression is associated with increased systemic oxidatively generated DNA and RNA damage, and that this increase is attenuated by an effective antidepressant treatment.METHODS: The urinary excretion of markers of systemic oxidatively generated DNA and RNA damage, 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), respectively, were determined in healthy controls (N=28), moderately depressed, non-medicated patients (N=26) and severely depressed patients eligible for electroconvulsive therapy (ECT) (N=29). In the severely depressed patient group, samples were also obtained 1 week after the completion of ECT.RESULTS: Systemic RNA damage from oxidation, as measured by 8-oxoGuo excretion, was higher with increasing severity of depression (controlsLIMITATIONS: Small sample size and the inclusion of both unipolar and bipolar patients in the severely depressed group.CONCLUSIONS: Severe depression is associated with increased systemic oxidatively generated RNA damage, which may be an additional factor underlying the somatic morbidity and neurodegenerative features associated with depression. Due to the lack of normalization by clinically effective ECT, the phenomenon does not appear to be causally linked to the depressive state per se.

AB - BACKGROUND: Depression has been associated with increased oxidative stress and hypothesized to accelerate aging. Nucleic acid damage from oxidation is a critical part of the aging process, and a suggested early event in age-related somatic morbidities that are also prevalent in depression, such as dementia and type 2 diabetes. We hypothesized that increased severity of depression is associated with increased systemic oxidatively generated DNA and RNA damage, and that this increase is attenuated by an effective antidepressant treatment.METHODS: The urinary excretion of markers of systemic oxidatively generated DNA and RNA damage, 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), respectively, were determined in healthy controls (N=28), moderately depressed, non-medicated patients (N=26) and severely depressed patients eligible for electroconvulsive therapy (ECT) (N=29). In the severely depressed patient group, samples were also obtained 1 week after the completion of ECT.RESULTS: Systemic RNA damage from oxidation, as measured by 8-oxoGuo excretion, was higher with increasing severity of depression (controlsLIMITATIONS: Small sample size and the inclusion of both unipolar and bipolar patients in the severely depressed group.CONCLUSIONS: Severe depression is associated with increased systemic oxidatively generated RNA damage, which may be an additional factor underlying the somatic morbidity and neurodegenerative features associated with depression. Due to the lack of normalization by clinically effective ECT, the phenomenon does not appear to be causally linked to the depressive state per se.

KW - Adult

KW - Biomarkers

KW - DNA Damage

KW - Deoxyguanosine

KW - Depressive Disorder, Major

KW - Electroconvulsive Therapy

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Oxidative Stress

KW - RNA

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.jad.2013.02.011

DO - 10.1016/j.jad.2013.02.011

M3 - Journal article

C2 - 23497793

VL - 149

SP - 355

EP - 362

JO - Journal of Affective Disorders

JF - Journal of Affective Disorders

SN - 0165-0327

IS - 1-3

ER -