Elevated levels of 8-oxoGuo and 8-oxodG in individuals with severe mental illness – An autopsy-based study

Martin Roest Christensen; Henrik Enghusen Poulsen; Trine Henriksen; Allan Weimann; Christina Ellervik; Niels Lynnerup; Jørgen Rungby; Jytte Banner

doi:10.1016/j.freeradbiomed.2018.08.029

Elevated levels of 8-oxoGuo and 8-oxodG in individuals with severe mental illness – An autopsy-based study

Martin Roest Christensen^*, Henrik Enghusen Poulsen, Trine Henriksen, Allan Weimann, Christina Ellervik, Niels Lynnerup, Jørgen Rungby, Jytte Banner

^*Corresponding author for this work

3 Citations (Scopus)

Abstract

Elevated systemic oxidative stress levels of 8-oxoGuo and 8-oxodG have been reported in individuals with severe mental illness (SMI). As no previous studies have addressed the link between local levels of 8-oxoGuo and 8-oxodG in the central nervous system (CNS), measured in cerebrospinal fluid (CSF), and urinary systemic levels, we employed autopsy-based material to elucidate this aspect. Additionally, we investigated the impact of 8-oxoGuo and 8-oxodG levels on the prevalence of somatic co-morbidities. Based on post mortem samples from deceased individuals with SMI (N = 107), we found significantly elevated urinary levels of both 8-oxoGuo and 8-oxodG compared to mentally healthy living controls. While we found an association between urinary and CSF 8-oxodG levels (r = 0.50, P < 0.001), a similar correlation was not evident for 8-oxoGuo (r = 0.15, P = 0.16). Additionally, the two r-values were significantly different (P < 0.001). Neither marker in urine or CSF was associated with obesity-related variables, metabolic syndrome or type 2 diabetes. The post mortem interval did not affect the results, but the agonal phase seemingly introduced bias. This study provided novel insights into the cellular oxidative stress levels in individuals with SMI. We demonstrated that increased oxidative stress locally and systemically is correlated and is a clear phenomenon in SMI. Although post mortem measurements contain some weaknesses, our study indicates DNA as the main site of oxidative stress modifications in the CNS in SMI. This may provide novel opportunities for treatment modalities. Additionally, our study demonstrated the applicability of post mortem material investigating systemic and local 8-oxoGuo and 8-oxodG levels.

Original language	English
Journal	Free Radical Biology and Medicine
Volume	126
Pages (from-to)	372-378
ISSN	0891-5849
DOIs	https://doi.org/10.1016/j.freeradbiomed.2018.08.029
Publication status	Published - 1 Oct 2018

Keywords

8-oxodG
8-oxoGuo
Autopsy
Bipolar disorder
Depression
Oxidative stress
Schizophrenia
Severe mental illness

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.freeradbiomed.2018.08.029

Cite this

@article{dfc456e144ea4ec8a97258b457ec469c,

title = "Elevated levels of 8-oxoGuo and 8-oxodG in individuals with severe mental illness – An autopsy-based study",

abstract = "Elevated systemic oxidative stress levels of 8-oxoGuo and 8-oxodG have been reported in individuals with severe mental illness (SMI). As no previous studies have addressed the link between local levels of 8-oxoGuo and 8-oxodG in the central nervous system (CNS), measured in cerebrospinal fluid (CSF), and urinary systemic levels, we employed autopsy-based material to elucidate this aspect. Additionally, we investigated the impact of 8-oxoGuo and 8-oxodG levels on the prevalence of somatic co-morbidities. Based on post mortem samples from deceased individuals with SMI (N = 107), we found significantly elevated urinary levels of both 8-oxoGuo and 8-oxodG compared to mentally healthy living controls. While we found an association between urinary and CSF 8-oxodG levels (r = 0.50, P < 0.001), a similar correlation was not evident for 8-oxoGuo (r = 0.15, P = 0.16). Additionally, the two r-values were significantly different (P < 0.001). Neither marker in urine or CSF was associated with obesity-related variables, metabolic syndrome or type 2 diabetes. The post mortem interval did not affect the results, but the agonal phase seemingly introduced bias. This study provided novel insights into the cellular oxidative stress levels in individuals with SMI. We demonstrated that increased oxidative stress locally and systemically is correlated and is a clear phenomenon in SMI. Although post mortem measurements contain some weaknesses, our study indicates DNA as the main site of oxidative stress modifications in the CNS in SMI. This may provide novel opportunities for treatment modalities. Additionally, our study demonstrated the applicability of post mortem material investigating systemic and local 8-oxoGuo and 8-oxodG levels.",

keywords = "8-oxodG, 8-oxoGuo, Autopsy, Bipolar disorder, Depression, Oxidative stress, Schizophrenia, Severe mental illness",

author = "Christensen, {Martin Roest} and Poulsen, {Henrik Enghusen} and Trine Henriksen and Allan Weimann and Christina Ellervik and Niels Lynnerup and J{\o}rgen Rungby and Jytte Banner",

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doi = "10.1016/j.freeradbiomed.2018.08.029",

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T1 - Elevated levels of 8-oxoGuo and 8-oxodG in individuals with severe mental illness – An autopsy-based study

AU - Christensen, Martin Roest

AU - Poulsen, Henrik Enghusen

AU - Henriksen, Trine

AU - Weimann, Allan

AU - Ellervik, Christina

AU - Lynnerup, Niels

AU - Rungby, Jørgen

AU - Banner, Jytte

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Elevated systemic oxidative stress levels of 8-oxoGuo and 8-oxodG have been reported in individuals with severe mental illness (SMI). As no previous studies have addressed the link between local levels of 8-oxoGuo and 8-oxodG in the central nervous system (CNS), measured in cerebrospinal fluid (CSF), and urinary systemic levels, we employed autopsy-based material to elucidate this aspect. Additionally, we investigated the impact of 8-oxoGuo and 8-oxodG levels on the prevalence of somatic co-morbidities. Based on post mortem samples from deceased individuals with SMI (N = 107), we found significantly elevated urinary levels of both 8-oxoGuo and 8-oxodG compared to mentally healthy living controls. While we found an association between urinary and CSF 8-oxodG levels (r = 0.50, P < 0.001), a similar correlation was not evident for 8-oxoGuo (r = 0.15, P = 0.16). Additionally, the two r-values were significantly different (P < 0.001). Neither marker in urine or CSF was associated with obesity-related variables, metabolic syndrome or type 2 diabetes. The post mortem interval did not affect the results, but the agonal phase seemingly introduced bias. This study provided novel insights into the cellular oxidative stress levels in individuals with SMI. We demonstrated that increased oxidative stress locally and systemically is correlated and is a clear phenomenon in SMI. Although post mortem measurements contain some weaknesses, our study indicates DNA as the main site of oxidative stress modifications in the CNS in SMI. This may provide novel opportunities for treatment modalities. Additionally, our study demonstrated the applicability of post mortem material investigating systemic and local 8-oxoGuo and 8-oxodG levels.

AB - Elevated systemic oxidative stress levels of 8-oxoGuo and 8-oxodG have been reported in individuals with severe mental illness (SMI). As no previous studies have addressed the link between local levels of 8-oxoGuo and 8-oxodG in the central nervous system (CNS), measured in cerebrospinal fluid (CSF), and urinary systemic levels, we employed autopsy-based material to elucidate this aspect. Additionally, we investigated the impact of 8-oxoGuo and 8-oxodG levels on the prevalence of somatic co-morbidities. Based on post mortem samples from deceased individuals with SMI (N = 107), we found significantly elevated urinary levels of both 8-oxoGuo and 8-oxodG compared to mentally healthy living controls. While we found an association between urinary and CSF 8-oxodG levels (r = 0.50, P < 0.001), a similar correlation was not evident for 8-oxoGuo (r = 0.15, P = 0.16). Additionally, the two r-values were significantly different (P < 0.001). Neither marker in urine or CSF was associated with obesity-related variables, metabolic syndrome or type 2 diabetes. The post mortem interval did not affect the results, but the agonal phase seemingly introduced bias. This study provided novel insights into the cellular oxidative stress levels in individuals with SMI. We demonstrated that increased oxidative stress locally and systemically is correlated and is a clear phenomenon in SMI. Although post mortem measurements contain some weaknesses, our study indicates DNA as the main site of oxidative stress modifications in the CNS in SMI. This may provide novel opportunities for treatment modalities. Additionally, our study demonstrated the applicability of post mortem material investigating systemic and local 8-oxoGuo and 8-oxodG levels.

KW - 8-oxodG

KW - 8-oxoGuo

KW - Autopsy

KW - Bipolar disorder

KW - Depression

KW - Oxidative stress

KW - Schizophrenia

KW - Severe mental illness

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U2 - 10.1016/j.freeradbiomed.2018.08.029

DO - 10.1016/j.freeradbiomed.2018.08.029

M3 - Journal article

C2 - 30145229

AN - SCOPUS:85053050287

SN - 0891-5849

VL - 126

SP - 372

EP - 378

JO - Free Radical Biology & Medicine

JF - Free Radical Biology & Medicine

ER -

Elevated levels of 8-oxoGuo and 8-oxodG in individuals with severe mental illness – An autopsy-based study

Abstract

Keywords

UN SDGs

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