TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=85053050287&partnerID=8YFLogxK
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 and Medicine
JF - Free Radical Biology and Medicine
ER -
