TY - JOUR

T1 - Higher systemic oxidatively generated DNA and RNA damage in patients with newly diagnosed bipolar disorder and their unaffected first-degree relatives

AU - Coello, Klara

AU - Bøgh, Helena Lykke

AU - Stanislaus, Sharleny

AU - Kjærstad, Hanne Lie

AU - Melbye, Sigurd A.

AU - Ormstrup Sletved, Kimie Stefanie

AU - Poulsen, Henrik Enghusen

AU - Vinberg, Maj

AU - Kessing, Lars Vedel

N1 - Publisher Copyright: © 2021 Elsevier Inc.

PY - 2021/5/20

Y1 - 2021/5/20

N2 - Background: Prior studies in bipolar disorders (BD) have suggested that oxidative stress and cellular ageing play a key role in the pathophysiology of BD. Nevertheless, oxidative stress has not been investigated in patients with newly diagnosed BD and in their unaffected first-degree relatives (UR), compared with healthy control individuals (HC). Methods: We investigated the level of systemic oxidative damage to DNA and RNA measured by urinary excretion of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo) levels, respectively, in 360 patients with newly diagnosed BD, 92 of their UR and 197 HC. Results: Independent of lifestyle and demographic variables, levels of both 8-oxoGuo and 8-oxodG was 17.1% (B = 1.171, 95%CI = 1.125–1.219, p < 0.001) and 21.2% (B = 1.212, 95%CI = 1.145–1.283, p < 0.001) higher, respectively, in patients with BD compared with HC and 13.3% (B = 1.133, 95%CI = 1.069–1.200, p < 0.001) and 26.6% (B = 1.266, 95%CI = 1.167–1.374, p < 0.001) higher, respectively, in UR compared with HC. Neither 8-oxoGuo nor 8-oxodG levels differed between patients with BD and UR. These findings were replicated in patients in full or partial remission and were consistent both in BD type I and II. Conclusion: Overall, the findings of higher oxidative stress in patients with newly diagnosed BD and their UR suggest that systemic nucleoside damage by oxidative stress is present prior to onset and in the early stages of BD thereby potentially representing trait markers of BD.

AB - Background: Prior studies in bipolar disorders (BD) have suggested that oxidative stress and cellular ageing play a key role in the pathophysiology of BD. Nevertheless, oxidative stress has not been investigated in patients with newly diagnosed BD and in their unaffected first-degree relatives (UR), compared with healthy control individuals (HC). Methods: We investigated the level of systemic oxidative damage to DNA and RNA measured by urinary excretion of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo) levels, respectively, in 360 patients with newly diagnosed BD, 92 of their UR and 197 HC. Results: Independent of lifestyle and demographic variables, levels of both 8-oxoGuo and 8-oxodG was 17.1% (B = 1.171, 95%CI = 1.125–1.219, p < 0.001) and 21.2% (B = 1.212, 95%CI = 1.145–1.283, p < 0.001) higher, respectively, in patients with BD compared with HC and 13.3% (B = 1.133, 95%CI = 1.069–1.200, p < 0.001) and 26.6% (B = 1.266, 95%CI = 1.167–1.374, p < 0.001) higher, respectively, in UR compared with HC. Neither 8-oxoGuo nor 8-oxodG levels differed between patients with BD and UR. These findings were replicated in patients in full or partial remission and were consistent both in BD type I and II. Conclusion: Overall, the findings of higher oxidative stress in patients with newly diagnosed BD and their UR suggest that systemic nucleoside damage by oxidative stress is present prior to onset and in the early stages of BD thereby potentially representing trait markers of BD.

KW - Bipolar disorders

KW - High-risk

KW - Newly diagnosed bipolar disorders

KW - Nucleoside damage

KW - Oxidative stress

KW - Unaffected relatives

U2 - 10.1016/j.freeradbiomed.2021.03.022

DO - 10.1016/j.freeradbiomed.2021.03.022

M3 - Journal article

C2 - 33798615

AN - SCOPUS:85103991792

VL - 168

SP - 226

EP - 233

JO - Free Radical Biology & Medicine

JF - Free Radical Biology & Medicine

SN - 0891-5849

ER -