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

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Klara Coello
Helena Lykke Bøgh
Sharleny Stanislaus
Hanne Lie Kjærstad
Sigurd A. Melbye
Kimie Stefanie Ormstrup Sletved
Poulsen, Henrik Enghusen
Vinberg, Maj
Kessing, Lars Vedel

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.

Originalsprog	Engelsk
Tidsskrift	Free Radical Biology and Medicine
Vol/bind	168
Sider (fra-til)	226-233
Antal sider	8
ISSN	0891-5849
DOI	https://doi.org/10.1016/j.freeradbiomed.2021.03.022
Status	Udgivet - 20 maj 2021

Bibliografisk note

Funding Information:
This study was supported by grants from the Mental Health Services, Capital Region of Denmark ( 164019 and the BIO study); The Capital Region of Denmark; The Augustinus Foundation; The Danish Council for Independent Research, Medical Sciences ( DFF-4183-00570 ); The A.P. Møller Foundation for the Advancement of Medical Science (15–55); Beckett-Fonden ( 48282 ); and The Lundbeck Foundation.

Funding Information:
However, some limitations apply to our study. First, our control group was recruited among blood donors without a personal or first-degree family history of psychiatric illness adding to the fact, that blood donors represent a super healthy population [56]. Nonetheless, the recruited blood donors were from the same catchment area as our patients with BD and matched with patients on sex and age. Education level was slightly higher in HC than in patients with BD and UR. However, it is possible that this reflects patients with BD being delayed in their studies due to their BD and in regard to UR possibly explained by the younger age. More patients with BD and UR were active smokers than HC. Nevertheless, results were still highly significant when adjusting for smoking as well as when excluding smokers. Alcohol intake was higher in HC than in patients with BD. This may, however, reflect that patients with newly diagnosed BD recently started in the Copenhagen Affective Disorder Clinic, where cessation is strongly recommended and supported. In the preceding months leading up to starting in the clinical program, many BD patients reported a substantially higher level of weekly alcohol intake exceeding the Danish Health Authority's recommended threshold. However, we only assessed alcohol intake based on the preceding month, therefore results regarding alcohol intake should be interpreted with caution. Alltogether, we consider our control group a pragmatic choice, as other ways to recruit HC such as via advertisements or national registers result in low response rates and likely selection bias.This study was supported by grants from the Mental Health Services, Capital Region of Denmark (164019 and the BIO study); The Capital Region of Denmark; The Augustinus Foundation; The Danish Council for Independent Research, Medical Sciences (DFF-4183-00570); The A.P. M?ller Foundation for the Advancement of Medical Science (15?55); Beckett-Fonden (48282); and The Lundbeck Foundation.

Publisher Copyright:
© 2021 Elsevier Inc.

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