Oxidation of DNA and RNA in young patients with newly diagnosed bipolar disorder and relatives

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Excessive oxidative stress-generated nucleoside damage seems to play a key role in bipolar disorder (BD) and may present a trait phenomenon associated with familial risk and is one of the putative mechanisms explaining accelerated atherosclerosis and premature cardiovascular diseases (CVD) in younger patients with BD. However, oxidative stress-generated nucleoside damage has not been studied in young BD patients and their unaffected relatives (UR). Therefore, we compared oxidative stress-generated damage to DNA and RNA in young patients newly diagnosed with BD, UR, and healthy control individuals (HC). Systemic oxidative stress-generated DNA and RNA damage levels were compared by analyzing urinary levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine and 8-oxo-7,8-dihydroguanosine in participants aged 15–25 years, including 133 patients newly diagnosed with BD, 57 UR, and 83 HC. Compared with HC, damage to DNA was 21.8% higher in BD patients (B = 1.218, 95% CI = 1.111–1.335, p = <0.001) and 22.5% higher in UR (B = 1.225, 95% CI = 1.090–1.377, p = <0.002), while damage to RNA was 14.8% higher in BD patients (B = 1.148, 95% CI = 1.082–1.219, p = <0.001) and 14.0% higher in UR (B = 1.140, 95% CI = 1.055–1.230, p = < 0.001) in models adjusted for sex and age after correction for multiple comparison. Levels did not differ between patients with BD and UR. Our findings support higher oxidative stress-generated nucleoside damage being a trait phenomenon in BD associated with familial risk and highlight the importance of early diagnosis and treatment to prevent illness progression and development of premature CVD.
OriginalsprogEngelsk
Artikelnummer81
TidsskriftTranslational Psychiatry
Vol/bind14
Udgave nummer1
Antal sider8
ISSN2158-3188
DOI
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
This study was supported by grants from the Mental Health Services, Capital Region of Denmark (PhD student 164019 and the BIO study), The Danish Council for Independent Research, Medical Sciences (DFF4183–00570), the A.P. Møller Foundation for the Advancement of Medical Science (15–55), Beckett-Fonden (48282) and The Lundbeck Foundation (1-year scholarship for IJOM). A special thanks to Anne Præstegaard for her logistic and laboratory assistance throughout the study. Finally, our deepest gratitude to the laboratories of clinical pharmacology at Rigshospitalet, Bispebjerg Hospital, and Frederiksberg Hospital for making it possible to obtain the 8-oxodG and 8-oxoGuo analyses.

Funding Information:
This study was supported by grants from the Mental Health Services, Capital Region of Denmark (PhD student 164019 and the BIO study), The Danish Council for Independent Research, Medical Sciences (DFF4183–00570), the A.P. Møller Foundation for the Advancement of Medical Science (15–55), Beckett-Fonden (48282) and The Lundbeck Foundation (1-year scholarship for IJOM). A special thanks to Anne Præstegaard for her logistic and laboratory assistance throughout the study. Finally, our deepest gratitude to the laboratories of clinical pharmacology at Rigshospitalet, Bispebjerg Hospital, and Frederiksberg Hospital for making it possible to obtain the 8-oxodG and 8-oxoGuo analyses.

Publisher Copyright:
© The Author(s) 2024.

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