TY - JOUR

T1 - Persistent increase over time in oxidatively stress generated RNA and DNA damage in patients with newly diagnosed bipolar disorder and their unaffected first-degree relatives – An up to 5-year prospective study

AU - Coello, Klara

AU - Forman, Julie Lyng

AU - Pedersen, Helle Holstad

AU - Vinberg, Maj

AU - Poulsen, Henrik Enghusen

AU - Kessing, Lars V.

N1 - Publisher Copyright: © 2022 Elsevier Inc.

PY - 2023

Y1 - 2023

N2 - Objectives: Increased oxidative stress generated nucleoside damage seems to play a crucial role in bipolar disorder (BD) pathophysiology. It may contribute to accelerated ageing and reduced life expectancy in patients with BD. Methods: In the five-year prospective “Bipolar Illness Onset study”, we investigated repeated measurements of oxidative stress generated RNA and DNA damage in 357 patients with newly diagnosed/first-episode BD (880 visits), 132 of their unaffected first-degree relatives (236 visits) and 198 healthy age- and sex-matched control persons with no personal or first-degree family history of affective disorder (432 visits). Amongst patients with BD, we further investigated associations of oxidative stress generated RNA- and DNA damage with affective phases and measures of illness load. Results: Patients newly diagnosed with BD and their unaffected relatives had higher levels of oxidative stress generated RNA damage than healthy control individuals and these differences persisted over time, whereas DNA damage was less consistently elevated. Neither illness load nor affective phase impacted the levels in patients with BD. Conclusions: Our findings support elevated oxidative stress generated RNA damage being a trait phenomenon in BD as indicated by persistent increase in RNA damage over time in patients newly diagnosed with BD and in their unaffected first-degree relatives compared with healthy control individuals. We did not detect state alterations in levels of oxidative stress.

AB - Objectives: Increased oxidative stress generated nucleoside damage seems to play a crucial role in bipolar disorder (BD) pathophysiology. It may contribute to accelerated ageing and reduced life expectancy in patients with BD. Methods: In the five-year prospective “Bipolar Illness Onset study”, we investigated repeated measurements of oxidative stress generated RNA and DNA damage in 357 patients with newly diagnosed/first-episode BD (880 visits), 132 of their unaffected first-degree relatives (236 visits) and 198 healthy age- and sex-matched control persons with no personal or first-degree family history of affective disorder (432 visits). Amongst patients with BD, we further investigated associations of oxidative stress generated RNA- and DNA damage with affective phases and measures of illness load. Results: Patients newly diagnosed with BD and their unaffected relatives had higher levels of oxidative stress generated RNA damage than healthy control individuals and these differences persisted over time, whereas DNA damage was less consistently elevated. Neither illness load nor affective phase impacted the levels in patients with BD. Conclusions: Our findings support elevated oxidative stress generated RNA damage being a trait phenomenon in BD as indicated by persistent increase in RNA damage over time in patients newly diagnosed with BD and in their unaffected first-degree relatives compared with healthy control individuals. We did not detect state alterations in levels of oxidative stress.

KW - Bipolar Disorder

KW - Newly Diagnosed

KW - Oxidative stress

KW - RNA and DNA damage, trait factors, prospective, longitudinal

KW - Unaffected Relatives

U2 - 10.1016/j.bbi.2022.12.011

DO - 10.1016/j.bbi.2022.12.011

M3 - Journal article

C2 - 36535609

AN - SCOPUS:85144248890

VL - 108

SP - 269

EP - 278

JO - Brain, Behavior, and Immunity

JF - Brain, Behavior, and Immunity

SN - 0889-1591

ER -