Oxidative DNA Damage in Bipolar Disorder

Abstract

Bipolar disorder (BD) poses a significant global health burden, linked to reduced life expectancy and heightened vulnerability to various somatic illnesses. Recent research has highlighted oxidative DNA damage as a potential underlying mechanism linking BD to somatic conditions. Oxidative DNA damage, resulting from reactive oxygen species (ROS) assaults, manifests in diverse forms including base and sugar damage, DNA-protein cross-links, and strand breaks. Studies have demonstrated elevated levels of oxidative DNA damage markers, particularly 8-hydroxy-2′-deoxyguanosine (8-OH-dG), in individuals with BD, indicating a potential trait or state marker for the disorder. However, conflicting findings exist regarding the association of oxidative DNA damage with mood states, medication, and clinical features. Furthermore, investigations into DNA repair mechanisms, particularly base excision repair (BER), have shown dysregulation in BD, with decreased expression of repair enzymes such as 8-oxoguanine glycosylase 1 (OGG1). This dysregulation may contribute to the accumulation of DNA damage and the subsequent pathophysiology of BD. While current research primarily focuses on BER, other repair pathways such as nucleotide excision repair and mismatch repair remain understudied in the context of BD. Understanding the role of oxidative DNA damage and repair mechanisms in BD could offer insights into its molecular underpinnings and inform potential therapeutic strategies. Longitudinal studies with standardized methods are crucial to understand the clinical relevance of oxidative DNA damage markers in BD, and exploring alternative repair pathways may offer insights into DNA repair dysregulation, presenting a promising avenue for mitigating age-related diseases and comorbidities in BD. © 2025 Springer Nature Switzerland AG.