Work

Oxidative DNA Damage Diminishes After Treatment of Unipolar and Bipolar Depressive Episodes: A Systematic Review and Meta-Analysis of Longitudinal Studies

Year: 2025

Type: preprint

Study designs: Systematic Review, Meta-Analysis

Abstract: Introduction Unipolar (UD) and bipolar depression (BD) have been associated with increased oxidative DNA damage, as measured by 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels. While existing meta-analyses rely on cross-sectional data, this study aims to systematically review and meta-analyze existing longitudinal studies on oxidative DNA damage changes after treating UD and BD. Methods A literature search for 8-OHdG with UD and BD studies was conducted in PubMed, Cochrane, Scopus, Web of Science, and Ovid-MEDLINE until 31/12/2024. Screening was performed via Covidence and statistical analyses were performed in SPSS 28.0 using Hedges’s g (95% CIs) under a random-effects model, assessing heterogeneity (I 2 ≥50%), publication bias (Egger’s test, funnel plots), and subgroup differences. Additionally, meta-regression on sex (%female) was performed. Results Out of 1512 studies, 10 met eligibility criteria, including 525 individuals (UD=376, BD =149). Meta-analysis revealed a post-pharmacotherapy reduction in 8-OHdG levels (g=-0.61, [−1.20, −0.02], p=0.04) with high heterogeneity (I 2 =0.95, Q=207.45, df(Q)=17, p<0.001) but no publication bias. In remitted patients (n=117), 8-OHdG levels significantly decreased (g=-0.42, [−0.81, −0.03], p=0.03). Subgroup analyses showed a significant decrease in BD population (g=-0.39, [−0.73, −0.05], p=0.02) with relatively high homogeneity (I 2 =0.49, Q=9.853, df(Q)=5, p=0.080). Significant reductions were observed in studies of pharmacological treatments (g=-0.88, [−1.56, − 0.19], p=0.001) and studies using urine samples (g=-0.61, [−0.84, −0.39], p<0.001). Moreover, meta-regression showed female sex as a significant moderator in the UD population (β=0.099, [0.065, 0.133], p<0.001). Conclusion Our findings support 8-OHdG levels as a potential biomarker in BD for treatment response. Further longitudinal studies are needed to validate these findings and to evaluate treatment-related changes.

Source: medRxiv

DOI: 10.1101/2025.05.20.25327903