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 (I2≥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 (I2=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 (I2=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.

The authors have declared no competing interest.

https://www.crd.york.ac.uk/PROSPERO/view/CRD42025630675

This research was funded by Koc University Research Center for Translational Medicine (KUTTAM). The funder had no role in the design, data collection, data analysis, and reporting of this study.

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