Systemic oxidative stress in children and adolescents with attention deficit hyperactivity disorder: a meta-analysis of oxidative and antioxidant biomarkers.

OBJECTIVE

Emerging evidence has shown that an exacerbation of oxidative stress and a reduction of antioxidant activity may be implicated in the pathophysiology of attention deficit hyperactivity disorder (ADHD). Nevertheless, differences in methodologies (e.g., participant age, biological sample type, and analytical tools) across studies may be attributed to variations in the findings. Thus, meta-analysis is needed to systematically assess oxidative stress and antioxidant biomarkers in children and adolescents with ADHD.

METHODS

Three electronic databases, including PubMed, Web of Science, and Embase, up to January 03rd, 2026, reporting data on the levels of oxidative stress and antioxidant biomarkers including total oxidant status (TOS), 8-hydroxy-deoxyguanosine (8-OHdG), malondialdehyde (MDA), nitric oxide (NO), total antioxidant status (TAS) and superoxide dismutase (SOD), measured in various biological sample types (e.g., urine, serum, and plasma) in children and adolescents with ADHD. Statistical analyses used standardized mean differences (SMDs) with 95% confidence intervals (CIs) under a random-effects model, with heterogeneity quantified by I2 and subgroup analyses by sample type.

RESULTS

A total of 20 studies, comprising 1,325 children and adolescents with ADHD and 1,272 healthy controls. The pooled data across studies have demonstrated that ADHD patients have higher blood levels of TOS (SMD = 0.94; 95% CI = 0.63 to 1.25; p < 0.00001) and urinary levels of 8-OHdG (SMD = 0.21; 95% CI = 0.07 to 0.35; p = 0.004), when compared to healthy controls. However, there were no differences in blood levels of 8-OHdG (SMD = -0.26; 95% CI = -0.62 to 0.10; p = 0.15), MDA (SMD = 0.21; 95% CI = -0.87 to 1.29; p = 0.70), and NO (SMD = 0.03; 95% CI = -0.31 to 0.33; p = 0.84) between ADHD patients and controls. Regarding antioxidant activity, ADHD patients have lower blood TAS levels (SMD = -0.53; 95% CI = -0.99 to -0.08; p = 0.02). However, there were no differences in blood levels of SOD (SMD = -0.75; 95% CI = -1.97 to 0.46; p = 0.22) between ADHD patients and the healthy controls.

CONCLUSION

The results indicate elevated blood TOS and urinary 8-OHdG levels and decreased blood TAS levels in children and adolescents with ADHD, further supporting a role for oxidative stress in the pathophysiology of ADHD.