by Davoud Amiri, Lamberto Briziarelli, Swetang J. Shah, Sara Amiri, Barry Karlsson, Amir Hossein Jalali Nadoushan

Abstract

Objective: Oxidative–antioxidant imbalance has been proposed as a biological contributor to attention-deficit/hyperactivity disorder (ADHD), yet findings across biomarkers, age groups and assay platforms remain heterogeneous. We synthesised evidence on oxidative damage markers (malondialdehyde [MDA], 8-hydroxy-2′-deoxyguanosine [8-OHdG]), global redox indices (total oxidant status [TOS], oxidative stress index [OSI], total antioxidant status [TAS]) and enzymatic antioxidants (superoxide dismutase [SOD], glutathione peroxidase [GPx], catalase [CAT]).
Method: Following PRISMA 2020 guidelines, we searched major databases for studies published between 2010 and 2025. Case–control studies and baseline data from trials reporting group means and standard deviations were eligible. Standardised mean differences (Hedges’ g) were pooled using random-effects models. Prespecified moderators included age group, medication status and assay or biological matrix.
Results: Across fifteen case–control studies, ADHD was associated with a consistent shift towards oxidative imbalance. Oxidative damage was higher in ADHD for MDA (g = 0.32, 95% CI 0.18–0.46), 8-OHdG (g = 0.27, 0.10–0.44), TOS (g = 0.35, 0.20–0.50) and OSI (g = 0.31, 0.16–0.46). Antioxidant capacity was reduced for TAS (sign-inverted g = 0.25, 0.08–0.42) and SOD (sign-inverted g = 0.22, 0.05–0.39), whereas GPx and CAT showed no consistent differences. Heterogeneity was low to moderate, with no evidence of publication bias. Effects were larger in drug-naïve paediatric samples than in adults or treated cohorts.
Conclusions: ADHD is associated with a small-to-moderate redox imbalance, most pronounced in untreated paediatric populations. These findings support oxidative–antioxidant dysregulation as a biologically meaningful dimension of ADHD and provide a framework for understanding heterogeneity in psychopharmacological response.

Key words: ADHD, oxidative stress, antioxidants, redox imbalance, meta-analysis