Breaking the cycle of oxidative stress for better behavioral health in autism spectrum disorder: A scoping review

Abstract

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition marked by socio-communicative and behavioral challenges. ASD is increasingly linked to oxidative stress, which stems from a destructive imbalance state whereby excessive reactive oxygen species (ROS) overwhelm antioxidant defenses. This redox imbalance triggers a cascade of cellular dysfunctions, which in neurons include synaptic inefficiency, altered receptor function, excitotoxicity, and chronic neuroinflammation. All these dysfunctions add an additional burden to the genetic and epigenetic contributions underlying autism pathophysiology in each single individual, ultimately exacerbating ASD core symptoms. Strikingly, children with ASD exhibit diminished antioxidant capacity, correlated with heightened behavioral severity and impaired quality of life. This scoping review explores the intricate relationship between oxidative stress and ASD, evaluating current therapeutic strategies aimed at restoring redox balance while identifying critical research gaps. Interventions such as N-acetylcysteine (NAC), vitamin and mineral supplementation, and dietary antioxidants have shown promise in mitigating oxidative damage and improving social responsiveness. Other strategies, in particular hyperbaric oxygen therapy (HBOT) and cleanroom environments, are highly controversial. Well-designed randomized placebo-controlled trials (RCTs) integrating clinical and psychodiagnostic measures with precision medicine frameworks, are crucial for developing targeted therapies that, restoring redox homeostasis, may optimize neurodevelopmental outcomes. By summarizing current evidence and addressing these gaps, this review underscores the therapeutic potential of oxidative stress correction in improving the quality of life of individuals with ASD.