Oxidant/antioxidant imbalance may contribute to the pathophysiology of autism spectrum disorder (ASD). We assayed urinary levels of oxidative stress related biomarkers, hexanoyl-lysine (HEL), total antioxidant capacity (TAOC), the DNA methylation biomarker 8-hydroxy-2'-deoxyguanosine (8-OHdG), and plasma levels of superoxide dismutase (SOD), which is major antioxidant enzyme. We examined the relationship between these four biomarkers and social responsiveness in 20 individuals with ASD and in 11 healthy controls. The sex (ASD group, 7/13 vs. control group, 4/7) and age distributions (ASD group, 10.7 ± 5.0 years vs. control group, 14.7 ± 6.3 years) were not significantly different between the groups. Social responsiveness was assessed using the social responsiveness scale (SRS). We used standardized regression coefficients to measure the effect size. The ASD group exhibited significantly lower urinary TAOC levels and significantly elevated urinary HEL levels than the control group. Urinary 8-OHdG levels and plasma SOD levels were not significantly different between the groups. The ASD group showed significantly higher SRS scores than the control group. Plasma SOD levels correlated significantly with urinary TAOC levels. Standardized regression coefficients revealed that TAOC levels had a larger effect size than HEL levels in urine. This study firstly reveals that an imbalance between urinary HEL and TAOC levels in favor of urinary TAOC levels may contribute to impaired social responsiveness in individuals with ASD. Plasma SOD levels may also affect urinary TAOC levels.

Individuals with autism spectrum disorders (ASD) have impaired detoxification capacity. Investigating　the neurobiological bases of　impaired antioxidant capacity is thus a research priority in the pathophysiology of ASD.　We measured　the urinary levels of hexanoyl-lysine (HEL) which is a new oxidative stress　biomarker, total antioxidant power (TAP) and DNA methylation biomarker 8-hydroxy-2'-deoxyguanosine (8-OHdG), and the plasma levels of superoxide dismutase (SOD), which is a major antioxidant enzyme. We examined whether the urinary levels of these enzymes and biomarkers may be related to symptoms of social impairment in 20 individuals with ASD (meanage,11.1±5.2years) and 12 age- and gender-matched healthy controls (meanage,14.3±6.2years). Symptoms of social impairment were　assessed using the Social Responsiveness Scale (SRS). The dietary TAP of the fruit juice, chocolate, cookies, biscuits, jam and marmalade were significantly higher in the ASD group than in the control group, although the intake of nutrients was not significantly different between the groups. The urinary TAP levels were significantly lower in the ASD group than in the control group. There were no significantly differences in urinary HEL and 8-OHdG levels between the ASD and control groups. The SRS scores were significantly higher in the ASD group than in the control group. Stepwise regression analysis revealed that urinary TAP levels and plasma SOD levels can differences in the biomarkers and the SRS scores between the ASD group and the control group. The endogenous antioxidant capacity may be deficient without altered urinary HEL and 8-OHdG levels in individuals with ASD. The plasma SOD levels may be related to reduced endogenous antioxidant capacity.

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Introduction: The imbalance between oxidants and antioxidants contributes to the pathophysiology of ASD.