Simultaneous evaluation of antioxidative serum profiles facilitates the diagnostic screening of autism spectrum disorder in under-6-year-old children

Abstract

This case–control study aimed to assess oxidative stress alterations in autism spectrum disorder (ASD). We used the MULTIS method, an electron spin resonance-based technique measuring multiple free radical scavenging activities simultaneously, in combination with conventional oxidative stress markers to investigate the ability of this MULTIS approach as a non-behavioural diagnostic tool for children with ASD. Serum samples of 39 children with ASD and 58 age-matched children with typical development were analysed. The ASD group showed decreased hydroxyl radical (·OH) and singlet oxygen scavenging activity with increased serum coenzyme Q10 oxidation rate, indicating a prooxidative tendency in ASD. By contrast, scavenging activities against superoxide (O2·−) and alkoxyl radical (RO·) were increased in the ASD group suggesting antioxidative shifts. In the subgroup analysis of 6-year-olds or younger, the combination of ·OH, O2·−, and RO· scavenging activities predicted ASD with high odds ratio (50.4), positive likelihood (12.6), and percentage of correct classification (87.0%). Our results indicate that oxidative stress in children with ASD is not simply elevated but rather shows a compensatory shift. MULTIS measurements may serve as a very powerful non-behavioural tool for the diagnosis of ASD in children.

Neuroinflammation and Oxidative Stress in the Pathogenesis of Autism Spectrum Disorder

“…Our previous study also reported increased oxidative stress in children with ASD [ 121 , 122 , 123 ]. Using lipidomics analyses, we identified 48 metabolites in ASD as novel targets involved in lipid biosynthesis and metabolism, oxidative stress, and synaptic function [ 121 ].…”

“…By comprehensive metabolome analysis, oxidative stress, mitochondrial dysfunction, elevated hormone levels, altered lipid profiles, and altered levels of phenolic microbial metabolites have been reported in the serum and feces of children with ASD [ 168 ]. We have also reported an increased oxidative stress in children with ASD [ 121 , 122 , 123 ]. In addition, specific metabolite levels to cysteine, methionine, and glutathione pathways were correlated with autism diagnostic observation schedule (ADOS) scores of ASD symptoms [ 168 ].…”

“…Although there are a lot of studies on oxidative stress and glutathione as blood biomarkers in children with ASD [ 99 , 119 , 120 , 121 , 122 , 123 ], the presence of oxidative stress and glutathione in the postmortem brain has not been well studied. In postmortem assessments of children with ASD, increased levels of 3-nitrotyrosine (3-NT), an oxidative protein damage marker, have been reported in the cerebellum [ 119 ].…”

“…Decreased GSH levels have been reported in several human ASD studies, and are associated with increased oxidative stress and decreased detoxification capacity [ 97 , 99 , 124 , 127 ]. On the other hand, our previous findings demonstrated that oxidative stress in children with ASD is not simply increased but shifted in a complicated pattern involving multiple types of ROS and antioxidants [ 122 ]. Decreased protection against hydroxyl radicals may be the fundamental mechanism underlying these changes.…”

Serum Free Radical Scavenging Capacity Profiles of Patients with Chronic Obstructive Pulmonary Disease

“…The characteristic changes in the scavenging capacity have been identified by MULTIS method in chronic kidney disease (CKD) 13 and in autism spectrum disorder. 14 These studies concluded that MULTIS profile may become a useful diagnostic tool in these patients. However, free radical scavenging capacity has not yet been evaluated by MULTIS method in patients with COPD.…”