Oxidative stress marker aberrations in children with autism spectrum disorder: a systematic review and meta-analysis of 87 studies (N\u2009=\u20099109)

Lei Chen,Yong Cheng,Hua Liu,Hua Wang,Xiao Mao,Lue-Ning Gui,Xiao-Jie Shi

doi:10.1038/s41398-020-01135-3

Abstract

There is increasing awareness that oxidative stress may be implicated in the pathophysiology of autism spectrum disorder (ASD). Here we aimed to investigate blood oxidative stress marker profile in ASD children by a meta-analysis. Two independent investigators systematically searched Web of Science, PubMed, and Cochrane Library and extracted data from 87 studies with 4928 ASD children and 4181 healthy control (HC) children. The meta-analysis showed that blood concentrations of oxidative glutathione (GSSG), malondialdehyde, homocysteine, S-adenosylhomocysteine, nitric oxide, and copper were higher in children with ASD than that of HC children. In contrast, blood reduced glutathione (GSH), total glutathione (tGSH), GSH/GSSG, tGSH/GSSG, methionine, cysteine, vitamin B9, vitamin D, vitamin B12, vitamin E, S-adenosylmethionine/S-adenosylhomocysteine, and calcium concentrations were significantly reduced in children with ASD relative to HC children. However, there were no significance differences between ASD children and HC children for the other 17 potential markers. Heterogeneities among studies were found for most markers, and meta-regressions indicated that age and publication year may influence the meta-analysis results. These results therefore clarified blood oxidative stress profile in children with ASD, strengthening clinical evidence of increased oxidative stress implicating in pathogenesis of ASD. Additionally, given the consistent and large effective size, glutathione metabolism biomarkers have the potential to inform early diagnosis of ASD.

Highlights

Autism spectrum disorder (ASD) is a complicated, pervasive, and heterogeneous disease[1], which is characterized by varying degrees of dysfunctional social communication, narrow interests, and repetitive behaviors[2,3]
After carefully reading the 212 articles, we excluded 125 articles because of the following reasons: no necessary data (n = 73), paper was retraced (n = 1), markers were analyzed in animal model (n = 2), without an healthy control (HC) (n = 24), samples were not from serum or plasma (n = 21), samples were from adult patients with ASD (n = 4)
Oxidative stress-related biomarker dysregulations in ASD Our meta-analysis revealed blood oxidative glutathione (GSSG), homocysteine, S-adenosylhomocysteine (SAH), copper, nitric oxide, and malondialdehyde (MDA) concentrations were significantly higher in ASD children than that of HC children, as showed in Table 1 and Figs. 1–4

Summary

Introduction

Autism spectrum disorder (ASD) is a complicated, pervasive, and heterogeneous disease[1], which is characterized by varying degrees of dysfunctional social communication, narrow interests, and repetitive behaviors[2,3]. Data from the Centers of Disease Control and Prevention showed that the prevalence of ASD reached 1/ 54 children in the United States. The social communication problem as the core diagnostic feature in ASD children has been extensively studied in the field. The non-diagnostic features in ASD children have attracted great attention over the past decade; these include gastrointestinal problem[7], sleep disorders[8], immune. It has been proposed that oxidative stress in the developing brains contributes to neuronal damage in genetically susceptible children, which is important in the pathophysiology of ASD.[6,17]. An increased oxidative stress was observed in the brains of ASD patients[18]

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