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The potential role of the antioxidant and detoxification properties of glutathione in autism spectrum disorders: a systematic review and meta-analysis.

ABSTRACT: BACKGROUND:Glutathione has a wide range of functions; it is an endogenous anti-oxidant and plays a key role in the maintenance of intracellular redox balance and detoxification of xenobiotics. Several studies have indicated that children with autism spectrum disorders may have altered glutathione metabolism which could play a key role in the condition. METHODS:A systematic literature review and meta-analysis was conducted of studies examining metabolites, interventions and/or genes of the glutathione metabolism pathways i.e. the ?-glutamyl cycle and trans-sulphuration pathway in autism spectrum disorders. RESULTS:Thirty nine studies were included in the review comprising an in vitro study, thirty two metabolite and/or co-factor studies, six intervention studies and six studies with genetic data as well as eight studies examining enzyme activity. CONCLUSIONS:The review found evidence for the involvement of the ?-glutamyl cycle and trans-sulphuration pathway in autistic disorder is sufficiently consistent, particularly with respect to the glutathione redox ratio, to warrant further investigation to determine the significance in relation to clinical outcomes. Large, well designed intervention studies that link metabolites, cofactors and genes of the ?-glutamyl cycle and trans-sulphuration pathway with objective behavioural outcomes in children with autism spectrum disorders are required. Future risk factor analysis should include consideration of multiple nutritional status and metabolite biomarkers of pathways linked with the ?-glutamyl cycle and the interaction of genotype in relation to these factors.

SUBMITTER: Main PA

PROVIDER: S-EPMC3373368 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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The potential role of the antioxidant and detoxification properties of glutathione in autism spectrum disorders: a systematic review and meta-analysis.

Main Penelope Ae PA Angley Manya T MT O'Doherty Catherine E CE Thomas Philip P Fenech Michael M

Nutrition & metabolism 20120424

<h4>Background</h4>Glutathione has a wide range of functions; it is an endogenous anti-oxidant and plays a key role in the maintenance of intracellular redox balance and detoxification of xenobiotics. Several studies have indicated that children with autism spectrum disorders may have altered glutathione metabolism which could play a key role in the condition.<h4>Methods</h4>A systematic literature review and meta-analysis was conducted of studies examining metabolites, interventions and/or gene ...[more]

PMID: 22524510

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Project description:BackgroundThe etiology of Autism Spectrum Disorder (ASD) has been recently debated due to emerging findings on the importance of shared environmental influences. However, two recent twin studies do not support this and instead re-affirm strong genetic effects on the liability to ASD, a finding consistent with previous reports. This study conducts a systematic review and meta-analysis of all twin studies of ASD published to date and explores the etiology along the continuum of a quantitative measure of ASD.MethodsA PubMed Central, Science Direct, Google Scholar, Web of Knowledge structured search conducted online, to identify all twin studies on ASD published to date. Thirteen primary twin studies were identified, seven were included in the meta-analysis by meeting Systematic Recruitment criterion; correction for selection and ascertainment strategies, and applied prevalences were assessed for these studies. In addition, a quantile DF extremes analysis was carried out on Childhood Autism Spectrum Test scores measured in a population sample of 6,413 twin pairs including affected twins.ResultsThe meta-analysis correlations for monozygotic twins (MZ) were almost perfect at .98 (95% Confidence Interval, .96-.99). The dizygotic (DZ) correlation, however, was .53 (95% CI .44-.60) when ASD prevalence rate was set at 5% (in line with the Broad Phenotype of ASD) and increased to .67 (95% CI .61-.72) when applying a prevalence rate of 1%. The meta-analytic heritability estimates were substantial: 64-91%. Shared environmental effects became significant as the prevalence rate decreased from 5-1%: 07-35%. The DF analyses show that for the most part, there is no departure from linearity in heritability.ConclusionsWe demonstrate that: (a) ASD is due to strong genetic effects; (b) shared environmental effects become significant as a function of lower prevalence rate; (c) previously reported significant shared environmental influences are likely a statistical artefact of overinclusion of concordant DZ twins.

Dataset Information

The potential role of the antioxidant and detoxification properties of glutathione in autism spectrum disorders: a systematic review and meta-analysis.

Publications

The potential role of the antioxidant and detoxification properties of glutathione in autism spectrum disorders: a systematic review and meta-analysis.

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