Tuesday, 24 April 2012

Glutathione and autism reloaded

I hope that I don't seem to be treading on old ground with this post on glutathione (GSH) and autism. I have covered some research on a possible link between glutathione and autism spectrum conditions previously (see here) following some interesting suggestions on the potential value of measuring GSH levels as a kind of biomarker for autism. The caveat being that despite an initial AUC=1 much more investigation is required.

This post is slightly different in that I wish to bring to your attention a review paper by Main and colleagues* (full-text) which highlights pretty much what we know, or think we know, about GSH and autism so far. Before progressing I think I should reiterate my caveat of not providing medical or other advice and strongly recommending that a medical physician be involved in all decision making aspects impacting health.

Aside from the content of the paper which I will run through shortly, a familiar name on the authorship list pulled me into this post. Dr Manya Angley, a Pharmacist from the University of South Australia, who has been involved in some really interesting work in autism research (here and here) was part of the team. Avid readers of this blog (if there are any!) might remember my first ever blog post on a paper with some pretty nifty techniques and results based on gut bacterial metabolites turning up in the urine of a group of children with autism. Well, Dr Angley was part of that authorship team also with some impressive company.

The current review carries a few interesting details:

  • It pretty much highlights all the work that has been done on measuring glutathione levels in autism up to November 2011. As anyone who has done a systematic review will tell you, this is no mean feat and perfect for answering an undergraduate exam paper such as 'Glutathione and autism: describe and critically discuss'.
  • Lower levels of GSH and alterations to chemical relations in cases of autism are a pretty consistent feature of the research carried out so far.
  • Serum cysteine levels also seem to be reduced and potentially associated with the severity of presented autistic symptoms. One has to wonder how this might fit into the sulphation issues previously highlighted in cases of autism and whether indeed as in some cases of schizophrenia also, cysteine in the form of NAC might be an area requiring much more serious investigation.
  • Serum homocysteine levels in cases of autism don't seem to show significant differences with control values. I was slightly shocked by this finding given previous research. Indeed a more recent paper not included in the current review suggested that hyperhomocysteinemia might be a useful biomarker for autism itself.
  • A significant increase in plasma vitamin B6 - pyridoxal-5′-phosphate - was noted in several studies potentially relating to issues with the bioavailability of the vitamin. Perhaps one reason why B6 never lived up to its potential

There is quite a lot of other information included in this review which should keep any interested parties content for a few hours. I would hasten to add that in this post I am not uniformly suggesting that everyone with autism has issues with glutathione, cysteine or homocysteine as per my mantra of heterogeneity and comorbidity.

One would however hope that with the continuing development of the third and final NICE guidance for autism in children and young people here in the UK, reviews like this one will figure strongly in informing the panel about potential areas of importance. If anything else this paper should invigorate some real interest into how amino acid and antioxidant chemistry in autism is not just alternative "biomedical" mumbo-jumbo.

To finish, the Carpenters and 'Top of the world'. Have a great day!

* Main PAE. et al. The potential role of the antioxidant and detoxification properties of glutathione in autism spectrum disorders: a systematic review and meta-analysis. Nutrition & Metabolism. April 2012.
DOI: 10.1186/1743-7075-9-35

2 comments:

  1. Hot off the presses just in time for your post

    Brain Region-Specific Glutathione Redox Imbalance in Autism

    Autism is a heterogeneous, behaviorally defined neurodevelopmental disorder. Recently, we reported a brain region-specific increase in lipid peroxidation, and deficits in mitochondrial electron transport chain complexes in autism, suggesting the role of oxidative stress and mitochondrial dysfunction in the pathophysiology of autism. However, the antioxidant status of the brain is not known in autism. Glutathione is a major endogenous antioxidant that plays a crucial role in protecting cells from exogenous and endogenous toxins, particularly in the central nervous system. The present study examines the concentrations of glutathione (GSH, reduced form; and GSSG, oxidized form) and the redox ratio of GSH to GSSG (marker of oxidative stress) in different regions of brains from autistic subjects and age-matched control subjects. In the cerebellum and temporal cortex from subjects with autism, GSH levels were significantly decreased by 34.2 and 44.6 %, with a concomitant increase in the levels of GSSG by 38.2 and 45.5 %, respectively, as compared to the control group. There was also a significant decrease in the levels of total GSH (tGSH) by 32.9 % in the cerebellum, and by 43.1 % in the temporal cortex of subjects with autism. In contrast, there was no significant change in GSH, GSSG and tGSH levels in the frontal, parietal and occipital cortices in autism versus control group. The redox ratio of GSH to GSSG was also significantly decreased by 52.8 % in the cerebellum and by 60.8 % in the temporal cortex of subjects with autism, suggesting glutathione redox imbalance in the brain of individuals with autism. These findings indicate that autism is associated with deficits in glutathione antioxidant defense in selective regions of the brain. We suggest that disturbances in brain glutathione homeostasis may contribute to oxidative stress, immune dysfunction and apoptosis, particularly in the cerebellum and temporal lobe, and may lead to neurodevelopmental abnormalities in autism.

    Interesting. . . .

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  2. Many thanks pD.

    It's true what they say about waiting for buses (none for hours and lots come along at once).

    I would think that this and the collected research of the Main review paper should be ample evidence for the initiation of some large scale investigations on GSH and relations in autism and the possibility of a similarly large double-blind, placebo-controlled, cross-over trial to test any effect?

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