Saturday, 15 June 2013

Autism, fetal alcohol syndrome and thyroid hormone?

Alcohol is the drug of choice for many people these days. For most, it's a case of the odd glass of wine here or there or a beer whilst sat outside in the garden during the summer we're supposed to be basking in at the moment.

The grape @ Wikipedia 
But there is no getting away from the fact that alcohol is a drug, and by all accounts, a drug which very readily impacts on the lives of many, many people. Outside of all the social ills associated with excessive alcohol consumption, there is also in some cases, a price to pay for infants born to those who drink alcohol to excess during pregnancy. The condition is called fetal alcohol syndrome or fetal alcohol spectrum disorder.

I've talked about FAS / FASD previously on this blog (see here). The crux of that post was the often confusing message sent out about how much alcohol is 'safe' to consume when a woman is pregnant and how one has to be very careful when presenting a potential link between FAS / FASD and a condition like autism.

Enter then a new study by Elif Tunc-Ozcan and colleagues* on the topic of a rodent model of FASD and some potentially interesting findings. There has already been some press discussion about this paper as per entries like this one.

Given the overlap between the presentation of FASD and autism (being very careful here), Tunc-Ozcan et al set out to see if they could identify some of the "molecular characteristics related to ASD in an animal model of FASD" to further inform both conditions. Rats were the participants of choice and as a starting point feeding pregnant rats one of a number of diets, one of which included supplementation with ethanol - the fancy chemical name for alcohol.

They then looked at the offspring of the various groups of rats based on examination of memory and social behaviours alongside the expression of certain genes tentatively related to autism in the hippocampus. They also looked at some of the facets of thyroid functioning as a function of supplementing one of the rat groups consuming ethanol with thyroxine. This last part stems from a body of work suggesting that in-utero exposure to alcohol might affect thyroid function which then subsequently impacts on facets of brain development**.

The results: well, keep in mind that this was a study of rats not humans, but alcohol did indeed impact on thyroid chemistry in exposed offspring. Males seemed to be particularly sensitive on measures of the behavioural effects of alcohol exposure. Talk about your fragile male. Quite a few of those candidate genes potentially involved in autism were also "significantly increased in the hippocampus of male offspring" exposed to alcohol.

Importantly, it seemed that co-administration of thyroxine with the inclusion of alcohol in the maternal diet seemed to have something of a protective effect on the areas studied in offspring. The word 'normalized' (North American spelling) is used to denote the various changes described.

As you might imagine, there is some interest in these results. I'll stress again that this was a study of rats and how rats are rats and not humans with all their complexities. The study authors have also made the important point that: "The study does not mean alcohol consumed by the mother is the cause of autism". With all the potential for stigma based on such results, I'll reiterate again that the authors are not saying that autism is caused by mothers drinking alcohol.

Again, I've talked about thyroid function with autism in mind quite a while back (see here). Within that entry was the suggestion (evidence-based suggestion***) that levels of thyroxine (T4) in the newborn might be to some degree linked to the risk of a later diagnosis of autism. One could also put this in the perspective of the results by Tunc-Ozcan and colleagues too.

I had a few additional thoughts about this study. I'm speculating so please humour me. I wondered for example, whether maternal consumption of alcohol talked about in this rat study might have had some more generalised effects on things like gut bacteria. It's quite widely known that alcohol is not great news for gut bacteria as per reports on consumption of alcohol and SIBO (see here). I'm speculating that this might also translate into potential effects for offspring too? Another even more outlandish thought for your consideration: auto-brewery syndrome. I know that this is not exactly an idea with a great deal of legal merit (see here) but the scientific literature is dotted with case studies suggesting that it can, and does happen**** as a consequence of some unusual fermentation in the deepest, darkest recesses. With all the focus on gut bacteria and autism, is it beyond the realms of possibility that something like this might show some subtle effect?

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* Tunc-Ozcan E. et al. Low-Dose Thyroxine Attenuates Autism-Associated Adverse Effects of Fetal Alcohol in Male Offspring's Social Behavior and Hippocampal Gene Expression. Alcohol Clin Exp Res. 2013 Jun 13. doi: 10.1111/acer.12183.

** Kornguth SE. et al. Impeded cerebellar development and reduced serum thyroxine levels associated with fetal alcohol intoxication. Brain Res. 1979; 177: 347-360.

*** Hoshiko S. et al. Are thyroid hormone concentrations at birth associated with subsequent autism diagnosis? Autism Res. 2011 Dec;4(6):456-63. doi: 10.1002/aur.219.

**** Dahsan A. & Donovan K. Auto-Brewery Syndrome in a Child With Short Gut Syndrome: Case Report and Review of the Literature. J Ped Gastroenterol Nutr. 2001; 33: 214-215.

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ResearchBlogging.org Tunc-Ozcan E, Ullmann TM, Shukla PK, & Redei EE (2013). Low-Dose Thyroxine Attenuates Autism-Associated Adverse Effects of Fetal Alcohol in Male Offspring's Social Behavior and Hippocampal Gene Expression. Alcoholism, clinical and experimental research PMID: 23763370