Tuesday, 19 February 2013

Amino acids and autism in China

Many happy returns @ Paul Whiteley
Questioning Answers is 2 years old today (19th February 2013). Happy Birthday to 'me', or should that be 'it'?

Still a relative newcomer to the blogosphere but still churning out posts on all things autism research and beyond. Just in case you thought that I did actually bake a cake for the occasion, I didn't. But if I had have done (and yes a man can make a cake), it would have looked like the cake shown alongside. So please loyal readers, take an imaginary bite and enjoy.

To task. I've had hold of the short paper by Wen-Jun Tu and colleagues* (open-access) for a few weeks/months but have only now have got round to posting about it. It continues some familiar themes on this blog on (a) the focus on the -omics and application of technologies like mass spectrometry to autism and (b) amino acids revealing some really quite interesting differences in cases of autism vs. not-autism, as they are doing in conditions like schizophrenia and chronic fatigue syndrome also. A bit out of left field but I was also interested to read the paper by Shingyoji et al on plasma amino acid profiles potentially predicting lung cancer too. Wow, these guys get around.

Anyhow. I say it is a short paper but actually the Tu paper is a letter, and although there is relatively little novelty in just looking at amino acid chemistry in autism - what's up and what's down - these days, it does look at autism in quite a different ethnic population (Chinese) compared to quite a lot of the other papers in this area.

Indeed China, as well as emerging as a world superpower albeit with some peculiarities, is also starting to put quite a bit more effort into autism as per papers like this one from McCabe** with the very interesting title: Bamboo shoots after the rain... (hence the cute picture of the baby panda shown below looking so inquiring).

The net findings reported by Tu and colleagues reflect a few things:

  • Based on quite a small participant group of children diagnosed with DSM-IV autism (n=20) compared with asymptomatic controls (n=20), there were some very distinguishing plasma amino acid results found.
  • Tandem mass spectrometry was the main analytical method for determining amino acids complemented by immunoassay for detecting circulating neurotransmitters such as plasma dopamine.
  • Levels of some amino acids were significantly elevated (lysine, glutamate - glutamic acid and homocysteine); others were depressed (tryptophan, tyrosine, glutamine) in the autism group compared with controls.
  • Ailuropoda melanoleuca @ Wikipedia  
  • When it came to the level of significance, the biggest group differences were in the elevated levels of leucine (p=0.000 apparently), higher homocysteine (same p-value again) and elevated plasma dopamine (ditto on the p-value).

Of course I don't really need to say too much about these findings that have not already been said. Glutamate and glutamine are already on the autism research radar for quite a few reasons; same goes for homocysteine and it's link into things like methylation and the folate metabolic pathway. Tryptophan is a potentially important one bearing in mind its metabolism into things like melatonin among other things. Leucine? Well think branched chain amino acids and that rather interesting study by Novarino and colleagues*** (see this post) in relation to autism, and one cannot help but wonder if there might be some overlap.

Interestingly, one of my papers on the gluten- and casein-free (GFCF) diet (open-access) gets a mention in the text, with the authors seemingly worried about how their results might be further worsened if and when a GFCF diet is instigated following on from some similar suggestion by Arnold and colleagues****. Indeed this is an issue which has more recently been discussed in the meta-analysis by Sharp and colleagues*****. I'm minded to respond that rather than worry about how things could 'get any worse', a closer inspection of why they have the results they have and indeed, dealing with what they actually found, might be a good starting point, accepting the study by Jim Adams and colleagues (see this post) on what might be achieved by micronutrient supplementation. That and the fact that they reference gastrointestinal (GI) issues as potentially being involved with their results which begs the question: why not try and 'sort out' the GI issues or least one of them?

From the ethnicity point of view, the Tu study is an important one given the overlap between their observations and what has been found in other more Western populations allowing for the genetic, environmental and epigenetic differences that one might envisage and the eternal question of whether autism is presented the same worldwide. Such research actually makes a really good case for doing a little bit more cross-collaborative work among different peoples in different countries with autism, based not just on genetics as seems to have been the case so far, but also more functional biochemistry too.

Because this blog is the big 2 now, and given the association between this age and the word 'terrible', a song which I always thought best encapuslates a toddler tantrum from Nirvana (sorry about the language). Toodle pip.

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* Tu WJ. et al. Application of LC-MS/MS analysis of plasma amino acids profiles in children with autism. J Clin Biochem Nutr. 2012; 51: 248-249.

** McCabe H. Bamboo shoots after the rain: Development and challenges of autism intervention in China. Autism. November 2012.

*** Novarino G. et al. Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy. Science. 2012; 338: 394-397.

**** Arnold GL. et al. Plasma amino acids profiles in children with autism: potential risk of nutritional deficiencies. J Autism Dev Disord. 2003; 33: 449-454.

***** Sharp WG. et al. Feeding Problems and Nutrient Intake in Children with Autism Spectrum Disorders: A Meta-analysis and Comprehensive Review of the Literature. J Autism Dev Disord. February 2013.

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ResearchBlogging.org Tu WJ, Chen H, & He J (2012). Application of LC-MS/MS analysis of plasma amino acids profiles in children with autism. Journal of clinical biochemistry and nutrition, 51 (3), 248-9 PMID: 23170055