Thursday, 6 October 2011

Amino acids in schizophrenia and autism

This is my Godzilla post on amino acids; indeed Godzilla and Godzooky all rolled into one. In fact this post is so big that it is split into two parts. So, nice cup of tea/coffee/cocoa (or something stronger if you wish), feet up and read on.

Part 1. Schizophrenia

Metabolomics. The word just rolls off the tongue. The science of reading biological samples for clues to symptoms, diseases, conditions. Not particularly fussy about which medium to use: urine, blood, saliva. The technology is spectacular; the physics and chemistry complicated, and in the past few years, metabolomics has become quite a 'sexy' area of research - 'your mass spectrometer or mine'.

I recently chanced upon an article published on the website Internal Medicine News about the application of metabolomics to schizophrenia. Another conference presentation; this time given at the 2011 annual congress of the European College of Psychopharmacology in Paris by Dr Dan Rujescu. Rujescu is no stranger to schizophrenia research, displaying an impressive PubMed reference list including some work on a cats best rat-catching compadre Toxoplasma gondii.

The current findings: seven compounds were found to discriminate samples (not sure what kind of samples) of people with schizophrenia (n=265) from controls (n=216). The compounds were: ornithine, arginine, glutamine, histidine, phosphatidylcholine acyl-alkyl C38:2, dodecenoyl carnitine, and octenoyl carnitine. Only ornithine was 'down-regulated'; the others were elevated. There is some further text on the use of gene-metabolite networks but I will let you read more of that for yourselves.

Intriguing that a panel of seven compounds, including several amino acids, might carry some discriminatory power for determining schizophrenia from not-schizophrenia. This is of course not the first time that amino acid patterns have been discussed in relation to schizophrenia as witnessed by this paper; one of several hundred detailing a possible connection. Takes me back to a few findings suggesting similar things for autism.

Part 2. Autism

The second part of this entry has been on my 'to do' list for a few weeks now. The reason why I wanted to get to it is because amino acids and their presentation in the various biological fluids in autism represents a growing research area. Perhaps more than that they tie into some important things already covered on this blog in relation to in-born errors of metabolism (like PKU)the various dietary factors associated to autism spectrum conditions and research pertinent to our old friend homocysteine. This could turn out to be a very long post indeed if I were to go through all the research on amino acids in autism so I will put on my cherry-picking goggles on in order to present a condensed version.

What are amino acids I thought I heard you say? Well, I should have said this in part 1 but the way I tend to look at it is that proteins, those long chains of amino acids, are equivalent to sentences. Peptides, short chains of amino acids, are the words of the sentence. The individual amino acids are the letters. Indeed when talking about amino acids, single letters are often used to denote specific amino acids (also alongside their three letter abbreviations also).

The earliest report that I can find discussing amino acid metabolism in relation to autism is this paper from 1958. I was however nudged into this post by this paper* by Tirouvanziam and colleagues appearing quite recently reporting on a few interesting findings in relation to amino acids and autism. The team from Stanford University analysed levels of plasma amino acids in children with autism spectrum conditions (n=27) and asymptomatic controls (n=20) and found lower levels of most neutral amino acids as well as others in the autism group. Importantly the authors also noted that various excitatory amino acids such as glutamate did not follow the usual age-related changes. The findings mirrored those presented in earlier investigations including this one which again found higher levels of plasma glutamate as did this one from Jim Adams and colleagues.

Now an even more recent paper has emerged by Shimmura and colleagues* (open-access) has confirmed the glutamate findings in relation to autism, or in the case of this paper, high-functioning autism. Indeed out of all the amino acids assayed for, only glutamine and glutamate were significantly different from controls: glutamate higher, glutamine lower. I could go on to talk about glutamate and the hyperglutamatergic hypothesis of autism. How about the link between glutamine and the gastrointestinal (GI) tract instead? Glutamine the 'food of the gut' and what happens when there 'aint enough of it. Glutamine and glutathione connected even?

If there was a take home message from this mega post it would be something like amino acids are important (we know that already); amino acids might be very, very important to conditions like autism and schizophrenia.

* Tirouvanziam R. et al. Distinct plasma profile of polar neutral amino acids, leucine and glutamate in children with autism spectrum disorders. JADD. June 2011.

** Shimmura C. et al. Alteration of plasma glutamate and glutamine in children with high-functioning autism. PLoS ONE. October 2011.