Friday, 18 October 2013

Not metabolomics and autism again...

I don't mind admitting that I am a bit of a nerd when it comes to certain things.

Yes I still thrill at watching the films of the 1970s / 1980s; in particular a certain trilogy of films almost known word for word ("delusions of grandeur..."). And yes, despite my very restricted competence on the issue, I do like looking through the odd study with the words 'metabolomics' or 'mass spectrometry' in the title as per the findings of Stein and colleagues* following up the limited research findings on phthalate metabolism and autism (see here).
Time of Flight? About 3 hours if you're lucky. @ Wikipedia 

Indeed on that last point of mass spectrometry, I was always going to be interested in the paper by Kuwabara and colleagues** (open-access) detailing their efforts of screening the plasma of a small group of adults diagnosed with an autism spectrum disorder compared to asymptomatic controls with a view to identifying "novel candidate metabolites as potential biomarkers".

I've talked about these types of studies before (see here and here) and how the technology is absolutely fantastic in what it enables science to do these days. The Kuwabara paper is a little bit different in terms of their chosen method being based on something called capillary electrophoresis (CE) or to put it more completely CE-ToF MS (CE Time of Flight Mass Spectrometry). You can find out more about CE here.

My memories of second supervising a PhD on this chosen method with autism biomarker research in mind, reminds me that CE was a particularly inviting technique when applied to biological samples in comparison to other more industry-standard methods such as HPLC (see here). So much so that other groups have also looked at CE with autism in mind as per the study by Soria and colleagues*** although I don't think things really progressed any further in this area despite the allure of CE.

Anyhow, the Kuwabara paper reported that based on a two-step identification and validation study using CE-ToF MS, a number of metabolites came up as being potentially important to autism cases including high plasma levels of the amino acids arginine and taurine and "significantly low levels of 5-oxoproline (p<0.001) and lactic acid (p = 0.031) compared with the controls".

I've mentioned before how amino acids, the building blocks of peptides and proteins, have been the source of quite a bit of study with regards to autism (and lots of other conditions). I should really formulate a mega-post on what the various studies of the amino acids have found so far with regards to autism, but at this point in time, the task is just a little too daunting. That being said, the Kuwabara results show some passing connection to other data in this area specifically with regards to taurine (see here) but as with everything seemingly linked to autism, there is nothing universal about this finding****. Indeed on that lactic acid finding (yes, I know it's not an amino acid) and in particular, the lower levels of lactic acid reported, one might say this was slightly at odds with other research (see here).

It is perhaps one of the downsides to the whole metabolomics and proteomics disciplines that whilst the technology is astounding in terms of findings and accuracy (accurate mass anyone?), when applied to a heterogeneous condition like autism, grouped and consistent results are often few and far between. Yes it very much depends on factors such as what medium you are sampling (blood, urine), when you sample (age of participants) and under what circumstances you sample (diet, medication, etc.). But as with the very complicated genetics (and epigenetics) of autism (see here), so the proteome and metabolome in relation seem to be also going the same way in terms of a lack of consistent and verifiable markers.

As I've indicated before, the whole concept of biomarkers 'for autism' is perhaps a moot point given issues like the rise of the autisms (see here) and all that comorbidity which can, and does, seem to follow a diagnosis (see here) interfering with any results. That's not however to say that there may be some benefit in continuing this line of investigation with some subtle alterations such as focusing on sub-groups (see here) or using the technology to explore intervention response for example (see here). Indeed with this in mind, I should also tip my hat to the study by Ramsey and colleagues***** (open-access) and their age-related "molecular trajectories" work in relation to autism which mimics where metabolomics seems to be going in other areas of medical research.

Oh and how about marrying up metabolomics with another very interesting -omic, the gut microbiome******?

To close, and especially for a very sensitive member of my brood who shed a tear at this part of the movie, the redemption of Anakin Skywalker. Bless you darling, don't ever change.

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* Stein TP. et al. Autism and Phthalate Metabolite Glucuronidation. JADD. 2013; 43: 2677-2685.

** Kuwabara H. et al. Altered Metabolites in the Plasma of Autism Spectrum Disorder: A Capillary Electrophoresis Time-of-Flight Mass Spectroscopy Study. PLoS One. 2013 Sep 18;8(9):e73814. doi: 10.1371/journal.pone.0073814.

*** Soria AC. et al. Data processing in metabolic fingerprinting by CE-UV: application to urine samples from autistic children. Electrophoresis. 2007 Mar;28(6):950-64.

**** Geier DA. et al. A prospective study of transsulfuration biomarkers in autistic disorders. Neurochem Res. 2009 Feb;34(2):386-93.

***** Ramsey JM. et al. Identification of an age-dependent biomarker signature in children and adolescents with autism spectrum disorders. Mol Autism. 2013 Aug 6;4(1):27. doi: 10.1186/2040-2392-4-27.

****** De Angelis M. et al. Fecal Microbiota and Metabolome of Children with Autism and Pervasive Developmental Disorder Not Otherwise Specified. PLoS ONE 8(10): e76993.

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ResearchBlogging.org Kuwabara H, Yamasue H, Koike S, Inoue H, Kawakubo Y, Kuroda M, Takano Y, Iwashiro N, Natsubori T, Aoki Y, Kano Y, & Kasai K (2013). Altered Metabolites in the Plasma of Autism Spectrum Disorder: A Capillary Electrophoresis Time-of-Flight Mass Spectroscopy Study. PloS one, 8 (9) PMID: 24058493