Friday, 21 December 2012

2012 autism research review on Questioning Answers

Hello... is anyone there?

What y'mean those stories about the end of the world weren't true after all? They what... they forgot about the leap years? And the whole idea, which just happened to converge on the date of the Winter Solstice, was a little far-fetched?

I digress.

Speaking of time, once again we reach the end of another year and have a nostalgic look back at some of the highlights of the blogging year that was 2012 on Questioning Answers. Because the World is still here, all 7+ billion of us and Blogger remains active, similar to last year, month by month, let's takes a sentimental journey through what happened in autism and other research in 2012. So cup of tea in hand (no milk, two sugars please), feet up, and onwards...

My research mix tape @ Wikipedia  
Well just before the New Year set in, Drs Dan Rossignol and Richard Frye produced their excellent review of autism research trends discussed in this post. It was heartening to see that so much more research these days is looking at the more concrete somatic / physiological features of autism over the slightly more abstract psychological theories of times gone by. I don't have an issue with psychology trying to describe what autism might be, but don't particularly like quite a few of the sweeping generalisations that it has made thus far. Brent Williams and colleagues also published their very novel findings on the potential role of Sutterella bacteria in cases of autism with comorbid gastrointestinal (GI) symptoms which remains one of my most read blog posts. Heather Close and colleagues asked the question: can you grow out of autism? and opened up a can of worms in the process, and my fascination with epigenetics and autism blossomed.

A speculative but interesting paper published by T. Andrew Clayton on gut bacteria and amino acids in relation to autism caught my eye and continued the interest in all things gut microbiota. One of the first ever controlled trials of N-acetylcystine (NAC) for autism was also published potentially opening up some very interesting areas for intervention and further study. Discussions on the role of glutamine and glutamate in autism also made for similar engaging reading continuing the amino acid theme.

I'd like to think my research home primarily circles the various investigations into the hows and whys of a gluten- and casein-free diet for cases of autism. So when Pennesi and Cousino Klein published their survey of parental experiences of the diet I was always going to be interested (yes, I know it's not a randomised-controlled trial). I should also at this point tip my hat to the consensus statement published by Anna Sapone and colleagues on the spectrum of gluten-related disorders (outside of just coeliac disease). The paper by Momeni and colleagues describing the basics of a blood-based biomarker for autism also grabbed my blogging attention given the focus on the use of metabolomics. It wasn't a perfect study by any means, but it is a good start. The question of how common autism might be in cases of schizophrenia was of interest, but the main event for March must be the release of the latest CDC estimates for autism in the US: a very sobering 1 in 88 8-years olds with an autism spectrum disorder (ASD) up from 1 in 110 in 2009. Debate still rages on as to why the change (hint: it's likely to be lots of factors) and the implications.

Lots and lots of research discussed in April 2012. Gastrointestinal inflammation and immune activation in schizophrenia from Emily Severance and colleagues (keep her name in mind for now) seemed to mirror some of the findings reported in autism; six developmental trajectories and autism bloomers; quickly followed by some research on maternal obesity and risk of offspring autism as part of the CHARGE initiative. De novo mutations and autism filled some column inches, although there is still some confusion about SES and which parental age is a risk factors for autism. For me, April also carried one of the autism research papers of the year with the meta-analysis by Main and colleagues confirming that we really need to start looking more seriously at glutathione and related metabolites with autism in mind.

I never thought I would be talking about the bowel habits of Star Wars characters but that's what I did in this post on how poo tells a story in autism. Indeed there was more discussion of the inner workings of the bowel in this speculative post on polycystic ovary syndrome (PCOS), GI bacterial dysbiosis and autism. If you're a little bit sick and tired of poo and bacteria, there was this post on maternal fever and offspring autism risk (CHARGE once again) or if you like, some important data on parental pre-diagnostic experiences of their children.

Here in the UK, NICE - the National Institute for Health & Clinical Excellence - published the second strand of their guidance on autism, detailing their response for adults with autism. Elsewhere, CHARGE again published another vits and SNPs paper with autism in mind, this time focused on folic acid and everyone's favourite Scrabble enzyme classic, MTHFR. Low serum IgA in cases of autism was also discussed, as was some interesting work on autism's environmental exposome detailing some preliminary results on fish exposure to drug residues. June also closed with a summary post on the dangermouse that is the BTBR mouse model of autism. Just on the periphery a very important announcement was made with the first publications from the Human Microbiome Project (HMP).

More evidence for a role for glutathione in cases of autism nestled amongst other research looking at the possible overlap between autism and autoimmunity. A possible link between childhood anxiety and autistic traits was also the source of some discussion. Outside of autism, there were some interesting findings on mitochondrial dysfunction in cases of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) (followed up here) from which I would like to see similar methods applied to autism. And then there was the fascinating research from Prof. Paul Patterson's laboratory on mouse modelling of autism and immune function, a very definite 'watch this space' piece of research bearing in mind the increasing interest in stem cells and autism (see here).

'No single SNP associated with autism' was a real talking point for quite a few people. Micah Mazurek's paper linking functional GI problems, anxiety and sensory issues in cases of autism also brought in some interesting ideas about how physiology, psychology and behaviour might be linked in autism. The weather in August here in my part of the UK was not as wet as the wash-out of previous 'summer' months this year, so it was quite apt that the Saudi-Egyptian research tag-team of Mostafa and Al-Ayadhi published on vitamin D levels in cases of autism and their possible link to autoimmunity. There was more de novo mutations and older dads too. Although not a peer-reviewed paper, an opinion piece in the New York Times created a bit of a stir and some suggestions about the immune system and autism.

Quite an interesting month for autism research. There was the suggestion of a new inborn error of amino acid metabolism potentially being related to a presentation of autism. Indeed amino acids or rather one amino acid in particular, glutamate and its receptor and signalling functions was a real topic of conversation as per the report on the use of arbaclofen and a role for endocannabinoids at least in autistic symptoms associated with Fragile X syndrome. Maternal IgG antibodies and offspring autism also cropped up. Slightly to the left (or right!) of autism research was the grand XMRV de-discovery paper by Ian Lipkin and colleagues, which on the bright side, now means a bank of blood samples are available for research from quite a well-defined group of people with CFS. I should also point out that just because XMRV is not linked to CFS doesn't mean that viruses are completely off the hook for this range of conditions.

Continuing the autism-schizophrenia link, Kenneth Gadow reported some thought-provoking results on the presentation of schizophrenia spectrum disorder symptoms being present in cases of autism. The issue of wandering and autism has been discussed for quite a few years in the autism community, although Connie Anderson's paper represents one of the more thorough research-based investigations on just how widespread it might be. In a similar vein, the prevalence of bullying in cases of autism also got some research attention. October 2012 was also a month of leaky gut speculation as (again!) Paul Patterson and his team elaborated on their immune-activated mouse model and some very preliminary discussion of gut hyperpermeability (which I'm reliably informed is under submission for peer-reviewed publication some time soon).

November (or even Movember)
It started with a metabolomics bang following some very interesting research from Xue Ming and colleagues following up earlier investigations on urinary amino acid and other differences present in cases of autism. Interestingly, the amino acid glycine was a target compound which makes me wonder about its possible involvement with things like sleep. It was also mightily pleasing to me to see the paper from Francis Bowling and colleagues appear looking at sulphation (sulfation) and autism and revealing some very interesting systems biology tie-ups. Both the journals Nature and Pediatrics had special editions on autism (and open-access too) including reference to some future work on vitamin D and autism which neatly slotted into that paper by Ann Neumeyer suggesting a role for the sunshine vitamin in the bone density findings recorded in cases of autism. I've got to mention the study on HERVs and autism because this adds a whole new dimension to the whole genes-environment discussions and how methylation issues might potentially have some really important knock-on effects. And then there was that absolutely fascinating study on Toxoplasma gondii infection potentially setting up immunological issues with gluten by Emily Severance and colleagues...

DSM-V was accepted by the American Psychiatric Association (APA) and into unknown territory we all head. Some interesting data by Walter Zahorodny and colleagues were published on the ever increasing prevalence rate of autism in New Jersey, USA with the absolutely "startling" figure of 1 in 35 boys diagnosed with an ASD. With comorbidity in mind, I also looked at the similarly startling statistic of 40% of people with autism estimated to have a problem with their eyes which might very well tie into a least some of the perceptual issues which are reported to be experienced by many people on the spectrum. Some very interesting data linking some of the genetics findings in relation to autism to immune function were also published. Indeed a very, very preliminary study from Bradstreet and colleagues reporting on nagalase and Gc-MAF added to the immune function link.

And rest.

Quite a year by all accounts but I'm not here to blow research trumpets when still many, many people with autism and their families see little or no benefit from this or the thousands of other research papers published in 2012 and further back.

I have though, no doubt that 2013 will provide even more scientific fodder for this blog and its discussions given that the big DSM change-over is scheduled for May 2013 and that NICE are due to report their final strand of guidance on the management of autism in children and young people here in the UK. Coupled with high expectations from autism research conferences like IMFAR 2013, 2013 is already destined to be a game-changer of a year.

Stay tuned, thanks for reading, seasons greetings to all and take it away Kirsty and Shane... (25 years old y'know).


A research highlight from 2012..... Main PA, Angley MT, O'Doherty CE, Thomas P, & Fenech M (2012). The potential role of the antioxidant and detoxification properties of glutathione in autism spectrum disorders: a systematic review and meta-analysis. Nutrition & metabolism, 9 PMID: 22524510