Friday, 27 December 2013

2013 autism research review on Questioning Answers

So, we're here again.

The end of another year and time to look back on some of the highlights of the blogging year that was 2013 on Questioning Answers. The question is: are we any further forward when it comes to the autism spectrum, it's aetiology, nature and improving quality of life?
Penshaw monument @ Paul Whiteley 

I'm going to be optimistic this year and say yes in some respects we are. But there is still much further to go...

Month by month here's a few posts on research that I thought were pretty important.


Well it all started with a bang. Deborah Fein and colleagues published their optimal outcomes paper detailing how in a well-defined group of children with a previous diagnosis of autism, their autistic symptoms had abated. As you can imagine, the notion that at least some autism might not be as immutable as was first thought caused quite a stir (see here) but the evidence is starting to pile up for at least one developmental trajectory fitting this optimal outcome grouping. Further evidence for a correlation between air pollution and autism was also published. And I was also involved in publishing a review paper on the use of gluten- and casein-free (GFCF) diets for autism (see here) which is a topic I'll be coming back to later in this post.

Functional gastrointestinal (GI) problems do seem to be over-represented in cases of autism according to the study by Susie Chandler and colleagues. I know that this is not necessarily new news but from a UK perspective, the source of the message was an important part of this paper, which also applies to later research talked about in December. This month also saw the start of a whole slew of papers in 2013 suggestive of an increased risk of offspring autism where certain antiepileptics were used during the nine months that made us (see here). Maternal autoantibodies to foetal brain tissue also registered on the research radar which again, I'll be coming back to. Personally, I was saddened to hear about the death of Prof. Ann-Mari Knivsberg who was there from the start when it came to the whole GFCF diet and autism research. Rest in peace Ann-Mari.

Common ground was a key message from the consortium looking at the genetic overlap between conditions like autism, ADHD, schizophrenia and the like. In many respects that conclusion set the tone for many debates on clinical nosology vs. real-life presentation which were aired during 2013. Parent-reported autism prevalence figures in the United States suggested that 1 in 50 children presented with an autism spectrum disorder (ASD) in 2011-2012. Transgenerational effects were put forward as another variable influencing autism risk as per the paper by Emma Frans (see here). And that most contentious of topics, bowel disorders and autism, received some welcome attention from Stephen Walker (see here).

Autism or the autisms? was a questioned posed by Andrew Whitehouse continuing the theme of real-life autism and all that heterogeneity that accompanies presentation. Many authors have seemingly begun to realise that whilst common symptoms unite under the diagnostic label of autism, the cause and path of those symptoms may very well be numerous. The paper by Chloe Wong and colleagues looking at the methylome and autism continued the rise and rise of epigenetic research in relation to those autisms. The question of a connection between Lyme disease and autism also came under the research spotlight, as did the folding placenta (see here) and some interesting speculations on gut bacteria (see here) though not necessarily portrayed accurately in the accompanying media.

IMFAR 2013 was held in the beautiful Basque Country. One talk in particular seemed to capture those changing perspectives about autism (sorry, the autisms) as the world was introduced to ESSENCE (see here) by Prof Gillberg. May also saw one of the most significant changes to autism for many years as the latest update to DSM - the DSM-V - came into being, and with it a reshape of how we come to define the condition. Alongside, we were introduced to RDoC (see here) and the diagnostic vs. research battle commenced. Whilst slightly outside of core autism, but nevertheless potentially relevant as comorbidity, Mary Rogers and colleagues talked about depression and its correlation with C.diff infection.

Flaming June certainly lived up to its name this year here in the UK. The prevalence of autism in Canada took up two posts in June (see here and here). I was particularly interested to read the paper by Lau and colleagues on immune reactivity to gluten in cases of autism (see here). The implication from their results of a non-coeliac gluten sensitivity as potentially being present in cases set the tone for further interesting work in this area in the following months. Indeed continuing that dietary strand, the study by David Ruskin and colleagues describing the results of a ketogenic diet on a mouse model of autism also provided some rather informative reading.

The gold-standard trial by Cheryl Claiman and colleagues looking at the use of tetrahydrobiopterin (sapropterin or BH4) for cases of autism reported some rather interesting results in terms of a positive impact on presented autism traits. I'm becoming quite interested in what BH4 might be able to do for some cases of autism building on its potential for the archetypal 'diet can affect behaviour' condition that is Phenylketonuria (PKU). Gut bacteria also emerged again as a target for autism research based on the work by Kang and colleagues (see here) suggestive that gut bacterial diversity differences might be linked to the presentation of autism outside of just any GI comorbidity. Similar research on those trillions of passengers we all carry was also detailed with regards to Myalgic encephalomyelitis / Chronic Fatigue Syndrome (ME / CFS). And there was the introduction of maternal autoantibody-related autism or MAR autism for short (see here). More on that shortly.

August was definitely a 'leaky gut' month. I posted a sort of overview of where autism research is currently up to when it comes to intestinal hyperpermeability and lo and behold, Laura de Magistris and colleagues go and add to the literature (see here). Still there was more to come. In other research news, there was an interesting update to the body of work looking at recurrence risk of autism in siblings (see here) and a nice case study on the potential value of NAC (N-acetylcysteine) for at least some autism (see here). Just outside of autism, the association between schizophrenia and everyone's favourite marker of inflammation, C-reactive protein also received some attention (see here). August also saw an important step forward for autism practice here in the UK with the publication of the last strand of guidance from NICE on managing children and young adults with autism (see here).

MAR autism y'say? Well, storm clouds appeared at the suggestion that such research might be translated into something like a commercial test (see here). Indeed, with that notion of maternal immune activation and offspring signs and symptoms in mind, observations from monkeys (not just rodents) suggested similar issues to be present (see here). The presentation of autistic-like symptoms in cases of eating disorders was reported. As was yet more discussion on the use of certain antiepileptics during pregnancy potentially impacting on offspring behaviour (see here). October however had two main highlights for me though: (i) the publication of our first follow-up paper to the ScanBrit study of a GFCF diet (see here) on potential best-responder characteristics, and (ii) the study from Jonas Ludvigsson and colleagues on issues with gluten in autism probably not being coeliac (celiac) disease but potentially something just as interesting (see here). The rise of non-coeliac gluten sensitivity? Indeed, the Ludvigsson paper prompted one Alessio Fasano to say something pretty monumental on his analysis of the study which I'll quote again: "In the past, we have had the believers and nonbelievers when it came to the role of gluten in autism ... Hopefully this paper can clarify, once and for all, that a subset of those with autism has gluten sensitivity, a condition triggered by gluten but distinct from celiac disease." [source is here].

Continuing the theme of dietary intervention and autism (I'm not obsessed honest!), the paper by Graf-Myles and colleagues caught my attention and their notion that, assuming correct nutritional support, the horror that is the GFCF diet might not be as rotten a diet as first thought. I was also interested in the review by Xu and colleagues who upon meta-analysing all the relevant data concluded that maternal diabetes did seem to show a connection with a heightened risk of offspring autism (see here). Parental stress and the various ways and means that autism research has suggested it could be tackled was also covered in October (see here); as was the news that the autism numbers game here in the UK might be showing a plateau in prevalence and incidence rates (see here). Scientific replication also played it's part in autism research as per the 'failure to replicate' paper from Robinson and colleagues when looking at SNPs predicting autism (see here). Oh and MAR autism also showed an autoimmunity side...

I was very interested to read the paper by Lynne Wang and colleagues replicating some earlier findings on a possible role for Sutterella in cases of autism (see here). That and the suggestion of a particularly high prevalence of autism associated with cases of Neurofibromatosis 1 (NF-1) from Garg et al. A possible role for iodine and autism was also the topic of some preliminary research chatter (see here) as was paracetamol exposure, albeit not exactly with autism in mind (see here). And then there was the suggestion of overlap between a specific part of the autism spectrum and the issue of synaesthesia (a mixing of the senses) to consider.... bearing in mind a few gaps in the presented study.

Two pretty big papers started the month of December. Beginning with one of, possibly the, largest study so far looking at the presence of functional bowel issues in cases of autism we were again reminded that autism does seem to be over-represented when it comes to such problems. This was followed by the paper by Elaine Hsiao and Paul Patterson (see here) and others which brought their earlier conference proceedings on the presence of leaky gut in the maternal immune activated mouse model to the peer-review arena. Words like 'incredible' were used to describe the potential of altering the gut microbiota and impacting on both gut permeability and presented 'autistic-like' symptoms in their mice. I was enthused but remind readers that mice are mice not humans. Indeed that same sentiment distinguishing mice from humans was similarly applied to some interesting work suggestive of GI issues in the valproate mouse model of autism. That all being said, we also got some more confirmation that leaky gut can appear in real people with autism as per the Dalton findings. I'd hazard a guess that I'll be blogging about gut permeability and autism further in 2014 and beyond.


And rest. Of course there was lots more research considered in 2013 but I assume you'll be too busy eating those turkey left-overs for me to overload you any further.

I think I am justified in repeating my optimistic appraisal that we know a little bit more about autism at the end of this year than we did at the beginning. The main themes as I see it are:

  • autism is probably better described as 'the autisms' with various different develomental trajectories present in different people,
  • there is so much more to autism than it just being related to 'the brain',
  • comorbidity is important; often very important, and
  • 'immutable and lifelong' are words which might not necessarily apply to every single case of autism bearing in mind we don't yet know for who and the precise reasons why. 

Finally, if you noticed the picture at the top of this post, it's one of my own taken back in September this year, of Penshaw monument (see here for more information) here in the bracing North-East of England. Oh and there's some legend to accompany this splendid structure... about a worm and no, not those kinds of worms, which I assume we'll be hearing more about in 2014 (see abstract T177).

And with that, here is to 2014 and no doubt, another interesting year for autism research ahead. Thanks for reading and a Happy New Year to you and yours.


It's a difficult task but my autism research paper of the year (2013) goes to....

Fein D. et al. Optimal outcome in individuals with a history of autism. J Child Psychol Psychiatry. 2013 Feb;54(2):195-205. doi: 10.1111/jcpp.12037.

---------- Fein D, Barton M, Eigsti IM, Kelley E, Naigles L, Schultz RT, Stevens M, Helt M, Orinstein A, Rosenthal M, Troyb E, & Tyson K (2013). Optimal outcome in individuals with a history of autism. Journal of child psychology and psychiatry, and allied disciplines, 54 (2), 195-205 PMID: 23320807