Tuesday, 30 December 2014

2014 autism research review on Questioning Answers

I like warm hugs...
Time flies doesn't it? And here we are yet again at the end of another research year and a time to reflect on the blogging highlights of 2014 on Questioning Answers. Once again the question is: are we any further forward when it comes to the autism spectrum, it's aetiology, nature and improving quality of life for those on the spectrum?

Once again, I'm going to be optimistic and say 'yes' in some respects we are, as autism research continues at a pace. The caveat being that there is still much more to do, particularly in translating research findings into practical strategies for improving quality of life for those on the autism spectrum and their loved ones who both want and require it.

As per previous years' reviews (see 2011, see 2012, see 2013), month by month I'm gonna give you an indication of some of things I thought were important enough to discuss on this blog, bearing in mind how blogging might just fill a gap between science and the translation of science.


Treatable inborn errors of metabolism in cases of autism was the first entry for 2014, beginning an important theme that the diagnosis of autism or autism spectrum disorder (ASD) should be a starting point for further investigations not an end-point process. The summary paper by Cao and colleagues talking about the gut microbiome and autism (so far) offers a new frontier for part of that research agenda combined with the growing emphasis of comorbidity clusters talked about in a few papers. And yes that includes gastrointestinal (GI) comorbidity, which I'll be coming back to shortly. The introduction of the DSM-5 diagnostic criteria covering autism also received a mention in January with a specific focus on how its use might affect the autism numbers game. The new label of social communication disorder (SCD) also got a mention.

Optimal outcome continued to receive research attention and further moves towards the idea that the autisms (plural) might include a number of different developmental trajectories. Anti-brain antibodies and autism was another theme in receipt of further study too, but with a few caveats still remaining. The fantastic resource that is the Taiwan National Health Insurance Research Database (NHIRD) continued to give in research terms as per the curious suggestion that a diagnosis of asthma might be a risk factor for autism. A few other areas previously discussed in the autism research literature also got further attention as per findings on bumetanide and autism and issues with the BCKDK gene in relation to at least some types of autism.

1 in 68. That was the revised autism prevalence estimate from the US CDC with lots of discussions around the hows and whys. Obesity and autism also continued to receive some well-deserved research attention reflective of another important focus in 2014 looking at the physical health and activity levels of those on the autism spectrum. A specific female phenotype of autism was also a discussion point this month. More generally, inflammation in relation to psychiatry was also covered.

I fulfilled a lifelong ambition in April 2014 when my book was published. One of the prominent themes of the book was how the use of a gluten- and/or casein-free diet might be indicated for 'some' autism, something which may very well tie into some interesting work done on the opioid antagonist naltrexone with autism in mind. Those GI issues that some people have been talking about for many, many years with autism in mind also continued to receive supporting research evidence on their over-representation in the autism spectrum. The paper from Suzanne Goh and colleagues talking about mitochondrial dysfunction being part of a neurobiological subtype of autism also represents an important addition to the research in that area.

'Environment as important as genes in autism' was one of the sentiments expressed by the findings from Sven Sandin and colleagues looking at heritability and relative recurrence risk with autism in mind. Continuing that theme was an interesting case report about autism following enterovirus encephalitis and even further congential CMV infection as potentially being related to some offspring autism. The paper from Luke Taylor and colleagues concluding that vaccines were not associated with autism (via meta-analysis) created some column inches, albeit including one paper which itself became the topic of quite a bit of discussion. Again with some self-indulgence in mind, my small contribution to a paper on formulating low dose naltrexone into a cream also hit the peer-reviewed shelves. Not exactly autism-relevant for now but...

What should autism research focus on? That was the question asked (and answered) by the paper from Pellicano and colleagues. The answer varied according to who was asked but it appears translational research impacting on day-to-day life is what is required more often than not. Sorry to keep going on about optimal outcome and autism but yet another paper was published on this topic and for the first time, the suggestion that certain intervention strategies might make a difference was presented. Vitamin D and autism is a topic in the research ascendancy in 2014 particularly following the results presented by Eva Kočovská and colleagues. I also covered the sunshine vitamin/hormone from another point of view in June: depression and vitamin D which might be relevant to comorbidity with autism in mind. Kata training might be a good way to keep in shape and help with a few other issues associated with autism was the conclusion reached in a post on the use of martial arts. And finally, cytokine involvement in autism got a meta-analysis concluding that there is potentially much more to see in this research area. I for one wouldn't disagree with that last sentence.

The document on medical comorbidities occurring alongside a diagnosis of autism from the parent group Treating Autism here in the UK was published. Free to download and pretty comprehensive is the recommendation that I would give, highlighting again that a diagnosis of autism is a starting point not an end-point for further clinical scrutiny. Mercury exposure and autism or ADHD (attention deficit hyperactivity disorder) got it's own meta-analysis suggesting that there may be more to see when it comes to certain sources of the heavy metal mercury. Staying on the topic of heavy metals and childhood development, lead (Pb) exposure also got a further research battering when it comes to neurodevelopmental outcome. There is seemingly very little good to say when it comes to lead exposure particularly during childhood. Gait issues and joint hypermobility in relation to the autism spectrum was discussed, again with the requirement for further work in this potentially important area. And the research net is seemingly closing in on how prenatal valproate exposure might affect developing brains.

Bipolar disorder might be frequent in adult Asperger syndrome was the conclusion reached by Vannucchi and colleagues. But it might not be straight-forward to diagnose. The more classical relationship between some autism and learning disability (intellectual disability) was also considered from a prevalence point of view. Continuing the comorbidity theme was the suggestion that three-quarters of youth with an ASD might meet the criteria for ADHD and that psychosis might be more likely to follow a childhood neurodevelopmental diagnosis. Real ESSENCE or autism plus in action. Oh, and beware the hype around oxytocin and [all] autism...

Another diagnosis got pluralised... the schizophrenias (apparently). Sally Rogers and colleagues talked treating autism very early with again, the requirement for a lot more work in this area. The difference between DSM-5 and DSM-IV autism diagnoses were also highlighted. Zinc and copper got discussed with autism in mind, and more evidence of a complicated relationship between anxiety, sensory issues and gut problems was put forward by Micah Mazurek and colleagues. Gut issues were also proposed to be a factor potentially impacting on the absorption and bioavailability of medications used for some people with autism. Slightly outside of autism research, epigenetics got a first look at Chronic Fatigue Syndrome (CFS).

[Most] children with autism do not lack the capacity to engage in physical activity but for some reasons, activity levels are down compared with those not on the autism spectrum. Pregnancy infection might elevate the risk of offspring autism was the conclusion from Lee and colleagues. There was more to see when it came to vitamin D supplementation, both with autism in mind and perhaps with other conditions in mind too, although I hasten to add that I'm not giving medical or clinical advice on this or any topic. How stable is a diagnosis of Asperger syndrome was the question asked by Helles and colleagues, and when it comes to anxiety and the autism spectrum, are we talking about an intolerance of uncertainty as a primary factor? Oh, and remember SCD? Well, it might just be the catch-all label for the broader autism phenotype, and of course, broccoli and autism, the mechanism for which might also tie into the growing suggestion that air pollution might affect autism risk.

More from Pellicano and colleagues was published on the topic of autism research, and where autism research producers and consumers agree and disagree. The growing suggestion of autism or autistic traits appearing in some cases of Down's syndrome also gathered pace with the suggestion of a new clinical entity: Down Syndrome Disintegrative Disorder. Metabolomics and autism was another research topic with a growing fan base as per the [monster] paper by Paul West and colleagues. The pendulum swung again on the question of what factors might be linked to the increasing numbers of cases of autism being diagnosed (at least up to the late 1990s). And then there was leaky gut... and where that concept might be heading with quite a few conditions in mind. There was also a new player introduced to autism research from the cascade of compounds derived from everyone's favourite aromatic amino acid tryptophan: N-acetylserotonin - watch this space?

'Rather than using just one parameter when looking at potential biomarkers for autism, why not use several' was the very logical thinking by Yang and colleagues looking at cytokines and cortisol as a potential diagnostic tag-team. I can't disagree with their strategy if perhaps worrying a little about the term 'biomarker' when applied to all autism, heterogeneity, comorbidity and all. The diagnosis of autism is seemingly protective of nothing when it comes to other medical comorbidity as per the findings from Chiang and colleagues looking at the small but present increased risk of cancer. I tried not to sensationalise that paper but at the same time didn't want to shy away from such evidence-based findings. Telomeres, the shoelace tips of chromosomes got a mention as did an overview of the (non)link between smoking during pregnancy and offspring autism risk (with caveats). The blogging year ended as is started with a look at another inborn error of metabolism with autism in mind. 'Screening' seems to be the important word when it comes to such issues...


So there you have it. Another year in the life of Questioning Answers and another year of autism research. With all the optimism and enthusiasm I have for such studies and investigations, there is still an awfully long way to go before anyone can start celebrating about how lives have been 'transformed' and inequalities reduced as a result. The Pellicano studies in particular, provide a stark reminder of how little we still know about autism and how far we need to go to make research truly translational including that of murine and related research.

At this point, I would normally pick one paper which really set a new standard in autism research in 2014. Given however the amount of research blogged about this year and some real moves towards 'big data' (be that based on that Taiwanese Insurance Database or other datasets) I'm struggling to select just one piece of research. So instead, three papers which I thought made an impact:


Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis. (Masi and colleagues).

Prevalence of autism spectrum disorder among children aged 8 years - autism and developmental disabilities monitoring network, 11 sites, United States, 2010. (Autism and Developmental Disabilities Monitoring Network Surveillance Year 2010 Principal Investigators)

Mitochondrial Dysfunction as a Neurobiological Subtype of Autism Spectrum Disorder. (Goh and colleagues).


And just before I go, a few tributes celebrating the lives of some of those who brought their considerable experience and expertise to bear on autism research: Lorna Wing, Elizabeth Newson and Paul Patterson. May you rest in peace.

Thanks for looking in, seasons greetings and a Happy New Year to all. Back in 2015 with lots more.


ResearchBlogging.org Masi A, Quintana DS, Glozier N, Lloyd AR, Hickie IB, & Guastella AJ (2014). Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis. Molecular psychiatry PMID: 24934179

ResearchBlogging.org Developmental Disabilities Monitoring Network Surveillance Year 2010 Principal Investigators, & Centers for Disease Control and Prevention (CDC) (2014). Prevalence of autism spectrum disorder among children aged 8 years - autism and developmental disabilities monitoring network, 11 sites, United States, 2010. Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002), 63 (2), 1-21 PMID: 24670961

ResearchBlogging.org Goh S, Dong Z, Zhang Y, DiMauro S, & Peterson BS (2014). Mitochondrial dysfunction as a neurobiological subtype of autism spectrum disorder: evidence from brain imaging. JAMA psychiatry, 71 (6), 665-71 PMID: 24718932