"Gaps in current autism research". What the great and good think...

I would encourage readers to have a good look through the commentary paper by David Amaral and many, many colleagues [1] discussing the important question: what's missing from current autism research?

Published in "advance of the 2019 INSAR Conference in Montreal, Quebec, Canada", the annual autism conference (see here) which starts later this week (1st May 2019), the commentary provides some details on where the gaps seem to be when it comes to autism research. Various views are provided by some of the great-and-the-good of autism research,

Lots of 'gaps' are highlighted, many of which have been discussed on this blog down the years. Things like: "the failure to take into account the heterogeneity of the autism spectrum disorder (ASD) category", the relationship between autism and mental health conditions, intervention, aetiology, "novel, efficient diagnostic processes", longitudinal research studies, early biomarkers, the use of neural stem cell research, ageing and autism, parenting and autism, self-injury and autism, autism and the criminal justice system, "Minimally verbal autistic people and those with severe autism who are overlooked across all stages of development and inquiry", "Distinguishing autism in intellectually able adults from conditions, such as bipolar disorder, personality disorders, and schizophrenia" and lots more besides are considered. All represent gaps which require much more investment and study.

The Amaral paper got me thinking what my response to such a question would be. Based on my 'for what their worth' musings down the years, I could probably suggest two primary issues that stick out: (1) autism is a label that describes symptoms/behaviours/traits but says little about how these manifest at an individual level; we need to come up with some way of expanding how we describe autism and what it actually describes as a plural condition, and (2) we need much more focus on translating research findings into real-life improvements. It's all well and good getting some fantastic research results that make big newspaper headlines, but for the child who is facing yet another school exclusion or for the adult living a life of seclusion and poverty for examples, what do such research findings do for them? This also includes translations covering detection, diagnosis, intervention, and a whole host of other things pertinent to improving quality of life of those diagnosed and their family and significant others. One particularly pressing part of this translation issue are the shocking figures on early mortality in relation to autism (see here) and the question of how they can be reversed.

The hows-and-whys of achieving such goals are a little more difficult. I do think autism research could learn quite a bit more from people like Prof. Gillberg and others who've talked for sometime about the concept of ESSENCE (Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations) (see here) and how autism rarely appears in some sort of diagnostic vacuum (see here). It could also do with listening more to lots of groups of people with a connection to autism: those who are autistic themselves, their parents and caregivers and other significant others, including siblings, and how they can help with the autism research agenda. And by listening I don't mean just attending to selected groups of people or those with the loudest voices. I mean listening to voices from across the entire autism spectrum [2], bearing in mind the oft-cited phrase: 'if you've met one autistic person, you've met one person with autism'.

Just before I leave this topic, I must also mention one thing that I don't wholeheartedly agree with that is highlighted in the Amaral paper: the notion from someone that "the genesis of autism spectrum disorder (ASD) occurs prenatally." The prenatal period is definitely important to autism; but there is ample evidence that the 'genesis' of 'some autism' is rooted long, long after the nine months that makes us (see here for example) or in some cases quite a bit before conception, pregnancy and onward (see here). In that respect, sweeping generalisations about autism - aetiology, life course, etc - are also perhaps something else that needs to be far less *seen* when it comes to the autism research agenda and the gaps that they can sometimes generate...

----------

[1] Amaral DG. et al. Gaps in current autism research: The thoughts of the Autism Research Editorial Board and Associate Editors. Autism Res. 2019 Apr 26.

[2] Russell G. et al. Selection bias on intellectual ability in autism research: a cross-sectional review and meta-analysis. Mol Autism. 2019 Mar 1;10:9.

----------

IMFAR, the autism numbers game and 12% showing 'optimal outcome'

A post recently published on the Spectrum website led to my blogging entry today, and the observation that: 'Alternative screen finds high autism prevalence in U.S. state'.

Discussing results delivered at IMFAR 2017 the research in question was that presented by Laura Carpenter and colleagues [1] (someone with quite a track record in autism research). This was a conference presentation and seemingly not yet peer-reviewed publication, so one needs to be a little cautious about making big claims just yet. That being said, there have been research hints that these results would be forthcoming [2] around this time.

The headline finding was that the prevalence of autism spectrum disorder (ASD) in one particular part of the United States for the birth year 2004 was probably quite a bit higher than that previously reported/estimated based on initial screening for possible ASD and then actual assessment. Details of the initiative used in this research - the South Carolina Children’s Educational Surveillance Study (SUCCESS) - can be found here.

Some 4100 children were "screened for ASD using the Social Communication Questionnaire." Those who were deemed 'at risk' for autism and a small proportion of those not hitting those *might be autism* thresholds were asked back for a more detailed interview. Although the number of children actually followed-up and interviewed who were eligible for further assessment was not particularly great, the authors were able to draw up an estimated prevalence of autism based on those who did complete the study. The figure: "ASD prevalence in this sample is 3.62%" roughly equivalent to 1 in 28 children. I say this in the context that in the United States and elsewhere, autism rates and/or numbers of cases are still high (see here and see here) and acknowledgement of the implications of such increases when it comes to services such as education, healthcare and the like.

The Spectrum article focuses quite a bit on the participation rate noted in the Carpenter study but another snippet of information is also included in the conference abstract that is worthy of discussion. A detail that reads: "Six children (6/52; 12%) had a clear developmental history of ASD but did not display clinically significant symptoms at the time of participation in this study." Further: "12% with a history of ASD no longer had significant ASD-related symptoms, providing further support for the potential for optimal outcomes in some individuals."

I'm rather interested in that 12% figure with 'optimal outcome'. Optimal outcome describes cases where a clear indication/diagnosis of autism has been seen/received, but for whatever reason(s) diagnostic thresholds are not longer met at a future assessment point. I've covered this group quite a few times on this blog, most notably in relation to a previous estimate of 9% of those diagnosed with autism potentially falling into this category (see here). Appreciating that such data challenges the assumption that *all* autism is a lifelong condition (indeed, stretching across the entire autism spectrum - see here), I'd reiterate that those described as being 'optimal outcomers' represent an important subgroup on the autism spectrum in these days of plural autisms (see here). Not least is the question: Why? Why do these children not maintain their diagnosis and what lessons (if any) can be learned for the wider autism spectrum, particularly also in the context that various quite disabling comorbidities might also be 'reduced' alongside core autism symptoms in this group.

We await formal peer-reviewed publication of the Carpenter findings and perhaps some further details.

To close, upon introducing my brood to the music of Kate Bush, I am yet again reminded just how good a singer/performer she really is...

----------

[1] Carpenter LA. et al. The Prevalence of Autism Spectrum Disorder in School Aged Children: Population Based Screening and Direct Assessment. IMFAR 2017.

[2] Carpenter LA. et al. Screening and direct assessment methodology to determine the prevalence of autism spectrum disorders. Ann Epidemiol. 2016 Jun;26(6):395-400.

----------

Carpenter LA, Boan AD, Wahlquist AE, Cohen A, Charles J, Jenner W, & Bradley CC (2016). Screening and direct assessment methodology to determine the prevalence of autism spectrum disorders. Annals of epidemiology, 26 (6), 395-400 PMID: 27230493

Autism research at IMFAR 2017: a few ones to watch...

As I always seem to do at this time of year, I offer up a sort of 'highlights' post of what there is to see at the premier annual autism research event called IMFAR (The International Meeting for Autism Research) this year, and what we can perhaps expect to see in the not-to-distant-future in the peer-reviewed science domain. No, I'm not in San Francisco for the event, but I am most definitely interested in some of the science being presented.

If you are a Twitterer(!), there is a hashtag to accompany this years IMFAR meeting (#IMFAR2017) so as to follow proceedings on social media. A few choice abstracts for your attention then, in no particular order:

• Anxiety Disorders in Adults with Autism: A Population-Based Study. Minus any medical or clinical advice given or intended nor any sweeping generalisations, other abstracts also talk about strategies for managing/treating anxiety.

• Autism and Depression in Young Adulthood: Cohort Studies in Sweden and England.

• Need for Valid, Reliable Gastrointestinal Symptoms Measurement Tool for Autism Spectrum Disorder. I can't argue with that in the context that gastrointestinal (GI) symptoms are well and truly over-represented in relation to autism (in both children and adults).

• Various medical conditions and symptoms are over-represented in relation to autism. And added to that abstract: Relationship Between Medical Comorbidity and Problem Behavior in Children with Autism Spectrum Disorder.

• Chymotrypsin: Evidence of a Novel Pancreatic Insufficiency in Children with ASD?

• Characterizing Children with Autism Spectrum Disorder (ASD) Who Respond to a Gluten-Free Casein-Free (GFCF) Diet. Two topics close to my research heart: use of dietary intervention for 'some' autism and the focus on best- and non-responders in these days of the plural autisms.

• Effects of a School-Based Exercise Intervention Program on Stress and Executive Functioning in Adolescents with Autism Spectrum Disorder or Other Special Education Needs. Exercise is important for every child/adolescent, and that includes those on the autism spectrum. 

• Food Selectivity and Nutritional Deficits in Children with Autism Spectrum Disorder: Electronic Medical Record Review. "These results suggest that in children with ASD [autism spectrum disorder] and food selectivity by type are not consuming a diet adequate in vitamins and minerals." Need I say anymore when it comes to a possible role for supervised nutritional supplementation?

• Wellbeing of Parents of Children with Autism Spectrum Disorder: Gender Difference within an Australian Population-Based Sample. Science and clinical practice needs to do more to care for the carers.

• Characteristics of Children with ASD Who Improve with Fever: Insights from the Simons Simplex Collection. Fever and autism eh? Even the dramatisation of autism has mentioned this issue...

• Record-Based ASD Annual Prevalence for Children Ages 0-8 in Taiwan, 2004-2013. 'Big data' Taiwan brings it's research weight to bear and concludes: "ASD prevalence increases over time from 2004–2013." Other abstracts similarly talk about this trend.

• Risk of Epilepsy and Autism in Full- and Half-Siblings: A Population-Based Cohort Study. The links continue to strengthen between autism and epilepsy. This data also begs the question: is epilepsy also a potential part of the broader autism phenotype (BAP)?

• Autism 30 Years Later: A Follow up Study of Children Diagnosed with ASD from 1970-1999. We need a lot more focus on what happens to autistic people in the longer-term and how wants, wishes, needs and desires change over the lifespan. 

In addition, a few papers also talk about research that has already appeared in the peer-reviewed science domain and some important 'where next?' questions/answers:

• Is There Evidence of Intergenerational Influences on Autism?  The Golding ALSPAC paper on 'smoking grannies'...

• Use of Biomarkers to Assess Outcomes in a Phase 1 Open Label Trial of Autologous Cord Blood in Young Children with Autism Spectrum Disorder. The Dawson paper on cord blood and autism...

• Microbiota Transfer Improves Gastrointestinal and Autism Symptoms: An OPEN Label Study. On poo(p) transplants and autism...

• Serum Metabolome Profile in GI Symptomatic ASD Children: A Pilot Study. And don't mention bowel disease and autism...

I believe there is something for everyone in that list of papers. Of course there is lots more science being presented on too so I'd encourage everyone to peruse the conference proceedings...

----------

Folate, autism and IMFAR: keep calm

IMFAR - The International Meeting for Autism Research - has just closed it's doors, bringing to an end one of the premier annual autism research conferences where one might expect quite a few of the presentations to eventually become (peer-reviewed) fodder for this blog.

This year (2016) has seen yet another startling array of research papers covering all manner of topics pertinent to autism; it's presumed aetiologies (plural as per the 'autisms'), diagnosis and management, all discussed and dissected. This year also saw some well needed focus on other important issues linked to autism such as various (medical and psychiatric) comorbidity linked to the label, the idea that children with autism become autistic adults (mostly) and the rather distressing idea that suicide (ideation or actual) seems to be over-represented when a diagnosis is received. Without trying to portray too negative an image of the very wide autism spectrum, autism can in some cases be a life-limiting as well as a life-changing condition (see here and see here).

As an outsider looking in on proceedings (#IMFAR2016) I was particularly interested in a few discussions that were covered during the event. This included the keynote address delivered by Irva Hertz-Picciotto on how, despite various environmental agents being traditionally correlated with some 'types' of autism (rubella, valproic acid), there are still challenges in terms of putting environmental factors on a par with genetic issues for example. Indeed, one or two tweets about her presentation kinda summed up the stark lack of knowledge and expertise in this area; specifically how 'chemical' insults (being careful with that word) potentially linked to cases of autism or at least autistic traits, already pervade the peer-reviewed literature (see here for example). It seems we need to further organise how research is done in this area, where exposure and genetic fragility are taken into account alongside the idea of synergy when it comes to the chemical soup that we all live in [1]; similar to the idea that multiple genes might be involved in multiple autisms so multiple non-genetic exposures might also show a connection (might I also suggest a greater focus on subgroups on the 'autisms' spectrum too?)

One of the other 'environmental' factors that was raised at IMFAR 2016 was that of folate (folic acid) and the possibility of a connection between pregnancy levels of this stuff and some autism as per the paper by Ramkripa Raghavan and colleagues [2]. For those who might already be well-read in autism research, the idea that maternal levels of folate during pregnancy might have a bearing on risk of offspring autism is not a new one (see here). With sentiments not a million miles away from those proposed by the late David Barker and the 'foetal programming hypothesis', the collected research on folate availability/supplementation during pregnancy impacting on the developing child is still the topic of some discussion (see here and see here). What is clear is that much like the need for folate during pregnancy to reduce the risk of neural tube defects, there may also be additional developmental requirements for suitable levels when it comes to other outcomes too.

Rather interestingly however, the data from Raghavan et al was not all one way when it came to 'risk' of offspring autism and levels of folate and a related nutrient, vitamin B12. To quote from their un-peer-reviewed paper: "In this urban low-income minority birth cohort, we observed an elevated risk of ASD [autism spectrum disorder] associated with high maternal plasma folate levels (>59 nmol/L), which far exceeds the excess cutoff suggested by the WHO (>45.3 nmol/L). Excess maternal vitamin B12 (>600 pmol/L) was also shown to be associated with greater ASD risk in offspring.  The risk of ASD was highest if mothers had both excess in folate and B12 levels." As you might imagine, the accompanying press release that followed this un-peer-reviewed paper was snapped up by various media outlets with titles like: "Taking too many vitamins during pregnancy 'can treble children's risk of being autistic'". Lo and behold, we have yet another 'scare story'...

Accepting that this was un-peer-reviewed research and that inflated press releases seem to abound in the domain of science communication (see here) I was a little less ruffled by the data reported by Raghavan and colleagues. I can see why such findings might make great headlines - "The risk was greatest for those children whose mothers had both high plasma folate (>59 nmol/L) and vitamin B12 (>600 pmol/L) (HR [adjusted hazard ratio]: 17.59; p value: <0.001)" - but this is not the first time that such sentiments have been expressed with relation to autism. Indeed, on a previous post asking whether some of the data of pregnancy folate levels/supplementation and offspring autism risk might not be just all about deficiency (see here) I discussed some rather speculative ideas (albeit peer-reviewed ideas) about how there may be a balance to be struck between potentially too little and too much of a good thing.

'Scientists urge caution over 'alarmist' claim of link between pregnancy folate and autism' was a rather more restrained headline in relation to the Raghavan report. I was much happier with this headline and coverage that put into perspective the preliminary nature of the report (yes, un-peer-reviewed) and how: “There are many epidemiologically based associations made of this sort – increasingly so in autism at the moment." Indeed there are, but unfortunately the commentator goes on to say that "Without details of the analysis, or any theory of action this looks like low-grade evidence."

Actually there are 'theories of action' and they've been discussed quite a bit in the peer-reviewed literature in this area. Not least, the idea that folate and vitamin B12 are important compounds in something called the folate cycle which intersects with another set of important metabolic process: the methylation cycle (see here) and all that DNA methylation stuff. There are a number of possible 'issues' that might be autism-relevant in these biological cycles, not least related to something called MTHFR (see here) and some emerging data on folate receptor autoantibodies (see here). Issues with these systems could very much impact on how folate is used and whether high plasma folate for example, might not be just as the result of too much supplementation. As per what we know from data from more formal medicines, drug metabolism can be quite an individual thing.

I do also want to bring in a little more data about vitamin B12 and 'some' autism as potentially being relevant. Accepting that there has been very little data on maternal vitamin B12 levels and offspring autism, there is certainly quite a bit of data out there about 'issues' with vitamin B12 being tied into specific cases of autism. This year (2016) we've seen the results of placebo-controlled study on the use of methyl B12 for aspects of autism (see here) as well as a suggestion that decreased brain levels of vitamin B12 might link cases of autism and schizophrenia (see here). That severe vitamin B12 deficiency has been linked to cases of Heller's syndrome is also potentially important (see here) given the focus on 'regression'...

Cumulatively what the Raghavan and other data point to is a potentially complicated relationship between mother's nutrition during pregnancy and offspring outcomes. I don't say this to somehow hark back to the darker days of autism theory in terms of 'blame' but rather, alongside other lines of evidence, to point out that nutrition during the nine months that made us (and perhaps earlier) plays an important role in making us who we are. The way that said nutrition is metabolised is also likely to vary from person to person. Minus sweeping generalisations and inflated media headlines, a greater research focus on how that nutrition might impact on at least some autism is very much implied again keeping in mind all that individuality in terms of how the body 'processes' nutrition. Indeed, for those mums identified in the Raghavan data as showing high levels of folate and vitamin B12, in the spirit of scientific endeavour, I'd be asking 'why?' and what does it mean for other related markers such as 'the big H' (homocysteine) for example?

For now however, keep calm and carry on with Love, love, peace, peace (song starts after 1 minute).

----------

[1] Boggess A. et al. Mean serum-level of common organic pollutants is predictive of behavioral severity in children with autism spectrum disorders. Sci Rep. 2016 May 13;6:26185.

[2] Raghavan R. et al. Maternal Plasma Folate, Vitamin B12 Levels and Multivitamin Supplement during Pregnancy and Risk of Autism Spectrum Disorders in the Boston Birth Cohort. IMFAR 2016; 22533. [NOT PUBLISHED IN A PEER-REVIEWED JOURNAL]

----------

Autism research at IMFAR 2014

So, here we go again as the annual IMFAR (International Meeting for Autism Research) meeting gets underway for 2014.

As in previous years (see here and see here), I am a watcher rather than an attender but do like to keep an eye on the conference because of the wealth of autism research talent it includes. That and also because the conference often provides a sort of 'heads-up' as to what might be appearing in the peer-reviewed literature over the coming months and hence future blogging material.

The on-line searchable program book is live (see here) but I'd like to draw your attention to a few abstracts which I found particularly interesting:

• The high prevalence of autism spectrum disorders among children with intellectual disabilities (see here).
• Psychiatric and medical conditions among adults with ASD (see here)
• Low endogenous fecal chymotrypsin: a possible biomarker for autism? (see here).
• Endogenous retrovirus expression in two mouse models of autism spectrum disorders (see here).
• Early characteristics of children who lose their autism diagnosis between age 2 and 4 (see here).
• Prevalence of obesity in autism spectrum disorders and associated risk factors (see here).
• The effectiveness of methylcobalamin and folinic acid treatment on adaptive behavior in children with autistic disorder (see here).
• Oxidative stress and immune cytokines in plasma of young children with autism spectrum disorder and recent language and/or social regression: a prospective case-control study (see here).
• Molecular analysis of inflamed ileocolonic tissue from GI symptomatic ASD children (see here).
• Placental features in ASD compared to controls: a community based cohort in Brooklyn (see here)
• Neonatal cytokines and chemokines and risk of autism spectrum disorder: the Early Markers for Autism (EMA) study (see here).
• Paternal age-related changes in DNA methylation from an autism-enriched cohort (see here)

There is a lot more research being presented, some of which I'm sure will be making headlines over the next few days. So, if you have a few hours free, head over to the conference website and see what's happening or if you're a Twitterererer, use #IMFAR2014 and follow proceedings there...

The Autism Impact Measure and more

It's the usual excuse from me, "the dog ate my homework sir", no not that one, the one about me having a busy week so not being able to post a particularly detailed blog entry this time around. Indeed although there is the usual plethora of research material to pick from, only a few studies have really caught me eye so far this week. But those studies are pretty interesting....

Must try harder @ Wikipedia  

I'm starting with the paper by Stephen Kanne and colleagues* and their description of the Autism Impact Measure or AIM for short. Yes, we knew this study was coming as per an entry at the 2012 IMFAR conference. Including one Micah Mazurek on the authorship list who was involved in that really rather interesting article about gut problems potentially being linked to anxiety and sensory issues in relation to autism (see here), I was really quite interested in the AIM proposal. I've said it before and I'll say it again, one of the very big holes in autism research is a measure which has the appropriate power and accuracy to determine change in autism (see here) so we can start to reliably assess what interventions might work and indeed for who. Very possibly also to be used to pick up what might be different about those optimal outcomers (see here) as per more information on this group being revealed. There's not much more for me to say on this study aside from it certainly looks like the AIM has passed the initial hurdles in terms of reliability and robustness. Fingers are definitely crossed that it continues across clear water.

Next up the paper from Kristelle Hudry and colleagues** talking about language profiles in infants at high-risk for autism. Part of the BASIS network, the idea here was to look at language profiles across infancy in these high-risk kids compared with low-risk controls and then compare across groups of children from the high-risk grouping who were subsequently diagnosed with autism, "other atypicality" and nothing (typically developing). The important part of the results outside of "few group differences appeared on direct assessment of language and parent-reported functional communication" was the issue of reduced receptive vocabulary 'advantage' present in the high-risk group and maintained in the autism and other atypicality group. I know this might not sound like much but identifying red flags, any potential red flags pointing towards a propensity to develop autism, has to be a good thing even from a screening point of view.

Finally is the paper by Sarah Sullivan and colleagues*** which is well outside of the autism research domain, looking at prenatal vitamin D status and offspring risk of psychosis at 18 years of age. I say outside of autism research but maternal vitamin D levels in relation to offspring risk of autism or autistic traits have been talked about before (see here) and very little found on that occasion. Actually that's about the sum total of the findings from Sullivan et al replacing autism or AQ scores for psychosis in early adulthood, at least in their birth cohort. But just before you say to yourself words to the effect of "y'mean vitamin D isn't linked to something' I'll draw your attention to the work of Barbara Gracious and colleagues (open-access) which I talked about in a previous post (see here) suggesting vitamin D levels, first-person levels, might show a connection to psychotic features. Unfortunately the Sullivan paper doesn't seem to ask about first person vitamin D levels...

So AIM, language profiles in children at high-risk for autism and maternal vitamin D levels in relation to offspring risk of psychosis (or rather not). Surely there can't be many places on the web that you'd get all that together?

To close, a song by Badly Drawn Boy - something to talk about anyway. We miss you Richard Whiteley (no relation by the way).

----------

* Kanne S. et al. The Autism Impact Measure (AIM): Initial Development of a New Tool for Treatment Outcome Measurement. J Autism Dev Disord. 2013 Jun 8.

** Hudry K. et al. Early Language Profiles in Infants at High-Risk for Autism Spectrum Disorders. J Autism Dev Disord. 2013 Jun 8.

*** Sullivan S. et al. Prenatal vitamin D status and risk of psychotic experiences at age 18 years-a longitudinal birth cohort. Schizophr Res. 2013 Jun 6. pii: S0920-9964(13)00270-3.

-----------

Kanne, S., Mazurek, M., Sikora, D., Bellando, J., Branum-Martin, L., Handen, B., Katz, T., Freedman, B., Powell, M., & Warren, Z. (2013). The Autism Impact Measure (AIM): Initial Development of a New Tool for Treatment Outcome Measurement Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-013-1862-3

Autism research at IMFAR 2013

"Kaixo!" That's hello by the way in Basque, or at least I think it is.

The beautiful Basque Country is currently welcoming the 2013 IMFAR conference and its delegates to its shores, as once again one of the premier autism research conferences brings together the minds (and souls) of many an autism researcher.

San Sebastian @ Wikipedia  

As per my previous posts on the IMFAR conference series - the 2011 conference and 2012 conference - hopes are high that more advances are being made into the autisms, their aetiology and pathology, and importantly those all-important real-world applicable findings to help improve quality of life for those on the spectrum, and their loved ones.

Well, the request for press coverage certainly looks interesting... including something about Kelly the Robot(!) and already some discussion on arbaclofen (see here), a drug which has already graced this blog. Indeed I am sad not to be able to attend the event.

With my research blogging hat on, IMFAR offers a tantalising look at what peer-reviewed research publications one might expect to see appearing in the coming months and onwards what I can expect to be discussing on this blog in the not-too-distant-future.

Enough of the chatter, a few sessions and abstracts which caught my eye from the searchable abstract finder:

• Session: 'The Role of Environmental Exposures in Autism Etiology: A Retrospective of the Last Decade, New Results and Frontiers for the Future' which includes an interesting title on insecticides and risk for autism.
• Session: 'Measuring Treatment Change in Core Symptoms: Novel Methods, Meaningful Outcomes' which I hope will be asking some important questions on just how we understand 'what works' when it comes to the myriad of intervention options on offer (see this post).
• Session: 'Epidemiology' which by all accounts seems to cover a lot more than just the numbers game; instead talking about (i) comorbidity and autism, (ii) the perinatal epigenome, (iii) maternal cholesterol and the topic of (iv) immunisation.
• Session: '30-Year Follow-Up of Autism in Adulthood' which promises some interesting observations about aging and autism (see here). 
• And finally... this abstract on a topic close to my research heart, the gut microbiome, which might just build on some other very interesting work (see here). That and Paul Patterson talking gastrointestinal symptoms, probiotics and mouse models (see here) as per his recent findings in this area.

No doubt there will be more to see and hear from the conference over the coming days. To close, hopefully no-one will need to use this phrase whilst in the Basque Country, but just in case... "Abokatu batekin hitz egin nahi dut". [roughly translated: "I want to talk to a lawyer".] Agur!

P.S. Jon Brock over at Cracking The Enigma is also presenting a couple of posters.

IMFAR 2012 a go-go: autism research to watch

A very brief post this one to direct your attention to the on-line publication of the program book for the 2012 IMFAR conference being held in Toronto.

IMFAR, the International Meeting For Autism Research, is an annual event which is probably one of the biggest autism research get-togethers currently in place. I do like to keep track of the various posters and presentations which form part of the conference, which sometimes give you a hint as to what research is likely to appear soon in the peer-reviewed domain.

A quick glance through the program book reveals some interesting work. So starting from back to front of the book (cos that's the kind of guy I am)

Page 96. 157.027 Gene Expression Profiles of Inflamed Bowel Biopsy Tissue in ASD Children Are Consistent with Inflammatory Bowel Disease (abstract here). Drs Stephen Walker and Arthur Krigsman are the names attached to this one.

Page 69. 133.212 The Role of a Biomarker in the Double Blind Placebo – Controlled Study of CM-AT in Children with Autistic Disorder Ages 3-8 (abstract here). Dr Joan Fallon and her very interesting studies of CM-AT.

Page 66. 133.212 Double-Blind Placebo-Controlled Trial of Methyl B12 Injections for Children with Autism (abstract here). (Dr Jill James)

Page 42. 118.078 Genome-Wide DNA Methylation in Pregnancy – Preliminary Results From the EARLI Study (abstract here). A link to my epigenetics 101 post is here.

Page 41. 118.067 Intrauterine and Neonatal Levels of Neurotrophic Factors and Matrix Metalloproteinases-9 and Risk of Autism Spectrum Disorders (abstract here).

Page 34. 112.212 Low Iron Status and Sleep Disturbance in Children with Autism (abstract here). My post from a while back on iron deficiency and autism is here.

Page 33. 112.197 Ambient Prism Lenses Modulate Spatial Attention in Autism: An Event-Related Potential Study (abstract here). A previous posts on visual perception and autism is here.

Page 29. 109.151 Global DNA Methylation Changes in Brain Tissues From Individuals with Autism (abstract here).

Page 26. 107.107 Glutamate / Glutamine in the Basal Ganglia Is Associated with Executive Function and Communication Impairments in Autism: A [1H]MRS Study (abstract here). I'm fast becoming a bit of a fan of amino acids chemistry and autism as per this post.

There is a lot more research which, quite frankly, I could see myself getting quite lost in for a few days had I been attending to the conference. I would be really interested if anyone attending IMFAR 2012 could have a look at these papers/posters and provide some comment.

Autism prevalence across the DSMs

IMFAR (International Meeting For Autism Research) is probably the biggest meeting of minds conferences for autism. I have, unfortunately, never attended the conference, not even when it came to the shores of Blighty back in May 2008. I do however take a great interest in the various talks and presentations given at the conference appearing in the searchable conference abstracts book on-line. Whilst reading through this years list (2011), I happened upon this interesting study* on the prevalence of autism. It is interesting because it is the kind of study that I have often thought needed to be done on prevalence, given the multitude of possible reasons why the prevalence of autism might be increasing.

The study (for which I only have the abstract) applied 3 versions of the the Diagnostic & Statistical Manual (DSM) - DSM-III (1980), DSM-IIIR (1987) and DSM-IV TR (2000) - on behavioural and developmental information taken from records of just over 5,000 8-year old children suspected to have an autism spectrum disorder (ASD) from a total population of 280,423. The authors reported the numbers of cases fulfilling criteria for autism and the wider pervasive developmental disorder (PDD) according to the version of DSM used:

• DSM-III (1980) autism = 1921, PDD = 2232
• DSM-IIIR (1987) autism = 1892, PDD = 2223
• DSM-IV TR (2000) autism = 2054, PDD = 2641

They then calculated the autism and PDD prevalences (per 1000) based on the total population figure (280,423):

• DSM-III (1980) autism = 6.9, PDD = 8.0
• DSM-IIIR (1987) autism = 6.7, PDD = 7.9
• DSM-IV TR (2000) autism = 7.3, PDD = 9.4

As you may see from the figures, the prevalence of core autism seems to remain fairly constant across the various DSM versions although perhaps shows a slight upward spike using the 2000 version. The prevalence for the wider PDD category is a little more variable; indeed more so when the DSM-IV TR criteria is used. Bear in mind that this is data based on the same group of 8-year old children. I think that this quite good support for saying that at least some of the increase in prevalence is due to the changes in diagnostic criteria. Based on these figures it suggests that about 18% of the increase in the wider PDD diagnosis might be due to changing criteria (I think!).

One might ask why DSM-IV (1994) was also not included in the dataset, but I think the changes made in DSM-IV TR from DSM-IV were more cosmetic than structural (both DSM-IV TR and DSM-IV define Asperger syndrome where DSM-III did not specifically do so). Combined with the issue of diagnostic substitution covered in a previous post, you can perhaps see that at least some of the increase in prevalence is due to factors other than a 'real' increase in cases. 

That is however not to say that all of the increase is due to such diagnostic factors. In the words of Prof. Sir Michael Rutter back in 2005 "a true risk due to some, as yet to be identified, environmental risk factor cannot be ruled out" (I will be coming back to Prof. Rutter in future posts). That added to an increasing prevalence and incidence of autism in certain geographical areas, leaves the door slightly ajar for maybe not just one environmental factor but quite a few, either working alone or cumulatively, spread evenly or not evenly geographically, impacting on the numbers of cases being diagnosed.

A final note. This paper appeared recently comparing DSM-IV TR and the proposed DSM-V criteria for autism. At the moment I don't have the full-text paper so cannot extensively describe and discuss. From the abstract it appears that some kind of comparison was made between those diagnosed with DSM-IV and might happen if DSM-V draft criteria were applied to the same group(?). The authors conclude in the abstract that DSM-V might be less sensitive regarding identification for those presenting with Asperger syndrome and high-functioning autism. What this might do to prevalence figures post-2013 publication is 'interesting'. I wait to see more. 

Thanks IMFAR and keep up the good work.

*Reference: Rice CE, Wiggins LD, Carpenter LA, Schieve LA, Fitzgerald RT, Pedersen A, Lee LC. Variation in the prevalence of the Pervasive Developmental Disorders by diagnostic criteria. IMFAR 2011.

The word on the street

A quick post this one.
A few bloggers in the autism field have already noted that the abstract book for the 2011 IMFAR conference is now live and can be accessed and searched (or downloaded) here.
There are a few choice articles that might be worth a look including this one on iron deficiency in autism (I have a post on this scheduled for later in the week), this one on PANDAS and catatonia (following my post on this) and this one on CAM use in autism.
I am also drawn to this abstract by Joan Fallon following the various interest in her CM-AT compound which is currently going through clinical trials.
There are lots of other abstracts and topics to peruse, so enjoy.