ADHD and a sunny disposition

'Light it up blue' is probably a familiar phrase to many of those involved with autism as being the message championed by Autism Speaks on World Autism Awareness Day (2 April). The intention is noble enough: to bring autism to the attention of the world at large and importantly, keep their attention and resources focused on autism. I might add that awareness is one thing; actually 'doing something about autism' - whether that means improving prospects or modifying the course of autism or just levelling the playing field - is quite another thing.

Light it up @ Wikipedia  

By a funny twist of Internet fate, I stumbled upon a review of the study published by Arns and colleagues* looking at the possibility of a link between solar intensity (SI) and the prevalence of attention-deficit hyperactivity disorder (ADHD). The very tentative light it up blue connection was a sentence or two in the study write-up which suggested that the sleep problems which apparently come with a diagnosis of ADHD might result from "exposure to blue-light during the evening" and that strong sunlight during the day "might reset the biological clock and act as an antidote to the evening exposure to artificial blue-light causing sleep onset problems". Yes, I know it isn't a great blue light pun, sorry about that.

It should be noted that the Arns paper appears in a pretty good journal (Biological Psychiatry) so whilst you might be thinking, 'solar intensity... eh?' this is a correlation which has passed what one would expect to have been quite a rigorous peer-review battlefield. I could at this point offer you some more detailed description of the paper but it seems that the authors have already done that on their website (see here - no endorsement given or intended).

In effect, they mapped the prevalence figures for ADHD across various parts of the US and beyond and cross-referenced them with official figures relating to SI. Yes, prevalence of ADHD were partly based on "self-report of professional diagnoses" but this was to some degree countered by the use of more formal assessment data in other sites. They found a correlation (negative correlation) between ADHD prevalence and SI when controlling for various potential confounders: "a lower prevalence of ADHD in areas with high SI for both U.S. and non-U.S. data".

Bearing in mind the issue of correlation/causation (see here), one could construe this data several ways. If for example you work for the tourist boards of Arizona, Nevada or California you have a potentially interesting advert: 'Come live here, we've got lots of solar resource and potentially less risk of your children developing ADHD'. Or words to that effect. And indeed, the CDC figures do seem to suggest that those high SI states might have a lower prevalence of ADHD (assuming that this doesn't reflect other issues such as awareness, identification, etc). On a more serious note are the suggestions that (a) ADHD might be related to circadian clock disturbances, and (b) that exposure to the various new-fangled technologies we are surrounded by might be part and parcel of those circadian clock disturbances.

Just before you reach for the click away button, like I almost did, mumbling 'blame it all on technology', there are a few papers to bring to your attention. Yes, sleep issues are associated with ADHD** and indeed if the recent paper from Blesch and Breese McCoy*** is anything to go by, we might also assume that ADHD - some cases of ADHD - could be mistaken for things like sleep apnoea. True also that issues with circadian function seem also to be tied into cases of ADHD as per studies like this one from Gamble and colleagues****. On balance, sleep seems to show some connection with ADHD.

That the part of the light spectrum labelled blue emanating from various technology use is the primary cause or significant contributor to the sleep issues noted even in some cases of ADHD is the slightly more difficult proposition for me to whole-heartedly (hoof hearted!) accept from this work. I don't doubt that many children and adults with ADHD use this kind of technology. But I have to ask whether their use and exposure to the artificial blue light is really any more significant than that of everyone else? Indeed, without being an expert on the different ranges or wavelengths of light and their physiological effects, are we just talking blue or are we talking other parts of the light spectrum too?

There are details from this study which I would like to see further explored given the potential for a relationship between SI and ADHD prevalence. Readers for example, might know that I am more than a little intrigued by another sun related variable, vitamin D, and its various connections (or not) to conditions like autism or chronic fatigue syndrome among others. The question would have to be whether the sunshine vitamin / steroid hormone might also show some relationship to the latest findings? Are vitamin D levels likely to be greater / the same / reduced in cases of ADHD dependent on the specific geography and SI? Vitamin D receptors all in good working order*****? No significant drug interactions where medication is being used? Indeed, whether other correlates such as altitude - which also seem to map onto the SI exposure plots - might come into play?

There are questions which require some follow-up from this work but for now, and with all caveats in good working order when it comes to population studies of association - as with other recent results too, I'm intrigued by the Arns data and the suggested overlap. And also that ADHD might not be the only condition being looked at with a sun-related variable (see this study by Davis & Lowell******, full-text).

To close, after recently watching the quite brilliant film 'Rock of Ages' which satisfied all my 1980s rock needs, a taste of Sheffield's finest.

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* Arns M. et al. Geographic Variation in the Prevalence of Attention-Deficit/Hyperactivity Disorder: The Sunny Perspective. Biol Psychiatry. March 2013.

** Yürümez E. & Kiliç BG. Relationship Between Sleep Problems and Quality of Life in Children With ADHD. J Atten Disord. March 2013.

*** Blesch L. & Breese McCoy SJ. Obstructive Sleep Apnea Mimics Attention Deficit Disorder. J Atten Disord. March 2013.

**** Gamble KL. et al. Delayed Sleep Timing and Symptoms in Adults With Attention-Deficit/Hyperactivity Disorder: A Controlled Actigraphy Study. Chronobiol Int. February 2013.

***** Malik S. et al. Common variants of the vitamin D binding protein gene and adverse health outcomes. Crit Rev Clin Lab Sci. 2013; 50: 1-22.

****** Davis GE. & Lowell WE. Variation in ultraviolet radiation and diabetes: evidence of an epigenetic effect that modulates diabetics' lifespan. Clinical Epigenetics. 2013; 5: 5.

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Arns M, van der Heijden KB, Arnold LE, & Kenemans JL (2013). Geographic Variation in the Prevalence of Attention-Deficit/Hyperactivity Disorder: The Sunny Perspective. Biological psychiatry PMID: 23523340

IACC and summary of research advances in autism 2012

I'm very much an outsider looking in when it comes to the goings-on at the US Interagency Autism Coordinating Committee (IACC). I'm a Limey working here in Blighty (translation: Brit working in the UK) not in the States and as far as I can see we don't have such an agency here in the UK. Yes, we do have the NICE review which is coming to a close shortly but nothing like the IACC which seems to orchestrate many autism-related activities in the States, including research.

Annually, the IACC produce a summary of autism research which kinda brings together the great and the good of progress in understanding what might constitute autism (the autisms). They've just released the 2012 review of autism research (see here) which contains some interesting studies including those covered on this blog.

A few choice studies and posts are presented for your attention:

Six developmental trajectories.... by Fountain and colleagues.
The branched chain amino acid phenotype.... by Novarino and colleagues.
De novo mutations and paternal age.... by Kong and colleagues.
Kum-ba-arbaclofen... by Berry-Kravis and colleagues.
Wandering.... by Anderson and colleagues.
Mortality.... by Bilder and colleagues.
1 in 88.... by the CDC.

'Nuff said.

The autism spectrum and the job interview

I'm very conscious of the fact that I tend to talk quite a lot about biological research on this blog and its potential implications for people on the autism spectrum and beyond. To some, this can seem a little one-sided in terms of how autism is viewed and indeed at the expense of a large proportion of people on the autism spectrum who are not necessarily looking to understand how cytokines or dietary intervention for example, might impact on their signs, symptoms or everyday quality of life.

You're hired @ Wikipedia  

Indeed, accepting that the autism spectrum is wide and heterogeneous, for some on the autism spectrum there are more pressing issues which impact on their daily life such as the impact of comorbidities including anxiety and/or obsessions, and under certain circumstances, how these features can truly disable a person.

In this post therefore I want to try and address some of the issues looking at a key part of many people's lives: employment and unemployment, and some of the variables around employment for adults with an autism spectrum condition which might help or hinder their efforts to enter the workplace with a particular focus on job-seeking.

I was brought to this topic by the paper from Dorothy Strickland and colleagues*, and their study looking at the potential usefulness of the JobTIPS employment program (free by the way) in helping a group of young adults with autism getting through the dreaded job interview.

Transition
Where to start, where to start? Well, in amongst the various issues that can impact the life of a person with autism, particularly those diagnosed with Asperger syndrome or the so-called 'high-functioning' autism, the transition from child to adult must rank as one of the more stressful periods. The jump from the very organised and very arranged world of school / home schooling and further education into the unknown jungle of adult life and the jobs market is riddled with pressures, not just for the individual but their family and carers too. And let's face it, with the current economic climate as it is, that jobs jungle is very much living up to its name, with many people often 'fighting it' out for each post.

The job spec
Consider how then a potential employer tries to find that ideal candidate and what qualities they generally look for in a person. Obviously they want someone who is qualified to do the job, someone who is reliable and someone who is enthusiastic. OK, no real surprises there. But then you get phrases like a 'good communicator', a 'team player' and the like also appearing in the job specification and suddenly the job spec is no longer about having certain skills for a job. I think you can perhaps see how daunting these additional specs might be for someone who is perhaps not a great talker (or indeed likes to dominate a conversation with their own talking) or who might not generally be at their most comfortable in that team player role.

The application form
Then comes the next hurdle: the application form. What is your name? OK, that's easy enough, as is the other information which is explicitly asked for with closed questions. Your educational achievements and your contact details, no real issues there too. But then come the open-ended questions. What do you like to do in your spare-time? What are your biggest achievements? Why do you think you are the best candidate for this job? How one answers such questions is very much going to depend on how one is able to translate these questions and in some cases how literally one understands such questions within their own experiences and interests.

The job interview
Assuming these hurdles are past, the final stage is the job interview. Y'know all those tips that seem to percolate through the web on 'how to get that dream job'. Be confident but not overly-confident. Eye contact and the occasional smile or other gesture to lighten up the whole experience. A bit of chit-chat on certain topics (as long as you stay on topic and answer the questions). In short: go in there and sell yourself.

All well and good if you are so inclined to such skills. But readers can perhaps see how for those who might be more than a little bit anxious about the whole process - in particular the 'not knowing' about the process - for those who perhaps don't read social cues as others might, or find that using and maintaining appropriate eye contact to be somewhat distressing, might be placed at some disadvantage. And then there are those seemingly obscure questions which seem to drop into interviews to either make the interviewee think on their feet or have some hidden psychological meaning....

The point I want to get across in this post is that one can perhaps see how the job interview process from start to finish is not exactly 'friendly' to many people on the autism spectrum and how some very subtle changes and amendments to elements of the process might level the playing field. I'm not necessarily supporting a call to introduce any positive discrimination or sheltered employment initiatives because such policies can create their own issues. That being said, for potential employers to look at their recruitment policies and think about how many very talented people might be slipping through their admissions net for the sake of a few details, might not be a huge undertaking bearing in mind that work also brings its own stresses.

To finish, a few dos and don'ts for any job interview and some handy hints for any would-be employer interviewing someone with an autism spectrum condition for a job courtesy of the NAS.

Oh, and the eagle-eyed reader might have spotted that the picture accompanying this post is the old (very old) Amstrad CPS 464. So posted because of the founder of Amstrad and his quite well-known catch-phrase 'You're fired/hired'.

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* Strickland DC. et al. JobTIPS: A transition to employment program for individuals with autism spectrum disorders. J Autism Dev Disord. March 2013.

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Strickland DC, Coles CD, & Southern LB (2013). JobTIPS: A Transition to Employment Program for Individuals with Autism Spectrum Disorders. Journal of autism and developmental disorders PMID: 23494559

Asperger syndrome in first-episode psychosis

There are some key 'go-to' peer-reviewed texts which I've found to be useful when talking about the various conditions on the autism spectrum. On the topic of Asperger syndrome, I've always tended to come back to the paper by Tom Berney* (open-access) charting the progression of the condition through childhood into adulthood.

The whisper of the Muse @ Wikipedia 

Despite being published nearly 10 years ago, the paper by Dr Berney weathers well and covers many of the discussions which have come to the forefront in recent years including education and employment prospects, the potential for overlap with the schizophrenia spectrum and the difficult issue of offending behaviour.

Indeed the first place I went looking after reading the paper by Conor Davidson and colleagues** highlighting the prevalence of Asperger syndrome (AS) in cases of first-episode psychosis (3.6%), was the Berney paper to see if this was something new, a rehash of what is already known about or just a chance event. Turns out there was a pearl of wisdom in there as per his observations on 'mistaking Asperger syndrome for psychosis' and in particular "high arousal in a developmental disorder can produce an acute and transient psychotic state with hallucinations and thought disorder".

I'm sorry that I can't post a link to the full-text of Dr Davidson's paper but take my word for it that it is an interesting piece of research, well thought out and well executed. Without wishing to plagiarise the work, there is an interesting case study nestled among the data, describing the experiences of one participant and his lifelong features of AS which were seemingly not picked up by any agency. In particular the description demonstrates how following the transition from home environment to University, the new social demands contributed to him "eschewing all human contact" and after a period of issues with eating and sleeping he developed grandiose delusions with a theme of absolute control over others: "I'm studying neuroscience to take over people's minds... take over the world... become immortal and invincible". Apparently Tony Attwood has previously described this 'God mode'.

OK, let's back up here a little and put this in context. I've said it many times before on this blog, how a diagnosis within the autism spectrum is seemingly protective of nothing when it comes to comorbidity. That people diagnosed and living with an autism spectrum condition might also be more prone to various other psychiatric comorbidity particularly into young adulthood is no big secret (see this paper by Lugnegård and colleagues*** for example) and has been raised before on this blog.

Yes, one could look to that recent Lancet study**** as being evidence that there may be a genetic 'fragility' towards common ground between autism and other conditions but let's not get too ahead of ourselves when it comes to all things genetic. The important caveats being that such psychiatric comorbidity is by no means a universal phenomenon to everyone with autism, and realising the potentially important effects that a person's environment for example, has on the presentation or protection against said comorbidity (social circles and support, living conditions, employment, finances, etc.). Oh and the possible involvement of a few more biological factors too...

Still I find myself intrigued by the Davidson findings and their suggestions about clinicians being "alert to the possibility of Asperger syndrome when assessing patients" presenting with psychosis. Not least because of the implications for the appropriate detection and assessment of Asperger syndrome; only in this study becoming apparent to health care professionals when the individual was presenting with first-episode psychosis.

Questions, questions, questions: why were these young adults not initially 'picked-up' for an autism spectrum conditions when younger, as per the Berney statement, was Asperger syndrome to 'blame' for their psychosis presentation, and what are the longer-term implications of Asperger syndrome for example related to other future episodes of psychosis and their management?

Added into the mix too are papers like this one from James MacCabe and colleagues***** which suggested that a decline in cognitive performance and verbal ability during the adolescent years might translate into an increased risk for psychosis in adulthood. If so, could this be a potential way of differentiating Asperger syndrome + psychosis from psychosis as a result of Asperger syndrome and that 'high arousal' quoted by Berney? Indeed on the back of the paper by Sönmez and colleagues****** (open-access) is there also a tie-up between first-episode psychosis, depression and Asperger syndrome too?

I haven't got any specific answers to these questions by the way, aside from reaffirming my line about a diagnosis of an autism spectrum condition being seemingly protective of nothing when it comes to somatic or psychiatric comorbidity. Oh and the need for appropriate services and support to identify and if possible, mitigate such comorbidity as and when it does present.

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* Berney TP. Asperger syndrome from childhood into adulthood. Adv Psychiatr Treat. 2004; 10: 341-351.

** Davidson C. et al. Prevalence of Asperger syndrome among patients of an Early Intervention in Psychosis team. Early Interv Psychiatry. March 2013.

*** Lugnegård T. et al. Psychiatric comorbidity in young adults with a clinical diagnosis of Asperger syndrome. Res Dev Disabil. 2011; 32: 1910-1917.

**** Cross-Disorder Group of the Psychiatric Genomics Consortium. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. The Lancet. February 2013.

***** MacCabe JH. et al. Decline in cognitive performance between ages 13 and 18 years and the risk for psychosis in adulthood. JAMA Psychiatry. 2013; 70: 261-270.

****** Sönmez N. et al. Depressive symptoms in first episode psychosis: a one-year follow-up study. BMC Psychiatry 2013; 13: 106.

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Davidson C, Greenwood N, Stansfield A, & Wright S (2013). Prevalence of Asperger syndrome among patients of an Early Intervention in Psychosis team. Early intervention in psychiatry PMID: 23472601

CNV duplication load, hotspots and autism

Viewers here in the UK might remember the catchphrase of one Michael Barrymore on the show 'Strike It Lucky': "What is a hotspot not? A good spot". It is with a rather different kind of hotspot in mind, that I'm posting about today: genomic hotspots and autism with a specific focus on copy number variants.

An intriguing paper by Santhosh Girirajan and colleagues* (open-access) popped up on my Twitter radar recently discussing copy number variant (CNV) load in relation to autism spectrum disorders. Whilst only being an amateur enthusiast when it comes to all things genes and genomic, I can't offer an expert opinion on what CNVs are, just that fairly similar to single-nucleotide polymorphisms (SNPs), we're talking physical alterations to the genome and in particular gains/losses to segments of DNA (I think!)

A hotspot indeed... @ Wikipedia  

I'll start by saying that this is not the first time that CNVs have cropped up on this blog either with autism in mind (see here) or with other conditions such as ADHD (see here) and intellectual disability (ID) in mind (see here).

Indeed readers who looked at that ID link will see that we are talking about another paper from Girirajan following the previous suggestion that ID might be particularly prone to a high CNV load. Keep that in mind for now.

Thankfully the latest paper has been very nicely covered by a ScienceDaily entry (see here with a sigh of relief) so as to patch over my considerable non-expertise in this area. Without plagiarising the paper or SD entry, the general gist of the work was to initially look at CNV data from over 500 people with autism (n=274) or asymptomatic controls (n=242) derived from the CHARGE initiative (see here), to ascertain exactly what the CNV load was and how it might link into some of the signs and symptoms of autism. There was also a further testing group to confirm "the increased duplication load" based on a further cohort of autism and control cases but I'm not going to bore you with all the details.

If I'm reading this right, there were some interesting findings to take from this study:

• Children with autism "exhibited a significantly elevated copy number load, represented principally as an increase in duplicated base pairs found in large CNVs". Importantly, this copy number load seemed to include quite a bit of de novo, so not passed from parents to offspring.
• Duplication over deletion seemed to be the important variable for autism cases, which as the authors note "is associated with genomic variants with more modest functional impact". As per that previous CNV work with ID in mind, I think the authors seemed to be suggesting a sort of sliding scale of phenotypes based on CNV profiles: ID at the more severe end of the spectrum (with more deletions also), autism somewhere in the middle and dyslexia at the less severe end of the spectrum in terms of functioning. I could be wrong and I could be over-simplifying the whole thing so accept my apologies if so.
• Copy number load in autism cases also seemed to show some relationship with certain aspects of behaviour. Significant negative correlations for example, were observed between CNV load and VABS scores in core areas of communication and socialisation. That being said, the correlations were not exactly all that great (p=0.048 and p=0.022 respectively) and should be compared with other gold-standard schedules such as the ADOS that did not turn up anything significant. 
• The notion of genomic 'hotspots' is also raised as a consequence of the results, suggesting that parts of the autistic genome already under the spotlight might be more susceptible to such CNVs. Those words-of-the-hour DNA methylation get a mention alongside the folate story (see here). Personally and with my non-expertise caveat in full working order, I'm also wondering about those archived portions of viruses called HERVs - human endogenous retroviruses - (see this post and this post) which dot the genome and whether they might be contributory in any way, shape or form to any genomic instability in target areas.

Putting aside the complexity of the genome when it comes to autism and the suggestion that we might want to be rethinking how we view the condition** (I've a post coming up on this paper fairly soon), there are some interesting themes emerging from the Girirajan paper. That for example CNV load and the type of CNV (duplication or deletion) might roughly fit into phenotypic differences between inter-related conditions including autism and ID is definitely something worth pursuing in future work. That also such CNVs might tie into genomic hotspot areas is also an important point particularly when it comes to things like systems biology. Lest we also forget the potential importance of any genomic instability and how, with the DNA methylation point in mind, this *might* be attenuated via changes to the environment (remember SAMe)?

To close Chuck Berry and a song about Johnny B Goode and his guitar-playing skills.

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* Girirajan S. et al. Global increases in both common and rare copy number load associated with autism. Hum. Mol. Genet. March 2013.

** Moreno-De-Luca A. et al. Developmental brain dysfunction: revival and expansion of old concepts based on new genetic evidence. The Lancet Neurology. 2013; 12: 406-414.

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Girirajan S, Johnson RL, Tassone F, Balciuniene J, Katiyar N, Fox K, Baker C, Srikanth A, Yeoh KH, Khoo SJ, Nauth TB, Hansen R, Ritchie M, Hertz-Picciotto I, Eichler EE, Pessah IN, & Selleck SB (2013). Global increases in both common and rare copy number load associated with autism. Human molecular genetics PMID: 23535821

Gastrointestinal comorbidity for World Autism Awareness Day

Today (Tuesday 2 April 2013) is World Autism Awareness Day (WAAD).

I don't exactly know how one is supposed to communicate this message ('Happy world autism awareness day' just doesn't roll off the tongue). So I guess all I will say is to reiterate the subtext of this blog on what the spectrum - the very wide spectrum - means: "To some it means a need for life-long support. To others it is part of the varied tapestry of humanity. To all it means a need to foster a welcoming society with appropriate support and opportunities."

Onwards. Having discussed the latest paper from Drs Stephen Walker and Arthur Krigsman on bowel pathology in cases of autism potentially denoting a distinct condition from other inflammatory bowel diseases and stumbling upon the paper by Peeters and colleagues* on functional defecation disorder and autistic traits, I thought it appropriate to pop into the DeLorean and revisit a paper which never really received the recognition it deserved.

The subject matter for today is the paper by Karoly Horvath and colleagues** published in 1999 as we begin another trip down the autism research memory lane, same as I did when covering the the Mary Goodwin paper from 1971 on the gut-brain axis and autism (see here) and the John Money autism and autoimmunity paper also from 1971 (see here).

Hadrian's Wall @ Wikipedia  

Remember my name
The name Karoly Horvath will probably be familiar to quite a few people who've been on the autism research scene for a while. Another of Dr Horvath's papers*** created a bit of stir a while back based on some very preliminary findings on the use of the digestive hormone, secretin for cases of autism.

Following some initial reports of "transient, marginally significant improvements in autistic behaviors" in some cases as per studies like the one from Coniglio and colleagues****, a whole slew of subsequent trials have painted a rather less positive picture on the use of secretin for autism as per the review by Krishnaswami and colleagues***** (open-access) which quite emphatically stated that "secretin as a treatment approach for ASDs warrants no further study".

I'm not one to normally challenge paper conclusions - particularly systematic reviews - but will perhaps contrast that quote with the closing remarks made by the Cochrane Library review of Williams and colleagues******. They left the secretin research door slightly ajar for those who were potentially able to  identify "important subgroups of children with ASD who could benefit from secretin because of a proven link between the action of secretin and the known cause of their ASD, or the type of problems they are experiencing". I'm a great believer in subgroups when it comes to autism, or rather the autisms, and how a diagnosis of autism is seemingly protective of nothing when it comes to other conditions/states, so you can perhaps assume which quote was my preference.

Factoids
Anyhow, back to the Horvath 1999 paper. A few interesting factoids from their report:

• Thirty-six children all diagnosed with an autism spectrum disorder (ASD), mean age 5.7 years, formed the participant group. Children were all referred to the gastroenterology (GI) clinic where the authors worked following the presence of various GI symptoms ranging from abdominal pain to chronic diarrhoea and various other presentations.
• As well as quite a bit of review of participants' medical history, various clinical investigations were undertaken which included a "full upper gastrointestinal workup", analysis of digestive enzyme function in the small intestine and some histological examination.
• Results: quite a few important findings. Reflux esophagitis was present in nearly 70% of participants (25/36). Chronic inflammation of the gastric mucosa was determined in 15 children. Reduced disaccharidase activity was present in approximately 60% of children, and in particular low lactase levels. Following administration of secretin, participants with autism and diarrhoea comorbid showed signs of increased pancreatico-biliary fluid output potentially indicative of "upregulation of the secretin receptors" itself potentially related to "either a defect in secretin production or a problem of release from the intestinal S cells".
• "There was no evidence of either fungal or bacterial overgrowth in the duodenum" was another finding.

I know there is a lot to take in from those results so I'm going to try and put them into some kind of perspective with some of the other related literature in the peer-reviewed domain.

Lactose intolerance
I'll start with the disaccharidase activity side of things. The Horvath results were in some respects ahead of their time with their findings in this area. I've talked previously about the Rafail Kushak paper and their findings of the frequency "of lactase deficiency was 58% in autistic children ≤ 5 years old and 65% in older patients". Notice the similarity in the percentages between Horvath and Kushak. Indeed, this whole area of carbohydrate malabsorption present in cases of autism was very nicely continued by the Brent Williams paper looking at enzyme activity and autism. I know a few people have talked about how some of these findings might overlap with for example, the various reports on the use and effectiveness of a gluten- and casein-free (cereal grains and mammalian dairy free) diet in some cases of autism. Certainly, I wouldn't rule out a possible overlap to account for any results.

Reflux and GERD
Gastroesophageal reflux and reflux esophagitis - states pertaining to inflammation of the esophagus - were also commonly reported in the participant group and indeed also correlated with various behavioural manifestations noted in some cases (nighttime wakening, signs of irritability, abdominal discomfort) which are "typically reported by non-autistic children with esophagitis". A little reading around this topic suggests that many cases of such esophagitis are tied into things like GERD - gastroesophageal reflux disease - which is basically about stomach acid rising up instead of staying where it should be and causing damage. That being said, other explanations have also surfaced to potentially account for the damage done during GERD (see the paper by Souza and colleagues*******) highlighting a possible role for cytokines in this process. I'm also conscious of the findings of eosinophilic esophagitis being reported in individual cases of autism (see here). In terms of management options and without heading down any medical advice giving path, I was very interested to see a body of work appearing supporting the use of baclofen for cases of GERD********, a derivative of which - arbaclofen - has recently been touted as a potential intervention option for cases of autism. One has to wonder whether kum-ba-arbaclofen might be doing so much more than just affecting GABA receptors?

I'm going to stop there with the Horvath paper and its quite important observations. Once again it is a good example of how, just because we see a rising tide of new findings on autism or any other condition or state, we shouldn't neglect the older literature (published pre-social media) and the valuable insights that it has provided. Indeed, I am going to champion the paper by Horvath et al as an important one; particularly when it came to the assessment of carbohydrate digestive enzyme activity because it was truly ahead of its time and very possibly something that you might hear more about in the coming years of autism research.

Importantly for WAAD, the Horvath paper is a stark reminder that awareness of the autism spectrum should extend beyond just the triad (very soon to be dyad) of core symptoms and into the range of often very pronounced comorbidities which can also exist and affect quality of life. And just in case you need a more recent example of this, have a look at this paper from Francisca van Steensel and colleagues********* (open-access) and their findings on the over 50% rate of psychiatric comorbidity reported in their pediatric cohort. Their focus on 'anxiety disorders' does not need any more chatter from me.

To close, something musically, a little more contemporary. Bruno Mars and Locked Out Of Heaven.

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* Peeters B. et al. Autism spectrum disorders in children with functional defecation disorders. J Pediatr. March 2013.

** Horvath K. et al. Gastrointestinal abnormalities in children with autistic disorder. J Pediatr. 1999; 135: 559-563.

*** Horvath K. et al. Improved social and language skills after secretin administration in patients with autistic spectrum disorders. J Assoc Acad Minor Phys. 1998; 9: 9-15.

**** Coniglio SJ. et al. A randomized, double-blind, placebo-controlled trial of single-dose intravenous secretin as treatment for children with autism. J Pediatr. 2001; 138: 649-655.

***** Krishnaswami S. et al. A systematic review of secretin for children with autism spectrum disorders. Pediatrics. 2011; 127: e1322–e1325.

****** Williams K. et al. Intravenous secretin for autism spectrum disorders (ASD). Cochrane Database Syst Rev. 2012; 4: CD003495.

******* Souza RF. et al. Gastroesophageal reflux might cause esophagitis through a cytokine-mediated mechanism rather than caustic acid injury. Gastroenterology. 2009; 137: 1776-1784.

******** Cossentino MJ. et al. Randomised clinical trial: the effect of baclofen in patients with gastro-oesophageal reflux - a randomised prospective study. Aliment Pharmacol Ther. March 2012.

********* van Steensel FJA. et al. Psychiatric comorbidity in children with autism spectrum disorders: a comparison with children with ADHD. J Child Fam Stud. 2013; 22: 368–376.

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Horvath K, Papadimitriou JC, Rabsztyn A, Drachenberg C, & Tildon JT (1999). Gastrointestinal abnormalities in children with autistic disorder. The Journal of pediatrics, 135 (5), 559-63 PMID: 10547242