Your Royal Highnesseseses

OK, nothing to do with research or anything else but today is the big day for HRH and Kate Middleton.
As a man, my default response to this televisual event should be 'I'm not going to watch' and various murmurings about going to the pub or taking the kids to the seaside instead to take advantage of the extra Bank holiday.
Truth is I am actually quite interested to see the whole event and the various Morning suits being brushed off and worn for the happy couples' day. If anything else just to answer that question 'where were you when..'. I don't have any particular opinion about the Monarchy or anything like that, just curious.
I can't resist posting a few links for viewers loosely related to today's event.
There is this one from a well-known mobile phone company which is currently doing the rounds.
And just in case you do fancy a drink instead of watching the Royal event, how about a drop of this new brew to celebrate?
Good luck your Royal Highnesseseses.

Iron deficiency in autism

Iron. The metal that had its own age. A metal we consistently find in extra-terrestrial material. A metal that carries several important roles in numerous bodily functions. A metal that even has its own superhero. It is in relation to the body and health that I will look at iron connected to autism and a few other things (although I am tempted to talk more about Iron Man given my childhood love of the Marvel comics).

I have, in a previous post, hinted at a possible issue with iron in some cases of autism. The limited research done on the topic of iron deficiency in autism suggests that it might be more widespread than you think.When taking into account ferritin levels as possible indicators of iron deficiency, the research does get a little bit serious in terms of the numbers potentially deficient. This last piece of research also suggests that things get potentially worse as chronological age increases.

So why is iron so important to autism and why might we be seeing the scientific results that we are?

Well like everything it is complicated. I will do my best but can't guarantee making things any clearer by the end of this post. We get our iron from a few sources: endogenous recycling following hemoglobin breakdown, dietary intake and the various supplements that we seem to be taking ever more of. Iron is important for lots of different bodily processes and where not enough is present, anaemia is diagnosed. For children, anaemia can affect growth measurements among other things.

One could assume that given the potential for dietary issues in some cases of autism, there might be some problem in consuming adequate levels of dietary iron. Indeed, quite a few studies have suggested that the recommended nutritional intake of iron (and lots of other things) might be less in autism than what they should be. I would however temper that statement by saying that controls were also tending to be low in iron intake also. Levels of ascorbic acid (vitamin C) which is also pretty important for the absorption of non-heme dietary iron has also been suggested to be 'different' in some cases of autism.

There is some suggestion that supplementing iron in autism might have some interesting knock-on effects with regards to ferritin levels and also sleeping patterns. The ferritin levels bit suggests that the metabolism of iron might not be particularly problematic in autism; rather low intake or some mechanism that depletes iron being more important. This is where I am going to be a bit speculative so please get that pinch of salt ready.

Regular readers might know that I talk quite a bit about coeliac disease as being potentially quite an important co-morbidity to some cases of autism. Coeliac disease has also been associated with iron deficiency whether through poor absorption of dietary iron or more controversially as a result of blood loss.

Question: could the low levels of iron present in some cases of autism be due to similar mechanisms?

I am not suggesting that every case of low iron in autism is due to coeliac disease; indeed nothing close. What I do however wonder is whether the proposed 3% of the autistic population with co-morbid coeliac disease might be populous in our low iron group? What about those with gut hyperpermeability also potentially affecting the amount of iron absorbed from diet?

If you want more information on testing for levels of iron, please have a look here on what testing involves and speak to your medical physician.

Because I can't resist it, here is a Marvel link that many of you may remember from days gone by.

[Update: 23 September 2014: Here is my take on the paper by Schmidt and colleagues looking at maternal iron supplementation during pregnancy and offspring autism risk]

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.

Adaptive..yawn..trial design

My name is Paul and I am interested in clinical trial design.
OK, it is hardly the chat-up line of the year. I also don't think I am going to win any awards for most interesting hobby; certainly not combined with my other interest in all things related to gut bacteria and gut hyperpermeability. I do, however, stand by my curious amateur/semi-professional interest in how clinical trials are designed and run and how such design can impact on the results obtained.
My interest was piqued recently by this communication from the National Institutes of Health (NIH) and their proposal to use adaptive trial design in HIV research.
There is a good description of what an adaptive trial could contain here in the curiously titled Orphanet Journal of Rare Diseases. The article by Chow and Chang is a keeper for me because they go through, in quite some detail, the various manifestations of adaptive design as well as providing a point-by-point checklist of things to watch out for when using such a trial design.
The basic premise of an adaptive design is that during a clinical trial, adjustments are made according to the data that is produced. So for example suppose you want to look at a specific intervention - dietary change for example. You have your randomly assigned groups (dietary change vs. diet as usual) and commence with the study. Suppose you set specific 'goals' for your dietary change group reflective of some change you are expecting, which at some point, you need to measure. You bring in an independent person to break the allocation codes and look at the data produced at that point. If you have reached / exceeded those goals, you then alter the trial to bring the diet as usual group onto the dietary change and continue with both groups in the experimental group. Its called a 'drop-the-loser' design and just happens to be the same design that we used on our ScanBrit trial.
This is just one example of an adaptive trial design. There are lots of other combinations. One of the main strengths of such a design is that it is flexible and responsive to what happens during your trial, particularly for very early clinical trials where a new drug, diet, instrument, etc is under preliminary evaluation.
Kudos to the NIH for bringing adaptive design centre stage.

Jaundice, bilirubin and autism

Jaundice is a common problem for the neonate. It is common because the figures suggest that anywhere up to 50% of newborns may present with jaundice during earliest infancy and even more frequently in those babies born slightly preterm.

The primary overt symptom of jaundice is the characteristic yellowing of the skin starting with the face and progressing throughout other areas of the body. The primary clinical correlate to this symptom is the increase in levels of bilirubin - a metabolite of heme.

Why is jaundice an important observation to the newborn? Well basically because bilirubin is toxic and has the ability to do some pretty terrible damage to the newborn; the end-point potentially being kernicterus (bilirubin encephalopathy).

OK so what is the connection to autism? Is there a connection?

Well this very much depends upon how you look at the research. I can remember many years ago talking to Dr Rosemary Waring, famed for the sulphate research in autism about bilirubin and its cousin, biliverdin. Rosemary (and a few others including Paul Shattock) had some interesting ideas about the effects of low sulphate levels on the metabolism/breakdown of bilirubin and biliverdin. These ideas still remain today albeit stagnant in research terms.

The more direct work on jaundice in autism is interesting. This paper suggested that various bilirubin levels might show some association with ADHD and developmental delays (to include autism). This paper said pretty much the same thing with specific regards to autism. One might get the impression that something was brewing with regards to a possible relationship between autism and hyperbilirubinaemia.

Well not so fast. There is some evidence to suggest that any relationship is not going to be so clear-cut. Indeed certain questions have been raised about research suggesting a link between jaundice and autism (and other issues of psychological development).

Where to go from here?

There may be yet more we can learn from examining any relationship between autism and jaundice / bilirubin. The fact that several 'conditions' have been linked to jaundice / bilirubin is still an intriguing finding and perhaps opens up avenues towards a more generalised relationship.

Increasing parental age and autism

I am trying to pitch at two proverbial birds with this stone of an entry. The title is quite ambiguous on purpose in that I am discussing both the suggestion of a link between advancing parental age at conception and 'risk of autism' but also the very important issue of aging parents and the provision of care for their children with autism. We will see how successfully this dual task is accomplished.

Reading through the research literature of 'risk factors' for autism, one thing outside of the sex ratio thing seems to crop up time and time again - how old parents were at the time of conception. In these times of more people having children later in life (the owness, rightly or wrongly, seemingly falling more on women than men), there is quite a lot of interest in what effects this may or may not be having on children born under such circumstances.

Whether it is mum's age or dad's age, several pieces of research have indicated a role of advancing parental years and later health and developmental outcomes. This quite large study for example, suggested that children of older dads did slightly worse on various cognitive measures compared to younger dads. Indeed, father's age has been the most interesting area when it comes to risk and conditions like autism - dare I say very strong evidence that crosses different populations?

At this point I think we have to be quite careful and remember my mantra about probability (not absolutes) and science. Yes, the results confirm a strong trend; but this by no means implies that every man in his late 40's+ fathering a child is 'predestining' that child towards autism. There are lots of other factors to consider, not least genetic influences, environment, etc; lest we start going back to the parental blame-game of times gone by.

The proposed mechanism for older dads and autism? Well there are several theories, many of which are explored on this blogsite, including methylation of DNA (something covered in my previous post on MTHFR), point mutations (SNPs), environmental factors, etc. It may be that other 'knock-on' factors such as low birth weight also come into play. Interestingly also, the calculations on what contribution older dads (and mums) have had to the rise in autism prevalence (at least in California) is not estimated to be massive. The bottom line: being an older dad carries a statistically significant association with childhood autism but lots of other factors are also potentially involved.

So then to the issue of aging parents and provisions of care for their children. This is a real issue and in years to come will, no doubt, become even more of an issue. Many parents have asked quite publicly 'what will happen to my child when I am old or when I am gone'?

Whilst appreciating that autism is a spectrum and that there are different types of presentation and different ability patterns within that spectrum, the issues of 'concern' and 'care' is pretty much a universal one given that even those at the high-functioning end of the spectrum have parents who still want to ensure the best for their child.

Many parents have blogged about this - one example is here. I read this entry and found it raised several important issues. Questions about a role for siblings in 'taking the reins'; questions about a role for 'social care'; and a very uncomfortable question about mortality. Although not by any means the same thing, similar questions have been asked about lots of other conditions not generally affecting life duration. There are no easy answers to this issue.

Assuming that there are siblings, one might expect them to take some "responsibility" if required, may be even assuming some kind of guardianship role where informed consent may not be easily given by a person with autism for example. Siblings are in a unique position because not only do they get an up-close look at autism, they follow the growth of their brother/sister and hence know more about them as a consequence.

The added benefit also being that siblings will have the best interests of their brother/sister at heart from a personal perspective rather than a social or financial ("what can the State afford") perspective. As this scenario becomes more of a reality, I expect to see many more brothers and sisters of people with autism becoming more vocal about such issues.

Some parents have talked about drawing up a personal plan of care of their child. Others have discussed drawing up wills and planning for the financial future of their child (which itself can have implications for benefits, etc). Planning seems all important to ensure that parental wishes are at least indicated.

PKU: Food can affect mental health

Despite the seemingly daily helping of new research and opinion suggesting that what we eat can influence our mental as well as physical health, there are still doubters. I have to say that I don't generally mind doubters. As long as the debate is polite and cordial and does not descend into mud-slinging, doubters sometimes bring a new perspective to an issue/problem/debate which might otherwise not be thought about or raised.

In the case of diet affecting mental health we have however a prototypical condition in Phenylketonuria (PKU). A condition which places the doubters in a bit of a quandry because PKU is a very, very widely accepted condition and is routinely screened for via the Guthrie test. Diet can very much affect mental health (at least in PKU).

For those really interested in the story of PKU, there is an excellent historical piece here. I will apologise in advance for some of the terminology used which is perhaps reflective of a different era of political correctness. For those like me, who prefer the Mr Men version it goes something like this.

Many years ago, a Doctor was presented with 2 children with developmental problems who had wee that 'smelled' a little bit funny. He looked in the patients' urine samples and found an interesting compound called phenylpyruvic acid using the most basic chemistry kit compared to today's high-spec methods. He realised that said toxic compound was related to the amino-acid phenylalanine and hey presto, one of the first documented inborn errors of metabolism is discovered, laying the foundation to saving and improving thousands of lives by a simple dietary modification. Yes sir, Dr Folling was a quite astonishing man.

Over the years PKU has recieved a lot of research interest from lots of different perspectives. I have an obvious interest from the (comorbidity) autism research side of things but also because of the dietary element integral to PKU. Indeed, the traditional treatment for PKU comprising of a low phenylalanine diet and tyrosine supplements is being slightly overshadowed by a few newer developments in the PKU intervention field which have caught my eye.

One such intervention is the use of tetrahydrobiopterin or BH4 or sapropterin. BH4 is an interesting (and quite expensive!) compound. BH4 is quite good at mopping up phenylalanine - hence the problems you get when you have BH4 deficiency. Would you believe me if I said that it might show some promise as a pharmacotherapy for certain aspects of autism also?

Well there is this paper which suggested that in a quite small participant group, levels of endogenous BH4 might be slightly reduced in some cases of autism. By the same author group (including Christopher Gillberg) supplementation with BH4 also showed some initial promise in an even smaller participant group, alleviating certain core symptoms in some children with autism. BH4 has also cleared the hurdle of the double-blind, placebo-controlled cross-over methodology to show some effect and is undergoing other trials at the moment.

So why might a compound initially used for PKU work for some cases of autism? The simple answer is I don't know. Nobody does at the moment. Outside of again mopping up excess phenylalanine, there might be some other clues to illuminate our way.

I was involved (very, very peripherally) in writing this paper some time ago on tryptophan metabolism and autism. It is not a peer-reviewed paper per se before you ask, but rather an information piece. The crux of the paper is that the amino acid tryptophan and its various manifestations seems to be important to some cases of autism.

The interest is specifically in one enzyme involved in the tryptophan pathway called tryptophan hydroxylase (TPH) (actually there are two known TPH isoforms). TPH has already popped up on the radar of autism a few times (here for example) but nothing too significant has thus far been noted. TPH is interesting because in order to do its enzymatic duties coverting tryptophan to 5-hydroxytryptophan (5-HTP), the precursor of serotonin, it needs BH4 as well as iron (as a cofactor). It's a sort of "all hold hands" (TPH, iron, BH4, etc) to make the reaction work.

BH4 as well as iron? Mmm, I wonder. Well we know that iron / ferritin levels are sometimes aberrant in autism; this paper from Latif and colleagues from a few years back told us that, despite the fact that it is still not routinely screened for. Hence, in some cases iron as a cofactor might be in short supply. Coupled with lower levels of BH4, the possibility exists that TPH might not be able to do its job as effectively as it should in that vital step from tryptophan to serotonin.

There is a degree of speculation in this entry and whilst I would love to take credit for working this out, I can't (standing on the shoulders of giants and all that). I don't think we will ever quite be able to put PKU and autism 'together' given the differences in presentation, possible aetiologies, etc. I would however like to think that within autisms (note the 's') there might be one small phenotypic group which share enough overlapping biochemistry with PKU so as to perhaps benefit from things like BH4 and provide further answers to the role that diet plays outside of just physical health.

Autism Now on PBS

Not so much a blog entry but more an blog-fomercial.
Us Brits don't really know much about PBS: Public Broadcasting Service on-air in the States. We don't normally get PBS and perhaps don't have the background that our American cousins have on the network or the shows it presents.
Through the marvels of the Internet we can however connect to the various programmes broadcast on PBS, including the recent series 'Autism Now' on PBS NewsHour. The link is to a week-long series of programmes on various areas/facets of autism reported by the programme co-founder Robert MacNeil and the very personal experiences of his family, and in particular his grandson Nick, who has autism. I would also, at this point, like to acknowledge Mr MacNeil's grand-daughter and sister to Nick, Neely. You will see what I mean when you watch programme number one.
The programmes cover a lot of ground and have included some pretty big names in autism research and practice such as Dr Tim Buie and Dr. Irva Hertz-Picciotto to name a few.
I would recommend a look.

Watching the waistline figures

'Food, glorious food' went the lyrics to the song from the musical Oliver!

Nowadays however, we are bombarded with messages that food might not be all that glorious, certainly not the types and amount of food that we, in the developed world, are all consuming in these modern times of plenty.

Being overweight or obese is a real issue nowadays. If you have the time, have a look at the figures being produced by the US CDC on prevalence rates over the past 20 years or so. It's the same message and same message here in the UK. Plenty = problems.

In amongst all this data, some reports have indicated that there might also be certain groups of people at increased risk of being overweight and obese; one of them being those diagnosed with learning and/or developmental disabilities where diet, feeding and exercise patterns may already be problematic. Yet another potential co-morbidity to look out for.

I could cite various papers to demonstrate this finding in learning disability but I will cite this one from 2008 simply because it has quite a big study group and controlled for lots of different factors. Their findings: well, obesity was running at about 20% of their subject group (based in the UK) which is actually about the same as for the rest of the UK population at a similar time. The authors do suggest that this figure might be an underestimation but I can't find anything substantially wrong with their methodology aside from the fact that 'intellectual disability' covers a lot of ground in terms of people and symptoms.

Overweight and obesity have also been looked at with reference to autism spectrum conditions and the question asked whether autism may be associated with increased risk of obesity. The contemporary figures where data is available are: USA - 2010 (30%) & USA - 2010 (23%), China - 2010 (31%). Going back a few years the figures are slightly different: USA - 2005 (19%), UK - 2004 (10%) (yes, this last one is mine). Plotting these figures onto the total population obesity figures and we get roughly the same sort of trend appearing in terms of overall prevalence and direction.

So to the question of whether there is an increased risk of obesity in autism. Mmm, the data appears to be saying that there is no doubt obesity is associated with autism, but nothing at the moment to say that levels are anything substantially different from that observed in the general population. A case of 'sauce for the goose'?

There are some obvious questions to ask about the data and the conclusions reached in this relatively brief post. Is the data collected the same way - objective measurements of height and weight, same criteria across all data collection? Are we comparing alike age-groups? Are we taking into account things like side-effects of medication, activity levels, feeding habits and patterns, etc?

And you would of course be right to ask such questions because I don't have all the answers - I am, once again, just questioning them.

Saccharomyces boulardii - Nescio quid dicas

Science is literally 'littered' with words and phrases in Latin. With a rudimentary knowledge of Latin (and Greek) I am sure that much of the 'fog' around Science would lift in an instant for many people. The title of this post says two things: saccharomyces boulardii which I will come to shortly, and the words 'I don't know what you are talking about' (I hope).

I have wanted to talk about saccharomyces boulardii for a while now for several reasons. Not only is it one of the coolest names for anything in Science, but this relatively modest yeast seems to have some surprising properties which might just tie into quite a few things I have blogged about previously.

S. boulardii (to those in the know!) is a handy little yeast which has been applied to a few conditions most of which have some connection to the gut or gastrointestinal problems. Diarrhoea (diarrhea), whether caused by things like certain Clostridia species or following the use of anti-microbials, has been a target of S. boulardii.  The evidence for effect, measured by randomised-controlled blinded trials, in these areas is actually quite impressive. There is also some suggestion that s.boulardii might be quite effective in managing certain types of inflammatory bowel disease such as ulcerative colitis and might have a beneficial effect on certain types of gut bacteria outside of Clostridia.

The discerning reader of this blog can perhaps see where I am going with this in relation to autism and the GI co-morbidity and gut bacteria issues present in some cases. Indeed, S. boulardii has been mentioned briefly in the research literature with regards to autism, combined with quite a few anecdotal reports scattered around the Internet about its possible usefulness (note, I am making no formal recommendations at this point).

How and why it works is another matter.

There is some speculation that S.boulardii might have more than one effect: anti-microbial, anti-inflammatory, etc.  One quite interesting possibility, specifically in relation to autism and the findings of reduced dissacharidase activity reported recently, is the suggestion that S.boulardii might increase such enzyme activity (at least in the rat model).

So there you have it. Saccharomyces boulardii, a simple yeast seemingly punching well above its weight. A bit of a John McClane character. Dic mihi solum facta, domina (translation: 'just the facts ma'am')

MTHFR and autism

If I say the letters 'MTHFR' would you know what I was talking about?

Up until about 4 or 5 years ago, I would have said something along the lines of 'some great consonants to play scrabble with'. But no, MTHFR in this case stands for methylentetrahydrofolate reductase. A bit of background first. MTHFR is an enzyme produced by the MTHFR gene which reduces (hence the name) the compound 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. That might not sound like much, but importantly this is a pretty vital step in one of the routes converting the amino-acid homocysteine to methionine.

Readers may already know that I have blogged about 'the big H' homocysteine (and homocystine) in relation to autism previously. Homocysteine is acquiring quite a following with regards to several things including risk of coronary heart disease (perhaps even greater a risk than cholesterol?).

Assume then that you have a problem with the MTHFR enzyme or gene which means that it does not quite perform the functions it is supposed to do. You could quite easily see how that conversion of homocysteine to methionine might not be as efficient as it should be and potentially lead to a build-up of homocysteine in plasma (and urine - homocystinuria). Not trying to scare anyone, just show how important MTHFR is.

MTHFR has also been of some interest in relation to autism spectrum conditions. There was this paper a few years back looking at a particular SNP (pronounced 'snip') of the MTHFR gene in relation to the methionine cycle and folate metabolism. The same SNP of the MTHFR gene has also been looked at in this paper and this paper. The suggestion being that problems with MTHFR isolated in these studies might indicate issues such as impaired methylation of DNA (a kind of switch which turns certain genes on or off) which linked to autism has been postulated in papers such as this one as being important.

There is still a lot more work needed on the central role of MTHFR in relation to autism and homocysteine, folate metabolism and DNA methylation.  Perhaps next time you get the letters M-T-H-F-R as your scrabble word collection or see them on Countdown, spare a thought for the importance of methylenetetrahydrofolate reductase in our lives.

The medicines cabinet and autism

The review articles on autism interventions recently published in Pediatrics have certainly created some discussion on the web and blogosphere. I have read through quite a lot of the media content and discussions following the reports, and opinions have certainly been formed and communicated by many people for all the various reviews; particularly when it comes to the one about pharmacotherapy for autism.

This got me thinking about an important issue raised following the review, namely what medications are 'used' in autism and more specifically, the data on the cost-benefit ratio. I might add that by using the term 'cost-benefit' I am not so much talking about the financials, but more the positive effect vs. side-effects or positive effect vs. no effect.

I will hold my hand up at the this point and say that I am not a medical Doctor or Pharmacist. My opinions are my own and based on the available information/research on the topic. I am just a daft old-ish researcher, so please, don't go changing meds or anything like that on the basis of any information here. Any such issues, changes, alterations or other advice about medication need to be discussed with the appropriate supervising Physician. OK, you (or I) have been officially disclaimed.

The use of medication 'for' autism has a bit of a love-hate relationship. On the one hand, some medications used to 'treat' some of the core and peripheral symptoms associated with autism spectrum conditions have been very well received on the whole (on the whole) - particularly where accompanied by good medicines management. One good example is melatonin for sleeping problems - melatonin by the way in the UK, is still a prescription-only drug despite being quite widely available elsewhere in the world.

On the other hand, other preparations have not fared so well for autism. The previous use of fenfluramine is one particular example (which was eventually withdrawn following indications of heart problems associated with general use). The recent Cochrane review on the use of SSRI medication for autism is potentially another example; although I would stress that SSRI outcomes are more down to a lack of significant effect in autism rather than a general safety issue. In some cases, medication is implicated in the very saddest outcome.

Somewhere in between these examples are the wide range of other pharmacotherapies used for various aspects of autism and its co-morbidities. I would, at this point, provide you with a link to a published paper which details the extensive list of medications used for autism outside of the recent Pediatrics review. The only problem is that said research into medication changes so fast that the links I would provide are slightly dated.

One of the most comprehensive links I can find is this one from the Autism Research Institute (ARI) and their survey of interventions for autism which include medications. The ARI list is extensive. Some medications seem a more obvious choice than others but I suppose it depends what you are trying to 'treat'. Bearing in mind also that people with autism are at least as prone as the general population to health and ill-health and hence likely to use the same meds.

The thing I like about the ARI data, as 'unscientific' as it may seem, is the fact that it details parent / caregiver / first-person experiences of whether medication was beneficial, detrimental or showed no effect. I say 'unscientific' here to mean that data is not derived from a clinical trial, where other modifying variables are perhaps controlled for. I could equally argue that first- and second-person observations are important, particularly where we are talking about n=1. Indeed, most physicians using medication for autism or anything else tend to be reliant on what happens to the patient rather than what a clinical trial might describe.

Some people might also question the authenticity of the ARI data, if for example, derived via the Internet and hence not subject to appropriate controls. I would agree that this might be an issue in some cases, although I fail to believe that 26,000+ people would be so wrong or so malicious. One also has to recognise that such methods of data collection are also receiving some validation in autism research.

Anyway, the ARI data provides some interesting information.

• A suggestion that the anti-epileptic drugs (AED) tend to be quite good at controlling seizure activity - a definite relief for all given my slightly grim posting on epilepsy and autism recently. Medications such as valproic acid and carbamazepine came out top (based on several hundred reports). When it came however to looking at behavioural changes on such meds, there was a definite shift in terms of positive reports.
• Allowing for different numbers of people reporting, the 'top' meds in terms of ratio of improvers/got worse were: the anti-fungals fluconzole and nystatin, the anti-viral valaciclovir (valtrex) and IVIG.
• The not-so-good meds in terms of ratio included some of the AEDs effects on behaviour (outside of epilepsy) and pemoline (cylert).

I will reiterate my previous disclaimer at this point on not giving medical advice before going on with a short analysis. I might not be a Physician but even I realise that there is something unusual about the list of meds supposedly most helpful for autism listed in this survey: none of them are, what you might call 'the usual meds' for treating/managing a developmental/behavioural/psychiatric (delete as appropriate) condition.

Don't get me wrong, medications like the neuroleptics are included in the ARI list: risperidone, for example, posts quite an admiral 2.8:1 (better:worse) ratio (n=1038). Its just that they don't seem to do as well, according to the reportees on the ARI site, as some of the more unfamiliar meds. Looking at the scientific literature on the 'top' meds, there is very little in the way of controlled trials of the various medications listed. Yes, there are lots of web entries about the experience of using things like nystatin and other potentially-related meds in autism but nothing spectacular in terms of clinical trials at the current time.

A similar story for the anti-virals, despite some initial evidence of why they might work in some cases. IVIG has been the subject of quite a bit of research related to autism (as well as oral immunoglobulin with results here and here). Here the research is best described as 'equivocal'.

Interestingly also that co-morbidities of autism seem to have been a target of these top meds, particularly a role for immune and gastrointestinal functions related to autism. I am not going to make too much more of this data for now. Only to say that if any willing organisation has a few millions pounds/dollars to spare, and would like to investigate a few potential intervention 'targets', perhaps look no further.

Autism and epilepsy

I must warn readers that this is probably not the happiest of posts that you will read on this blog. In this post I intend to talk about mortality and a few other not-so-nice things. If you've had a bit of a bad day and really don't want to make it any worse, I won't be offended if you click away now. Might I suggest this link as an alternative?

To quote from the abstract of a recent article appearing in the Journal of Child Neurology: "..there is a higher than expected rate of mortality in individuals with autism and epilepsy than autism alone". Similar studies have confirmed this grim finding related to autism and one of its more frequent co-morbidities. Most people would find it very difficult to say that there are any 'positives' related to having epilepsy or other seizure-type disorder on quality of life either when co-morbid to autism or stand-alone.

Even looking on the Epilepsy Society website there is little to alter such an opinion. Yes, epilepsy can be managed, and managed quite well by things like medication, and yes for the vast majority of people it is not a consistent, on-going problem.

The only thing is that unfortunately people do perish following conditions like status epilepticus and even the anti-epilepsy medications are not without their potential side-effects and developmental effects. [At this point I give a disclaimer on not stopping or altering any medication without seeking medical advice].

Epilepsy and seizure-type disorders have long been associated with autism. The figures are slightly variable as to the extent of the overlap but generally range between 5-40% of people with an autism spectrum condition presenting also with epilepsy at some point in their life. There are lots of different types of epilepsy / seizure-type disorders and quite a few other conditions carrying a higher rate of epilepsy.

With regards to co-morbidity with autism, no-one really knows why there is a heightened risk of epilepsy. There is a correlation, of sorts, between various genetic syndromes presenting with autistic features and epilepsy which could indicate some genetic involvement.

Time of onset of epilepsy in autism might also suggest some variable effect from either environmental or maturational processes. I previously blogged about puberty and autism and a potential relationship there. Other authors have described behavioural regression as being a key correlate with seizure activity onset. I am sure that there are other potential correlates between autism and epilepsy; this article discusses a link between epilepsy and encephalitis following on from the suggestion of a link between autism and viral infection.

Management of epilepsy usually involves medication (as previously discussed) but in some cases can also include things like diet and supplementation of other compounds for certain types of epilepsy. The same kind of diet (ketogenic) has also been suggested for autism without epilepsy; I might come back to this in a future post.

Other, more radical ideas such as the application of vagal nerve stimulation, used for the treatment of epilepsy, to autism remain under investigation.

I apologise again to readers for the grimness of this post. I do stress that epilepsy co-morbid to autism is not an automatic pathway to early mortality - not by any means at all. With the right medicines management, epilepsy can be managed, and managed well.

I suppose the take home message is that epilepsy, in any one of it's many guises, can be common to autism and because of its health implications, really deserves appropriate screening in at-risk groups. Making it a research priority might also be a good idea.

Its rude to point...

Children have an uncanny nack of picking out details and saying the most embarrassing things sometimes - a lack of 'theory of mind' perhaps? Some examples: moustache - "what's that hairy thing on that man's face?", glasses or spectacles - "why is that woman wearing windows?", the list can go on.

In most of these examples, such questions would probably be followed by a very definite pointing of the index finger towards said object/thing/person, just to make sure that everyone knows what is being described and where it is (for maximum embarrassment impact). The usual response is an awkward smile from the parent / caregiver and a gesture or action for the child to stop pointing (the 'inner child' of many adults is though, also having a secret giggle about such childhood observations no doubt). Pointing in these case is socially undesirable.

A lot has been made about pointing - it's various manifestations and uses - with regards to autism. I was interested in this post as to how pointing is potentially related to autism and the link to things like joint attention. What to do about a failure to point, is also of interest. I might add that I won't be discussing pointing with regards to Facilitated Communication in this post.

The first time I came across pointing as being related to autism was upon reading the ADI-R and ADOS instruments used for assessing autism. In ADOS, pointing forms part of various sections of the schedule including the first-stage module 1 assessment (administered to those with no speech) as an indication of language and communication. In the ADI-R 'pointing to express interest' as part of spontaneous communication of interest is also listed; importantly also including coordinated eye gaze. What this suggests is that pointing, or a lack of it, seems to be quite important during the assessment of autism spectrum conditions. Indeed some authors suggest that it is one of the key markers of symptom onset and potentially tied into regression.

I would add at this point out that there are various forms of pointing (not the construction type) related to what meaning is trying to be conveyed. Pointing to indicate interest - "look over there" is known as proto-declarative. Proto-imperative pointing is the "I want that" form of pointing. Pointing therefore, is a means to an end of direct interest but also serves as an 'attention-grabber' for needs and requirement.

The research on pointing and autism is quite bountiful in terms of communication and use of gestures. What it appears to suggest, specifically with regards to autism, is that proto-declarative pointing, the 'social pointing', seems to be the area of most interest.

I suppose this is to be expected in autism given the emphasis (rightly or wrongly) on the social features being paramount. The thing about proto-declarative pointing also is that it bridges communication and social interaction areas of current diagnostic manuals and is perhaps even the prototype behaviour of the proposals on social affect in DSM V (the words 'pointing' though not appearing in the manual revisions so far). I stress the social and communication domains together because pointing in children with autism seems to differ from pointing in children with a language delay.

The question of what to do about it has also been examined. It appears that you can teach a person to point - at least as part of a joint attention programme. Going back to my point above, the question is whether you are teaching pointing as merely a communicative tool or truly as a social-communicative tool.

Early infant feeding practices

Feeding babies, or more precisely, what to feed babies and young infants has been quite a long-running debate.
I don't think anyone would really argue with the fact that breast milk is nature's way of providing everything a young infant needs to grow in those tentative early days, weeks and months, packaged up at just the right temperature with no late-night sterilisation of bottles or teats required. Perfect also for the groggy husband who grumbles to himself as he patters downstairs at 3am to do his paternal preparation duties.
Whether or not new mums want to, or can use this 'natural' option is another matter entirely.
I approach this subject with caution being, as I am, the wrong gender to make such a choice. I do however follow quite closely the various guidelines and debates on 'breast vs. bottle' and 'when to start weaning' as a matter of professional interest. Not least because of the link between very early weaning and increased risk of coeliac disease. Not least also because of the possible link between early feeding issues and autism as described in my posts here and here.
In recent times the question of 'when to start weaning' has been the source of some debate. One of the main issues is the age at which infants should start eating solid food and the conflicting advice being offered in this area. Here in the UK the official guidance is very clear: recommending exclusively breast / bottle feeding (or combined) for the first 6 months of life and weaning on to solid foods thereafter. This advice is backed up by the World Health Organisation (WHO) no less.
That would be all well and good if a report from the European Union hadn't mixed things up a little by suggesting that for some children, earlier weaning (from about 4 months onwards) might be OK and possibly advantageous. Added to that an article appearing in BMJ questioning our 6-month rule and again suggesting that there may be a case for revising guidance (backed up by the British Dietetic Association, BDA).
A case perhaps of the head saying do one thing, and the arms and fingers perhaps wanting to do something else.
I have thought about this issue quite a bit. Working backwards from the notion that all babies are different; have different constitutions, raised under different environments, raised by different parents one could argue that the n=1 principle might apply. Thinking also to what happens when research and guidelines get too generalised to a population there may be perhaps some scope for taking on board some of the suggested revisions at least for some infants (although please do not base your decision on my analysis, speak to your physician and healthcare provider about this).
The idea also that there is a window of opportunity for developing tolerance to foods is also an interesting concept. Readers may know of my interest in all things diet and gut-related, and in particular, the concept of the hyperpermeable gut (leaky gut) in connection to lots of things. One of the most interesting parts of how gut hyperpermeability might tie into weaning patterns is trying to ascertain when the gut is 'unpermeable' enough to tolerate food without permeability potentially leading to allergy or intolerance. The infant gut is quite permeable on purpose because: (a) it is still maturing, and (b) it has to allow the passage and absorption of all those goodies in breast milk (and formula) into the CNS, some of which are quite large molecules. Gut hyperpermeability may also have a role to play in producing that lovely soporific effect that babies love following their milk from all those warming opioid peptides and how this may relate to neural growth.
I will be interested to see where this debate goes eventually and how it may (may not) influence guidance and practice.

Registering research: present Sir.

Another quick post just to drop in a few interesting links.
The title of the post refers to the increasingly important use of clinical trial registries in research. Our ScanBrit trial looking at the use of gluten- and casein-free diets for children with autism was registered with the US National Institutes of Health (NIH) trial registry - ClinicalTrials.gov.
The reason being that many scientific journals nowadays make clinical trial registry a pre-requisite before even entertaining the thought of publishing a paper. It also allows a degree of transparency of trial protocol, outcomes, and even posting of results for everyone to see.
There are other trial registries such as this one from the World Health Organisation (WHO) - the International Clinical Trials Registry Platform.
All these registries are searchable and often provide a wealth of information about studies recruiting, underway or completed on a specific topic. I am particularly interested in this and this trial related to autism when they eventually report.
A new clinical trial register has also joined the party - the EU Clinical Trials Register. As part of a directive from the European Medicines Agency there is now a commitment to further transparency in European-produced research (I don't suppose the fact that everyone was registering with the NIH or WHO had anything to do with it!)
I would encourage readers to use these valuable resources. They are all open-access and really do make science accessible and provide an important window into the inner workings of evidence-based practice.

Diagnostic substitution and autism prevalence

I don't know if it is still part of the autism debate, but I remember a while back there was a lot of interest in whether or not diagnostic substitution was a factor in the increasing prevalence of autism spectrum conditions.
The argument went something like this: 20-odd years ago, children were diagnosed with intellectual disability (ID) even though they may have presented with either autism or autistic features. In more recent times, said children who would have been diagnosed with ID would now be classified as having autism or an autism spectrum condition as a primary diagnosis. The shift is due to either a greater awareness of autism, changing diagnostic criteria for autism or clinicians getting better and more accurately diagnosing autism.
I have to say that I always had mixed feelings about this argument. Mixed feelings because this would suggest that despite autism being included in the diagnostic manuals for quite a few years, clinicians were basically, pardon my language, either crap at diagnosing it during the 80s and 90s (perhaps into the noughties) or were so swayed by the diagnostic 'fads' of the time that they did not diagnose it. I know a few clinicians and have to say that I can't buy this being such a universal phenomena. If anything else what does this tell us about the criteria for autism being used?
On the other side of argument is the various research which has more than hinted at a reduction of ID diagnoses corresponding with an increase in autism diagnoses. It is not just in the US that this trend has been noted, but also in Canada. The 'Californa data' has been pivotal in this argument / debate.
The common consensus is that diagnostic substitution has probably contributed to the increase in autism prevalence (at least in the USA and Canada); as a percentage roughly ranging from anywhere between a quarter to about a half of cases.
I say all this because an interesting paper has emerged on PLoS ONE titled: Autism and intellectual disability are differentially related to sociodemographic background at birth. The full-text of the paper is happily available here.
You are right - the paper does not, from the title, seem like it is going to deal with the issue of diagnostic substitution, but look further, particularly at Figure 1 and there are some interesting numbers to crunch.
I think it is worthwhile stating at this point that this paper looked at Australian trends in diagnosis so we cannot really say too much other than this is what happened to Australian trends. I have talked about Australian prevalence trends in a previous post.
From Figure 1: mild-moderate ID diagnostic prevalence (without autism) by birth year peaked in 1992 and by 1999 was quite a few orders lower. Severe ID (without autism) by contrast seemed to show a quite unstable pattern throughout the whole period of study (1984-1999) with lots of peaks and troughs.
Autism (with or without ID) grew in prevalence up to 1996. At that point autism and no ID seemed to drop off (I wonder if this was a change point where Asperger syndrome became more 'fashionable' a diagnostic label to use?) whilst autism with ID continued its steady climb upwards.
The conclusion: well it is a complicated picture. It does appear as though there are some 'opposite' trends in ID and autism diagnoses but the relationship is not completely straight forward.
This is of course just my own interpretation of the figures; complete with my own biases et al. Others have their own take on the data and results. I would encourage readers to take a look at the figures themselves and draw their own conclusions on this very complicated part of the autism debate.

Bacteria, PANDAS and anti-psychotics

I don't know why but I seem to be repeatedly seeking out the most spine-tingling things to blog about. First it was gut parasites and fecal transplantation and now I am moving on to parasites "controlling" the mind. I really do need to cut out the horror flicks and drink more relaxing cups of tea.

This post stems from a programme broadcast on BBC Radio 4 titled: Voodoo wasps and Zombie worms. I attach a link to the programme here (bearing in mind that this link might change to something else in the not too distant future when a new programme uses the same link - so don't be surprised if I just linked to 'butter vs. margarine: the debate' or something like that).

The crux of the programme is that parasitic organisms might have the ability to affect the mind as well as the body. The programme uses the example of Toxoplasma gondii and how the bacteria might affect rats to relinquish their fear of cats, thus making them easier prey, and with it aiding the transfer of the bacteria (bacterium?) from rat to cat. T gondii (to those in the know) is then discussed in relation to schizophrenia, the manufacture of dopamine and just possibly, how some of the anti-psychotics might stop T gondii from replicating in the brain. This article from Faith Dickerson and colleagues sums it up.

I don't know about you but all that just gave me a chill down my spine. Real Sci-Fi stuff.

I had heard about T gondii before in relation to toxoplasmosis and why pregnant women should not handle used kitty litter. Those who remember that interesting film Trainspotting might also remember the link between one of the protagonists and death by toxoplasmosis following IV drug use.

The notion that bacterial or viral agents can conceivably affect the mind and behaviour has been mentioned in relation to lots of things, including autism spectrum conditions; think encephalitis for example. I even found this paper with onset of autistic symptoms and a possible temporal association post-malaria (remembering the adage 'correlation does not imply causation').

I say autism, but one of the most interesting areas relates to something called PANDAS. Before you start questioning why I am talking about those lovable, bamboo-eating bears, I will stop you and say I am not. PANDAS stands for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections.

PANDAS is a controversial concept. There are quite a few reports on the web talking about PANDAS and how it affected people. The suggestion is that a particular type of strep infection for one reason or another starts to manifest behavioural symptoms quite rapidly, possibly following a mechanism to that described in Sydenham's chorea. The basal ganglia is a target in PANDAS - as it is in autism also.

I find this whole area absolutely fascinating. The same kind of fascinating when studies suggest for example, that gut bacteria can affect behaviour. What it suggests is that we may think that 'we' control our actions and behaviour, but the question is, to what extent?

Coming back to autism, and assuming that there may be a specific 'type' of autism tied into such a mechanism, what are the possible implications? Well for one thing, it suggests that presentation of somatic conditions (moderated by viral or bacterial infection) in autism might be doing more than just affecting the physical body.
Kanner  talked about strep infection in one of his original cases - 'Alfred' - who was frequently ill with 'chickenpox, strep and impetigo'. Yes it could be coincidence; maybe, maybe not. Impetigo is something that I have been interested in for quite a while now - here and here - in relation to autism (or more accurately Asperger syndrome). I don't think I can make any link on the basis of the available data, but it is still interesting.

There might also be some implication for treatment of said infections and how it impacts on behavioural presentation. Remember Sandler and colleagues who reported on anti-microbial use impacting on the presentation of autistic behaviour? That combined with the suggestion that some of the anti-psychotic medications may impact on parasitic infections opens up a whole new world of possibilities.

In the words of Nick Ross ex-presenter from Crimewatch - "don't have nightmares".

Autism-friendly and other advances

Is the world a better place for people with autism now compared to say, 20 or 30 years ago?
Think back 30 years to 1981. 'Raiders of the Lost Ark' - "bad dates", 'For Your Eyes Only',  and Shakin' Stevens (the Welsh Elvis!). It was 2 years after Lorna Wing and Judy Gould published their paper on the epidemiology of autism and the same year that Lorna Wing popularised Asperger syndrome (it would take over 10 years to make it into the diagnostic manuals).
I ask the question following a few interesting stories that have appeared in various media.
The BBC carried a report recently on the subject of an 'Autism-friendly city'. I have seen similar reports using the words 'autism-friendly'; where for example the top 10 autism-friendly US cities have been recently posted by Autism Speaks and places like cinemas offer autism-friendly screenings.
I think most people would like the idea of something being 'autism-friendly'.
In these times of equality and diversity, there have been huge advances, socially, culturally and legally in making our world a more inclusive place for everyone.
In the UK with the onset of the Disability Discrimination Act in 1995 (replaced by the Equality Act in 2010) we saw things like statutory rights in terms of access to buildings for people with physical disabilities and making various reading material available in larger print. Such measures have been fundamental in shaping our infrastructure, policies and opinions on ability and disability. The only real surprise is that it took so long for such legislation to become enacted - people in wheelchairs or who are visually-impaired did not just suddenly 'spring up' in the 1990s.
The introduction of the UK Autism Act in 2009 represents a similar step forward for autism; the National Autistic Society and partners are to be commended for their efforts in getting this bill enacted. The Act is probably the only piece of law specific to a 'condition' in the UK and sets important goals for Government in terms of recognising the needs of adults with autism. The Act focused on adults with autism simply because there was a gap after children's services ended - some might describe the gap as more like a void.
Alongside the increasing awareness of autism, the die seems to have been cast. Assuming also that the NICE guidelines due for autism (adults and children) are well described and implemented in the not-too-distant future, I hope I don't speak out of turn when I say that one really gets the feeling that changes are slowly being made to benefit people with autism and their families. The IACC on the other side of the Pond is another very positive step forward.
Everything is not universally 'rosy' with the world for all people with autism. There are still some harrowing stories of real hardship in relation to employment, financial independence and basic equality. Periodically more extreme events are reported potentially as a result of stress. One must also be mindful that there are quite a few people with autism who are perfectly happy to exist with themselves as they are and are not necessarily seeking such great social inclusion (as exemplified by direct person-to-person contact) - see this link on autism and 'Second Life' for an example. In these times of austerity, there may yet also be a sting in the tail for many people following proposed changes which are being vehemently opposed.
Perhaps in another 30 years I can come back and ask the same question: is the world a better place for people with autism?

The King's speech - celebrities and science

Yet another 'other musings' post but I think you will like this one.
Most people will know the actor Colin Firth either from his recent film success portraying King George VI (QE II's father) in The King's Speech or failing that from his other roles including 'that pond scene' a few years back as Mr Darcy in the BBC adaptation of Pride & Prejudice.
But did you know that he recently co-authored a research paper published last week on Brain structure and political orientation?
I have to say that when I first heard this I thought it was a delayed April Fool's joke. But no, really, he is a co-author on this paper and apparently has some interest in this area of research. Some of the background and links has been blogged about here.
Kudos to Colin for becoming involved in science. Who knows.. a new potential film topic to add to his repertoire.

Is autism the same all over the world?

Modern human beings, homo sapiens sapiens. A term which unites us all because it reflects us all.

Move however further across the biological and ethnic sub-categorisations of homo sapiens sapiens and we slowly begin to differentiate ourselves from each other on the basis of gender and race. Further across, and including some societal, cultural and individual 'personality' differences mixed in with experience and environment, and we go from all being one and the same to all being uniquely different.

You could probably apply the same logic to anything. Start with a generic term, say 'autism spectrum condition' as described in the proposed DSM-V manual; move across the various categorisations, say sub-diagnosis, then move further across societal and individual differences et al and hey presto, unique and one-of-a-kind.

The reason for such a grandiose beginning to this entry is to show how similarity and differences can often be influenced by the level of description and semantics used.

Autism is defined by DSM and ICD diagnostic listings. This means that wherever in the world a child or adult is diagnosed, theoretically they should be similar in terms of the presentation of core symptoms fulfilling the diagnostic criteria. But does this guarantee that presentation and pathology of autism is the same the world over?

I was brought to this question by an article appearing recently suggestive that Israeli children with autism do not appear to show the same trend of macrocephaly as has been described in other studies from other parts of the world. The authors of the Israeli study attribute this difference to 'a different genetic background'. I know macrocephaly is not a core trait of autism but it got me thinking. What other research has been done on the similarities/differences between autism populations around the world, and in particular on the presentation of symptoms?

Well cryptically quite a bit and not very much at all. I will explain.

Ethnicity, and the other societal factors associated with ethnicity, has been quite extensively studied in autism. We know that although not uniform, certain ethnic groups not indigenous to a specific country tended to be under-represented in cases of autism. Take for example this study from the Netherlands which suggested if you were White European (by both parents), you were more likely to diagnosed with autism than if one or both of your parents were non-European. This tends to follow similar trends from research outside of autism.

An ethnic reason, genetic reason, environmental reason or a cultural reason?

There is also a suggestion that 'risk' of autism may be greater where mums are, for example, born in parts of Asia when compared to indigenous Australian parents with European heritage according to this study; following on from more recent suggestions of increased risk of autism in Somali populations.

Fine, but what about those who already have been diagnosed?

Well this is where the research dries up a little. There is a little about presentation of autism in various countries outside of the main research-bearing nations; so we have papers from Saudi Arabia for example describing autism in Saudis. There are no doubt other examples from other countries.

Very little has however been produced in the way of comparing country against country or ethnicity against ethnicity on symptom presentation. Those few studies that have been performed on this issue suggests some minor differences (language?) but nothing concrete, and tend to be plagued by methodological issues such as low participant numbers for example.

Would it be so difficult to look at 500 people with various autism diagnoses from each of the 5 (inhabited) continents (n=2500) and compare and contrast, using the array of questionnaires, schedules and observation tools on offer in autism research, their core and peripheral symptoms? Too much...?

If they were all (roughly) the same, fine - we have confidence that autism is (roughly) globally the same. If they were different though, what would that suggest?

Self-injurious behaviour and autism

Self-injury, auto-aggression, self-mutilation call it what you will, can be a relatively frequent occurrence in children with autism spectrum conditions, as in other developmental and intellectual conditions. The Research Autism entry on self-injurious behaviour (SIB) [behavior to our US cousins] suggests that such behaviour can take many forms; ranging from head-banging to hair pulling to eye gouging.

Having only witnessed such behaviour once or twice during my research contact with children with autism, I can testify how unnerving such behaviour can be and how the sight of a child in particular, hurting themselves really can be quite distressing. I cannot begin to imagine how a mother or father (or sibling) feels when they see this type of behaviour from their child/brother/sister over and over again. Might it be a significant contributor to stress?

In this post, I want to look at some of the research and dialogue on SIB and autism; in particular, looking at the antecedents, outcome and 'management/coping' strategies. I am focusing on 'self-aggression' rather than aggression directed towards others in this post. I stress as always that I am not offering any advice on SIB management, merely describing what the literature seems to be telling us.

I think most parents will have seen some degree of SIB in their child at some point in their development, irrespective of the presence of autism. Frustration and irritability are generally seen as the main precursors - why can't I have that toy, food, DVD [insert other item/thing/concept here] coupled with an immaturity in expressing such emotions through social or communicative mediums.

What this tells us is that certain degrees, or episodes of SIB are a part of growing up. Potentially also it gives us a developmental clue as to why such behaviours might be seen in autism, given that autism is not a failure to develop but rather a slightly different course of development. It also suggests that there may be many different routes to SIB and that it is the frequency and extensiveness of SIB presentation that perhaps distinguishes such pathology in autism or other conditions.

So what causes SIB in autism? Well, how long have you got. The Autism Research Institute (ARI) offer quite a comprehensive list of potential reasons for, and antecedents to, SIB and autism (available here). Outside of possible genetic explanations, there are several interesting issues raised, a few of which I will touch upon here.

Severity of autism is a prominent risk factor for SIB. More severe cases of autism are more likely linked to things like greater dependency on caregivers and less frequent acquisition of functional daily living skills - in short, less day-to-day independence. Knowing what happens to children when, for example, they enter their 'terrible twos' it is perhaps understandable that for a child with severe autism, such a lack of 'independence' could be a significant issue.

Communication issues also tie into increasing severity. Where for example, a child has only limited verbal or non-verbal skills the question needs to be asked, how does that child communicate wishes, preferences and intentions?

Communication, whether verbal or non-verbal, is therefore perhaps an important issue for SIB. Place yourself in a child's shoes: suppose you came back to your room and were looking for your favourite toy or book and realised it was not where you last put it. How would you communicate your query / desire / displeasure if verbal language was absent? It will be interesting to see what becomes experimentally of the recent discussions on the use of assistive technology such as the various Apple equipment for communication in autism and further towards SIB.

The sensory issues associated with autism are also a potential point of interest to SIB. I have blogged previously about hearing and autism and the issue of hyperacuity. Where people with autism have been able to describe such experiences, on some occasions it sounds very much to me as though such hyperacuity might fall somewhere between irritation and downright pain. Again same scenario as above - how do you communicate those feelings without language or with limited language?

Since we are talking about pain, it is perhaps also worth mentioning here about a possible relationship between physical discomfort and SIB. Communication again - how does a non-verbal person communicate physical discomfort or pain? Toothache for example. You might try and pull the tooth out yourself. Those wisdom teeth pushing through - how do you tell someone they hurt? Headache (whether tension-type, migraine or other) is another example and perhaps more complicated given that there is no objective way of determining a headache - at least outside of a hospital or laboratory. Bang your head perhaps to try and make it go away or indicate that pain in your head?

Other physical discomforts have been discussed in the literature also. Functional bowel problems such as constipation have been linked to incidence of SIB (and reduced when treated accordingly). The point is that the many complicated issues potentially attached to autism make it a likely candidate for the presentation of SIB.

So what to do about SIB?

Here I think we need to be very careful. The natural reaction might be just to try and treat the SIB as a 'challenging behaviour'. But wait a minute. What if SIB is not just another challenging behaviour - what if it is a means of communication?

This is where the detective work starts. Looking at things like the onset of SIB, the frequency and the duration. If SIB starts when a child changes school for example or when they reach that funny little point in life called puberty, is it a case of reaching for the anti-challenging behaviour meds straight away?

I am not saying that all SIB should be just passed over as a communication issue or a sensory issue when it comes to possible treatment options because, whilst being impractical for the child and their parents, this may also put the child at some significant risk of hurting themselves permanently. The suggestions are to look closely first and see what is around - devise a checklist of possibilities (teeth, head, tummy, cold, fever, etc)  and, as far as possible, rule out the simplest explanations first before moving on to the more complex issue of environment (lights, sounds, that singer on the TV with the screechy voice, etc) and finally ending on other potential causation.

I did intend to talk about the possible biological implications of SIB related to things like reduced pain sensitivity and that wonderful opioid-excess hypothesis and the use of naltrexone. I have decided not to on this occasions because of the risk of 'medicalising' SIB too quickly.

IACC and summary of advances in autism

Another quick post since we are on the theme of research and intervention to end the working week. The Autism Speaks blog carried a link yesterday to the IACC summary of advances for 2010. The IACC (Interagency Autism Coordinating Committee to us Brits) seem to be really starting to bring things together with regards to autism research and practice under the US Federal Government banner.
It got me wondering: what is the UK or European equivalent? Do we have an equivalent? If not, why?

Intervention and autism

This week's posts seem to have been dominated by a common theme: intervention.

We had the Pediatrics review of interventions for autism and then the evidence-based practice posting yesterday. Don't get me wrong, I am not obsessed with intervention and autism. It has purely been chance the way things work out or, in statistical terms, a type 1 error on the significant relationship between blogging entries and intervention. Anyway, onwards.

'Intervention' can, like many things in life, have several different meanings depending on the context in which it is used and the person who uses it. It can mean acting to mediate in a dispute for example; or interfering in specific affairs. From a healthcare point of view, intervention is generally read to mean 'administering something to improve a condition, disease, illness or injury'. Intervention is generally seen as a positive thing which on the whole is welcomed.

I was drawn to writing this entry following my previous posts on the use of evidence-based practice in autism and the involvement of NICE in formulating guidelines for autism. I do also try to keep up with all the latest research on intervention (and other things) in autism as part of my job, so it is also of some interest to me professionally. I must stress that when I use the word 'intervention' in this post, I am covering the whole spectrum of interventions (education, behaviour and biomedical) used with the aim of either ameliorating specific symptoms or improving quality of life.

There are several different opinions about the use of interventions for autism around. Many opinions are strongly held, and strongly argued on the web and via other media including the research literature. My quite unscientific survey suggests opinions circle around those who: (a) are vehemently opposed to any intervention for 'autism spectrum conditions' (I have stressed 'autism spectrum conditions' because by using this term I refer to the entire autism spectrum and all its manifestations); (b) are the polar opposite and actively seek as much intervention as possible for autism; (c) are somewhere in-between.

When looking at the number of people falling into these categories, I assume it is something like a normal distribution curve - most people fall into category (c) and fewer people populate the peripheries. I might add that people's opinions of intervention are potentially also not fixed; so at different points in time, they may move in and out of the various categories of opinion. Why is there such diversity in opinion on the use of intervention for autism?

Whilst I can't offer a definitive answer to this, I would guess that there is more than one factor at work.

(i) Diagnosis and heterogeneity is one suggestion. When we say autism or autism spectrum condition, we are not talking about one condition, state, etc but many presentations and manifestations. Within this spectrum we have people who can talk, communicate, live independent lives; indeed many who are extremely articulate (more so than some of the so-called neurotypicals). We also, within this spectrum, have people who have never, and probably will never speak, who will require constant support for the basic essentials of living and will, in all probability, never live truly independent lives. The often profound 'disability' present puts such a group of people at significantly greater risk of illness or early mortality (whether on the basis of autism or additional co-morbidity). I have not even touched upon issues such as 'wandering' and autism which is being discussed more and more these days. Different presentation and level of severity of presentation is key. Remember my post on autism and n=1?

(ii) 'Perception' of autism is another potential factor. Ask a 'professional' what autism is, and most probably (unless they are a parent of a person with autism or a person with autism themselves) they will list the symptoms in clinical fashion - 'autism is this, this and this'. Normally such a description would concentrate first on 'deficits' - the triad (dyad?) of impairments maybe. I hold my hand up here because that is exactly what I tend to do - just look at one of my presentations. Ask a person with autism - high-functioning autism or Asperger syndrome - or even some parents of people with autism, and the answer might be slightly different. They may talk about the difficulties of autism of course, but perhaps in some cases, it might be a little more positive - 'he is very good with computers' or 'I am very reliable and conscientious' for example. Perceptions of autism as a condition, illness, etc are balanced against perceptions of 'difference' (see for example this paper analysing neurodiversity and autism).

(iii) As previously blogged about, the fact that the evidence base for intervention generically in autism is still quite shaky is another potentially interfering factor. Show me an intervention suggested for autism and given enough time, I am sure that I can find some fault with it and the evidence put forward to support it or some contrary indication. Take my own area of interest - the use of a gluten- and casein-free diet. I could say that the studies on such an intervention are so far not conclusive on whether diet works or not (indeed whether it is gluten and/or casein or something else like carbohydrates), the studies are poorly controlled, they don't say whether diet affects autism or some other co-morbidity, etc, etc (steady on!). With this level of 'uncertainty', interventions for autism can easily be questioned and often are.

(iv) 'Who suggests intervention' is another bone of contention. Knowing all the controversies past and present in autism, it is likely that some people, perhaps with an affiliation to a certain idea or hypothesis, are more or less likely to be labelled as a 'credible' or 'less credible' a source when it comes to promoting a specific intervention. One of my first posts (all the way back last month) was titled: Should I mention gastrointestinal symptoms in autism? Catch my drift?

There are other factors in this equation but I have neither the time nor inclination to list them all here. Suffice to say that there are lots of different issues determining the various views on intervention and autism. Where does this lead us then? Well I don't think that there is ever going to be a true consensus on the use of 'intervention' for autism spectrum conditions. There is just too much variability and opinion on the matter. Indeed, with the potential onset of DSM-V and the proposal to remove Asperger syndrome as a distinct category in place of 'autism spectrum disorder', I foresee that discussion on 'intervention' will intensify as the years go on.

I do however think that in this era of 'choice' all options should be kept open. For a young child with autism, I believe that parents know what's best for their child. Assuming that they are able to make an informed decision about intervention A or intervention B (or any combination), etc and using the guidance available to them on efficacy and safety, they should be allowed to make a choice on intervention (or not). Professionals, I might add, can do much to aid this process ('aid' being the important word).

For a young / older adult with autism, things change slightly. In the UK we have something called Gillick competency which basically is a legal test of whether or not someone can make decisions about their health and any treatment. When someone approaches (exceeds) such a test and/or chronological age allows, decisions on things like intervention alter, and decisions shift to the person themselves. See the Charter of Rights for Persons with Autism by Autisme Europe for more information

Finally, intervention is about making a positive impact on a person and their life. When it does work, great... encourage it and study it - find out why it works, what areas it worked on, the cost-benefit ratio and who else it potentially might also work for. Where it doesn't work.. don't be afraid to stop intervention, don't be afraid to say 'it didn't work' and don't be afraid to look at other alternatives if so inclined.