Thursday, 30 June 2011

Tick, tick, tick...boom

Despite the very dramatic title of this post, I am not going to be discussing explosives nor even the Will Smith (not forgetting Jazzy Jeff) song which carried such lyrical swagger, but rather a few things related to the small but mighty tick (and no, not that tick either). For those of a squeamish disposition who prefer not to see creepy-crawlies and their various effects on body parts, I would perhaps suggest not clicking on this link (or even worse this link) which describes, in quite some detail, how the tick and its bite is potentially linked to a condition called Lyme disease.

For those who didn't click on the link but are still curious, Lyme disease is an inflammatory disease which occurs when a tick harbouring the bacteria Borrelia burgdorferi bites and transmits said bacteria to humans. The name Lyme comes from the place Lyme, USA where an outbreak of the disease leading to a cluster of cases of juvenile arthritis led to the first comprehensive description. The symptoms can include things like lethargy, fever, headaches, muscle pain and in more serious cases, joint inflammation and changes to behaviour. This last symptom relating to behaviour is a little non-descript although some people have speculated that this could include autistic-like behaviours. Bacteria affecting behaviour also conjours up some interesting links with the many and varied posts made on this blog relating to how external organisms might be able to affect our presented behaviour; but I digress.

Looking on the web, there is quite a lot of interest in a possible connection between Lyme disease and lots of different conditions. Chronic, persistent Lyme disease has found some overlap with conditions such as Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS/ME) and fibromyalgia (FM) given the described similarities in symptoms. Indeed, there is some evidence that Lyme disease may co-exist alongside conditions such as FM, although a universally causative relationship has not yet been established. As mentioned, a particular form of arthritis is one of the more serious symptoms associated with Lyme disease but there are a variety of other effects linked to the nervous system for example.

Autism has also been speculatively linked to Lyme disease, although I would perhaps emphasise the 'speculatively' side of things. The evidence for an association is sparse to say the least, and currently non-existent (at least in PubMed listed journals) in terms of data on things like serological co-morbidity and any potential effects on autistic symptoms following infection or treatment for Lyme disease. That being said, the prescribed treatment schedule for Lyme disease utilising antibiotics such as the tetracyclines has found some initial favour in the management of symptoms in autism-linked conditions such as Fragile X syndrome albeit tied into potential effects outside of antimicrobial activity.

Although the data is sparse, there is some common sense reason for looking at the potential involvement of Lyme disease in some cases of autism. As per my comments in previous posts, autism is not protective of developing other conditions/diseases/infections, so one could perhaps see that a child with autism walking in woodland with their parents would be at equal risk of being bitten by a tick as everyone else. Whether or not there would be some increased likelihood of being bitten is not known. Gestational Lyme disease, diagnosed on the presence of anti-Borrelia burgdorferi antibodies, can be associated with adverse neonatal and post-natal outcomes for the infant. This, despite the fact, that pregnancy might actually provide some protective immunological effects. Some of the adverse outcomes described by Nadal and colleagues show some possible connection to autism (hyperbilirubinaemia, hypotonia, macrocephaly) but it is altogether a different thing to say that such outcomes related to autism might be caused by secondary Lyme disease. Further research would perhaps be required.

I appreciate that for some people thinking about ticks and what they could do is spine-tingling stuff. Suffice to say that the risk of getting a tick bite is pretty low assuming that a few precautions are taken, not least keeping away from tick hotspots (long grass off the beaten track where deer may roam).

Wednesday, 29 June 2011

The man who mistook his wife for a hat

There are a few constants in the world of undergraduate psychology. Milgram's classic obedience experiment, the magic number 7 (plus or minus 2) and Oliver Sacks' book 'The man who mistook his wife for a hat'. It is on this latter point that I make this very short post following an interesting TV programme last night on BBC1.

The programme 'Imagine' with Alan Yentob (he of the BBC) took an up-close look at Dr Oliver Sacks, the man, the neurologist, the patient. It was indeed a revelation in yesterday's programme to learn that Sacks, who famously describes and discusses various 'unusual' conditions including his pioneering accounts depicted in the film 'Awakenings', is himself 'face blind' or suffering from the more technical term prosopagnosia.

There are quite a few reviews of the programme today, and for those lucky UK readers, a link to the BBC iPlayer to watch the whole programme again. I would strongly recommend the programme if you can see it; if not only because the man who popularised face blindness, himself provides an exquisite account of his own struggles with recognising faces.

I leave with a final link to some advancement in the area of prosopagnosia from optician Ian Jordan which might indeed be relevant to autism (at least in some cases).

Tuesday, 28 June 2011

Asthma and autism

I recently attended a conference which gave me great hope. Hope that our contemporary model of autism and quite a few other behaviourally-defined conditions as somehow being 'stand-alone' entities is shifting and adapting as all good models should. Incorporating the fact that autism, whilst being an important diagnosis, does not seem to confer any protection against developing or presenting alongside other more somatic conditions.

I have discussed this issue on several other posts relating to things like diabetes, overweight and obesity, etc. The crux of the problem seems to be that a diagnosis of autism might be a barrier to receiving screening or treatment for these other conditions if co-morbid, as it also appears to be the case for conditions like schizophrenia for example. In this post I turn my attention to another big health issue for many people, asthma, and its links (or not) to autism following on from my recent post on allergy and intolerance.

Conceptually at least, asthma and autism share some commonality. Both are what I would term a 'cloud' condition. That is, you can see the cloud in the sky and so know it is there, but determining where the edges of  the cloud are, where the cloud starts and finishes, takes a little bit more of an effort particularly when there are lots of clouds in the sky. So it is with autism. Asthma is a bit of a catch-all terms used to describe various symptoms such as wheezing, breathlessness and coughing; most people will have at some point in their lives have presented with one or more of these symptoms for one reason or another although it is the frequency and timing of symptoms that seems to be important in diagnosis. Definitions of asthma are abound but very few (if any) places provide specific guidance on how to categorise severity or frequency as part of asthma descriptive guidelines.

Although a chronic inflammatory condition associated with acute phases, when it comes to the question of what causes asthma and how does the disease manifest physically, there are still quite a few gaps in the evidence base. Asthma UK have some excellent information about all things asthma here. It is known that inflammatory processes are connected to airway remodeling as a result of increased mucus secretion, a thickening of the airway membrane and enlargement of the smooth muscle mass. In cases of fatality which unfortunately there are in asthma, the finding of a mucus plug, consisting of mucus and various immune cells including our old friends the eosinophils, is often present.

An estimated 5.2 million people in the UK are currently receiving treatment for asthma including just over a million children and young adults and the figures aren't much better in the US either. An important aspect of controlling asthma alongside preventative and relief inhalers is the identification of trigger factors leading to the exacerbation of symptoms. A variety of trigger factors have been suggested for asthma, ranging from foods to exercise to environmental pollutants to animal hair. Like other 'allergic' diseases, the trigger factors vary from person to person.

So what about asthma in cases of autism?

Well as you might imagine there has been some work done looking at various aspects of the two conditions and in connection to some surprisingly interesting areas. The basics first: prevalence of asthma in autism? Well that's a bit of a tough one because as things stand at the moment, I can't actually find any reliable data on this. The best I can say is that yep, both conditions are showing an increase in prevalence over the past few decades and by my 'autism is not protective against other conditions' rule of thumb, I would argue that very little tells me that asthma prevalence rates are any lower in autism than they are in the wider population although I might be wrongThis paper provides quite a good overview of how the two conditions perhaps share some interesting characteristics in terms of genes and environment touching also upon that prevalence issue.

Although I am quite wary of the concept of 'risk' particularly when applied on a population-level, there is some suggestion that familial asthma and allergy might increase the risk of autism or intellectual disability in offspring, possibly as a function of either exposure patterns or as a result of a more generalised relationship with autoimmunity. Carrying on the theme of risk, this study suggested, amongst other things, that an early asthma diagnosis might be tied into later diagnosis of autism influenced also by levels of airborne phthalates. I have to admit that I am intrigued by this proposition particularly given the recent focus on pollutants and risk of autism; intrigued but not yet thoroughly convinced by the data presented so far. Medication has also been speculatively linked to asthma and autism; this paper suggesting that acetaminophen (paracetamol to us UK folk) use may be linked, although I note that the original assertions linking asthma to such analgesic use is coming under further scrutiny. Various other classes of medication used for the management of asthma have similarly been suggested to be linked, although please remember correlation does not imply causation.

Another area that cropped up on my various searches for this post was the possible common link with the so-called leaky gut (gut hyperpermeability if I am to be factually correct). One of my favourite papers from recent years by Liu and colleagues discusses how increased intestinal permeability is a common denominator in many conditions including autism, type-1 diabetes and also asthma. The precise reasons why such intestinal hyperpermeability is present and related (or not) to conditions like asthma is unknown; whether due to more generalised connective tissue problems or whether providing a route through which antigens could trigger asthma or suggesting involvement for the whole mucosal immune system in asthma - there remain some questions to be answered.

I would perhaps conclude from the data that there may be some interesting relationships between asthma and autism which need further investigation. I have not touched upon the issue of asthma management in relation to autism and whether medication and compliance are affected by core and peripheral autistic symptoms for example.

To end this post there is no link to a music video or funny picture but rather I am going to be serious for a moment and link to some information on what to do during an asthma attack as provided by Asthma UK. This is advice from them not from me. Hopefully you will never need to use it.

[Update: March 2014: Readers might also wish to read my post titled: 'Asthma as a risk factor for autism?']

Sunday, 26 June 2011

XMRV marks the spot?

In quite a few posts on this blog, the nature of the relationship between humans and the various smaller organisms which have populated our planet for many millions of years in one form or another, has been explored. Take for example the possible relationship between Toxoplasma gondii and schizophrenia covered in this post, and you can see that there is the potential for an interesting relationship between the human body, mind and various infective agents. The research of course does not say that we are all singularly at the mercy of such external organisms or that somehow free will is just an illusion; merely that our health and functioning might be influenced by lots of different factors, some of which we are only beginning to realise and understand.

My attention in this post is on an area of research which has been speculated to straddle quite a few conditions including autism and the various fatigue-related conditions. Readers might remember a post a few days back where I 'attempted' to look at some of the preliminary research commonalities between autism and chronic fatigue syndrome / myalgic encephalomyelitis (CFS/ME). If true, the focus of this post could be a very important commonality - if true.

Xenotropic Murine Leukemia Virus-Related Virus (XMRV) has had quite a bit of exposure in the research (and media) world of late. This retrovirus has been linked to quite a few different conditions, most notably prostate cancer, with some evidence presented for a possible association. I say linked, but be under no illusion that the evidence base is conclusive in this area. Indeed, with regards to prostate cancer, there have been several reports detailing no universal connection between XMRV and such cancer. One of the most recent studies from the CDC no less can be read here and details only a very low prevalence of XMRV in prostate cancer (1.9%). Of course that 1.9% is a reality for 1.9% of prostate cancers, but I think most people would admit that this is quite a small percentage of cases and is certainly not grounds for a universal relationship.

XMRV has perhaps found most controversy in its proposed relationship to CFS/ME. I don't really have the time or space to provide the full story linking the two conditions together so would perhaps refer you to this page for a summary. The paper which first suggested an association is this one published in Science, whereby XMRV was reported in PBMCs of people with CFS (67%) over and above controls (~4%).  The authors suggested that such a significant finding could either be indicative of an aetiological factor for CFS and/or could suggest potential 'treatment' options via the use of anti-retroviral drugs. CFS/ME is no stranger to a possible viral connection: ME has also been known as post-viral fatigue syndrome (PVFS) (not even mentioning the Royal Free incident of 1955). Indeed viral infections including glandular fever and even SARS have also been reported to be associated with symptoms. The subsequent research carried out on XMRV and CFS/ME has not however exactly provided a ringing endorsement for a possible connection between the two, despite some tentative confirmation of aspects related to the original findings. There are numerous papers suggesting no link between ME/CFS and XMRV including this one from the UK and this one from the USA. A good summary of the results so far is here. I am not going to say much more on the XMRV-CFS/ME relationship in this post aside from the fact that the controversy continues. There are various reasons to potentially account for the results obtained and there are many people better qualified than I to offer their informed opinion.

Autism spectrum conditions have also been discussed in connection with XMRV, at least preliminarily. I can't say for sure where and why XMRV was first related to autism but I seem to remember someone at the original study location, the Whittemore-Peterson Institute, suggesting that autism may also show some correlation based on other (unpublished) results. Viral infections accompanying autism have been the topic of some debate down the years with several suggestions put forward for a possible connection (see here and here). There have been some case reports detailing the diagnosis of XMRV infection in autism, but at this stage I cannot confirm whether the same issues potentially related to ME/CFS (i.e. cross-contamination) are applicable or not given the lack of information on testing protocols. The limited published group evidence on any connection between autism and XMRV is pretty categorical: no presence of XMRV in cases of autism (see here and here). As per the mantra of this blog, science is about probabilities not absolutes. In the case of XMRV and autism, I have to say that the data (so far) is quite explicit in the direction of its findings.

The initial interest in XMRV has perhaps abated slightly given the number of studies that have been completed. I think there are a few interesting points to note from this whole issue including the concept of universality (and what it means when potentially assigning a correlate to all or a large proportion of people with often nebulous symptoms), correlation and causation (one does not equal the other - even in those cases where XMRV has been detected, the various data do not yet provide any indication that treating XMRV actually impacts on presented symptoms outside of just reducing viral load) and population differences. Because of the small number of trials specifically looking at autism spectrum conditions, I would perhaps like to see some further data on XMRV and whether issues such as age, geographic population, sub-diagnosis and co-morbidity show any potential effects before drawing a line under the XMRV story and the question of whether XMRV really does mark the spot.

Saturday, 25 June 2011

Asperger syndrome and hacking

A very, very short post this one in response to a recent news item here in the UK.

First it was Gary McKinnon. Now it is Ryan Cleary. Two young men diagnosed with Asperger syndrome. Two young men under Police and media scrutiny for their (alleged) computer activities. You can imagine that this has been the topic of some discussion and questions are starting to be asked about the relationship between Asperger syndrome and hacking. I am not getting too far into the debate at this time because the facts have not been proven, and until they are, it is conjecture and speculation.

One question I would perhaps raise: does Asperger syndrome predispose to hacking or does it predispose to getting caught?

Occupational therapy and autism: the archetypal all-rounder

I will readily admit that I have always been a little bit confused when it comes to occupational therapy (OT). Confused because the name 'occupational therapy' does not really provide the most satisfying answer as to what occupational therapy involves and in what ways occupational therapists can help. There are various definitions on the web about OT; probably the most satisfying that I have found is this one from NHS careers, although I tip my hat to the Wikipedia entry also.

Basically OT is all about enabling people who otherwise might be described as disabled. OT covers a lot of ground in terms of who therapists work with (people with physical and mental health problems, older people, etc), but generally their role includes: (a) looking at everyday tasks and seeing how they are carried out and might be done differently to either make life easier or fit in with a persons strengths and weaknesses, (b) providing advice and help in making referrals to other support agencies, (c) providing advice on speciality equipment, adaptations or training which might improve a person's quality of life. I was quite surprised when I read this job description because in my ignorance, I had always assumed that solving problems with mobility and movement was the mainstay of the profession. I admit I was wrong and apologise to occupational therapists everywhere.

Given the job description for an occupational therapist, one could perhaps see how the profession might be of some use to people diagnosed with an autism spectrum condition for various reasons. Lisa Jo Rudy at provided a good overview a few years back of some of the ways that OT might help, coupled with quite a few 'glowing' reports on the use of OT available on the web. The American Occupational Therapy Association also have a good overview of OT and autism. When it comes to the research-side of things, there are quite a few studies that have utilised facets of OT and produced some quite surprising data. Various areas of interest have been reported on including:

  • Sensory issues (see here and here)
  • Motor and movement abilities (see here)
  • The use of animal-assisted therapies (see here and here)
  • Employment issues (see here)
  • Relationships and social interactive behaviours

I get the impression that OT is the hidden 'all-rounder' for many different conditions including autism. An all-rounder because OT seems to be the group which are supposed to provide the 'overview' of what might be best practice to bring out the best of an individual, day-to-day. Making day-to-day living easier is the goal of many interventions related to autism, for early behavioural and speech and language therapy, through to things like dietary intervention, although often any benefits are more generalised. OT is perhaps at the coal-face because of its emphasis on practical daily living skills and tangible benefits from things like a person learning to dress themselves or using assistive technologies to communicate. Another issue that strikes me from looking at the various information on OT is that whilst having being evaluated for effectiveness, many of the strategies used are quite individualised, hence quite difficult to empirically test under normal experimental conditions (n=1 perhaps?). This combines with the fact that OT normally works alongside other professions such as speech and language therapy; deciphering what is having an 'effect' is perhaps secondary to the cumulative effect from such combined efforts.

I end this post therefore with a salute to occupational therapy; the archetypal all-rounder.

Thursday, 23 June 2011

How do ketogenic diets work?

Perhaps I have said it before and please excuse me if I am repeating myself, the influence of diet on both our physical and mental health is a bit of an interest of mine.

When I say interest, please don't infer that I have any dietetic training on the various components of our diet and the details of what we should or shouldn't eat outside what research in the public domain tells us. No, my interest and comfort zone is more about measuring and analysing the final outcomes from diet, particularly the psychological and behavioural endpoints.

Although the gluten- and casein-free diets lie at the centre of my interest, I have found myself drawn to other kinds of diet and their various uses in medicine down the years. Phenylketonuria (PKU) is one example; how a diet low in phenylalanine (combined with tyrosine supplements?) can so completely transform a person's life, indeed even save a life. Another type of diet has also been on my radar for a while now, the ketogenic diet.

My interest in the ketogenic diet has been piqued recently by a few things. Emily Deans over at Evolutionary Psychiatry has posted a few entries mentioning the ketogenic diet which make for some very interesting reading (see here). I also had the good fortune to attend a conference recently where dietitian Sue Wood presented some of her findings on the use of the ketogenic diet in practice. Both provide some tantalising suggestions about the ketogenic diet including much of what this post details. I might add that both Emily and Sue are trained healthcare professionals; this is not some dietary 'fad' being touted as alternative medicine.

If I had summarise a ketogenic diet in as few words as possible it would be something like this: high fat, low carbohydrate. Most people will probably have heard about the ketogenic diet or at least something related, under a pseudonym - the Atkins diet - and its proposals for weight loss. A ketogenic diet has been suggested as being a possible management option for quite a few conditions including Rett syndrome, Tuberous Sclerosis and other conditions. It is with certain types of epilepsy and seizure disorders in mind that the diet has found its primary function.

The precise theory behind the ketogenic diet and why it seems to be able to reduce/eliminate seizures in certain cases is... well, I dunno. Current thinking suggests that by using the diet to invoke the production of ketones, compounds normally produced when the body is in starvation mode, said compounds might have an anti-seizure effect. There is quite a bit of research to support this suggestion and who am I to argue. I have for quite a while, thought quite a bit about the whole ketone story and whether there may be other explanations for the results suggested in reducing seizures.

One of the interesting things for me is the overlap between a ketogenic diet and a gluten-free diet. Both diets are generally associated with the removal/reduction of carbohydrates although perhaps for different reasons. Yes, I know that gluten-free foods will often contain carbohydrates but there is some evidence to suggest that overall carbohydrate intake is reduced on a gluten-free diet whether due to the taste of the alternative foods or general nutritional preference. Granted also, that the ketogenic diet replaces said carbs with fat as an alternative energy source (adding fat to the diet is considered almost heresy in some circles today) but the overlap between the two diets is carbohydrate reduction. There are then a few lines of evidence that lead me to think that the ketogenic diet might be doing more than just putting the body into ketosis; the primary evidence coming from some results from the various trials on gluten- (and casein-) free dietary intervention for autism amongst other things.

It was Prof. Ann-Mari Knivsberg and colleagues who first reported on the effect of the GFCF outside of just core autistic symptoms. It was almost a secondary finding when they said that there was a reduction in the number of seizures experienced by some of their autistic participant group (pp230-231). Indeed in our own 1999 paper on examining the gluten-free diet for autism, we reported the experiences of one child who, coincidentally when coming off the gluten-free diet back on to a gluten-load diet, experienced a seizure at the same time as gluten reintroduction (pp50-51). I remember that at the time my colleagues and I thought such an individual observation was purely coincidental knowing about the association between autism and epilepsy. Combined with the Knivsberg results and a few years thought in-between, I do wonder if this was not just a chance finding.

On the basis of such preliminary evidence, the question posed is whether carbohydrate or a gluten reduction-removal might be an active anti-epileptic component working alone or in union with ketones? At this point I will remind readers that I am not offering medical advice or opinion on such 'strategies', merely exploring possibilities based on the research evidence available. Please speak to your medical physician and dietitian before making any changes to diet or medication particularly where epilepsy or seizure disorder is indicated. Don't mess with epilepsy.

Gluten has been linked to epilepsy on quite a few occasions (here and here for example). Of course being linked to a condition does not necessarily imply direct involvement in that condition; that is aside from the case studies like this one and this one which reported in cases of epilepsy and co-morbid coeliac disease, that a gluten-free diet improved both sets of symptoms. Precisely why a gluten-free diet had such an effect is unclear and beyond the limits of my competence. Trying also to find research which can disentangle an effect from gluten reduction or carbohydrate reduction is difficult.

I will perhaps leave things there. I could go on and talk about how those pesky gluten exorphins might play a role or how the ketogenic diet has shown some effectiveness in ameliorating autistic symptoms or how a gluten-free in some cases might put the body into starvation mode given the significant drop in calories expected at least in the early days of the diet or even the various discussions on the specific carbohydrate diet. But I won't. Instead I will stay here in my comfort zone.

To finish, Weird Al and a nice food link.. Eat It!

Wednesday, 22 June 2011

The technological phenotype

On the question of cognitive styles possibly linked to autism, I have previously touched upon some of the various theories put forward. Ranging from problems with theory of mind, through to weak central coherence through to executive dysfunction, quite a bit of research has been devoted to this topic down the years providing psychologists in particular with plenty of experimental fodder to digest.

Perhaps the most interesting candidate in recent years has been the systemising-empathising hypothesis as expounded by Prof. Simon Baron-Cohen and colleagues. The basic tenets of the theory are relatively simple: according to Prof. SBC, the triad of 'deficits' linked to autism (social, communication, perspective-taking) are all in areas of empathising, whilst the various 'strengths' linked to autism (obsession with systems, repetitive behaviours, islets of ability) are all in areas of systemising. I touched upon this theory in a recent post. Gender has also been suggested to have a hand in the hypothesis (males = better systemisers; females = better empathisers) running alongside the gender ratios noted for autism, but for the purposes of brevity, I would direct you to this paper for a more comprehensive overview.

A recent paper reported here and also discussed here has caused a little bit of a stir in relation to the empathising-systemising (E-S) hypothesis of autism. The suggestion was that differing prevalence rates of autism might be accounted for by the level of technological expertise present in that particular geographical location. When I say technological expertise, I am not talking about those who are just 'internet-savvy'; no, here we are talking about people who are involved in highly technical (systemised) careers like engineers, IT and software, and maths and statistics, on the basis of some older research from SBC, that such techhy people are at the extreme of the E-S disparity and hence systemisers might be more likely to have a child with autism.

The current study in question looked at different regions in the Netherlands and based on quite a large sample suggested that the relative population density of such systemisers could be a potential pointer towards a higher prevalence of autism. Similar suggestions have been raised in previous times to, for example, account for the quite extraordinary rise in autism prevalence in places like California - California being HQ to quite a few tech companies, as well as being home to Silicon Valley. It all is suggested to tie into the theory of assortative mating also proposed by SBC.

There are a few interesting things to take from such research. Primary is that prevalence rates of autism are most likely not going to be uniform geographically potentially as a result of this, and lots of other factors, both genetic and environmental. I am happy to see that from this latest paper there have been suggestions that the results could be also be in part due to the fact that a more technologically focused area is liable to have a lot more disposable money and as a result better services for things like diagnosing autism compared to a less techhy place; not even taking into account possible people differences in knowledge and awareness of autism. The post on SES and autism dealt with this in more detail.

As with all the cognitive theories put forward for autism, the E-S theory 'might' be applicable in some cases: more systemised parental career choices could be a 'risk' factor for transferring the cognitive style attributed to autism. I say cognitive style, because more and more we realise that autism is probably not genetically transmitted, but there might be some transmission of the 'spirit' of the traits described a la evidence from the broader phenotype. Having said that, I can't envisage a universality for the theory for quite a few reasons; not least that autism is an extremely heterogeneous condition and as far as I am aware covers the entire population demographic in terms of familial composition and parental career patterns. The recent debates between SBC and Cordelia Fine, which have filled many pages of the Psychologist in recent months perhaps also should be brought into this post also. As always such research makes no reference to anything but autism, so co-morbidities whether behavioural or physical and their potential impact, don't get a look in unfortunately.

To end, did you know that video killed the radio star...

Tuesday, 21 June 2011

The US crime figures

I know that as a Limey I am probably not best placed to talk about our American cousins and their various day-to-day activities. I would in this short post however like to post a few comments about a story appearing on the BBC website titled: US crime figures: Why the drop?

It's an interesting fact that crime, as measured by things like murder and robbery, in the US has witnessed quite a bit of a drop since about the early to mid-1990s. Indeed, looking at the presented graph based on figures from the FBI, murder has dropped in incidence from about 9 per 100,000 population to 5 per 100,000 population and robbery from 250 per 100,000 to about 120 per 100,000 population over a 40-year period. The drop was not a consistent downward gradient, but as the BBC suggest, all the more impressive given the current financial climate and the various social knock-on effects to things like unemployment which have shown more than a casual relationship to certain types of crime.

I was interested in the various arguments put forward to account for the decrease; ranging from the 'Obama' effect, a drop in the demand for various drugs of abuse and the implementation of various social policies. Amongst the top 10 reasons listed on the BBC website for the drop is the removal of lead from petrol suggested by an economist of all people. The person in question, Jessica Wolpaw Reyes has published some work in this area (here). I was intrigued by this suggestion in particular, acknowledging that there are probably going to be lots of reasons for the drop in crime also varying according to where you are in the States. Lead is well known to have quite a few harmful effects particularly on the young and developing child, and at relatively small quantities. I might do a separate post on this in the near future.

I was thinking about the other possible contributors to such a drop in crime, and for some reason, was brought back to a post made over at Evolutionary Psychiatry looking at the link between nutrition and behaviour amongst prison inmates and the work of Bernard Gesch and colleagues. Without reciting the whole post, the take-home message was that improved nutrition correlated with some improvements in behaviour and particularly a reduction in antisocial behaviour. Without wishing to stretch such findings too far, I do wonder what effect nutrition might have had on the crime rate given the increasingly loud voice being used by Government and other agencies to push (rightly or wrongly) things like the 5-a-day agenda.

Whatever the reasons behind the fall in figures, the news is welcomed and as stated by the BBC, the numbers of lives spared is perhaps the most important part of the news.

D-I-V-O-R-C-E and autism

D-I-V-O-R-C-E went the song from Dolly Parton. Dolly herself has little reason to sing such a song with her pretty long-lasting marriage to her husband Carl Dean - and good luck to them too. When it comes the general population however, many people are not as lucky as Dolly and Carl, with current divorce rates hovering around the 10.5 per 1,000 marriages in the UK (2009) and 3.4 per 1,000 marriages in the USA (2010).

I have to say I was surprised at the UK and US figures. Like many people in the UK, I was always under the impression that divorce was much more common in the States than here in Blighty given the media portrayal and the almost constant references to things like the pre-nuptial. I would therefore like to apologise to our American cousins for my tainted view of the divorce statistics.

Before I go on, I would perhaps mention that whilst divorce is often (always?) a stressful and difficult time for parents, it can be equally, if not more distressing for any off-spring who might also be caught up in the middle, also dependent on their age and understanding of the implications. There are for example, quite a few studies which have confirmed the detrimental effects of divorce in terms of the longer-term outcome including the child's subsequent self-esteem, identity and skills and abilities to form long-lasting relationships. Even childhood bed-wetting may be tied into the experience of divorce.

When it comes to autism spectrum conditions, there is quite a lot of speculation as to whether the divorce rate may be different amongst parents who have a child with autism compared with the general population. As you would imagine this is a very delicate area to discuss given the implications of divorcing where autism 'might' be a factor and what light this potentially puts autism in. I would add that I am not judging, merely reviewing the available data.

This paper suggested that there was a significant difference in divorce rates among parents of children with autism and controls (23.5% vs. 13.8%). Interestingly, the authors also found that whereas divorce rates in the control group tended to drop off after a child had emerged from infancy, the divorce rate amongst the autism parent group did not. The explanation was that the continuing 'dependency' demands of children with autism on their parents may have had an effect.

The collected data is however not unanimous in postulating that having a child with autism is a risk factor for divorce. This recent paper found no increased risk of divorce (or as they put it 'living in a household not comprised of their two biological or adoptive parents'). The same data was also presented at the 2010 IMFAR conference.

I found this recent article which provides some qualitative data on the possible effect of autism on cases of parental divorce; the report data suggesting that half of all divorces where autism was involved, cited autism as 'one' reason for the divorce. It is interesting that stress in one form or another was listed as a factor related to autism and the breakdown of the marriage. There are often considerable stresses and strains which have been experimentally shown to occur when raising a child/children with autism; indeed beyond those of raising a child with an intellectual disability such as Down syndrome for example. The types of strain which can occur are numerous and include relatively simple things like just getting enough sleep (those of you that read my post on sleep and autism might get a flavour of this issue). The impact of stress (whether connected to autism or for other reasons) on the effectiveness of intervention has also been examined and a possible relationship found.

I don't quite know what conclusion to draw from this combined data. Yes, there does some to be some connection between having a child with autism and divorce. I don't however think that we can say that every parent who has a child with autism is likely to divorce because divorce is a very complicated thing, and the reasons behind it are pretty personal and numerous. Take for example, this recent analysis which suggested that husbands playing video games to the detriment of talking to their wives was suggested as a factor in up to 15% of cases of divorce.

There are also a couple of aspects missing from the evidence base. Things like whether the 'type' of autism has any impact and whether also co-morbidity such as intellectual disability or epilepsy or other things might also be contributory to or protective against divorce. I would also like to see further research on how things like coping mechanisms, the impact of other children and extended family support, finance and monetary issues and faith and religion might also affect a parental decision to stay together or not. Such data could also be useful when it comes to mediation before any final decisions are made.

I would finally point out that divorce is an agreement between two people - 'the final termination of a marital union' to put it into cold, hard words. Unless one or both of those persons have autism themselves, the decision to divorce or not, is ultimately about those two individuals and their relationship, everything else including the house, the kids, the possessions and yes, autism, is secondary.

How about a more up-beat song from Dolly?

Monday, 20 June 2011

The perfect fruit juice?

One of the benefits I have noticed since becoming a blogger is that I tend to keep my eyes open for interesting things to blog about. Autism is obviously the focus of this blog and is a rich source of research and practice. But around the various research that is published and lands in my in-box, little nuggets appear every now and again which whilst being outside of the core focus, are nevertheless of potential interest.

One such nugget was this paper which describes the science behind the perfect fruit juice. The team, based at the University of Strasburg aimed to create a berry fruit juice that could lower the risk of cardiovascular disease based on maximising polyphenol content. Polyphenols have a rich history related to health; particularly their correlation (not necessarily causation) with a reduced risk of cardiovascular disease via antioxidant activity and vasodilation.

According to the press release from the Royal Society of Chemistry (RSC), after quite a bit of work, the team pronounced the following blend to be that which maximised vasodilation as well as tasting not too bad: a base of grape juice (63% of the total drink volume) blended with strawberry (10%), blueberry (10%), apple (10%), lingonberry (5%), acerola (4%) and aronia (4%).

So the next time you are at the juice bar and the server asks 'what's your poison?' make sure you make yours the healthiest kind.

Sunday, 19 June 2011


My previous post on calcium led me into some interesting reading on the various vitamins and minerals required for optimal health. I say 'optimal health' but really I believe less and less there is such a concept, given the huge heterogeneity present among the human race and the myriad of environmental and genetic influences constantly tugging at our health and well-being. Probably a better way of describing it would be 'get-through-the-day health' which, whilst not being so catchy in title, is better reflective of our changing nutritional requirements dependent on so many different factors.

One particular area of interest that I came across relates to zinc.

I have to say that I have a new found appreciation for zinc after reading about its various biological uses. After iron, zinc is one of the most common metals used in various enzymatic reactions around the body. Thinking about going out for a few drinks on a Friday or Saturday night? Well make sure that you have packed your zinc, which is an important co-factor for alcohol dehydrogenase, the primary pathway for breaking down alcohol (God knows here in the UK, we need it). Zinc has also found some favour with helping some of us get over the common cold more quickly (bearing in mind there is more than one virus that can cause a cold). There are lots of other uses for zinc throughout the body and certainly I would recommend spending some time looking at them if you are so inclined.

When it comes to autism spectrum and related developmental conditions there are some interesting studies and ideas on zinc which are worthy of discussion. One of the earliest references to zinc and autism that I found was this one from 1978. In it the authors reported that plasma levels of zinc and a few other things were within normal ranges in autism, and that their results indicate that "..autism cannot simply be attributed to a disorder of zinc metabolism". I was wondering quite a bit about this last statement and the implied suggestion that autism was due to disordered zinc metabolism. Has autism ever been described in such a way, if so by who? There is also some suggestion that zinc might also show some involvement in cases of pica - the eating of non-edible material - a co-morbidity for various developmental conditions including autism. Evidence of pica being associated with low zinc levels in both the learning disability population and in the general pediatric population has been presented. I have yet to find anything in the research literature that explicitly links pica in autism as being related to zinc deficiency but there are some interesting personal and second-person accounts suggestive of a possible link. As with everything however, zinc may not be an entirely positive thing. A few papers have reported an excess of zinc as being present in autism. This paper for example, suggested that high levels of zinc in autism (measured by hair analysis and our old friend ICP Mass spectrometry) perhaps showed some connection with  low muscle tone. I am not in any way suggesting that zinc caused the hypotonia - low muscle tone (which is itself a feature of quite a few cases of autism) but the association is an interesting one.

Outside of core autism and perhaps moving into the realm of autism co-morbidities, there is also some interesting data on zinc and a few potentially relevant conditions. ADHD and zinc seems to have forged some connection. Studies like this one and this one have suggested that where low levels of zinc are presented, there may be some tie in to the presentation of certain symptoms such as inattention, anxiety and conduct problems.  Where supplementation has been assessed by clinical trial the results have also suggested some promise in ameliorating symptoms (although not universally and potentially also tied into other components of the supplement).

Inflammatory bowel disease (IBD) has also been associated with zinc. Several reports have correlated the presence of various IBDs and low levels of zinc, including in pediatric populations (see here). There is still quite a lot of speculation as to why such an association should be present, but certainly calprotectin, a marker of inflammation, may show some effect in the presence of zinc; as indeed, zinc has quite a role to play in normal immune function. Supplementation with zinc in cases of IBDs also seems to show some promising effects on various markers of disease and severity.

I am mindful that I have extolled the virtues of zinc in this post and paid only lip service to the more potentially negative effects, particularly the relationship with cadmium and its onwards toxicity and the possible interactions with various medications and other nutritional supplements. Going back to my original assertion of 'get-through-the-day health', I would perhaps forward the view that zinc, in the right amounts, plays a very important role in maintaining a healthy body.

Saturday, 18 June 2011

What do we know about autism?

There have been, and continue to be, quite a lot of big personalities and reputations that have brought their knowledge and experience to bear on autism research down the years. I don't want to name names but between the Ivy League and Oxbridge set (and the many, many institutions in-between) there has been a considerable body of knowledge generated on many facets of autism. I appreciate that questions still remain as to the extent to which that knowledge has transferred from 'laboratory to real life' and positively impacting and improving quality of life for people with autism. I am however drawn to the various philosophical notions about the time taken from discovery to practical application being generally measured in decades and years rather months or weeks. Sciences it seems, is a slow process.

I say all this because of a fairly recent post which appeared on one of the Psychology Today blogs [who have had their fair share of controversy of late] which, rather pessimistically in my opinion, seemed to suggest that autism research has had its day with regards to the numbers and talent available and involved. As you might imagine I took umbrage at this suggestion, not personally I have to say, but because there are some very, very good researchers undertaking some very worthwhile investigations into autism. Indeed one could perhaps describe the current position as being a bit of a golden age for autism research in terms of the people, disciplines, resources and importantly, funds involved - 'we've never had it so good' to mis-quote one Statesman.

For one of the more contemporary snapshots, of where autism research currently is, I draw your attention to this presentation given by Prof. Sir Michael Rutter as part of the 2008 National Autistic Society (NAS) conference. If you click on the link titled 'Historical perspectives - what have we learnt from research?' you can download the full Powerpoint presentation for yourself. Whilst acknowledging the contribution of Rutter to autism research, including the development of the ADI-R, I have to say I have never had that much direct exposure to his involvement in autism, aside from watching a few tutorial videos on how to correctly administer an ADI. Bearing in mind that a person's particular field of interest and grounding can readily affect their view of a concept/condition/event, there are some very interesting points to take from Rutter's 2008 presentation. For me, some of these include:

  • Validation that autism is distinct from other conditions manifesting behavioural/psychiatric symptoms but can manifest with various co-morbidities.
  • Lower cognitive abilities and a lack of language are key predictors of outcome.
  • The existence of a broader autism phenotype (extending into non-clinical relevance).
  • Autism is not, generally speaking, a localised brain abnormality.
  • The finding of increased head size in some cases of autism reflects increased brain size.
  • Genetics are (variably) important but autism can also arise from other medical conditions.
  • The validity of the concept of regression in autism.
  • A lack of convincing evidence of a neurochemical or immune abnormality specifically associated with autism.
  • A lack of convincing evidence that medication impacts on core symptoms.
  • A lack of convincing evidence of EEG patterns specifically related to autism.

I have posted about a few of these issues before (regression, medication, etc) and am planning some future posts on some of the other details mentioned. Rutter does discuss quite a few other things in his presentation and I would encourage readers to view the whole document (if anything else just to see what I cherry-picked). Reading through this list, one might get a slightly negative impression of the state of research, what with the repeated use of the words 'lack of..'. I don't however see it this way. I see something rather more interesting; much of which goes back to the various issues around the heterogeneity of autism and the different presentations of the autism: autism is not autism but rather autisms.

It is perhaps interesting, but not unexpected, that Rutter also embraces the concept of gene-environment interactions in relation to autism. Anyone who has read his papers on Romanian orphans presenting with an astonishing rate of autistic behaviours (present in about 6%) will understand why he adopts such a position. Indeed, in his latter slides on the 'puzzles and challenges' remaining he asks some very reasonable questions on the impact of advancing paternal age, immune effects over neurotransmitter effects, the role of environmental agents and, knock my socks off(!), whether or not diet could play a role in some cases of autism and why.

I appreciate that it is easy for me to sit at my computer and churn out posts like this 'celebrating' what a wonderful job science is doing for autism, research-wise, whilst people with autism, their parents, guardians and families face daily challenges related to lots of different aspects of autism. In no way do I wish to take away the reality of what autism means to many, particularly in light of these tough economic times. From a research perspective, I do however feel optimistic that there are considerable numbers of people, talent, resources and money who are genuinely concerned with discovering more about autism, and who continue to contribute to the all-important research base from which Government and Society can formulate suitable policy to ensure that the relevant support and opportunities are available to all people on the spectrum.

Thursday, 16 June 2011

Allergy and intolerance and autism

Summer is upon us yet again. The sun is shining, birds are singing and oh yes, people sneezing thanks to that most exquisite allergy to pollen, hay fever. With this in mind, so begins my mega-post on allergy and intolerance.

When I was about 10 years old, I discovered I had an allergy. Although my memory of events is a little vague, the story went something like this. My parents and I were visiting friends who had a long-haired cat. I don't remember the mugshot of the moggie in question, but I remember it had long hair. After a while stroking and playing with said moggie a la Blofeld, I remember my eyes beginning to water and becoming very itchy. As a youngish child, I couldn't resist the urge to try and rub and scratch them to try and relieve the itch. After a while of doing this, my parents noticed that I was looking a little bit worse for wear - my face was turning very red and I started to take on that boxer-look around the eyes. So much so that a quick trip down to the Accident & Emergency department of the local hospital was in order. At the hospital I remember watching all the doctors and nurses running around and all the walking wounded waiting patiently for their turn. When it was my turn my memory is faded aside from a nice medical type drawing little circles on my arm and pricking it with quite a few needles. One needle prick in particular started to become red and itchy - cat hair. And so began my long running cat allergy. Needless to say this was quite a shock to me and my parents. I had been in contact with lots of cats during my childhood, although we had never owned one. I am still cautious to this day about my contact with cats, particularly the long-haired variety, lest my Henry Cooper look makes another appearance.

Years later I found out about the science behind my allergy experience. The needles on my forearm formed part of the skin prick test and I had/have a type-1 IgE sensitivity to cat hair. The day of my cat experience, I joined quite a large number of people who have an allergy, but what exactly does that mean?

Allergy is probably one of the most nebulous terms in medicine. Nebulous because it covers such a wide range of things and is a term used interchangably (rightly or wrongly) with things like intolerance and hypersensitivity. There is quite a good lay-persons overview of allergy here. The clinical defintion of allergy is that it is a hypersensitivity reaction to some allergen initiated by an immunological reaction. Probably the most famous classification of allergy is that by Gell and Coombs who originally divided hypersensitivity into 4 types: type 1 (immediate), type 2 (cytotoxic), type 3 (immune complex) and type 4 (delayed hypersensitivity).

Type 1 immediate hypersensitivity mediated by the IgE isotype is perhaps the gold standard allergy (also called atopy) reflecting the production of allergen specific IgE, followed by the release of histamine. This is also the mechanism through which anaphylaxis is thought to operate of which peanut allergy is perhaps the most famous. Type 2 cytotoxic antibody hypersensitivity is mediated by IgG and IgM isotypes.

Intolerance, by contrast, is defined as a non-allergic hypersensitivity where IgE isotypes are specifically not involved. I have already blogged about intolerance in previous posts, most notably when talking about lactose intolerance and autism. Indeed, lactose intolerance really sums up food intolerance - the body's inability to handle a food because of problems in producing sufficient quantities of the enzyme(s) needed to digest that food. The IgG isotype has in recent years found a home in the term intolerance; indeed gluten intolerance has been noted in relation to IgG in various conditions. The suggestion being that protein fragments / peptides not properly broken down because of enzyme deficiencies enter the circulation and begin accumulating IgG antibodies. Mmm, I've heard something similar before with the opioid-excess theory and that pesky leaky gut theory.

Having spent quite a portion of this post in describing mode, I should perhaps also talk about where autism may fit (or not) in this chain of events. I have quite an interest in allergy and autism if only for the reason as to why the various dietary changes discussed in autism might potentially work. For those of you who want the full peer-reviewed scientific piece, have a look at a paper here that my colleagues and I published around this topic a few months back. For those, like me, who prefer the 'Mr Men' version, it goes something like this.

Overall, the currently available evidence seems to suggest that people with autism are perhaps more likely to suffer from various allergies as are their parents. The evidence for co-morbidity of specific IgE-mediated allergy in autism spectrum conditions suggests however no overall greater frequency to be present than in the general population (although with some evidence to the contrary specifically with Asperger syndrome in mind). It seems therefore that where allergy exists alongside autism, it does so in the most part outside of the classic type-1 hypersensitivity as witnessed by the various papers suggestive of such an association. There are caveats to these very sweeping conclusions I have made not least the n=1 principle. Determining exactly what are the main allergens causative of such as reaction is, understandably, a more individual thing.

The final question is really a question of what can we do about allergy in autism. Assuming that the underlying biochemistry of allergy is the same in autism as not-autism, the obvious answer is to avoid the allergens. Going back to the work from Harvard on lactose intolerance and autism, and the suggestions of excluding casein where milk allergy might be indicated, there is perhaps some good sense in this approach. The fact that such dietary changes might also have some knock-on effects to core and peripheral autistic symptoms is an area that requires much more description about the possible mechanisms as to why.

Although based on IgE-mediated allergy, there may also be some ground to cover with various other interventions for allergy. Before proceeding, I would add that my caveat about not giving medical advice comes into full force at this point; talk to your Medical Doctor or Pharmacist before starting any kind of medication or treatment regime. The use of anti-histamines such as cetirizine is often the first-line for treating mild allergies such as hayfever. The anti-histamine part is the important bit in that such medications are designed to block the receptors to which histamine attaches. It is interesting to note that some of the medications designed to block H2 receptors have also been looked at more directly in relation to autism. An interesting point indeed.

Another potentially relevant avenue of treatment is that of allergen-injection immunotherapy which involves graded dosages of a particular allergen building up over a period of time until tolerance is acheived. I always equate this with people like Dr Len McEwen and his similar work on enzyme potentiated desensitisation which is all but the same thing - introducing small doses of an allergen - although alongside the addition of beta glucuronidase. The evidence base is unfortunately pretty much non-existent for both these options in relation to treating allergies alongside autism at the moment, but that is not to say that they are not viable options for treating allergy more generally. The obvious problem is also that such allergy therapy involves needles and quite a few people with autism (like the rest of us supposedly strong men) don't like needles.

Allergy and intolerance are still pretty vague concepts, in terms of their description and biological mechanisms, which might have some varying applicability to some cases of autism. These are big areas of health which I have only been able to give a brief overview about without even touching on things like mast cell activation and how humoral immunity might tie into cell-mediated immunity, which have both been linked into autism in some way, shape or form.

For those unfortunate enough to suffer with allergies like hay fever, I end with some scenes which are reminiscent of symptom-free times from my part of the world.

Wednesday, 15 June 2011

Target practice and nudge theory

This is one of my other musings entries, and for the ladies out there, hopefully an intimate look into the male psyche (shouldn't take too long). If you are easily offended, please look away now; if not maybe have a giggle and think about the important message.

There is no other way to say this than being direct and upfront: when men pee at a urinal, we tend to 'aim' at various things. If there is a fly or remnants of another creature in the urinal, as often there are in public toilets, most men will immediately revert to 'target practice' - take aim and shoot at said object or creature. I don't quite know why we do it; perhaps the process of going for a pee is such a boring thing to do, that we have to find something to keep us focused. Perhaps the sub-conscious fighter pilot comes into play. I dunno.

This not-often talked about phenomenon has been quite brilliantly manipulated by some clever boffins who in one experiment in particular sought to determine whether such 'target practice' could reduce spills and accidents and improve cleanliness. The experiment was conducted at Amsterdam's Schiphol airport, whereby a motif made to look like a fly or small insect was embossed on the bowl of the men's urinals. The results suggested an 80% reduction in spills and overall greater cleanliness in the toilets, which for one of the world's largest airports might have some positive knock-on effects (tip: don't take your shoes off when flying or if you do, throw your socks away once home).

The urinal experiment is one example of nudge theory in action. Nudge theory is an interesting psychological concept which suggests that rather than trying to overtly 'change' peoples behaviour, views or opinions, you instead try and subtly direct people down a particular path by altering their environment for example. Basically being encouraged to change rather than compelled to change. We see it in action nearly every day and for some good causes. Pictures drawn by school children put outside schools to slow motorists down, putting graphic pictures on tobacco packs rather than banning their sale; all subtle ways of positively engineering the environment to make us head to a particular view or opinion, which for something like Politics is a great concept to use.

I don't like to think of us humans as passive animals in our thoughts and decisions. What nudge theory suggests however is that we are perhaps all 'vulnerable' to the various trappings and subtleties of the environment around us, positive and negative.

Don't push me... nudge me.

Pathological Demand Avoidance

This is a bit of a different post in that it's more descriptive than opinion. I would however say that the subject matter is important, particularly given the upcoming changes to the DSM criteria for 'autism spectrum disorders' that have been the subject of so much discussion and speculation.

Pathological Demand Avoidance (PDA). I first heard about PDA quite a few years ago at a small conference held in North-East England. Prof. Elizabeth Newson and colleagues from Nottingham presented some data on the definition of PDA and the varied ways in which PDA was distinguished from, and related to, other autism spectrum conditions. The main features of PDA (as taken from Newson et al*) are:

  • A passive early history (watching not interacting) which merges into becoming actively passive (objecting to normal demands).
  • Demand avoidance characterised by resisting the ordinary demands of life via social manipulation.
  • Apparent lack of sense of social identity, shame or pride (no sense of responsibility).
  • Mood lability and a need for control.
  • No problem with role playing or pretend play.
  • Language delay as a result of passivity.
  • Obsessive behaviour.
  • Neurological impairment (clumsiness, physical awkwardness).

There are quite a few summaries of this information (one of which can be viewed here). The main differences I take from these description compared with autism seems to focus on the child's intentions, and in particular, the active use of 'social manipulation' in PDA to action those intentions, coupled with no evidence of role and/or pretend play problems. I don't see any plans to formally include PDA in DSM or any other diagnostic text and am a little uncertain why, given that conditions such as Oppositional Defiant Disorder (ODD) have found a place in the diagnostic texts (and will continue to do so).

That's it. And because this was such a short post I leave you with probably the best music video ever - 'Buddy Holly' by Weezer for all you fans of the Fonz.

* Newson E, Le Marechal K, David C. Pathological demand avoidance syndrome: a necessary distinction within the pervasive developmental disorders. Archives of Disease in Childhood. 2003; 88: 595-600.

Tuesday, 14 June 2011

Purine metabolism and autism

Autism is replete with different areas of research and investigation. Trends in the various lines of inquiry taken down the years have tended to coincide with the various scientific 'fashions' of the times. Outside of the more psychological themes, there was in the early days up to the mid-1990's, research which seemed to be very heavily biochemistry-focused in autism. Serotonin, dopamine, endorphins and enkephalins and other like-minded compounds took centre stage in the era of biological psychiatry. The brain (and its chemical minions) was King.

Then began the era of genetics which jumped with a loud 'ta-da' onto the autism research stage. The initial mapping of the human genome was the impetus and all and everything was about genes. It initially started with the various population-wide studies of genes, moving in later years to the realisation that autism, like many conditions, is not a 'single gene condition'. Increased interest in the various descriptions of the broader autism phenotype, together with advancing technology, heralded the age of SNPs and CNVs into autism research. Genes were King.

At the current time, I think we are evolving again; currently being in the process of another shift in the research paradigm, with the onset of epigenetics and gene-environment interactions. 'We are all a consequence of our genes and environment' - or so the fashion tells. Certainly the conclusions from many studies seem to be heading in that direction. The brain, genes and environment all sit on the same throne.

For this post I am venturing back a few years to those olden' days of biochemistry and autism, and in particular, research on purine metabolism in relation to autism. Mary Coleman was a main player in purine research in autism. She was no stranger to autism research by any means and credited with some very interesting (and early) observations including the suggestion that about a quarter of people with autism also presented with a co-morbid defined medical disorder.

To the post at hand. What are purines? Stand-by for biochemistry 101. There is quite a complex description of purines here. Basically purines are a class of compound which all share two particular details in their chemical structure called a pyrimidine ring and imidazole ring. Pyrimidines and purines are of some interest to geneticists generally because the nucleotides which form our DNA [(A)denine, (G)uanine, (C)ytosine, (T)hymine] are pyrimidines (C & T) and purines (A & G). Aside from forming the base nucleotides, purines have quite a few other roles to play body-wide, notably in relation to things like ATP as a main energy source for cells.

Purines have been of some interest to autism for a while. The connection between purines and autism seems to have been predominantly due to the excessive excretion of a particular purine, uric acid, reported by some authors (including Coleman). Many people might have heard about uric acid in relation to conditions such as gout (one of the 'many' diseases suggested to be carried by King 'Enry VIII) but there are quite a few other conditions potentially connected to elevated levels of uric acid. Coleman and colleagues estimated that about 20% of people with autism might present with elevated uric acid levels (hyperuricosuria) although whether this is co-morbidity or specifically tied into presented symptoms is unclear. There is a case report by Ted Page (who worked with Coleman) suggesting that treatment with uridine correlated with positive changes to presented autistic symptoms, with regression when treatment was halted. This was followed up by a small trial (n=9) where benefits were noted up to 8 years later. Interestingly, uridine is found in quite a few foods including brewer's yeast (saccharomyces cerevisiae) - a cousin (but not the same as) of our old friend saccharomyces boulardii.

As per my previous disclaimers, I am not suggesting that uridine or brewer's yeast in this context is in any way, shape or form an 'intervention' option for autism or anything else. The Page papers, whilst interesting, reported on only small participant numbers and as far as I can see no-one has yet done anything further on this issue to decide whether raised uric acid levels are a chance finding or if not just epiphenomenal. It is therefore difficult to ascertain proper safety or efficacy data in this area; an area which seems to have gone the same way as the sulphate (sulfate) research.

Sunday, 12 June 2011

Evolutionary autism?

My sister blog 'Feed me research' (named in honour of everyone's favourite monster) carries a link to a recent article published in the journal Evolutionary Psychology by Jared Reser. The name of the journal perhaps gives away what the aim of the paper was: conceptualising autism from an evolutionary psychology perspective.

Probably best if I start from the beginning. Evolutionary psychology is a branch of psychology which sees the various human psychological traits and abilities as being the result of adaptations down the ages in much the same way as that of evolutionary biology. The main premise is that, psychologically, we are what we are today as a result of our overcoming various struggles and barriers that have confronted humankind in the past. So setting the wayback machine to several thousand years ago, our ancestors lived close to nature, very close to nature. After perhaps a few thousand or million encounters with spiders and snakes for example (particularly the poisonous variety), by some, as yet unknown process, a fear response is passed down the ages, and hey presto... 'get that spider away from me' or worse, arachnophobia and ophidiophobia. A classic gene-environment partnership at work perhaps?

Bearing this in mind, the paper in question goes into quite some detail describing how the various behaviours associated with 'modern-day' autism might have come about as a result of our ancestral lives, with particular focus on the 'solitary forager' hypothesis [forthwith to be called the SF hypothesis]. The SF hypothesis is based on the fact that before we were able to pop down to the supermarket and buy our tinned baked beans, even before we started cultivating beans as crops, humans were reliant on finding and eating what they could. I use beans as an example here but because the flux capacitor on my DeLorean is not quite in time-travelling mode at the moment, I can't precisely confirm how long haricot beans have been around. You get the gist anyway: we had to search out or 'forage' for our food. The solitary side of things stems from, well.. acting and being on one's own. In this case, searching out those all important food sources without the aid of a social group, which is perhaps advantageous particularly when food is scarce (who want's to share anyway).

Reser quite extensively goes through the various symptoms associated with autism together with other lines of enquiry to develop the SF theory. The obvious correlation made is the proposed social interactive side of autism, where like other species, the suggestion is that early humans were in the most part programmed to live the solitary life for most of their existence and so social skills were put on the backburner until required for those je t'aime Serge Gainsbourg moments. There are various other examples laid out, including how repetitive and inflexible behaviour patterns may have been beneficial for looking for certain types of food in certain areas as well as detecting and responding to threats. The support for the SF hypothesis comes from areas such as the 'extreme male brain' hypothesis and the 'map-reading = good, being a vicar = bad' skills suggested therein.

So what's the verdict on the SF hypothesis?

Well generally speaking, I have some time for the evolutionary perspective... at least to a degree. If you scroll down to the bottom of this blog you will see a link to Emily Dean's Evolutionary Psychiatry blog, which does an excellent job at highlighting how our modern-day living is perhaps a few steps ahead of what we humans were originally programmed for and the potential effects on our physical and mental health. Indeed, my research interest on the use of gluten- and casein-free diets as potential effectors of some cases of autism, inclines me to think that there might be something in concepts such as Paleo and Paleo 2.0; heavily dependent on where we were and where we are today and the disparity between the two. Drinking the secretions from another animal? Eating only recently cultivated grains? Probably not something that our early ancestors were doing in great quantities, although I admit that the evidence is not yet conclusive. Additional note: who first pressed their lips to a cows udder and thought 'mmm, that's not so bad'?

Reser does make quite a good attempt in portraying autistic symptoms in an evolutionary 'positive' light and some bloggers have seen something in the proposed theory. I suppose taking the example of natural selection, if autistic symptoms were not at some point 'beneficial', or in some cases, remaining beneficial, would they have not been naturally-selected out? A post for another day on assortative mating perhaps.

I can see the counter perspective also. We should be cautious in how we apply such a hypothesis to modern-day autism particularly with the potential for the more negative side of such writings relating to evolution and advancement. I understand that Reser did not set out to write this piece with such ideas in mind, but for some people this could be construed as offensive. There is, as far as I am aware, no physical evidence to corroborate 'evolutionary autism' or indeed the fact that all the traits were present, and present all at once, in any or every person of the Paleolithic era. Autism is an extremely heterogeneous condition, which covers a wide, wide, wide spectrum of presentations and abilities (and co-morbidities). Autism or autisms? In cases where daily living skills are not impaired, I could see how superior focus on details a la weak central coherence and repetitive patterns of behaviour would be advantageous if not life-saving when spotting lions in the grass or keeping a mental record of which berries are poisonous and which are safe, tasty and nutritious (no, iPads weren't around in the Paleolithic era unless there was the Flintstones equivalent - the iRock). I do find it a little more difficult to generalise such skills to those cases where autism is so extreme that almost constant care is required to do the most basic of things. Don't also even get me started on questioning what the evolutionary advantage of accompanying iron deficiency or bowel problems or ADHD or learning disability or other co-morbidities might have (not) been.

This is not the first time that 'evolutionary autism' has been suggested and discussed, and no doubt won't be the last. We all come from somewhere and I suppose this paper takes a good a shot as any at where and how. The final questions however have to be: what is the benefit of such hypotheses to people with autism in the modern world? Is it empowering to know that hunter-gatherers might have shown certain autistic traits? Is such information going to significantly improve quality of life for people on the autism spectrum today or tomorrow? Questions that I can't answer.

To finish, have a read of a previous post on drawing lines.