Apologies if you tuned in for a post about autism, but this is another 'other musings' entry (although I might mention autism at some point). Please, stay with me (this is not an April Fool) because I hope it might be of some interest; if anything else it might make for a few factoids vis-a-vie Steve Wright round the water-cooler at work the next day.
What's to say about urine? A waste product that we all produce in copious amounts throughout our lifetime. Constitution-wise it contains quite a bit; a good idea of what and how much is shown here. More recently urine, or rather the analysis of urine has been central to a relatively new branch of biological chemistry called metabolomics - studying the chemical 'fingerprints' left behind by biological processes.
The theory is that the pattern of our waste products in urine for example, whilst being unique to each individual, contains enough information for science to start looking at groupings based on compounds or levels of compounds excreted, which may eventually lead to predictions on our risk of disease or alternate biological markers for particular conditions or diseases.
Don't believe me? Well have a look at these abstracts suggestive of urine markers for kidney cancer, coeliac disease and depression to name but a few.
Last year there was quite a bit of excitement when a team based in London published this paper suggestive of potential urine biomarkers for autism. Accepting a few criticisms of the paper, some of the markers indicated for autism samples such as taurine, glutamate and various potential gut dysbiotic markers have been discussed previously as being possibly relevant, in various biological mediums.
Any more convinced? Yes... No...
OK, back to urine. One of the many differences, both intra- and inter-person, with regards to urine is concentration; that is, how concentrated or dilute our urine is. Urine concentration is affected by many different things; how hydrated our body is, whether we have engaged in any exercise, etc. Concentration of urine is important in working out the total amount of a compound or set of compounds also. If we imagine that a concentrated urine sample will contain higher levels of compounds quantitatively than a more dilute sample, you can see how sample concentration might affect studies looking at quantitative urinary biomarkers for a specific condition.
There are various ways of 'correcting' for urine concentration/dilution. Probably the most widely used is to measure urinary creatinine and correct sample concentration against creatinine. Whilst not wishing to provide Biochemistry 101 for creatinine metabolism, it is important at this point to make a distinction between creatinine and a related compound, creatine (although the two are connected).
So then normally when someone is trying to quantify one or more compounds in urine they may say something like: 100mg compound X / g/l creatinine. This means that 100 miligrams of compound X was detected per gram per litre of creatinine. (There are other units of concentration also used but I will not complicate things).
Creatinine is not alone as a marker for urine sample concentration (spot samples or 24-hour samples). There are others. One measure is the specific gravity (SG) of the sample. Anyone who has an interest in home brewing beer might know something about SG. SG is the ratio of the density of a sample relative to the density of water, assuming equal temperature and pressure. Pure water under set conditions has an SG of 1. A urine sample with all its dissolved compounds should have an SG greater than 1. Before you look away, this is as technical as I am getting.
Measuring the SG of urine is a tried and tested method and, in many respects, an easier option than assaying for creatinine (which depending on your method of analysis can include some quite 'explosive' steps). What's the difference between creatinine levels and SG I thought I heard you say...?
Well, there shouldn't be too much. There has been a long running debate about whether creatinine is a better marker of concentration over SG and vice-versa. The light at the end of the tunnel seems to suggest that there is little or no difference between the two measures when applied to the general population.
Fine, end of story. Not quite. There has been, for quite a few years now, some initial evidence to suggest that levels of creatinine in autism for example, are perhaps slightly aberrant compared to not-autism. Not trying to be a blatant self-publicist here, but I put my hand up because my colleagues and I have published on this a few years back. More recently also, similar findings have been reported by other authors; although I stress that this is not without some controversy.
Why might creatinine levels be unusual in autism? I dunno - potentially lots of reasons ranging from fluid intake to activity levels through to how much meat there is in the diet. What I do know is that if creatinine levels are somehow more consistently perturbed (lower), using it as a concentration corrector might, I stress might, indicate that comparator compounds are present in higher levels than they really are. I will stop there.
Next time you pop to the WC for a sprinkle, take a moment to think about what exactly is going into the bowl and how science stands to gain so much from it.
Thursday, 31 March 2011
When it works, it works well
Another short post. Don't worry (or perhaps worry), I have a few more detailed posts on various topics coming up in the next few days or so.
Anyway, I read this morning a press release about the issue of autism and wandering. 'Wandering' is an issue in the spotlight at the moment following quite a lot of chatter at the US IACC meetings for example; based on what is often, a common problem in autism which can have very tragic consequences.
My post does not relate specifically to wandering; instead to the very welcome meeting of minds who are becoming involved in looking at this issue.
Reading the press release and other blogs it is heartening to see that groups like Autism Speaks, the Autism Science Foundation and the Autism Research Institute, who perhaps share some differences of opinion on several matters related to autism, can put their differences aside and 'team up' on important issues such as this.
A case of when it works, it works well.
Anyway, I read this morning a press release about the issue of autism and wandering. 'Wandering' is an issue in the spotlight at the moment following quite a lot of chatter at the US IACC meetings for example; based on what is often, a common problem in autism which can have very tragic consequences.
My post does not relate specifically to wandering; instead to the very welcome meeting of minds who are becoming involved in looking at this issue.
Reading the press release and other blogs it is heartening to see that groups like Autism Speaks, the Autism Science Foundation and the Autism Research Institute, who perhaps share some differences of opinion on several matters related to autism, can put their differences aside and 'team up' on important issues such as this.
A case of when it works, it works well.
Monday, 28 March 2011
Remembering Leo Kanner 30 years on
This is a short post to remember the passing of a man who influenced countless people.
Emeritus Professor of Child Psychiatry, Leo Kanner passed away on 3 April 1981. Thirty years after his death, his name lives on, and his important work still resounds world-wide.
During this years World Autism Awareness Day (2 April), spare a thought for Kanner and perhaps take a little time out to read his original paper. Rest in peace.
Emeritus Professor of Child Psychiatry, Leo Kanner passed away on 3 April 1981. Thirty years after his death, his name lives on, and his important work still resounds world-wide.
During this years World Autism Awareness Day (2 April), spare a thought for Kanner and perhaps take a little time out to read his original paper. Rest in peace.
Saturday, 26 March 2011
Whatever happened to ToM and autism?
Don't get me wrong about this post; I am not trying to cause trouble. I am just doing what this blog is supposed to do - questioning answers. My question in this case is: what has happened to the 'theory of mind' concept related to autism spectrum conditions?
A lack of 'theory of mind' (ToM) connected to autism was, during my undergraduate education and early autism research career, like ham and eggs, Laurel and Hardy, Woody and Buzz. I remember reading paper after paper describing how autism was 'exemplified' by a lack of ToM, over and above every other explanation that psychology could offer (executive dysfunction, weak central coherence, etc).
From a psychology perspective, a lack of ToM was very interesting stuff. It was quite a simple concept to understand - 'putting yourself in another's shoes'; it seemed to concur with an important aspect of autism; and it was relatively easy to test for - ideal for the psychology undergraduate project. The research papers flowed in their hundreds on ToM and autism.
In recent years however, I have heard less and less about ToM in relation to autism. You still get quite a few papers on ToM and autism but less and less I see it being discussed either in the research world or in the blogosphere. Maybe it is just me. Maybe I am not as attentive as perhaps I once was. Maybe I am not going to the right websites and conferences.
One could argue that everything that needed to be said about ToM, has been said and that journals are perhaps less likely to publish on something which has, in all likelihood, already been published before. Similarly it is not outside the realms of possibility that ToM and autism is so installed into our psyche hard-drive that we don't need to hear any more about it. Possibilities anyway.
Perhaps also there are other reasons for the 'reduction' in ToM exposure?
Several authors (including those with autism or Asperger syndrome) have talked about ToM. Some of them are supportive of the concept of ToM as perhaps being a key aspect of autism spectrum conditions. Others have perhaps been less enthusiastic about ToM's attachment to autism. It seems to be a very personal thing to talk about; varying from person to person.
What does the research say?
Well, I don't think anyone can dispute the fact that for some people on the autism spectrum, a problem with ToM is present. There is little point in me posting the papers showing this because we would be here all night (search Google Scholar) - lots of experimental evidence which shows a good correlation between ToM and autism - at least in the laboratory setting.
The research literature also shows that ToM has changed and adapted as all good theories should when new evidence comes to light. ToM went to/was consumed by the concept of 'mindblindness', which then itself seems to have been taken up in the 'extreme male brain theory of autism' which seems also to be tied into the 'testosterone theory' of autism. The main changes highlight the fact that a specific cognitive style is perhaps apparent in at least some cases of autism, which includes ToM as part of its presentation. Apparent also is the movement from psychological theory to biological theory.
But ToM has not had a completely easy ride through autism.
A global relationship between ToM and autism has been questioned because of the lack of apparent specificity of ToM. Remember first my autism and n=1 post. ToM problems are seen in a diverse array of conditions and states including schizophrenia, depression and Alzheimer disease; also noted in studies of alcoholism. Unless one accepts that these and other conditions are somehow related to autism in some way (directly not peripherally), ToM problems in autism could just as well be linked to other cognitive processes or personality traits outside of autism, that are shared with these other conditions. Think also about the cultural differences in ToM ability, as detailed by this study of English and Italian children.
A second issue relates to the use of the term 'autism' in ToM problems. One of the earliest studies on ToM and autism is this one from 1985. Note the use of the word 'autism'. Why? Well, Asperger syndrome (AS) as a discrete diagnostic entry was not around at the time; indeed not around until 1992 in the ICD criteria and 1994 in the DSM diagnostic manual. The question therefore is this: are ToM problems related more to 'autism' or are they more relevant to Asperger syndrome?
Again, not an easy question to answer, and the research is confusing on this issue. Some authors suggested that AS is not on the whole affected by ToM problems; others suggest the opposite position. Much of this boils down to whether or not any fundamental differences are inferred between autism and AS. Is ToM present therefore purely as a function of some co-morbid intellectual disability?
Finally, there is a question about whether it matters if someone does or does not possess a theory of mind, and can people improve their ToM skills? Think about it, the ability to infer the mental states of another person. Mmm, how many people in the 'general' population have, and use this ability? The husband who sits on the sofa expecting to be 'waited on hand and foot'? The person who parks in a disabled car-parking space just because it is close to the shops? The employer who does not praise his/her employees when they do a good job? The burglar who steals from a house? ToM or no ToM?
Finally, finally! Can we ToM-train? The jury is still out on this one. A recent RCT suggests not; but perhaps further studies are required on this topic.
A lack of 'theory of mind' (ToM) connected to autism was, during my undergraduate education and early autism research career, like ham and eggs, Laurel and Hardy, Woody and Buzz. I remember reading paper after paper describing how autism was 'exemplified' by a lack of ToM, over and above every other explanation that psychology could offer (executive dysfunction, weak central coherence, etc).
From a psychology perspective, a lack of ToM was very interesting stuff. It was quite a simple concept to understand - 'putting yourself in another's shoes'; it seemed to concur with an important aspect of autism; and it was relatively easy to test for - ideal for the psychology undergraduate project. The research papers flowed in their hundreds on ToM and autism.
In recent years however, I have heard less and less about ToM in relation to autism. You still get quite a few papers on ToM and autism but less and less I see it being discussed either in the research world or in the blogosphere. Maybe it is just me. Maybe I am not as attentive as perhaps I once was. Maybe I am not going to the right websites and conferences.
One could argue that everything that needed to be said about ToM, has been said and that journals are perhaps less likely to publish on something which has, in all likelihood, already been published before. Similarly it is not outside the realms of possibility that ToM and autism is so installed into our psyche hard-drive that we don't need to hear any more about it. Possibilities anyway.
Perhaps also there are other reasons for the 'reduction' in ToM exposure?
Several authors (including those with autism or Asperger syndrome) have talked about ToM. Some of them are supportive of the concept of ToM as perhaps being a key aspect of autism spectrum conditions. Others have perhaps been less enthusiastic about ToM's attachment to autism. It seems to be a very personal thing to talk about; varying from person to person.
What does the research say?
Well, I don't think anyone can dispute the fact that for some people on the autism spectrum, a problem with ToM is present. There is little point in me posting the papers showing this because we would be here all night (search Google Scholar) - lots of experimental evidence which shows a good correlation between ToM and autism - at least in the laboratory setting.
The research literature also shows that ToM has changed and adapted as all good theories should when new evidence comes to light. ToM went to/was consumed by the concept of 'mindblindness', which then itself seems to have been taken up in the 'extreme male brain theory of autism' which seems also to be tied into the 'testosterone theory' of autism. The main changes highlight the fact that a specific cognitive style is perhaps apparent in at least some cases of autism, which includes ToM as part of its presentation. Apparent also is the movement from psychological theory to biological theory.
But ToM has not had a completely easy ride through autism.
A global relationship between ToM and autism has been questioned because of the lack of apparent specificity of ToM. Remember first my autism and n=1 post. ToM problems are seen in a diverse array of conditions and states including schizophrenia, depression and Alzheimer disease; also noted in studies of alcoholism. Unless one accepts that these and other conditions are somehow related to autism in some way (directly not peripherally), ToM problems in autism could just as well be linked to other cognitive processes or personality traits outside of autism, that are shared with these other conditions. Think also about the cultural differences in ToM ability, as detailed by this study of English and Italian children.
A second issue relates to the use of the term 'autism' in ToM problems. One of the earliest studies on ToM and autism is this one from 1985. Note the use of the word 'autism'. Why? Well, Asperger syndrome (AS) as a discrete diagnostic entry was not around at the time; indeed not around until 1992 in the ICD criteria and 1994 in the DSM diagnostic manual. The question therefore is this: are ToM problems related more to 'autism' or are they more relevant to Asperger syndrome?
Again, not an easy question to answer, and the research is confusing on this issue. Some authors suggested that AS is not on the whole affected by ToM problems; others suggest the opposite position. Much of this boils down to whether or not any fundamental differences are inferred between autism and AS. Is ToM present therefore purely as a function of some co-morbid intellectual disability?
Finally, there is a question about whether it matters if someone does or does not possess a theory of mind, and can people improve their ToM skills? Think about it, the ability to infer the mental states of another person. Mmm, how many people in the 'general' population have, and use this ability? The husband who sits on the sofa expecting to be 'waited on hand and foot'? The person who parks in a disabled car-parking space just because it is close to the shops? The employer who does not praise his/her employees when they do a good job? The burglar who steals from a house? ToM or no ToM?
Finally, finally! Can we ToM-train? The jury is still out on this one. A recent RCT suggests not; but perhaps further studies are required on this topic.
Friday, 25 March 2011
Hears, ears and autism
It has been mentioned on quite a few occasions.
Parents or caregivers initially suspect that their young child presents with a hearing problem when, for example, the child seems non-responsive to their name being called or when their attention is sought (see item 14 of the M-CHAT). The child submits to a hearing test and some of the time, nothing untoward is found. The question is then asked: could it be autism?
Likewise, there have been occasions when parents have initially suspected autism and, following a hearing test, it has transpired that the child has hearing problems. You can see that there is some overlap here.
Like visual impairment, hearing impairment (deafness, hard-of-hearing, if you wish) moves across quite a bit of ground; ranging from the source of the problem, through to the extent of the loss. Also like sight, many people would describe hearing as probably being one of the more primary senses in terms of its importance to daily life - language and communication, social interaction, balance, etc (some of these sound familiar?).
Hearing is so important a sense that, certainly here in the UK, the day of (or day after) birth, newborns have a hearing screen complimentary of the NHS Newborn Hearing Screening Programme. From what I am aware, there is no equivalent programme offered for sight throughout infancy; allowing though, for the difficulties of objective vision testing in newborns.
Looking at the rates of hearing loss in autism and in the general population, the RNID estimate that 1 in 1,000 children (0.1%) in the UK are deaf at age 3. The figures for other age-groups are slightly more complicated but between the ages of 16-60 years, the estimated prevalence of all types of deafness is 6.6%.
In autism, the estimated occurrence of co-morbid hearing loss (all types) is round about 10% in children and adolescents (note that this is a study published in 1999 carried out in Sweden). Obviously the age ranges don't exactly match up with the RNID figures, but the general suggestion is that hearing loss may be more prevalent in autism compared with the general population figures.
Issues with hearing in autism are not solely confined to a loss of function. Some people with autism (and their parents / caregivers) report issues with the perception of hearing; that is things like hyperacusis. There is some good evidence to suggest that the perception of loudness might be perturbed in some cases of autism. Indeed, for some children, the option of ear defenders / ear plugs is a vital course of action to block out what can often be quite disturbing sensory input.
What causes such hyperacuity? I don't think anyone has an answer for that yet. There is some suggestion that it might be down to sensory gating or temporal processing in specific groups on the autism spectrum but much more research is required. Readers may remember my recent entry on vision and autism; perhaps there is some shared mechanism with the perceptual issues highlighted in that area too - whereby our senses are linked together?
What can be done about hyperacusis? Again, there are no universally 'right' answers to this. My first thought would be that adapting the environment to the child/person with autism should be key. It is however probably impossible to remove all sound altogether - also impractical for a person who might have to go to school, go outside, etc.
Like the various comments on vision processing in autism, one course of action proposed is to think about ambient noise and its potential effect. The humming of the lights; certain pitches in people's voices; singing; dogs barking etc - these are all things which have been suggested by people with autism to be a source of often, real irritation (obviously there are a lot of other things too).
I previously mentioned ear defenders as one option, and indeed this young lady found them to be useful for her (also her iPod - no advertisement intended). Various other options have also been suggested, including things like auditory integration therapy (AIT) - although make sure that you do your research first. One final point of information and help may also come from a referral for the child to their local audiologist.
Most guidelines for autism screening and diagnosis do include some reference to hearing assessment. Hopefully also this will be included in the upcoming NICE guidelines on autism, and indeed research also expanded on the important issue of how hearing and autism are connected.
Parents or caregivers initially suspect that their young child presents with a hearing problem when, for example, the child seems non-responsive to their name being called or when their attention is sought (see item 14 of the M-CHAT). The child submits to a hearing test and some of the time, nothing untoward is found. The question is then asked: could it be autism?
Likewise, there have been occasions when parents have initially suspected autism and, following a hearing test, it has transpired that the child has hearing problems. You can see that there is some overlap here.
Like visual impairment, hearing impairment (deafness, hard-of-hearing, if you wish) moves across quite a bit of ground; ranging from the source of the problem, through to the extent of the loss. Also like sight, many people would describe hearing as probably being one of the more primary senses in terms of its importance to daily life - language and communication, social interaction, balance, etc (some of these sound familiar?).
Hearing is so important a sense that, certainly here in the UK, the day of (or day after) birth, newborns have a hearing screen complimentary of the NHS Newborn Hearing Screening Programme. From what I am aware, there is no equivalent programme offered for sight throughout infancy; allowing though, for the difficulties of objective vision testing in newborns.
Looking at the rates of hearing loss in autism and in the general population, the RNID estimate that 1 in 1,000 children (0.1%) in the UK are deaf at age 3. The figures for other age-groups are slightly more complicated but between the ages of 16-60 years, the estimated prevalence of all types of deafness is 6.6%.
In autism, the estimated occurrence of co-morbid hearing loss (all types) is round about 10% in children and adolescents (note that this is a study published in 1999 carried out in Sweden). Obviously the age ranges don't exactly match up with the RNID figures, but the general suggestion is that hearing loss may be more prevalent in autism compared with the general population figures.
Issues with hearing in autism are not solely confined to a loss of function. Some people with autism (and their parents / caregivers) report issues with the perception of hearing; that is things like hyperacusis. There is some good evidence to suggest that the perception of loudness might be perturbed in some cases of autism. Indeed, for some children, the option of ear defenders / ear plugs is a vital course of action to block out what can often be quite disturbing sensory input.
What causes such hyperacuity? I don't think anyone has an answer for that yet. There is some suggestion that it might be down to sensory gating or temporal processing in specific groups on the autism spectrum but much more research is required. Readers may remember my recent entry on vision and autism; perhaps there is some shared mechanism with the perceptual issues highlighted in that area too - whereby our senses are linked together?
What can be done about hyperacusis? Again, there are no universally 'right' answers to this. My first thought would be that adapting the environment to the child/person with autism should be key. It is however probably impossible to remove all sound altogether - also impractical for a person who might have to go to school, go outside, etc.
Like the various comments on vision processing in autism, one course of action proposed is to think about ambient noise and its potential effect. The humming of the lights; certain pitches in people's voices; singing; dogs barking etc - these are all things which have been suggested by people with autism to be a source of often, real irritation (obviously there are a lot of other things too).
I previously mentioned ear defenders as one option, and indeed this young lady found them to be useful for her (also her iPod - no advertisement intended). Various other options have also been suggested, including things like auditory integration therapy (AIT) - although make sure that you do your research first. One final point of information and help may also come from a referral for the child to their local audiologist.
Most guidelines for autism screening and diagnosis do include some reference to hearing assessment. Hopefully also this will be included in the upcoming NICE guidelines on autism, and indeed research also expanded on the important issue of how hearing and autism are connected.
Thursday, 24 March 2011
Food, feeding and autism
It's Bacon Conoisseurs’ Week this week here in the UK. Er.. happy Bacon Conoisseurs’ Week. Enjoy your er... bacon.
I know that this is a bit of a flaky way to start a post on food but please bear with me. The main reason that I am taking a look at food and feeding in autism spectrum conditions now is because of one of my previous posts on Kanner's original descriptions of autism and the fact that 6 of his 11 patients presented with early feeding problems. This really got me thinking about food (not just early feeding problems) as an issue.
Also, last night I chanced upon a programme called Supersize vs Superskinny Kids on Channel 4 and quite frankly I was pretty shocked by what I saw - not Mary Whitehouse shocked - but taken aback by the scale of food and feeding problems amongst quite a lot of kids nowadays in general. It got me thinking and questioning (hence the blog name): what are the main feeding issues present in childhood in autism, and are they so different from what seems to be happening with many kids in general, in these modern times?
Many years ago my colleagues and I published the results of a small scale trial looking at food and feeding behaviour in autism. It was not the best study ever done (i.e. no control group) but certainly also, not the worst. We asked parents about their child's food intake and feeding patterns, noted them in qualitative fashion and came up with a few, quite interesting things.
We found out for example that the children with autism in our group tended to have quite a restrictive diet in terms of the range of foods eaten. Nothing really earth-shattering there, given that various patterns of 'restricted' behaviour are core to diagnosis so why should feeding also not be affected?
When asked about the types of food which were included in the 'core' diet, there was some variability in the response. Some kids only liked 'dry' foods (crispy, crunchy); others only like soft foods (mushy, wet). For some kids it would be very 'bland' foods; for others it would be very 'strong' foods (I remember one child who enjoyed drinking neat cordial fruit juice without the water). Food refusal was pretty common. In some extreme cases there were reports of new foods being met with retching and/or vomiting even just by sight or smell, before taste. Food packaging also seemed to be quite important to some children. What brand, box, tin or bottle the food came from dictated whether it would be eaten or not. Some parents told us that they had taken to 'hiding' new foods in 'desired' food packages with varying degrees of success.
Looking at the other literature on food and feeding issues in autism, it looks like our study seemed to have captured the main issues: problems with food selectivity, food sensitivity (with regards to the perception of food eaten, not allergy or related mechanism) and an effect from food packaging.
Aside from the functional issues highlighted, we turn also to the more pathological aspects of food problems - when a feeding issue turns into a clinical issue - an eating disorder. There is still some controversy about whether eating disorders can/are present in autism spectrum conditions to any greater degree than in the general population. Allowing for the fact that there may be some similarity in the cognitive profiles in autism and anorexia for example, there is only limited research on the prevalence of eating disorder in autism. One potential factor is gender: autism is male-dominated; anorexia is female-dominated; another is the varying impact of social factors which are thought to influence eating disorders. At this point I should mention that I am not going to discuss issues such as weight, BMI and diet in this post - perhaps in another post, but not this one.
We turn then to the question of whether such feeding issues are exclusive to childhood autism. Answer: probably not. Feeding problems are present in lots of different conditions including learning disability. Studies of LD seems to indicate similar issues to those noted in autism - food refusal, food selectivity, etc. Where a physical 'disability' is present, such as a cleft palette, food difficulties are exacerbated.
In the general population also, feeding problems seem to be quite prevalent. I found some difficulty in ascertaining exactly how prevalent given that lots of different factors can affect feeding habits. But many authors seem to say yes, they are prevalent to varying degrees; moderated by many things including age.
What then can we surmise from all this?
Autism is associated with food and feeding issues - yes. Other conditions are also associated with food and feeding issues - yes. Lots of children in the general population are affected by food and feeding issues - yes. Whilst not trying to downplay the effects of feeding problems in childhood autism spectrum conditions, the take-home message is that parents of children with autism are not alone on this issue.
I know that this is a bit of a flaky way to start a post on food but please bear with me. The main reason that I am taking a look at food and feeding in autism spectrum conditions now is because of one of my previous posts on Kanner's original descriptions of autism and the fact that 6 of his 11 patients presented with early feeding problems. This really got me thinking about food (not just early feeding problems) as an issue.
Also, last night I chanced upon a programme called Supersize vs Superskinny Kids on Channel 4 and quite frankly I was pretty shocked by what I saw - not Mary Whitehouse shocked - but taken aback by the scale of food and feeding problems amongst quite a lot of kids nowadays in general. It got me thinking and questioning (hence the blog name): what are the main feeding issues present in childhood in autism, and are they so different from what seems to be happening with many kids in general, in these modern times?
Many years ago my colleagues and I published the results of a small scale trial looking at food and feeding behaviour in autism. It was not the best study ever done (i.e. no control group) but certainly also, not the worst. We asked parents about their child's food intake and feeding patterns, noted them in qualitative fashion and came up with a few, quite interesting things.
We found out for example that the children with autism in our group tended to have quite a restrictive diet in terms of the range of foods eaten. Nothing really earth-shattering there, given that various patterns of 'restricted' behaviour are core to diagnosis so why should feeding also not be affected?
When asked about the types of food which were included in the 'core' diet, there was some variability in the response. Some kids only liked 'dry' foods (crispy, crunchy); others only like soft foods (mushy, wet). For some kids it would be very 'bland' foods; for others it would be very 'strong' foods (I remember one child who enjoyed drinking neat cordial fruit juice without the water). Food refusal was pretty common. In some extreme cases there were reports of new foods being met with retching and/or vomiting even just by sight or smell, before taste. Food packaging also seemed to be quite important to some children. What brand, box, tin or bottle the food came from dictated whether it would be eaten or not. Some parents told us that they had taken to 'hiding' new foods in 'desired' food packages with varying degrees of success.
Looking at the other literature on food and feeding issues in autism, it looks like our study seemed to have captured the main issues: problems with food selectivity, food sensitivity (with regards to the perception of food eaten, not allergy or related mechanism) and an effect from food packaging.
Aside from the functional issues highlighted, we turn also to the more pathological aspects of food problems - when a feeding issue turns into a clinical issue - an eating disorder. There is still some controversy about whether eating disorders can/are present in autism spectrum conditions to any greater degree than in the general population. Allowing for the fact that there may be some similarity in the cognitive profiles in autism and anorexia for example, there is only limited research on the prevalence of eating disorder in autism. One potential factor is gender: autism is male-dominated; anorexia is female-dominated; another is the varying impact of social factors which are thought to influence eating disorders. At this point I should mention that I am not going to discuss issues such as weight, BMI and diet in this post - perhaps in another post, but not this one.
We turn then to the question of whether such feeding issues are exclusive to childhood autism. Answer: probably not. Feeding problems are present in lots of different conditions including learning disability. Studies of LD seems to indicate similar issues to those noted in autism - food refusal, food selectivity, etc. Where a physical 'disability' is present, such as a cleft palette, food difficulties are exacerbated.
In the general population also, feeding problems seem to be quite prevalent. I found some difficulty in ascertaining exactly how prevalent given that lots of different factors can affect feeding habits. But many authors seem to say yes, they are prevalent to varying degrees; moderated by many things including age.
What then can we surmise from all this?
Autism is associated with food and feeding issues - yes. Other conditions are also associated with food and feeding issues - yes. Lots of children in the general population are affected by food and feeding issues - yes. Whilst not trying to downplay the effects of feeding problems in childhood autism spectrum conditions, the take-home message is that parents of children with autism are not alone on this issue.
Wednesday, 23 March 2011
Kanner's original autism descriptions
You will find some recurrent themes in this blog. This includes notions of how information can become distorted from the original source over time and the value of corroborating evidence when purporting to make statements of fact.
The first notion in particular may relate to this blog entry; analysing the original clinical descriptions of autism suggested by Dr Leo Kanner in 1943. It is perhaps timely that, in a few days, it will be 30 years since Kanner passed away (3 April 1981); indeed coincidental also that World Autism Awareness Day is on 2nd April (I wonder why they did not make it 3rd April instead?). I digress.
From the outset I want to acknowledge that, whilst Kanner's clinical descriptions form the basis for what we know as autism, I am by no means suggesting that he was the first to 'discover' autism given the many and varied texts from further back in history. Indeed, several other papers have suggested autism to have been present to some extent for many years prior to Kanner; although not labelled as 'autism' at the time (a label which did not exist).
I have always been keenly interested in Kanner's original 1943 paper 'Autistic disturbances of affective contact'. So much so, that my PhD drew heavily on his key clinical descriptions of 11 children who presented with symptoms including: inability to relate to themselves, extreme autistic aloneness, monotonously repetitious, anxiously obsessive desire for the maintenance of sameness and limitation in the variety of spontaneous activity. I have used but a few choice phrases from his text which have echoed down the diagnostic halls ever since.
There are however a few other phrases included in his 1943 text which, for one reason or another, did not quite receive the same subsequent acclaim. There are many reasons why such phrases and descriptions did not 'make the final cut' but I assume most were down to the old adage: a cobbler should stick to his last. Kanner was a Psychiatrist in the 1940s and hence specialised in 'disorders of the mind'. Subsequent interpretations of his text (e.g. DSM) have been undertaken specifically with Psychiatry in mind. Read on and you'll see what I mean.
'Food' (p.244) is mentioned in the 1943 text. Six of the children originally described by Kanner presented with various feeding difficulties; ranging from early vomiting, having to be 'tube-fed' and presenting with 'severe feeding difficulty from the beginning of life'. By early feeding problems I am assuming that this means problems with either mother's milk or the early formula milks (if they were even invented at this point). Six out of eleven cases, that's... er, over 50%. OK, he did not have a control group given that this was a case series description. Yet despite this, have early feeding difficulties ever been included in the diagnostic texts for autism? No, not even as an ancillary risk factor. Not once. Not never (not that I know anyway!). I know a few authors have offered potential explanations for early feeding difficulties in autism relating to the mechanical aspects of feeding and the 'perceptual' side of things. I am not saying that these may not be explanatory of what Kanner was perhaps describing. A few days ago however I blogged about a recent study from Harvard on the likelihood of lactose intolerance in cases of autism. Makes you wonder if today's technology were around during Kanner's tenure, would he be reporting lactose intolerance also?
Another example included in the original text. Kanner discusses the fact that 'several of the children were somewhat clumsy in gait and gross motor performances'. Gait and motor problems have similarly not been included in the diagnostic texts down the years. Unlike feeding problems however, there has been a slow realisation that such issues might be of relevance. It has however taken quite a few years for these elements to be 'realised' in cases of autism. One of the most recent studies being this one on the mechanics of gait in autism which is crying out for further replication.
The point I want to make with this post is that aside from going to the source for evidence, the original descriptions of autism from Kanner contained so much more than just behaviour relating to the triad (or should that be 'dyad'?) of impairments. Kanner did what any good scientist does - he observed and recorded things; not just behaviour but also developmental history and importantly somatic issues (see bottom of page 234).
I appreciate that today Kanner's autism has perhaps been 'subsumed' into this larger spectrum of autistic conditions. I often wonder how many of Kanner's original cohort would be diagnosed with autism, or an autism spectrum disorder, or even Asperger syndrome nowadays (bearing in mind that Hans Asperger did not define his patient group until a year later in 1944, and then light years away in Austria).
The first notion in particular may relate to this blog entry; analysing the original clinical descriptions of autism suggested by Dr Leo Kanner in 1943. It is perhaps timely that, in a few days, it will be 30 years since Kanner passed away (3 April 1981); indeed coincidental also that World Autism Awareness Day is on 2nd April (I wonder why they did not make it 3rd April instead?). I digress.
From the outset I want to acknowledge that, whilst Kanner's clinical descriptions form the basis for what we know as autism, I am by no means suggesting that he was the first to 'discover' autism given the many and varied texts from further back in history. Indeed, several other papers have suggested autism to have been present to some extent for many years prior to Kanner; although not labelled as 'autism' at the time (a label which did not exist).
I have always been keenly interested in Kanner's original 1943 paper 'Autistic disturbances of affective contact'. So much so, that my PhD drew heavily on his key clinical descriptions of 11 children who presented with symptoms including: inability to relate to themselves, extreme autistic aloneness, monotonously repetitious, anxiously obsessive desire for the maintenance of sameness and limitation in the variety of spontaneous activity. I have used but a few choice phrases from his text which have echoed down the diagnostic halls ever since.
There are however a few other phrases included in his 1943 text which, for one reason or another, did not quite receive the same subsequent acclaim. There are many reasons why such phrases and descriptions did not 'make the final cut' but I assume most were down to the old adage: a cobbler should stick to his last. Kanner was a Psychiatrist in the 1940s and hence specialised in 'disorders of the mind'. Subsequent interpretations of his text (e.g. DSM) have been undertaken specifically with Psychiatry in mind. Read on and you'll see what I mean.
'Food' (p.244) is mentioned in the 1943 text. Six of the children originally described by Kanner presented with various feeding difficulties; ranging from early vomiting, having to be 'tube-fed' and presenting with 'severe feeding difficulty from the beginning of life'. By early feeding problems I am assuming that this means problems with either mother's milk or the early formula milks (if they were even invented at this point). Six out of eleven cases, that's... er, over 50%. OK, he did not have a control group given that this was a case series description. Yet despite this, have early feeding difficulties ever been included in the diagnostic texts for autism? No, not even as an ancillary risk factor. Not once. Not never (not that I know anyway!). I know a few authors have offered potential explanations for early feeding difficulties in autism relating to the mechanical aspects of feeding and the 'perceptual' side of things. I am not saying that these may not be explanatory of what Kanner was perhaps describing. A few days ago however I blogged about a recent study from Harvard on the likelihood of lactose intolerance in cases of autism. Makes you wonder if today's technology were around during Kanner's tenure, would he be reporting lactose intolerance also?
Another example included in the original text. Kanner discusses the fact that 'several of the children were somewhat clumsy in gait and gross motor performances'. Gait and motor problems have similarly not been included in the diagnostic texts down the years. Unlike feeding problems however, there has been a slow realisation that such issues might be of relevance. It has however taken quite a few years for these elements to be 'realised' in cases of autism. One of the most recent studies being this one on the mechanics of gait in autism which is crying out for further replication.
The point I want to make with this post is that aside from going to the source for evidence, the original descriptions of autism from Kanner contained so much more than just behaviour relating to the triad (or should that be 'dyad'?) of impairments. Kanner did what any good scientist does - he observed and recorded things; not just behaviour but also developmental history and importantly somatic issues (see bottom of page 234).
I appreciate that today Kanner's autism has perhaps been 'subsumed' into this larger spectrum of autistic conditions. I often wonder how many of Kanner's original cohort would be diagnosed with autism, or an autism spectrum disorder, or even Asperger syndrome nowadays (bearing in mind that Hans Asperger did not define his patient group until a year later in 1944, and then light years away in Austria).
Tuesday, 22 March 2011
Mental health and autism
This is a topic I have been wanting to blog about for quite a while. There are lots of reasons why; mainly centred around discussions on the resources and facilities available to support and improve good mental health for people with autism in these times of austerity and cuts, but also to do with the conversations I have had with various people about factors potentially determining quality of life for people with autism (perhaps another post in itself).
First a definition: what are the mental health problems commonly associated with autism? Well the term 'mental health problem' is really a catch-all for lots of different things which according to the UK National Autistic Society (NAS) includes: depression, anxiety, obsessive-compulsive disorder (OCD) and schizophrenia. I know that there are probably other conditions which fit under the umbrella (eating disorders such as anorexia being one of them), but these are the main ones which seem most relevant to the majority of the autism spectrum conditions.
An important distinction to make at this point relates to chronological age. Some of the mental health issues highlighted above are relevant across the age groups (early infancy?). Others become more of a 'problem' as a child with autism / Asperger syndrome turns into an adult with autism / Asperger syndrome. Added to this are the issues of acute vs. chronic episodes and also the changing nature of mental health patterns, including where multiple conditions are overlapping.
So, how prevalent are mental health problems in autism? Well it very much depends on what sample you are looking at and what you define as a mental health problem as to what the research tells us.
A recent study documented behaviour and emotional problems as being present in approximately three-quarters of children with high-functioning ASD. This European study determined varying rates of mental health problems amongst adults with an autism spectrum condition ranging from mood disorders (53%) to anxiety disorder (50%), and changing according to sub-diagnosis. Prevalence is further complicated by other issues such as co-morbidity (physical and/or psychiatric) alongside the autism diagnosis.
What we can probably infer from these and other studies is that a sizeable proportion of people with an autism spectrum condition will also present with a mental health problem at some point in their lives. It does sound a little bit scary when put like this; and of course we must also take into account that many people without autism also present with mental ill-health at some point in their life. Depression for example is estimated to be present in approximately 15% of the UK population over a lifetime influenced by factors as diverse as physical ill-health and co-morbidity with other mental health problems.
What can, and do we do about mental health problems in autism? Another million dollar question (probably a billion dollar question nowadays with the rate of inflation). I would perhaps forward the view that this depends on which professionals become involved and what services are 'on offer' geographically given the shortage of national (and international) guidance on this issue.
A Psychologist or similar professional might be more inclined to examine the usefulness of the so-called 'talking therapies' as an intervention option. Certainly there is a growing evidence base to suggest that psychological interventions like cognitive behaviour therapy (CBT) can be quite successful for helping things like anxiety in Asperger syndrome. More work is required however to ascertain success rates and what elements (if any) of successful intervention might also be transferable to other autism sub-diagnoses.
The use of pharmacotherapy is another potential option. There are several good review papers discussing the various drugs of choice for tackling mental health issues; one or two have been included in one of my previous posts. Medication, whilst useful in some cases, does not however have a great reputation either in autism or outside of autism with regards to mental health problems. I don't know if it is something to do with the notion of putting something into the body, or the fact that many preparations have such powerful effects on the body and brain - see discussion on the so-called 'chemical cosh'. People generally feel a little uneasy about pharmacotherapy.
Aside from the various 'issues' raised with some medications, there is some disquiet on the potential side-effects from various formulations and indeed some fairly unfavourable reviews on how effective certain preparations are specific to autism. This, however has to be balanced against the number of people who do show positive effects from various medications aimed at alleviating mental health problems; especially when accompanied by good medicines management and appropriate monitoring.
I must add a disclaimer at this point that I am not making any judgements on the effectiveness or safety of any particular intervention for a mental health problem, merely presenting some facts.
There are other approaches that may similarly positively impact on mental health in autism spectrum conditions. The use of spirituality and meditation come to mind, and in particular the writings of people like Chris Mitchell who discusses his use of Theravada Buddhism to tackle worry and anxiety. These are quite fascinating areas of interest which have been barely touched by scientific research.
Societal effects have neither hitherto been mentioned in this post. If one were to assume that some of the underlying source/s of certain mental health problems could lie in the multitude of issues confronting particularly an adult with autism (money, employment, relationships, etc) one could also suggest that some 'adaptation' on the part of society could also be used to improve mental health. How many people for example in the general population develop depression as a result of a lack of employment? Likewise, how does gaining employment affect depression? How would employment affect any co-morbid depression in autism or Asperger syndrome?
As you can see, this is a very, very complicated area of autism research and practice.
First a definition: what are the mental health problems commonly associated with autism? Well the term 'mental health problem' is really a catch-all for lots of different things which according to the UK National Autistic Society (NAS) includes: depression, anxiety, obsessive-compulsive disorder (OCD) and schizophrenia. I know that there are probably other conditions which fit under the umbrella (eating disorders such as anorexia being one of them), but these are the main ones which seem most relevant to the majority of the autism spectrum conditions.
An important distinction to make at this point relates to chronological age. Some of the mental health issues highlighted above are relevant across the age groups (early infancy?). Others become more of a 'problem' as a child with autism / Asperger syndrome turns into an adult with autism / Asperger syndrome. Added to this are the issues of acute vs. chronic episodes and also the changing nature of mental health patterns, including where multiple conditions are overlapping.
So, how prevalent are mental health problems in autism? Well it very much depends on what sample you are looking at and what you define as a mental health problem as to what the research tells us.
A recent study documented behaviour and emotional problems as being present in approximately three-quarters of children with high-functioning ASD. This European study determined varying rates of mental health problems amongst adults with an autism spectrum condition ranging from mood disorders (53%) to anxiety disorder (50%), and changing according to sub-diagnosis. Prevalence is further complicated by other issues such as co-morbidity (physical and/or psychiatric) alongside the autism diagnosis.
What we can probably infer from these and other studies is that a sizeable proportion of people with an autism spectrum condition will also present with a mental health problem at some point in their lives. It does sound a little bit scary when put like this; and of course we must also take into account that many people without autism also present with mental ill-health at some point in their life. Depression for example is estimated to be present in approximately 15% of the UK population over a lifetime influenced by factors as diverse as physical ill-health and co-morbidity with other mental health problems.
What can, and do we do about mental health problems in autism? Another million dollar question (probably a billion dollar question nowadays with the rate of inflation). I would perhaps forward the view that this depends on which professionals become involved and what services are 'on offer' geographically given the shortage of national (and international) guidance on this issue.
A Psychologist or similar professional might be more inclined to examine the usefulness of the so-called 'talking therapies' as an intervention option. Certainly there is a growing evidence base to suggest that psychological interventions like cognitive behaviour therapy (CBT) can be quite successful for helping things like anxiety in Asperger syndrome. More work is required however to ascertain success rates and what elements (if any) of successful intervention might also be transferable to other autism sub-diagnoses.
The use of pharmacotherapy is another potential option. There are several good review papers discussing the various drugs of choice for tackling mental health issues; one or two have been included in one of my previous posts. Medication, whilst useful in some cases, does not however have a great reputation either in autism or outside of autism with regards to mental health problems. I don't know if it is something to do with the notion of putting something into the body, or the fact that many preparations have such powerful effects on the body and brain - see discussion on the so-called 'chemical cosh'. People generally feel a little uneasy about pharmacotherapy.
Aside from the various 'issues' raised with some medications, there is some disquiet on the potential side-effects from various formulations and indeed some fairly unfavourable reviews on how effective certain preparations are specific to autism. This, however has to be balanced against the number of people who do show positive effects from various medications aimed at alleviating mental health problems; especially when accompanied by good medicines management and appropriate monitoring.
I must add a disclaimer at this point that I am not making any judgements on the effectiveness or safety of any particular intervention for a mental health problem, merely presenting some facts.
There are other approaches that may similarly positively impact on mental health in autism spectrum conditions. The use of spirituality and meditation come to mind, and in particular the writings of people like Chris Mitchell who discusses his use of Theravada Buddhism to tackle worry and anxiety. These are quite fascinating areas of interest which have been barely touched by scientific research.
Societal effects have neither hitherto been mentioned in this post. If one were to assume that some of the underlying source/s of certain mental health problems could lie in the multitude of issues confronting particularly an adult with autism (money, employment, relationships, etc) one could also suggest that some 'adaptation' on the part of society could also be used to improve mental health. How many people for example in the general population develop depression as a result of a lack of employment? Likewise, how does gaining employment affect depression? How would employment affect any co-morbid depression in autism or Asperger syndrome?
As you can see, this is a very, very complicated area of autism research and practice.
Autism and developmental history recall
The diagnosis of an autism spectrum condition is predominantly (nay exclusively) based on a subjective judgement of whether clinical behavioural criteria are met, also incorporating an analysis of a person's developmental history.
In other words, parents and caregivers are often vital to the diagnostic process as a function of their recall of their child's early medical and developmental onset history, and events leading towards the presentation of symptoms.
Early diagnosis of autism is the goal; although often, because of the way symptoms present or the finite resources available to access assessment services, there are delays from time of symptom onset / recognition to receipt of a formal diagnosis. In some cases, this delay registers in the years rather than months or weeks.
I say all this because a new paper by Cathy Lord and colleagues discusses an important issue relating to the recall of symptoms, the 'telescoping' effect in caregiver reports - that is, a bias based on the reporting of events. Telescoping can be forward or backwards; so remembering events either closer or more distant than they really are.
Before anyone takes this issue too personally, I must add that we all do it. Ask someone about when a recent event happened and the chances are that they will be slightly outside of the actual time frame - 'when did I last go out for a meal?', 'when did I last call my parents', 'at what age did my children start to walk' - all biased by our failing memory (assuming that there is no other corroborating evidence such as videos or diary entries).
Lord and colleagues suggested some significant telescoping effects when the Autism Diagnostic Interview (ADI) was administered to caregivers over various occasions of their child's early years (2,3,5,9 years of age), specifically in the area of language milestones (acquisition of language, use of phrase speech, etc). Importantly however, when it came to the age of first concern over symptoms, caregivers seemed to be pretty consistent.
What does this all mean?
Well when it comes to dating when symptoms started, current psychological theory would perhaps suggest that this date is an anchor point for parents / caregivers. Whether due to a realisation that symptoms present and the subsequent emotional effects of this (emotions and memory seem to be strongly connected) or the associated interactions with other people (teachers, health visitors, physicians) as a result, age of first concern seems to stick in the memory.
Dating the various features of language acquisition proved more difficult. I assume much of this is because many things related to language are not tied into just one date. Remember the scene in Meet the Fockers when the little boy utters his first words (I won't repeat them here!). Unless a child says such an extreme word, chances are most people won't be able to date accurately when their child's first word happened just from memory. Likewise can anyone name the date when their child went from using single words to phrase speech? With all the will in the world, most people will be inaccurate because again our memory needs some kind of anchor and such a transition process is often not tied into one date.
One final thing related to this paper: at the end of the abstract, the authors say: "Results support proposals to remove specific age-based criteria in the diagnosis of ASD". For those who read my post on the new proposals for the DSM-V entry for autism, and in particular the proposed changes to a 'dyad of impairments', this sounds to me like the DSM-V proposal is shortly going to become a reality.
In other words, parents and caregivers are often vital to the diagnostic process as a function of their recall of their child's early medical and developmental onset history, and events leading towards the presentation of symptoms.
Early diagnosis of autism is the goal; although often, because of the way symptoms present or the finite resources available to access assessment services, there are delays from time of symptom onset / recognition to receipt of a formal diagnosis. In some cases, this delay registers in the years rather than months or weeks.
I say all this because a new paper by Cathy Lord and colleagues discusses an important issue relating to the recall of symptoms, the 'telescoping' effect in caregiver reports - that is, a bias based on the reporting of events. Telescoping can be forward or backwards; so remembering events either closer or more distant than they really are.
Before anyone takes this issue too personally, I must add that we all do it. Ask someone about when a recent event happened and the chances are that they will be slightly outside of the actual time frame - 'when did I last go out for a meal?', 'when did I last call my parents', 'at what age did my children start to walk' - all biased by our failing memory (assuming that there is no other corroborating evidence such as videos or diary entries).
Lord and colleagues suggested some significant telescoping effects when the Autism Diagnostic Interview (ADI) was administered to caregivers over various occasions of their child's early years (2,3,5,9 years of age), specifically in the area of language milestones (acquisition of language, use of phrase speech, etc). Importantly however, when it came to the age of first concern over symptoms, caregivers seemed to be pretty consistent.
What does this all mean?
Well when it comes to dating when symptoms started, current psychological theory would perhaps suggest that this date is an anchor point for parents / caregivers. Whether due to a realisation that symptoms present and the subsequent emotional effects of this (emotions and memory seem to be strongly connected) or the associated interactions with other people (teachers, health visitors, physicians) as a result, age of first concern seems to stick in the memory.
Dating the various features of language acquisition proved more difficult. I assume much of this is because many things related to language are not tied into just one date. Remember the scene in Meet the Fockers when the little boy utters his first words (I won't repeat them here!). Unless a child says such an extreme word, chances are most people won't be able to date accurately when their child's first word happened just from memory. Likewise can anyone name the date when their child went from using single words to phrase speech? With all the will in the world, most people will be inaccurate because again our memory needs some kind of anchor and such a transition process is often not tied into one date.
One final thing related to this paper: at the end of the abstract, the authors say: "Results support proposals to remove specific age-based criteria in the diagnosis of ASD". For those who read my post on the new proposals for the DSM-V entry for autism, and in particular the proposed changes to a 'dyad of impairments', this sounds to me like the DSM-V proposal is shortly going to become a reality.
Monday, 21 March 2011
Back to gluten sensitivity and coeliac disease?
As a man of my word I have, in this post, come back to the recent paper published by Sapone and colleagues in BMC Medicine detailing some apparent gastrointestinal differences between coeliac disease and non-coeliac gluten sensitivity.
The authorship team to this paper reads like a Who's Who in gluten research. Two authors stick out for me: Alessio Fasano who many would argue is one of the leaders in the field of gluten, coeliac disease (CD) and intestinal permeability research, and Laura de Magistris, who autism research followers will know from the recent intestinal permeability paper which I blogged about here.
Their paper is quite a complex one and in some areas I am a little baffled myself - more to do with the limitations of my knowledge rather than their manuscript - so please excuse any errors in my interpretation.
What I think I can decipher from the recent paper is that the main aim of the study was to look at intestinal barrier function and various immune responses in non-coeliac gluten sensitivity (GS) compared to coeliac disease.
The participant numbers: 26 well-defined GS (-ve CD serology, normal gut mucosa and an effect from use of a gluten-free diet), 42 with active CD and just for good measure, 39 controls (not CD or GS). All participants were adults (mid-20s to 30s) and mostly female.
The findings:
So there we have it. My simple reading of these results (and I do stress 'simple') is that outside of the immune system differences highlighted, whether or not intestinal hyperpermeability is present is an important differentiating factor between CD and GS.
Where does autism fit into this?
Well, the paper by de Magistris and colleagues related to autism did indicate intestinal hyperpermeability as being present in about a third of cases that they looked at. They also reported that use of gluten-free diet seemed to 'reduce' the level of permeability present (similar to what might happen in CD). They did however rule out CD in the autism participant group, so findings were not due to CD.
One area of interest in the latest study overlaps with the de Magistris autism paper and perhaps requires further study. That is the role of anti-gliadin antibodies (AGA) (IgA / IgG). Nearly 50% of the GS patients in the latest trial were AGA +ve compared with about 3/4 of the CD group (all the controls were -ve). de Magistris reported that 2 of her autism groups showed high AGA IgG which in both cases were associated with 'normal' intestinal permeability (similar to the GS group?) and elevated fecal calprotectin levels associated with inflammation. Elevated IgG AGAs have been reported previously in autism by Vojdani and colleagues (see here and here) although without accompanying gastrointestinal findings detailed in the recent paper.
What this potentially suggests is that the effect of gluten on some cases of autism is perhaps due to more than one scenario: intestinal hyperpermeability (as in CD) linked perhaps to other compounds, or high AGA IgG (IgA?) levels and inflammation or perhaps due to bog standard co-morbid CD. I would hasten to add that there may well be other mechanisms to add to this list.
This is a fascinating area of research and along with several other recent papers is providing further insights into the shadowy nature of our relationship with gluten, outside of coeliac disease.
The authorship team to this paper reads like a Who's Who in gluten research. Two authors stick out for me: Alessio Fasano who many would argue is one of the leaders in the field of gluten, coeliac disease (CD) and intestinal permeability research, and Laura de Magistris, who autism research followers will know from the recent intestinal permeability paper which I blogged about here.
Their paper is quite a complex one and in some areas I am a little baffled myself - more to do with the limitations of my knowledge rather than their manuscript - so please excuse any errors in my interpretation.
What I think I can decipher from the recent paper is that the main aim of the study was to look at intestinal barrier function and various immune responses in non-coeliac gluten sensitivity (GS) compared to coeliac disease.
The participant numbers: 26 well-defined GS (-ve CD serology, normal gut mucosa and an effect from use of a gluten-free diet), 42 with active CD and just for good measure, 39 controls (not CD or GS). All participants were adults (mid-20s to 30s) and mostly female.
The findings:
- quite a few of the GS participants showed positive for one or more of the DQ2 / DQ8 heterodimers,
- intestinal hyperpermeability was not as prevalent in the GS group compared to the CD group, associated with a milder gut histology in GS potentially due to the expression of various tight junction (TJ) related genes,
- GS participants presented with increased CD3+ intraepithelial lymphocytes (IELs) relative to the control group but lower than that of the CD group; along with a few other parameters this suggests an 'intermediate, low-level' role for the adaptive immune system in GS and a role for innate immune mechanisms (inflammation).
So there we have it. My simple reading of these results (and I do stress 'simple') is that outside of the immune system differences highlighted, whether or not intestinal hyperpermeability is present is an important differentiating factor between CD and GS.
Where does autism fit into this?
Well, the paper by de Magistris and colleagues related to autism did indicate intestinal hyperpermeability as being present in about a third of cases that they looked at. They also reported that use of gluten-free diet seemed to 'reduce' the level of permeability present (similar to what might happen in CD). They did however rule out CD in the autism participant group, so findings were not due to CD.
One area of interest in the latest study overlaps with the de Magistris autism paper and perhaps requires further study. That is the role of anti-gliadin antibodies (AGA) (IgA / IgG). Nearly 50% of the GS patients in the latest trial were AGA +ve compared with about 3/4 of the CD group (all the controls were -ve). de Magistris reported that 2 of her autism groups showed high AGA IgG which in both cases were associated with 'normal' intestinal permeability (similar to the GS group?) and elevated fecal calprotectin levels associated with inflammation. Elevated IgG AGAs have been reported previously in autism by Vojdani and colleagues (see here and here) although without accompanying gastrointestinal findings detailed in the recent paper.
What this potentially suggests is that the effect of gluten on some cases of autism is perhaps due to more than one scenario: intestinal hyperpermeability (as in CD) linked perhaps to other compounds, or high AGA IgG (IgA?) levels and inflammation or perhaps due to bog standard co-morbid CD. I would hasten to add that there may well be other mechanisms to add to this list.
This is a fascinating area of research and along with several other recent papers is providing further insights into the shadowy nature of our relationship with gluten, outside of coeliac disease.
Saturday, 19 March 2011
Enzyme activity, milk and autism
Remember the old Namco classic Pac-Man? That yellow circular pixelated fellow running around a maze gobbling up dots and the odd power pellet making him invulnerable to the ghosts. I must have spent days of my life playing that game as a child (yeah.. er, as a child).
Pac-Man is not a bad metaphor for our gastrointestinal enzymes and the job they do gobbling up various proteins, peptides and sugars derived from our diet and spitting them out into their constituent parts for more manageable digestion, absorption and use. OK such enzymes don't look like Pac-Man and they don't exactly just gobble up and spit out dots; just a little creative flair on my part to save a long laborious biochemistry lesson.
There is quite a bit of evidence to suggest that gut enzyme function in some cases of autism is perhaps not what it should be. The various -ases (proteases / peptidases, disaccharidases) have all pretty much come under the spotlight at one time or another in relation to autism. The proposed association between autism and various gastrointestinal conditions and dietary elements have brought some enzymes centre-stage as result. A recent paper from Harvard adds to the research evidence. The team, which includes Tim Buie, lead for the recent American Academy of Pediatrics guideline document on autism and gastrointestinal conditions, have published in this area before.
Last time they reported that disaccharidase activity (an enzyme that breaks down two component sugar compounds, disaccharides, into single sugar components, monosaccharide) was looking a little bit shaky in quite a few people with autism. In particular they noted that several dissacharidases were related to specific conditions in autism, including lactase. Lactase is essential for breaking down lactose, the sugar in milk and dairy products.
The more recent paper details similar findings with regards to problems with lactase and suggested that lactose intolerance might be pretty widespread in autism. The authors went on to suggest that this could account for some of the observed abdominal discomfort, pain and 'aberrant behaviour' observed in some cases of autism. I remember quite a while ago Afzal and colleagues reported that milk consumption was one of the primary predicting factors for constipation in autism.
This is an important paper. Not only is it a replication of previous work, it highlights what seems to be a common problem in autism particularly related to milk and dairy products. If I say the words 'casein-free diet and autism' would that perhaps ring any bells? A few words of caution are required. First lactose intolerance can be quite widespread in the general population; the map shown here claims to show population level risk of lactose intolerance. If for example you are Chinese in ethnicity, you have a very high chance of developing lactose intolerance. As with coeliac disease and the Irish population, the theory is that the traditional Chinese diet is probably not as high in milk and dairy products as that of other parts of the world, or incorporates different types of milk sources and hence exposure to lactose is perhaps not as great as in other parts of the world. It's a case of use it or lose it.
Chronological age is also a factor. Babies tend to be better protected against lactose intolerance given that milk (mothers or formula) are a staple foodstuff as such an age. The interesting thing about the recent Harvard paper is that they reported over 50% of children under 5 were showing lactase deficiency. So when the kids needed the enzyme the most it was perhaps not present. Mmm. Reminds me of some of the original cases described by Leo Kanner particularly cases 4, 7, 8, 10 who all experienced early feeding problems. Coincidence?
We have also to think about the old adage 'correlation does not imply causation'. It is possible that such enzyme problems are purely epiphenomenal and unrelated to autism. Possible at least. One final word about the new research. One of the most interesting statements in the Harvard paper is that of the last sentence of the abstract: 'Most autistic children with lactose intolerance are not identified by clinical history'. Meaning that if you don't go looking for it directly, the chances are that problems with the disaccharidases are not going to be picked up by reading a developmental history alone. I guess what this is telling us is that just because a person has an autism spectrum condition, don't assume that they are somehow protected against other conditions. Coeliac disease? Iron deficiency?
Readers of this blog will know that I have some views on the use of gluten- and casein-free diets as a potential tool for ameliorating some core and peripheral symptoms associated with autism. Anything that can help identify that autism 'phenotype' where diet may be related is welcome news.
Pac-Man is not a bad metaphor for our gastrointestinal enzymes and the job they do gobbling up various proteins, peptides and sugars derived from our diet and spitting them out into their constituent parts for more manageable digestion, absorption and use. OK such enzymes don't look like Pac-Man and they don't exactly just gobble up and spit out dots; just a little creative flair on my part to save a long laborious biochemistry lesson.
There is quite a bit of evidence to suggest that gut enzyme function in some cases of autism is perhaps not what it should be. The various -ases (proteases / peptidases, disaccharidases) have all pretty much come under the spotlight at one time or another in relation to autism. The proposed association between autism and various gastrointestinal conditions and dietary elements have brought some enzymes centre-stage as result. A recent paper from Harvard adds to the research evidence. The team, which includes Tim Buie, lead for the recent American Academy of Pediatrics guideline document on autism and gastrointestinal conditions, have published in this area before.
Last time they reported that disaccharidase activity (an enzyme that breaks down two component sugar compounds, disaccharides, into single sugar components, monosaccharide) was looking a little bit shaky in quite a few people with autism. In particular they noted that several dissacharidases were related to specific conditions in autism, including lactase. Lactase is essential for breaking down lactose, the sugar in milk and dairy products.
The more recent paper details similar findings with regards to problems with lactase and suggested that lactose intolerance might be pretty widespread in autism. The authors went on to suggest that this could account for some of the observed abdominal discomfort, pain and 'aberrant behaviour' observed in some cases of autism. I remember quite a while ago Afzal and colleagues reported that milk consumption was one of the primary predicting factors for constipation in autism.
This is an important paper. Not only is it a replication of previous work, it highlights what seems to be a common problem in autism particularly related to milk and dairy products. If I say the words 'casein-free diet and autism' would that perhaps ring any bells? A few words of caution are required. First lactose intolerance can be quite widespread in the general population; the map shown here claims to show population level risk of lactose intolerance. If for example you are Chinese in ethnicity, you have a very high chance of developing lactose intolerance. As with coeliac disease and the Irish population, the theory is that the traditional Chinese diet is probably not as high in milk and dairy products as that of other parts of the world, or incorporates different types of milk sources and hence exposure to lactose is perhaps not as great as in other parts of the world. It's a case of use it or lose it.
Chronological age is also a factor. Babies tend to be better protected against lactose intolerance given that milk (mothers or formula) are a staple foodstuff as such an age. The interesting thing about the recent Harvard paper is that they reported over 50% of children under 5 were showing lactase deficiency. So when the kids needed the enzyme the most it was perhaps not present. Mmm. Reminds me of some of the original cases described by Leo Kanner particularly cases 4, 7, 8, 10 who all experienced early feeding problems. Coincidence?
We have also to think about the old adage 'correlation does not imply causation'. It is possible that such enzyme problems are purely epiphenomenal and unrelated to autism. Possible at least. One final word about the new research. One of the most interesting statements in the Harvard paper is that of the last sentence of the abstract: 'Most autistic children with lactose intolerance are not identified by clinical history'. Meaning that if you don't go looking for it directly, the chances are that problems with the disaccharidases are not going to be picked up by reading a developmental history alone. I guess what this is telling us is that just because a person has an autism spectrum condition, don't assume that they are somehow protected against other conditions. Coeliac disease? Iron deficiency?
Readers of this blog will know that I have some views on the use of gluten- and casein-free diets as a potential tool for ameliorating some core and peripheral symptoms associated with autism. Anything that can help identify that autism 'phenotype' where diet may be related is welcome news.
Friday, 18 March 2011
Sleep, melatonin and autism
"Look into the eyes, not around the eyes, into the eyes.. and.. you're under". Famous words from Kenny Craig the Stage Hypnotist from Little Britain. If you could add the words "you will sleep for 8 hours... 3,2,1.. you're back in the room" after that and it works, many people would be very, very, very happy.
Ask any person with children, irrespective of an autism diagnosis or not, what are the toughest things about raising a child and I bet many will list a lack of sleep in the early years as being fairly close to the top of their list. Gone are the heavenly 8-hour slumberthons that were taken for granted each night. Replaced instead by 1-2 hours, then 2-3 hours, etc working up to a full night by about a year (if you are lucky) and even then not in uniform stages.
For the first few months of your child's life, you wake up looking and feeling like the living dead; despising the sound of the morning chorus which you heard start at 4am, constantly thinking about how you are going to get through the day without crashing the car and yearning for those golden 8-hour nights to return. The world passes by in slow motion. It is not something that the mind and body ever really gets used to and demonstrates how powerful a thing sleep deprivation can be, and how it impacts on many parts of your life.
Think then to how a child who suffers similar sleeping problems might also feel as a result of disturbed, unrefreshing, qualitatively poor sleeping patterns; where the body clock just somehow does not seem to keep time with the environment around them and the time spent sleeping is limited.
Think about what impact this might have on the developing body and brain and how irritability, non-compliance, and inattention at home and school (so-called 'challenging behaviours') might come about as a result. Interesting thought isn't it?
Autism including Asperger syndrome, similar to conditions such as learning disability, impacts on sleep. That's what we think anyway - autism impacts on sleep, or does sleep impact on autism? Whichever way round, there is a wealth of research to suggest that sleeping problems are common for a large group of people on the autism spectrum above and beyond the early years.
The UK National Autistic Society has a very large on-line document about autism and sleep which kinda gives a flavour of how pervasive and widespread the issue is. Dr Jacqui Jackson gave a good insight into her experience of sleeping problems related to autism (and other co-morbidities) in her family back in 2006.
The published research in this area suggests that children with an autism spectrum condition are more likely to present with shorter overall sleep time, less REM sleep (see description here), more incidents of night-waking, and indications of disordered circadian rhythms (see description here) when compared to non-autism and developmentally delayed controls. I would imagine that all that could/would cause a lot of stress and anxiety both to the child and their parents if delivered over a sustained period of say, years.
The questions then: what causes such sleeping problems in relation to autism and what can be done about it?
Unfortunately there are no cut-and-dried answers; only fragments of information which potentially point to many different mechanisms and once again, variability in the mode of action across the spectrum.
Before delving into the world of circadian rhythms and melatonin, which seem to provide the best explanations of sleeping problems in autism, I want to go back to something mentioned in the BBC report on Jacqui Jackson's family: the issue of co-morbidity.
As mentioned many times on this blog, several types of co-morbidity can be, and are, present alongside autism, including learning disability and attentional problems (ADHD). Both these example co-morbidities are associated with sleeping problems.
In ADHD, sleep problems are reported to be present in between a quarter and a half of children diagnosed. Given that autism can often be co-morbid with ADHD, there is perhaps a case for suggesting that at least some sleeping problems may be more related to the ADHD-symptoms/label over the autism? The point I am trying to make is that autism alone cannot perhaps be held responsible for all sleep disturbances at least in some children.
Back to circadian rhythms and melatonin. Our circadian rhythm is our internal clock. Working with our external environment (light and dark), it regulates many different functions including most importantly our sleep-wake cycle.
I remember quite a few years back speaking to several parents who indicated that their child's sleep-wake patterns were cyclical. That is for a few days of the month, sleep would not be a problem, but the days either side, the child seemed to sleep at different times outside of those normally expected with a more variable sleep quality.
This is an interesting phenomena. One would hope that our circadian rhythm runs parallel to our 24-hour clock. The reality however is that we all make subtle changes to our clock as a result of our environment (light or dark) and other factors. Could it be that this modification is unresponsive somehow?
Well, we do know that measures of stress such as cortisol levels are different in autism, and whilst trying not to make sweeping generalisations, it appears that stress levels continue into the evening where perhaps they should be dropping. Could this explain some of the sleep problems?
There is also a suggestion that some of the so-called 'clock genes' might be under-performing in autism (although this does require a lot more study and needs to take on board a few issues previously blogged about).
We also have a potential role for melatonin. Melatonin is a naturally-occurring metabolite of tryptophan. In its commercial form it is the drug of choice for overcoming jet-lag being widely available in the USA, although not licensed for sale in the UK at present.
There is quite a bit of research on melatonin and autism. There is research that suggests a tendency towards abnormal melatonin synthesis in autism (bearing in mind it is a derivative of serotonin, 5-HT, which already has an interest to autism). There is research that suggests lower levels of melatonin is secreted in autism. There is also a suggestion (not so much research) that pineal function in autism may be altered. There are also quite a few studies indicating that supplementation with melatonin might be beneficial for some cases of sleep problems in autism; a view backed up by Research Autism (two ticks = strong evidence).
One could therefore assume that melatonin may play at least some role in the sleep problems reported in autism. Is it the main cause? I dunno.
We perhaps should not discount that sleep is often not just about biology; it is environment, it is psychology, it is routine, it is about lots of things combined. If sleeping problems are present to some considerable degree, we should perhaps also be more 'aware' of its possible impact on presented behaviour rather than immediately reaching for the anti-challenging behaviour handbook.
A final word for those familiar with Kenny Craig - "cupboardy". If you are not familiar, watch the video.
Ask any person with children, irrespective of an autism diagnosis or not, what are the toughest things about raising a child and I bet many will list a lack of sleep in the early years as being fairly close to the top of their list. Gone are the heavenly 8-hour slumberthons that were taken for granted each night. Replaced instead by 1-2 hours, then 2-3 hours, etc working up to a full night by about a year (if you are lucky) and even then not in uniform stages.
For the first few months of your child's life, you wake up looking and feeling like the living dead; despising the sound of the morning chorus which you heard start at 4am, constantly thinking about how you are going to get through the day without crashing the car and yearning for those golden 8-hour nights to return. The world passes by in slow motion. It is not something that the mind and body ever really gets used to and demonstrates how powerful a thing sleep deprivation can be, and how it impacts on many parts of your life.
Think then to how a child who suffers similar sleeping problems might also feel as a result of disturbed, unrefreshing, qualitatively poor sleeping patterns; where the body clock just somehow does not seem to keep time with the environment around them and the time spent sleeping is limited.
Think about what impact this might have on the developing body and brain and how irritability, non-compliance, and inattention at home and school (so-called 'challenging behaviours') might come about as a result. Interesting thought isn't it?
Autism including Asperger syndrome, similar to conditions such as learning disability, impacts on sleep. That's what we think anyway - autism impacts on sleep, or does sleep impact on autism? Whichever way round, there is a wealth of research to suggest that sleeping problems are common for a large group of people on the autism spectrum above and beyond the early years.
The UK National Autistic Society has a very large on-line document about autism and sleep which kinda gives a flavour of how pervasive and widespread the issue is. Dr Jacqui Jackson gave a good insight into her experience of sleeping problems related to autism (and other co-morbidities) in her family back in 2006.
The published research in this area suggests that children with an autism spectrum condition are more likely to present with shorter overall sleep time, less REM sleep (see description here), more incidents of night-waking, and indications of disordered circadian rhythms (see description here) when compared to non-autism and developmentally delayed controls. I would imagine that all that could/would cause a lot of stress and anxiety both to the child and their parents if delivered over a sustained period of say, years.
The questions then: what causes such sleeping problems in relation to autism and what can be done about it?
Unfortunately there are no cut-and-dried answers; only fragments of information which potentially point to many different mechanisms and once again, variability in the mode of action across the spectrum.
Before delving into the world of circadian rhythms and melatonin, which seem to provide the best explanations of sleeping problems in autism, I want to go back to something mentioned in the BBC report on Jacqui Jackson's family: the issue of co-morbidity.
As mentioned many times on this blog, several types of co-morbidity can be, and are, present alongside autism, including learning disability and attentional problems (ADHD). Both these example co-morbidities are associated with sleeping problems.
In ADHD, sleep problems are reported to be present in between a quarter and a half of children diagnosed. Given that autism can often be co-morbid with ADHD, there is perhaps a case for suggesting that at least some sleeping problems may be more related to the ADHD-symptoms/label over the autism? The point I am trying to make is that autism alone cannot perhaps be held responsible for all sleep disturbances at least in some children.
Back to circadian rhythms and melatonin. Our circadian rhythm is our internal clock. Working with our external environment (light and dark), it regulates many different functions including most importantly our sleep-wake cycle.
I remember quite a few years back speaking to several parents who indicated that their child's sleep-wake patterns were cyclical. That is for a few days of the month, sleep would not be a problem, but the days either side, the child seemed to sleep at different times outside of those normally expected with a more variable sleep quality.
This is an interesting phenomena. One would hope that our circadian rhythm runs parallel to our 24-hour clock. The reality however is that we all make subtle changes to our clock as a result of our environment (light or dark) and other factors. Could it be that this modification is unresponsive somehow?
Well, we do know that measures of stress such as cortisol levels are different in autism, and whilst trying not to make sweeping generalisations, it appears that stress levels continue into the evening where perhaps they should be dropping. Could this explain some of the sleep problems?
There is also a suggestion that some of the so-called 'clock genes' might be under-performing in autism (although this does require a lot more study and needs to take on board a few issues previously blogged about).
We also have a potential role for melatonin. Melatonin is a naturally-occurring metabolite of tryptophan. In its commercial form it is the drug of choice for overcoming jet-lag being widely available in the USA, although not licensed for sale in the UK at present.
There is quite a bit of research on melatonin and autism. There is research that suggests a tendency towards abnormal melatonin synthesis in autism (bearing in mind it is a derivative of serotonin, 5-HT, which already has an interest to autism). There is research that suggests lower levels of melatonin is secreted in autism. There is also a suggestion (not so much research) that pineal function in autism may be altered. There are also quite a few studies indicating that supplementation with melatonin might be beneficial for some cases of sleep problems in autism; a view backed up by Research Autism (two ticks = strong evidence).
One could therefore assume that melatonin may play at least some role in the sleep problems reported in autism. Is it the main cause? I dunno.
We perhaps should not discount that sleep is often not just about biology; it is environment, it is psychology, it is routine, it is about lots of things combined. If sleeping problems are present to some considerable degree, we should perhaps also be more 'aware' of its possible impact on presented behaviour rather than immediately reaching for the anti-challenging behaviour handbook.
A final word for those familiar with Kenny Craig - "cupboardy". If you are not familiar, watch the video.
Thursday, 17 March 2011
Parasitic worms, bacteria and more
For those of a squeamish disposition, I would suggest that this is perhaps not the post for you. If the thought of parasitic infestation and other things related to our gut and nether regions fill you with that 'euch' feeling, best to stop here now.
For those brave souls who continue with me (hopefully not too shortly after a large meal), this is another one of my 'other musings' posts which might have some relevance to autism spectrum conditions at some points. Unlike other articles on this topic, I am not posting any graphic images showing tapeworm infection or anything like that; just my words and your imagination - now there's a psychology experiment.
Parasitic infestation. It conjours up some kind of Hollywood horror film like one of my favourites the 1978 'Invasion of the Body Snatchers' starring Donald Sutherland. Unfortunately like many things, parasitic infestation has been given a bad rap in recent years. The truth is that without such infestation, it is questionable whether any of us would be here at all.
My very limited knowledge of parasites and worms (not the earth-variety) has been growing in recent weeks. Partly as a result of an interest in how such parasitic infestations of the human gastrointestinal tract might actually be beneficial from an immune point of view at least in some cases, and partly because of the potential applications of such a 'therapeutic' tool to various autoimmune conditions.
Many authors who adhere to the 'hygiene' hypothesis as potentially explanatory of the rise of allergic diseases in modern society have talked about our increasing preoccupation with cleanliness and how various infestations that would once have been considered the 'norm' not so many hundreds of years ago are now seen as abnormal and perverse. Granted there are some infestations (such as head lice) which don't seem to serve any immediate benefit to their host (i.e. us). More and more it seems though that certain, specific infestations could carry a more symbiotic relationship potentially offering equal benefits to us and the worms wishing to reside inside our murky depths.
A recently published trial looking at the potential benefits of hookworm infestation on gluten challenge in coeliac disease caught my eye today. The paper suggested that such a therapy was well-tolerated but unfortunately showed little effect on symptoms following a gluten challenge. This however follows other trials using such helminthic therapy suggestive of a more positive effect for other gastrointestinal conditions such as Crohn's disease and other inflammatory bowel conditions.
Don't get me wrong: I know that many other studies have highlighted the potential negative effects of parasitic infestation on health, particularly in Africa and other developing nations. It strikes me that factors such as age, general health, environment (i.e. clean water) and specific pathology seem to be the major forces in balancing benefits against negatives of such infestations; also allowing for the fact that different organisms present with different effects to their host.
How does this tie into autism? Well it doesn't per se. Aside from a few posts about co-morbid parasitic infections in autism on the internet, things like giardia causing giardiasis (related to pica?), there is perhaps no immediate benefits to be seen. If one however explores the possibility that a co-morbid inflammatory bowel problem may be present alongside the autism, the potential perhaps seems more apparent [please note I am not recommending this as an intervention option merely as a potential area for further investigation].
Right moving from worms to bacteria. Many of my posts seem to end up talking about gut bacteria and its possible connection to all sorts of conditions including autism. I would not say that I am obsessed with gut bacteria but I can't help but feel that it is a much under-rated part of our physical being.
OK formalities out of the way, how would you feel about a fecal transplantation? Yes you heard me; taking the stuff-that-nobody-likes-to-talk-about and transplanting it to another person. Mmm, you are probably thinking is he serious? Well, yes I am.
Fecal transplantation (under various names) is something under investigation and being used for quite a few different things including pseudomembranous colitis (caused by clostridium difficile infection). The theory goes that our stools contain our gut bacterial fingerprint, and in cases where not-so-nice bacterial species take hold, a donor provides a 'sample' which supposedly helps to recolonise the gut with the much-better bacteria.
I could see quite a bit of consumer resistance to such a therapy. It is perhaps not surprising that it tends to be the last line of treatment when it is used. The theory however does not seem as outlandish as first thoughts suggest; indeed if one were able to overcome the palatability of the intervention (i.e. being given an enema and being fed through a nasogastric tube, made up from another person's stool) one might suggest it could be of interest. There is also some development in PR in this area in terms of formulating the stool into an oral dosage form to further help its image.
There are lots of questions still to answer about this form of therapy. The first issue I thought about was all the other 'stuff' in our stools and whether we yet know enough about the gut microflora to be able to 'transplant' it without creating new problems (remember HIV transmission and hemophilia). I know that the transplantations are normally from family members and are screened for known agents (emphasis on 'known') but there is still lots and lots of questions to answer. Some of these questions are hopefully being answered through studies such as this one.
Again back to autism - how does this fit in? Well there is some evidence accumulating to suggest some cases of autism are associated with unusual gut bacterial profiles and in particular the role of specific clostridia species. Likewise, selective decontamination of the gut with drugs like vancomycin have been shown to potentially affect autistic symptoms (at least in the short-term - homeostasis?). The question is whether the area of fecal transplantation represents a next step or a step too far?
I hope that readers have not been too grossed out by all this talk of worms and poo. I promise my next post will be something altogether more pleasant. Over to you Donald Sutherland..
For those brave souls who continue with me (hopefully not too shortly after a large meal), this is another one of my 'other musings' posts which might have some relevance to autism spectrum conditions at some points. Unlike other articles on this topic, I am not posting any graphic images showing tapeworm infection or anything like that; just my words and your imagination - now there's a psychology experiment.
Parasitic infestation. It conjours up some kind of Hollywood horror film like one of my favourites the 1978 'Invasion of the Body Snatchers' starring Donald Sutherland. Unfortunately like many things, parasitic infestation has been given a bad rap in recent years. The truth is that without such infestation, it is questionable whether any of us would be here at all.
My very limited knowledge of parasites and worms (not the earth-variety) has been growing in recent weeks. Partly as a result of an interest in how such parasitic infestations of the human gastrointestinal tract might actually be beneficial from an immune point of view at least in some cases, and partly because of the potential applications of such a 'therapeutic' tool to various autoimmune conditions.
Many authors who adhere to the 'hygiene' hypothesis as potentially explanatory of the rise of allergic diseases in modern society have talked about our increasing preoccupation with cleanliness and how various infestations that would once have been considered the 'norm' not so many hundreds of years ago are now seen as abnormal and perverse. Granted there are some infestations (such as head lice) which don't seem to serve any immediate benefit to their host (i.e. us). More and more it seems though that certain, specific infestations could carry a more symbiotic relationship potentially offering equal benefits to us and the worms wishing to reside inside our murky depths.
A recently published trial looking at the potential benefits of hookworm infestation on gluten challenge in coeliac disease caught my eye today. The paper suggested that such a therapy was well-tolerated but unfortunately showed little effect on symptoms following a gluten challenge. This however follows other trials using such helminthic therapy suggestive of a more positive effect for other gastrointestinal conditions such as Crohn's disease and other inflammatory bowel conditions.
Don't get me wrong: I know that many other studies have highlighted the potential negative effects of parasitic infestation on health, particularly in Africa and other developing nations. It strikes me that factors such as age, general health, environment (i.e. clean water) and specific pathology seem to be the major forces in balancing benefits against negatives of such infestations; also allowing for the fact that different organisms present with different effects to their host.
How does this tie into autism? Well it doesn't per se. Aside from a few posts about co-morbid parasitic infections in autism on the internet, things like giardia causing giardiasis (related to pica?), there is perhaps no immediate benefits to be seen. If one however explores the possibility that a co-morbid inflammatory bowel problem may be present alongside the autism, the potential perhaps seems more apparent [please note I am not recommending this as an intervention option merely as a potential area for further investigation].
Right moving from worms to bacteria. Many of my posts seem to end up talking about gut bacteria and its possible connection to all sorts of conditions including autism. I would not say that I am obsessed with gut bacteria but I can't help but feel that it is a much under-rated part of our physical being.
OK formalities out of the way, how would you feel about a fecal transplantation? Yes you heard me; taking the stuff-that-nobody-likes-to-talk-about and transplanting it to another person. Mmm, you are probably thinking is he serious? Well, yes I am.
Fecal transplantation (under various names) is something under investigation and being used for quite a few different things including pseudomembranous colitis (caused by clostridium difficile infection). The theory goes that our stools contain our gut bacterial fingerprint, and in cases where not-so-nice bacterial species take hold, a donor provides a 'sample' which supposedly helps to recolonise the gut with the much-better bacteria.
I could see quite a bit of consumer resistance to such a therapy. It is perhaps not surprising that it tends to be the last line of treatment when it is used. The theory however does not seem as outlandish as first thoughts suggest; indeed if one were able to overcome the palatability of the intervention (i.e. being given an enema and being fed through a nasogastric tube, made up from another person's stool) one might suggest it could be of interest. There is also some development in PR in this area in terms of formulating the stool into an oral dosage form to further help its image.
There are lots of questions still to answer about this form of therapy. The first issue I thought about was all the other 'stuff' in our stools and whether we yet know enough about the gut microflora to be able to 'transplant' it without creating new problems (remember HIV transmission and hemophilia). I know that the transplantations are normally from family members and are screened for known agents (emphasis on 'known') but there is still lots and lots of questions to answer. Some of these questions are hopefully being answered through studies such as this one.
Again back to autism - how does this fit in? Well there is some evidence accumulating to suggest some cases of autism are associated with unusual gut bacterial profiles and in particular the role of specific clostridia species. Likewise, selective decontamination of the gut with drugs like vancomycin have been shown to potentially affect autistic symptoms (at least in the short-term - homeostasis?). The question is whether the area of fecal transplantation represents a next step or a step too far?
I hope that readers have not been too grossed out by all this talk of worms and poo. I promise my next post will be something altogether more pleasant. Over to you Donald Sutherland..
Wednesday, 16 March 2011
Interesting developments in the autism-gut debate
Just this evening I happened upon a new paper published in the open-access journal BMC Gastroenterology on the potential link between autism and gastrointestinal (GI) symptoms. The paper (which is free to view - thank you!) published by Jim Adams and colleagues caught my eye for several different reasons.
The formalities first: autism group (n=58) vs. controls (n=39); age-matched (sort of); diagnosis based on 'already received' so not independently validated including a spread across the autism spectrum; gender splits were slightly unequal; control group criteria were no ADD/ADHD, no sibling with autism (I assume no autism diagnosis although this is not stated in the paper) and seemingly physically well; stool samples were the sole indicators.
I am not going to regurgitate all the paper's findings in their entirety, but several interesting points were raised including: (a) autism severity was linked to GI symptom severity, (b) a suggestion that levels of so-called 'beneficial bacteria' were different in autism vs. controls, (c) levels of so-called 'dysbiotic' bacteria showed no difference between autism and controls, (d) levels of cultured yeast were rare and not significantly different between groups, and (e) markers of inflammation were in general not significantly different between the groups aside from lower levels of lysozyme in the autism group. I have picked these particular findings out as being of interest but there were others relating to things like probiotic and fish oil use which might form later posts.
Why are these findings important? Well, first of all the authors suggest that reported gastrointestinal problems are more strongly associated with an autism diagnosis than a non-autism control. I am not going to disagree with this because other studies have showed the same thing and I have blogged about this in past posts. If I was to be a nit-picker I would perhaps argue that without any other control groups (e.g. learning disability), it is not possible to ascertain how far this finding is specific to autism (and not to learning disability) given also the lack of information on participant characteristics including the level of intellectual development.
The added value from the paper on GI disorders (bearing in mind this is functional GI disorder such as constipation, diarrhoea et al) is the connection proposed between increasing autism severity and increasing GI disorders. That is, the more severe the autism, the more severe the functional GI disorders.
I am not either going to quibble with their measure of autism severity by use of the ATEC given the recent revelations that ATEC is actually quite a good instrument, or at least as good as anything else we have. Again, the nit-picker would perhaps question the validity of the GI severity index used to probe GI symptoms (which seems to be a truncated version of the one used for this study) over other more robust measures. Additionally it is not altogether clear from the paper how the GI data was derived (interview, questionnaire, etc).
Gut bacteria is something which has been linked to autism in one form or another for many moons. It was interesting that this study seemed to suggest that whilst levels of beneficial bacteria were lower in the autism group, levels of so-called dysbiotic bacteria showed no significant difference. There is a caveat to this: the levels of dysbiotic bacteria only included 5 strains of bacteria and as mentioned in the paper discussion, they unfortunately did not look at one of the prime candidate bacteria, clostridia species which is indeed a shame.
Moving on, the lack of any significant detection of yeast in either autism or controls is slightly at odds with a lot of the discussions on autism and the gut particularly on the internet. Many times I have heard people suggest that an overgrowth of yeast such as Candida albicans is related to autism; indeed another recent study has suggested some difference in levels of this yeast in autism vs. controls. But Adams and colleagues reported no difference between their groups, and so nothing more to be said there.
Finally, markers of inflammation (GI inflammation). Interestingly there were no significant differences in white blood cells (WBC) or levels of lactoferrin. This suggests that there was no significant difference in immune activation in these particular participant groups. The lower levels of lysozyme in the autism group were the exception here and perhaps complement other older research by the late Reed Warren and colleagues looking at underlying genetic differences in the way the body handles things like bacterial infections.
So, an interesting paper, which whilst carrying some potential methodological issues provides a further insight into the complex interaction between autism and gastrointestinal symptoms. Yes, functional GI symptoms seem to be more present in cases of autism, and potentially there may be a connection with gut microflora. How this pans out in further replication studies remains to be seen.
The formalities first: autism group (n=58) vs. controls (n=39); age-matched (sort of); diagnosis based on 'already received' so not independently validated including a spread across the autism spectrum; gender splits were slightly unequal; control group criteria were no ADD/ADHD, no sibling with autism (I assume no autism diagnosis although this is not stated in the paper) and seemingly physically well; stool samples were the sole indicators.
I am not going to regurgitate all the paper's findings in their entirety, but several interesting points were raised including: (a) autism severity was linked to GI symptom severity, (b) a suggestion that levels of so-called 'beneficial bacteria' were different in autism vs. controls, (c) levels of so-called 'dysbiotic' bacteria showed no difference between autism and controls, (d) levels of cultured yeast were rare and not significantly different between groups, and (e) markers of inflammation were in general not significantly different between the groups aside from lower levels of lysozyme in the autism group. I have picked these particular findings out as being of interest but there were others relating to things like probiotic and fish oil use which might form later posts.
Why are these findings important? Well, first of all the authors suggest that reported gastrointestinal problems are more strongly associated with an autism diagnosis than a non-autism control. I am not going to disagree with this because other studies have showed the same thing and I have blogged about this in past posts. If I was to be a nit-picker I would perhaps argue that without any other control groups (e.g. learning disability), it is not possible to ascertain how far this finding is specific to autism (and not to learning disability) given also the lack of information on participant characteristics including the level of intellectual development.
The added value from the paper on GI disorders (bearing in mind this is functional GI disorder such as constipation, diarrhoea et al) is the connection proposed between increasing autism severity and increasing GI disorders. That is, the more severe the autism, the more severe the functional GI disorders.
I am not either going to quibble with their measure of autism severity by use of the ATEC given the recent revelations that ATEC is actually quite a good instrument, or at least as good as anything else we have. Again, the nit-picker would perhaps question the validity of the GI severity index used to probe GI symptoms (which seems to be a truncated version of the one used for this study) over other more robust measures. Additionally it is not altogether clear from the paper how the GI data was derived (interview, questionnaire, etc).
Gut bacteria is something which has been linked to autism in one form or another for many moons. It was interesting that this study seemed to suggest that whilst levels of beneficial bacteria were lower in the autism group, levels of so-called dysbiotic bacteria showed no significant difference. There is a caveat to this: the levels of dysbiotic bacteria only included 5 strains of bacteria and as mentioned in the paper discussion, they unfortunately did not look at one of the prime candidate bacteria, clostridia species which is indeed a shame.
Moving on, the lack of any significant detection of yeast in either autism or controls is slightly at odds with a lot of the discussions on autism and the gut particularly on the internet. Many times I have heard people suggest that an overgrowth of yeast such as Candida albicans is related to autism; indeed another recent study has suggested some difference in levels of this yeast in autism vs. controls. But Adams and colleagues reported no difference between their groups, and so nothing more to be said there.
Finally, markers of inflammation (GI inflammation). Interestingly there were no significant differences in white blood cells (WBC) or levels of lactoferrin. This suggests that there was no significant difference in immune activation in these particular participant groups. The lower levels of lysozyme in the autism group were the exception here and perhaps complement other older research by the late Reed Warren and colleagues looking at underlying genetic differences in the way the body handles things like bacterial infections.
So, an interesting paper, which whilst carrying some potential methodological issues provides a further insight into the complex interaction between autism and gastrointestinal symptoms. Yes, functional GI symptoms seem to be more present in cases of autism, and potentially there may be a connection with gut microflora. How this pans out in further replication studies remains to be seen.
Autism and n=1
The post carries a warning that it is best to read whilst sitting comfortably with a glass of wine and an open mind. Sitting comfortably? Feet up? Then I shall begin.
Without wishing to sound condescending to the non-scientist, a bit of explanation is required about this entry (to the scientists also, apologies in advance for any over-simplification). One of the ways that the letter n is used in science and mathematics is to denote the number of people (subjects, participants, etc) taking part in a particular experiment or study (or arm of a study). I use 'people' as an example, but n can also denote other things (living, dead or inanimate) under investigation.
The use of n in this 'science-y' way stems from the premise that greater evidence of any effect (or non-effect) from a particular 'thing' (drug, intervention, pollutant, etc) is garnered by increasing the number of n's in order to make a finding more generalisable to a larger population from that being studied - in effect increasing the chances that 'chance' alone does not account for a particular finding or connection based on a large sample size.
Still with me? OK. Now as large an n as is possible drawn from a particular population (sample) without actually looking individually at an entire population (which would be impractical) is one of the things that science strives towards in order to show the probability of an effect or non-effect.
This notion however makes some important assumptions; primarily that all your grouped n's are the same or roughly the same, and that the specific 'thing' you are testing in respect of your sample/s represents the only thing you are testing and hence is not affected by other 'things' which could bias your result.
A textbook example is that of the effect of a particular antibiotic on a bacterial organism or strain. Antibiotic A is proposed to affect organism B; add antibiotic A to organism B sitting in a petri dish (which will have an n of many thousands or millions); compare the same antibiotic with organism C sitting in another petri dish (which should show little or no effect) and watch how many organisms B and C die as a result of A in their respective petri dish. If antibiotic A kills many thousands of n's of organism B but only a few of organism C, you could suggest that A probably is quite an effective antibiotic against B but not C. Your logic is therefore based on and confirmed by a large n.
Works well in this example doesn't it? Well, that is until you start applying the same 'petri' dish logic to humans not bacteria or more precisely when applying it to certain human characteristics which might not be as measurable as the binary 'life or death' response of a bacterial organism.
Don't get me wrong. I am not saying that applying n in this fashion is completely useless; far from it. What it does however confirm is that our use of science as a measure of 'absolute' particularly when applied to human beings, is flawed; whereas using science to ascertain 'probability' is closer to what is probably(!) produced.
So where does autism come into this? Well we know that autism is an extremely heterogeneous condition; the presentation varies from person to person and is affected by lots of different things such as genetic make-up, age and maturation, other co-morbidities and the environment. Whenever a particular hypothesis is tested with regards to autism, say that intervention A might help ameliorate behaviour B or if factor C makes behaviour D more likely, we generally employ the rule of larger n (in amongst lots of other methodological rules and methods) to see if there is any effect, bearing in mind the end-point of generalising a finding to a population.
The fundamental flaw in this design is, going back to the title of this post, n=1. That is: how do we know that we have a homogeneous group in amongst a heterogeneous condition? Answer: we don't. Autism like many other 'behaviourally-led' conditions in its strictest definition has to fall into a n=1 category, i.e. each person is 'different' and unique.
Yes, we try and control for different things during our various studies. We try and make sure that ages are similar in our large n, we try and match our n's for things like gender, intellectual level, co-morbidity; we even try and look at n's who present 'similarly' in terms of core autism symptoms. Ultimately however we can never make all our n's the same; hence bias is introduced.
The moral of this story is this: studies showing A related to B often using large n's in autism are not showing anything approaching an absolute as a result of the 'n=1' argument. They show that many different n=1's when grouped together provide a signpost to the probability of an effect or non-effect. Within this group of n=1's are participants who, because of their various differences, may show a large effect to a particular thing being tested, whereas other n=1's might show no effect at all. The implication for autism research is to start looking at the characteristics of those 'responders' and 'non-responders' rather than giving blanket 'yes' or 'no' answers and importantly, to communicate this effectively (see my previous post on evidence-based medicine).
So the next time you hear someone say 'oh that does not work' or 'oh that is not linked' with regards to autism, remember the n=1.
Without wishing to sound condescending to the non-scientist, a bit of explanation is required about this entry (to the scientists also, apologies in advance for any over-simplification). One of the ways that the letter n is used in science and mathematics is to denote the number of people (subjects, participants, etc) taking part in a particular experiment or study (or arm of a study). I use 'people' as an example, but n can also denote other things (living, dead or inanimate) under investigation.
The use of n in this 'science-y' way stems from the premise that greater evidence of any effect (or non-effect) from a particular 'thing' (drug, intervention, pollutant, etc) is garnered by increasing the number of n's in order to make a finding more generalisable to a larger population from that being studied - in effect increasing the chances that 'chance' alone does not account for a particular finding or connection based on a large sample size.
Still with me? OK. Now as large an n as is possible drawn from a particular population (sample) without actually looking individually at an entire population (which would be impractical) is one of the things that science strives towards in order to show the probability of an effect or non-effect.
This notion however makes some important assumptions; primarily that all your grouped n's are the same or roughly the same, and that the specific 'thing' you are testing in respect of your sample/s represents the only thing you are testing and hence is not affected by other 'things' which could bias your result.
A textbook example is that of the effect of a particular antibiotic on a bacterial organism or strain. Antibiotic A is proposed to affect organism B; add antibiotic A to organism B sitting in a petri dish (which will have an n of many thousands or millions); compare the same antibiotic with organism C sitting in another petri dish (which should show little or no effect) and watch how many organisms B and C die as a result of A in their respective petri dish. If antibiotic A kills many thousands of n's of organism B but only a few of organism C, you could suggest that A probably is quite an effective antibiotic against B but not C. Your logic is therefore based on and confirmed by a large n.
Works well in this example doesn't it? Well, that is until you start applying the same 'petri' dish logic to humans not bacteria or more precisely when applying it to certain human characteristics which might not be as measurable as the binary 'life or death' response of a bacterial organism.
Don't get me wrong. I am not saying that applying n in this fashion is completely useless; far from it. What it does however confirm is that our use of science as a measure of 'absolute' particularly when applied to human beings, is flawed; whereas using science to ascertain 'probability' is closer to what is probably(!) produced.
So where does autism come into this? Well we know that autism is an extremely heterogeneous condition; the presentation varies from person to person and is affected by lots of different things such as genetic make-up, age and maturation, other co-morbidities and the environment. Whenever a particular hypothesis is tested with regards to autism, say that intervention A might help ameliorate behaviour B or if factor C makes behaviour D more likely, we generally employ the rule of larger n (in amongst lots of other methodological rules and methods) to see if there is any effect, bearing in mind the end-point of generalising a finding to a population.
The fundamental flaw in this design is, going back to the title of this post, n=1. That is: how do we know that we have a homogeneous group in amongst a heterogeneous condition? Answer: we don't. Autism like many other 'behaviourally-led' conditions in its strictest definition has to fall into a n=1 category, i.e. each person is 'different' and unique.
Yes, we try and control for different things during our various studies. We try and make sure that ages are similar in our large n, we try and match our n's for things like gender, intellectual level, co-morbidity; we even try and look at n's who present 'similarly' in terms of core autism symptoms. Ultimately however we can never make all our n's the same; hence bias is introduced.
The moral of this story is this: studies showing A related to B often using large n's in autism are not showing anything approaching an absolute as a result of the 'n=1' argument. They show that many different n=1's when grouped together provide a signpost to the probability of an effect or non-effect. Within this group of n=1's are participants who, because of their various differences, may show a large effect to a particular thing being tested, whereas other n=1's might show no effect at all. The implication for autism research is to start looking at the characteristics of those 'responders' and 'non-responders' rather than giving blanket 'yes' or 'no' answers and importantly, to communicate this effectively (see my previous post on evidence-based medicine).
So the next time you hear someone say 'oh that does not work' or 'oh that is not linked' with regards to autism, remember the n=1.
Monday, 14 March 2011
The big H and autism
Only a short post this one. PubMed has been alive and kicking with a few articles of interest in recent days. Some interesting work on the potential difference between coeliac disease and gluten sensitivity has been published; harking back to my previous post on the subject. I will perhaps blog more about this at a later date.
More directly pertinent to autism is the publication of a preliminary report looking at urinary levels of homocysteine in autism (note the use of homocysteine not homocystine, which is a relation) backing up some previous findings in this area.
In brief the paper (which is available full-text from the publishing journal) recorded higher levels of homocysteine compared to controls. It is only a small study (n=34 autism; n=21 controls) but they do seem to have put in the work when it comes to the assay used for detection (bearing in mind that identifying just homocysteine and not also its homocystine relation is quite difficult). The same team also published this paper quite recently on levels of the amino acid tryptophan; it looks like they are going through all the amino acids for any potential effects.
Homocysteine seems to be a bit of a dark horse when it comes to human health. The role of this amino acid on things like cardiac health seems to be growing although at the moment there hasn't been any major sea change in this area. Probably more important for autism is the relation between homocysteine and its parent amino acid cysteine particularly going back to the dusty book which is sulphate and autism.
The authors suggest that perturbed levels of homocysteine might suggest a few things related to vitamin and mineral deficiencies but I do wonder if this is but one effect bearing in mind what this stuff is supposed to do to proteins such as collagen and elastin and also its proposed link with the MTHFR gene (also implicated in autism).
Finally what to do about it? Well that is the million dollar question. Proposals to supplement with specific B vitamins and folic acid have been put forward; interestingly also the use of trimethylglcine (TMG) (betaine hydrochloride), a sibling of dimethylglycine (DMG) being used in autism, in order to affect homocysteine levels (note I am not making any recommendations about this!).
One to watch perhaps?
More directly pertinent to autism is the publication of a preliminary report looking at urinary levels of homocysteine in autism (note the use of homocysteine not homocystine, which is a relation) backing up some previous findings in this area.
In brief the paper (which is available full-text from the publishing journal) recorded higher levels of homocysteine compared to controls. It is only a small study (n=34 autism; n=21 controls) but they do seem to have put in the work when it comes to the assay used for detection (bearing in mind that identifying just homocysteine and not also its homocystine relation is quite difficult). The same team also published this paper quite recently on levels of the amino acid tryptophan; it looks like they are going through all the amino acids for any potential effects.
Homocysteine seems to be a bit of a dark horse when it comes to human health. The role of this amino acid on things like cardiac health seems to be growing although at the moment there hasn't been any major sea change in this area. Probably more important for autism is the relation between homocysteine and its parent amino acid cysteine particularly going back to the dusty book which is sulphate and autism.
The authors suggest that perturbed levels of homocysteine might suggest a few things related to vitamin and mineral deficiencies but I do wonder if this is but one effect bearing in mind what this stuff is supposed to do to proteins such as collagen and elastin and also its proposed link with the MTHFR gene (also implicated in autism).
Finally what to do about it? Well that is the million dollar question. Proposals to supplement with specific B vitamins and folic acid have been put forward; interestingly also the use of trimethylglcine (TMG) (betaine hydrochloride), a sibling of dimethylglycine (DMG) being used in autism, in order to affect homocysteine levels (note I am not making any recommendations about this!).
One to watch perhaps?
Wednesday, 9 March 2011
Diagnostic stability and instability in autism
Stability (and instability) has many different meanings depending on what area you are looking at. For the purposes of this post, I am talking about what happens to a diagnosis of autism/Asperger syndrome/ASD or PDD-NOS as a function of changes to presented symptoms; and in particular, the factors potentially affecting diagnostic stability such as age, co-morbidity, symptom severity and various interventions.
I use the words 'potentially affecting' because as with many things, it is very difficult (impossible?) to say definitively that one or other factor alone/combinatorially contributed to change something, bearing in mind the basis of science being probability not absolutes.
Stability with regards to autism diagnoses is a surprisingly unstable thing. Think about it: we diagnose on the basis of a prescribed pattern of symptoms being present and observable and occurring within a set chronological time frame. On the basis of such controlled but ultimately subjective judgements we specify 'autism', 'Asperger syndrome' or one of the other sub-diagnoses as being present as detailed in the DSM or ICD schedules.
OK, you're right, we do have various standardised schedules to aid diagnosis (ADI, ADOS, etc) but remember, these are only complementary to the diagnostic (or assessment) process and not confirmatory per se.
Final diagnosis is therefore dependent on factors such as who makes the diagnostic decision (their skill, experience and diligence), where and under what circumstances the diagnosis is made (home, school, clinic, all of the above), what kind of contributory assessment tools were used, and at what age the diagnosis is made (young or older age). Lots of different variables and lots of room for variability to occur.
As I posted in my previous entry on the proposed DSM revisions, there is nothing currently or in the planned revisions to the diagnostic manuals to say that an autism diagnosis is anything but a fixed feature; autism is after all a lifelong condition according to organisations such as the National Autistic Society.
Taking the issue of chronological age first, there are a few things worth noting. Autism research has, frankly become quite obsessed with early diagnosis. Lots of different studies have been conducted to look for the 'magical' set of behaviours and characteristics which would allow screening or assessment measures to universally identify the 'autistic child' at 3 months, 6 months or 12 months, etc of age.
Why you may ask? Well because there is a suggestion (and it is quite a strong suggestion) that the earlier that symptoms are identified and a diagnosis given, the earlier that intervention can be adopted in order to somehow influence the course of development. Given the proposed plasticity of organs such as the brain at these critical early developmental periods, the logic is that through play, speech and language and other therapies and interventions (mainstream and complementary), it may be possible to affect brain development, directly or peripherally, and hence potentially affect symptoms presentation.
There appears to be little wrong with this logic given the evidence available for its component parts: the brain for example during early infancy is a busy little bee adding (and pruning) various neural connections at a pretty spectacular rate over those early years. One side-effect from this whole order of developmental events is perhaps the conflict with the view of autism 'being a purely genetic condition'; whereby genes, and only genes, dictate the course of developmental events and because they are genes, they are somehow immovable.
The contrary logic of early diagnosis and early intervention presenting behaviour as plastic and malleable suggest pre-determination may not be 'the' key element of autism or at least 'some' autisms (perhaps a blog entry of its own on this topic is merited).
The reality is that we do not have a universally clear idea of early autism presentation (we need only look at studies on tools such as the CHAT and M-CHAT to know this) accepting also that age is a modifying variable on autism symptom presentation and diagnosis. Several studies have shown that there is quite a large degree of diagnostic instability as a function of age, particularly in the early months/years; most probably as a function of the rapid changes in physical and psychological development that occur during these formative years.
Moving on to co-morbidity. We know that autism can occur alongside several other linked / non-linked conditions, some of which may have a significant effect on how and what symptoms are presented. Learning disability (LD) is perhaps the most widely cited co-morbidity but things like epilepsy / seizure-type disorders have also been noted. Like autism, LD ebbs and flows in terms of presentation. Epilepsy also is not a static entity with a suggestion that it can impact on autistic symptom presentation (although the nature of the relationship still requires further study).
The severity of symptoms and the connection to which diagnosis is given has also been suggested to further contribute to diagnostic instability. Recent meta-analysis has suggested that greater variability in symptom presentation is evident amongst the ASD / PDD-NOS diagnosis when compared to classical autism. Does this mean that classical 'Kanner' autism is governed more by immovable genetics than environment when compared to other sub-diagnoses?
Finally we have the potential role of intervention on diagnostic stability. There are many different types of intervention or management strategies suggested for autism; educational, behavioural, pharmacotherapy, etc. all with varying degrees of evidence for efficacy (and importantly safety). Time and time again reports similarly emerge of children whose symptoms abate (disappear?) and what interventions might be contributory. I am not getting into the nitty-gritty of whether such reports are accurate or not (I am hardly in a position to question a parent's view of their own child). What such reports do suggest is that movement across the diagnostic autism spectrum is potentially possible (at least in some cases) and correlates with intervention (remembering of course that correlation does not imply causation).
So there we have it; lots of different factors pulling, yanking, tearing at a diagnosis. I will finish with a reiteration: stability with regards to autism diagnoses is a surprisingly unstable thing.
I use the words 'potentially affecting' because as with many things, it is very difficult (impossible?) to say definitively that one or other factor alone/combinatorially contributed to change something, bearing in mind the basis of science being probability not absolutes.
Stability with regards to autism diagnoses is a surprisingly unstable thing. Think about it: we diagnose on the basis of a prescribed pattern of symptoms being present and observable and occurring within a set chronological time frame. On the basis of such controlled but ultimately subjective judgements we specify 'autism', 'Asperger syndrome' or one of the other sub-diagnoses as being present as detailed in the DSM or ICD schedules.
OK, you're right, we do have various standardised schedules to aid diagnosis (ADI, ADOS, etc) but remember, these are only complementary to the diagnostic (or assessment) process and not confirmatory per se.
Final diagnosis is therefore dependent on factors such as who makes the diagnostic decision (their skill, experience and diligence), where and under what circumstances the diagnosis is made (home, school, clinic, all of the above), what kind of contributory assessment tools were used, and at what age the diagnosis is made (young or older age). Lots of different variables and lots of room for variability to occur.
As I posted in my previous entry on the proposed DSM revisions, there is nothing currently or in the planned revisions to the diagnostic manuals to say that an autism diagnosis is anything but a fixed feature; autism is after all a lifelong condition according to organisations such as the National Autistic Society.
Taking the issue of chronological age first, there are a few things worth noting. Autism research has, frankly become quite obsessed with early diagnosis. Lots of different studies have been conducted to look for the 'magical' set of behaviours and characteristics which would allow screening or assessment measures to universally identify the 'autistic child' at 3 months, 6 months or 12 months, etc of age.
Why you may ask? Well because there is a suggestion (and it is quite a strong suggestion) that the earlier that symptoms are identified and a diagnosis given, the earlier that intervention can be adopted in order to somehow influence the course of development. Given the proposed plasticity of organs such as the brain at these critical early developmental periods, the logic is that through play, speech and language and other therapies and interventions (mainstream and complementary), it may be possible to affect brain development, directly or peripherally, and hence potentially affect symptoms presentation.
There appears to be little wrong with this logic given the evidence available for its component parts: the brain for example during early infancy is a busy little bee adding (and pruning) various neural connections at a pretty spectacular rate over those early years. One side-effect from this whole order of developmental events is perhaps the conflict with the view of autism 'being a purely genetic condition'; whereby genes, and only genes, dictate the course of developmental events and because they are genes, they are somehow immovable.
The contrary logic of early diagnosis and early intervention presenting behaviour as plastic and malleable suggest pre-determination may not be 'the' key element of autism or at least 'some' autisms (perhaps a blog entry of its own on this topic is merited).
The reality is that we do not have a universally clear idea of early autism presentation (we need only look at studies on tools such as the CHAT and M-CHAT to know this) accepting also that age is a modifying variable on autism symptom presentation and diagnosis. Several studies have shown that there is quite a large degree of diagnostic instability as a function of age, particularly in the early months/years; most probably as a function of the rapid changes in physical and psychological development that occur during these formative years.
Moving on to co-morbidity. We know that autism can occur alongside several other linked / non-linked conditions, some of which may have a significant effect on how and what symptoms are presented. Learning disability (LD) is perhaps the most widely cited co-morbidity but things like epilepsy / seizure-type disorders have also been noted. Like autism, LD ebbs and flows in terms of presentation. Epilepsy also is not a static entity with a suggestion that it can impact on autistic symptom presentation (although the nature of the relationship still requires further study).
The severity of symptoms and the connection to which diagnosis is given has also been suggested to further contribute to diagnostic instability. Recent meta-analysis has suggested that greater variability in symptom presentation is evident amongst the ASD / PDD-NOS diagnosis when compared to classical autism. Does this mean that classical 'Kanner' autism is governed more by immovable genetics than environment when compared to other sub-diagnoses?
Finally we have the potential role of intervention on diagnostic stability. There are many different types of intervention or management strategies suggested for autism; educational, behavioural, pharmacotherapy, etc. all with varying degrees of evidence for efficacy (and importantly safety). Time and time again reports similarly emerge of children whose symptoms abate (disappear?) and what interventions might be contributory. I am not getting into the nitty-gritty of whether such reports are accurate or not (I am hardly in a position to question a parent's view of their own child). What such reports do suggest is that movement across the diagnostic autism spectrum is potentially possible (at least in some cases) and correlates with intervention (remembering of course that correlation does not imply causation).
So there we have it; lots of different factors pulling, yanking, tearing at a diagnosis. I will finish with a reiteration: stability with regards to autism diagnoses is a surprisingly unstable thing.
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