For most of us in the Industrialised world we have certain luxuries. Luxuries like a roof over our head to keep out the elements, and in particular those savage Winters we have been having recently, radiators and air conditioning to keep us at the right temperature all year round, just about any food imaginable within walking distance for most and a life relatively free from rodents and pests to hopefully keep us free from lots of not-so-nice disease-causing bacteria and viruses. It sounds pretty good doesn't it?
What if however I was to suggest to you that our warm, clean, pest-free lives might actually be the cause of some ill-health. That our modern obsession with all things clean and sterile might be counter to what we were originally made for. Would I be spoiling things? Welcome to the hygiene hypothesis and the suggestion that modern health and hygiene might just be too clean.
I am sure that most people will have heard about the hygiene hypothesis in some shape of form. The theory is that our collected efforts to eradicate anything and everything which might not meet with our exacting standards of cleanliness and 'sterility' might actually be putting our immune system in infancy out of a job, with some possible consequences to our health later in life. Whilst the theory remains just a theory, there is some evidence to corroborate this interesting view including some interesting stories about life down on the farm. I was drawn in particular to this recent article and the suggested link between asthma and Helicobacter pylori (also covered here) following my recent posts about asthma and allergy in relation to autism.
The article by Arnold and colleagues looked at exposure patterns to H. pylori in mice and how early exposure to the bacterium seemed to guide immune response to asthma-inducing allergens: the earlier that mice were exposed to H. pylori, the less they reacted to the allergens, a process modified by regulatory T-cells. When I first read this article, the first thing that went through my mind was H. pylori and its relationship to peptic ulcers and that Nobel prize for Medicine awarded in 2005 leading to triple therapy. H. pylori = bad, and eradication of H. pylori = good.
Not so, at least in mice, according to this recent article. I am of course minded to say that correlation does not necessarily imply causation and further replication of the results is required, not least in how such findings relate to humans. I do however appreciate the notion that the various bacteria that traditionally colonised us, having perhaps been modified time after time to survive in places like the human gut, might have quite a lot of effects in relation to health and moderating our risk of things like allergic disease. I partially covered this in a previous post on that lovely helminthic therapy (not for those of a squeamish disposition).
I don't for one minute advocate rolling babies and young children in dirt and detritus or adopting a pet pig just to ensure that they have their full allocated early exposure to bacteria (and viruses) to potentially help with later health. I do however follow the view that children should be allowed to be children; to roll in the short grass being careful of those pesky ticks, make those mud pies and for parents not to be too put off by the appearance of the odd dirty fingernail here and there. Soap and water was good enough for most of us, not forgetting to wash behind the ears. How about a visit to an exhibition on the history of dirt for a real insight?
As if to prove a point, take a look at this young lad from a few years back... I wonder if he ever suffered from an allergy?
News and views on autism research and other musings. Sometimes uncomfortable but rooted in peer-reviewed scientific research.
Saturday, 30 July 2011
Friday, 29 July 2011
Our brilliant gut bacteria
Another short post on some pretty special research on our gastrointestinal ecosystem published in the last few days. PLoS ONE, the premier journal from the Public Library of Science, has published two articles which begin to answer some interesting questions potentially related to autism and beyond.
The first paper by Jalanka-Tuovinen and colleagues from Finland and the Netherlands, sought to try and answer a fundamental question in relation to our gut bacteria: how stable is it, and what happens to it when we present with functional symptoms such as abdominal bloating and pain. The answers (or at least the preliminary observations) suggest that (a) our gut bacterial populations are normally fairly stable, and (b) apart from when we suffer from functional bowel problems or present with illness or take antimicrobials. I have to say that I do like this paper. I like it because it suggests that in much the same way we have immunological changes when we get ill, or our normal homeostasis is somehow interrupted, our gut bacterial rulers also change.
The second paper by Peris-Bondia and colleagues from Spain suggests that although we have literally trillions of bacteria residing in our deepest, darkest recesses, (a) some are normally more active than others and that (b) we may all carry our own unique bacterial 'fingerprint'. They also reported that we still have quite a way to go in identifying quite a proportion of our gut bacteria; their estimate was that about 40% of the bacteria they tried to read belonged to 'unclassified families'.
It is hard to read these papers and not appreciate the spectacle which is our gut bacteria. Why go looking in the deepest forests of the Amazon for new species, when your average Joe or Jane walking the street, is a world within a world.
The first paper by Jalanka-Tuovinen and colleagues from Finland and the Netherlands, sought to try and answer a fundamental question in relation to our gut bacteria: how stable is it, and what happens to it when we present with functional symptoms such as abdominal bloating and pain. The answers (or at least the preliminary observations) suggest that (a) our gut bacterial populations are normally fairly stable, and (b) apart from when we suffer from functional bowel problems or present with illness or take antimicrobials. I have to say that I do like this paper. I like it because it suggests that in much the same way we have immunological changes when we get ill, or our normal homeostasis is somehow interrupted, our gut bacterial rulers also change.
The second paper by Peris-Bondia and colleagues from Spain suggests that although we have literally trillions of bacteria residing in our deepest, darkest recesses, (a) some are normally more active than others and that (b) we may all carry our own unique bacterial 'fingerprint'. They also reported that we still have quite a way to go in identifying quite a proportion of our gut bacteria; their estimate was that about 40% of the bacteria they tried to read belonged to 'unclassified families'.
It is hard to read these papers and not appreciate the spectacle which is our gut bacteria. Why go looking in the deepest forests of the Amazon for new species, when your average Joe or Jane walking the street, is a world within a world.
Thursday, 28 July 2011
SSRIs and autism
I start this post with a disclaimer or two. I am not a Medic or healthcare professional. I am not giving medical advice. Please speak to your prescribing physician if you have any worries, complaints or comments about any current or planned medication regime. Please don't shoot the messenger.
In this post I want to discuss some of the research done on the use of, and 'possible' relationship between, selective serotonin reuptake inhibitors (SSRIs) and autism. SSRIs are, in as few words as possible, a class of drugs which are believed to act upon the serotonergic system, and in particular inhibiting the removal of serotonin so allowing more serotonin to be available. The theory is that serotonin among its many jobs seems to have some connection to enhancing mood; hence more serotonin = sustained better mood. There are various types of SSRIs available, approved mainly for use for things like depression; although also used for conditions like various anxiety disorders.
SSRIs, whilst quite a successful class of medication for many people, have not been without their problems down the years as can be seen here on the MHRA website and for those in the UK, the link here to those BBC Panorama investigations a few years back. I don't want to become embroiled in any of these debates given them being outside my area of competence and am not offering any opinion either way on the various issues suggested.
A few things brought me to this entry on SSRIs and autism. The recent study looking at maternal antidepressant use during pregnancy and risk of autism (here) and the conclusions drawn from the 2010 Cochrane review on SSRI use in autism (here) are perhaps the main articles. SSRI use as part of the pharmacotherapeutic management of certain behaviours/conditions associated/co-morbid with autism, although perhaps not commonplace, is fairly widespread. Up until the 2010 Cochrane Review, the data seemed to suggest that the various SSRI drugs used were quite successful and fairly well tolerated assuming correct medicines management. Even then however, questions were being asked about the drug profiles in terms of benefits and costs.
No matter how you look at it, the 2010 Cochrane Review of SSRI use for autism does not make great reading. For those who don't know about the Cochrane Reviews and Library, Cochrane represents a database of systematic reviews on various health and medical research - a kind of one-stop shop for meta-analyses and reviews. A selection of their other reviews on autism can be found here and here (there is also a review of dietary intervention from 2008 here). Anyhow, the 2010 report suggested that based on the current evidence, there was little indication of effect for SSRI use with children with autism, and only limited evidence for effect for adult use. I should perhaps temper the children's use statement by saying that several SSRIs are not currently licensed for use with pediatric populations so perhaps were not intended for this age-group anyway.
The paper by Lisa Croen and colleagues was published in the Archives of General Psychiatry, the same journal as the recent twin study which has received so much comment. Their findings: out of nearly 300 children diagnosed with an autism spectrum condition, mums of 6.7% reported taking antidepressant medication in the year prior to birth, compared with only 3.3% of 1507 randomly selected controls. I say antidepressants but this included various medications including the SSRIs; indeed of the 20 mums reporting medication use, 13 were prescribed SSRI monotherapy and a further two used SSRIs in combination with another antidepressant. The remaining 5 mums reported using non-SSRI pharmacotherapy. These medication combination percentages were roughly the same as that of the control group. The authors concluded that maternal use of SSRIs a year before delivery, so covering pre-natal and peri-natal stages, was associated with just over double the risk of her child presenting with autism. The risk increased if medication was being taken during the first trimester of pregnancy, with an odds ratio of 3.8 (CI 1.8-7.8).
Dr Croen and her colleague Judith Grether have quite a long history in looking at various 'risk' factors and autism. Their various research topics include: autism and ultrasound scans (here), parental age (here) and outdoor air quality (here). There was even some early hinting at their involvement in looking at twins and autism (here). The OR of 3.8 mentioned in their SSRI-autism study seems to represent quite a risk when taking into account their other data on environmental factors such as air pollutants and paternal age.
Given the leaning towards environmental factors potentially being associated with autism, I do wonder where we go from here in terms of what the evidence is suggesting. The authors state that the use of anti-depressants such as the SSRIs was comparatively low in their participants group, and certainly the advice (so far) about using such drugs during pregnancy is airing on the side of cautious monitoring rather than a complete ban. I have blogged about the concept of risk previously and how, because there are still so many gaps in the research literature, one has to be careful how research like this is translated. I should give mention that SSRI use associated with raised serotonin levels had been speculatively suggested as being a risk factor for autism a few years back.
With all due respect, I do find it interesting that some mums of children later diagnosed with autism were perhaps at greater risk of requiring medication for depression (assuming that was what it was being used for) prior to the birth of their child, which has been mentioned in the research literature previously. With my science hat on, could one perhaps argue for some effect from maternal depression serious enough to require medication as itself being a risk factor for autism as has recently been suggested with asthma? Does maternal depression translate into immune effects for example? Caution as always needs to be applied to such research. Caution that the dark times of the blame game do not re-emerge as a result of such observations and that the concept of risk is put into context.
Enough of all this talk about risk and boiling people down into numbers and odds ratios. How about a spot of The Housemartins to finish? (the singing doesn't start until about 45 seconds into the video so be patient)
In this post I want to discuss some of the research done on the use of, and 'possible' relationship between, selective serotonin reuptake inhibitors (SSRIs) and autism. SSRIs are, in as few words as possible, a class of drugs which are believed to act upon the serotonergic system, and in particular inhibiting the removal of serotonin so allowing more serotonin to be available. The theory is that serotonin among its many jobs seems to have some connection to enhancing mood; hence more serotonin = sustained better mood. There are various types of SSRIs available, approved mainly for use for things like depression; although also used for conditions like various anxiety disorders.
SSRIs, whilst quite a successful class of medication for many people, have not been without their problems down the years as can be seen here on the MHRA website and for those in the UK, the link here to those BBC Panorama investigations a few years back. I don't want to become embroiled in any of these debates given them being outside my area of competence and am not offering any opinion either way on the various issues suggested.
A few things brought me to this entry on SSRIs and autism. The recent study looking at maternal antidepressant use during pregnancy and risk of autism (here) and the conclusions drawn from the 2010 Cochrane review on SSRI use in autism (here) are perhaps the main articles. SSRI use as part of the pharmacotherapeutic management of certain behaviours/conditions associated/co-morbid with autism, although perhaps not commonplace, is fairly widespread. Up until the 2010 Cochrane Review, the data seemed to suggest that the various SSRI drugs used were quite successful and fairly well tolerated assuming correct medicines management. Even then however, questions were being asked about the drug profiles in terms of benefits and costs.
No matter how you look at it, the 2010 Cochrane Review of SSRI use for autism does not make great reading. For those who don't know about the Cochrane Reviews and Library, Cochrane represents a database of systematic reviews on various health and medical research - a kind of one-stop shop for meta-analyses and reviews. A selection of their other reviews on autism can be found here and here (there is also a review of dietary intervention from 2008 here). Anyhow, the 2010 report suggested that based on the current evidence, there was little indication of effect for SSRI use with children with autism, and only limited evidence for effect for adult use. I should perhaps temper the children's use statement by saying that several SSRIs are not currently licensed for use with pediatric populations so perhaps were not intended for this age-group anyway.
The paper by Lisa Croen and colleagues was published in the Archives of General Psychiatry, the same journal as the recent twin study which has received so much comment. Their findings: out of nearly 300 children diagnosed with an autism spectrum condition, mums of 6.7% reported taking antidepressant medication in the year prior to birth, compared with only 3.3% of 1507 randomly selected controls. I say antidepressants but this included various medications including the SSRIs; indeed of the 20 mums reporting medication use, 13 were prescribed SSRI monotherapy and a further two used SSRIs in combination with another antidepressant. The remaining 5 mums reported using non-SSRI pharmacotherapy. These medication combination percentages were roughly the same as that of the control group. The authors concluded that maternal use of SSRIs a year before delivery, so covering pre-natal and peri-natal stages, was associated with just over double the risk of her child presenting with autism. The risk increased if medication was being taken during the first trimester of pregnancy, with an odds ratio of 3.8 (CI 1.8-7.8).
Dr Croen and her colleague Judith Grether have quite a long history in looking at various 'risk' factors and autism. Their various research topics include: autism and ultrasound scans (here), parental age (here) and outdoor air quality (here). There was even some early hinting at their involvement in looking at twins and autism (here). The OR of 3.8 mentioned in their SSRI-autism study seems to represent quite a risk when taking into account their other data on environmental factors such as air pollutants and paternal age.
Given the leaning towards environmental factors potentially being associated with autism, I do wonder where we go from here in terms of what the evidence is suggesting. The authors state that the use of anti-depressants such as the SSRIs was comparatively low in their participants group, and certainly the advice (so far) about using such drugs during pregnancy is airing on the side of cautious monitoring rather than a complete ban. I have blogged about the concept of risk previously and how, because there are still so many gaps in the research literature, one has to be careful how research like this is translated. I should give mention that SSRI use associated with raised serotonin levels had been speculatively suggested as being a risk factor for autism a few years back.
With all due respect, I do find it interesting that some mums of children later diagnosed with autism were perhaps at greater risk of requiring medication for depression (assuming that was what it was being used for) prior to the birth of their child, which has been mentioned in the research literature previously. With my science hat on, could one perhaps argue for some effect from maternal depression serious enough to require medication as itself being a risk factor for autism as has recently been suggested with asthma? Does maternal depression translate into immune effects for example? Caution as always needs to be applied to such research. Caution that the dark times of the blame game do not re-emerge as a result of such observations and that the concept of risk is put into context.
Enough of all this talk about risk and boiling people down into numbers and odds ratios. How about a spot of The Housemartins to finish? (the singing doesn't start until about 45 seconds into the video so be patient)
Wednesday, 27 July 2011
Decoding coeliac disease
One of my short unscheduled 'add-in' posts this one, on what is a bumper crop of papers recently published, or appearing on the research indexes, on coeliac (celiac) disease (CD) and a few related concepts covered on this blog.
The August 2011 issue of the journal, International Reviews of Immunology is a special issue dedicated to all things coeliac disease. The editorial summary can be viewed here. A few papers caught my eye which interested readers might want to follow-up further. This paper on animal models (sorry!) of CD is an interesting one given its summary of the various types of animal model being created to characterise strands of the disease pathology present in CD. The primary conclusion from the work done so far is the leaning towards independent areas of innate, adaptive and auto-immunity all coming together to make CD what it is. This paper connecting CD to intestinal microflora is about as up-to-date as you can get (at least at the time of writing this post) on how our bacterial masters might be tied into CD.
A few other papers on CD to mention also. This paper published in the Journal of Reproductive Medicine highlights an interesting association between problems of female infertility and positive serology for CD. The authors report CD in approximately 6% of their study group presenting with unexplained fertility problems. Perhaps some implications for CD screening? This also follows similar work reporting an association between CD and reproductive life disorders. Although not specifically related to this area, I am reminded of a recent post on risk of CD and your method of entry into the world.
Finally, this paper published in the journal Cellular & Molecular Immunology makes some very interesting observations about the connection between CD and other autoimmune conditions, in this case, type-1 diabetes (T1D). Their findings suggested that where CD and T1D were comorbid in participating children, markers indicated greater intestinal permeability and a 'stronger' immunological response to be present when compared with asymptomatic and mono-CD controls. It seems that an increased autoimmune load might have some cumulative effects, or should that be the other way around?
The August 2011 issue of the journal, International Reviews of Immunology is a special issue dedicated to all things coeliac disease. The editorial summary can be viewed here. A few papers caught my eye which interested readers might want to follow-up further. This paper on animal models (sorry!) of CD is an interesting one given its summary of the various types of animal model being created to characterise strands of the disease pathology present in CD. The primary conclusion from the work done so far is the leaning towards independent areas of innate, adaptive and auto-immunity all coming together to make CD what it is. This paper connecting CD to intestinal microflora is about as up-to-date as you can get (at least at the time of writing this post) on how our bacterial masters might be tied into CD.
A few other papers on CD to mention also. This paper published in the Journal of Reproductive Medicine highlights an interesting association between problems of female infertility and positive serology for CD. The authors report CD in approximately 6% of their study group presenting with unexplained fertility problems. Perhaps some implications for CD screening? This also follows similar work reporting an association between CD and reproductive life disorders. Although not specifically related to this area, I am reminded of a recent post on risk of CD and your method of entry into the world.
Finally, this paper published in the journal Cellular & Molecular Immunology makes some very interesting observations about the connection between CD and other autoimmune conditions, in this case, type-1 diabetes (T1D). Their findings suggested that where CD and T1D were comorbid in participating children, markers indicated greater intestinal permeability and a 'stronger' immunological response to be present when compared with asymptomatic and mono-CD controls. It seems that an increased autoimmune load might have some cumulative effects, or should that be the other way around?
Tuesday, 26 July 2011
The placebo effect
This post probably best falls into my other musings description of this blog. Don't however assume that it does not tie into autism or other developmental conditions though, as will hopefully be revealed.
Placebo, aside from being a band, refers to a sham intervention, normally medical, provided during an intervention study. Normally just a sugar pill or some other similarly innocuous substance or intervention, the placebo is designed to act as a control, a standard against which a proposed efficacious compound or substance or intervention is tested. To boil it down, it works something like this:
There are various other ways of using a placebo during such experimental study (the cross-over study, comparing more than one treatment option). You can perhaps see how placebo should provide a gold-standard for such trials and how confidence should be high from any changes obtained against placebo. Simple. Well, not quite...
One of the possible side effects of using a placebo is the so-called placebo effect, whereby a proportion of participants given a placebo actually report an improvement in their symptoms. A recent paper illustrating the placebo effect in action is this one comparing St. John's wort, an anti-depressant and a placebo in the treatment of mild depression. The results of the study by Rapaport and colleagues not only suggested that SJW and citalopram could not be separated by significance as the best treatment course for mild depression, but that a placebo, a sham intervention, a sugar pill, actually improved some of the symptoms of mild depression at a rate similar to that found in the more recognised treatment modalities.
Similar results from the placebo effect have been reported with regards to pain management, hypertension, asthma and even Parkinson's disease. Little wonder that the humble placebo has been touted as a potential treatment option for various things (not that I am recommending this option).
The question of how and why the placebo effect works is a little more challenging. There is a strong case for some brain-related changes following invokation of the placebo response. Having said that the precise areas involved (note the plural areas) remain under investigation. Mind over matter probably plays a hand, or at least the effects that a little knowledge and social expectation might bestow on reported health. Apparently the ideal placebo effect involves giving more than one placebo (two pills), branded by a well-known pharmaceutical company on the pill, for the treatment to be perceived as expensive, accompanied by information and direction, from a doctor wearing a white coat, on their proposed positive effects.
How does this all tie into autism?
Placebos have been used quite extensively as part of autism research. My post a few days back on the use of levocarnitine is a good example of placebo in action. With regards to the placebo effect in relation to autism, the information base is slightly lacking. Lisa Jo Rudy discussed the placebo effect in relation to autism in a post a few years back. As she pointed out, the placebo effect might be attenuated by lots of different factors such as age, and certainly might not be as strong in younger children with autism as older children as a result of differences in things like experience and expectation. I have to say that age independent of autism is still under investigation when it comes to the placebo effect. This meta-analysis of drug resistant epilepsy suggested that the placebo effect was actually magnified in children compared to adults.
I do wonder how such age differences might manifest themselves in relation to a developmental condition like autism. So, is any placebo effect moderated by cognitive-intellectual development or social development? Would any placebo effect be moderated by the presence of comorbid learning disability? Interestingly I have not been able to find very much looking experimentally at such issues. Assuming that there is a social aspect to the placebo effect ("this pill will reduce your symptoms"), young adults with high-functioning autism, are at least as likely as non-autistic controls to act on social cues as illustrated by this small study on magic and sleight of hand. So conceivably the placebo effect might be as strong in autism as that seen in not autism?
There are quite a few philosophical issues raised by the placebo effect. Placebo used as part of our yearning for an evidence-based medicine society is an important concept. Similarly however, one could question how much the placebo effect 'interferes' with results and could potentially lead to errors in our judgement of what does and does not provide potentially efficacious results.
Placebo, aside from being a band, refers to a sham intervention, normally medical, provided during an intervention study. Normally just a sugar pill or some other similarly innocuous substance or intervention, the placebo is designed to act as a control, a standard against which a proposed efficacious compound or substance or intervention is tested. To boil it down, it works something like this:
- Compound A is a proposed treatment for condition X. Compound A is made into a tablet or something similar and submitted for experimental testing.
- Compound B is a placebo with no claim or connection to condition X. It is also formulated into a tablet exactly the same as compound A in appearance, smell, taste, etc.
- During an experimental trial, patients are, without knowledge of which, either allocated compound A (experimental treatment) or compound B (placebo).
- The effects of compounds A and B are compared.
- Should compound A show some effect for condition X, one would expect significantly better results compared with compound B, the placebo.
There are various other ways of using a placebo during such experimental study (the cross-over study, comparing more than one treatment option). You can perhaps see how placebo should provide a gold-standard for such trials and how confidence should be high from any changes obtained against placebo. Simple. Well, not quite...
One of the possible side effects of using a placebo is the so-called placebo effect, whereby a proportion of participants given a placebo actually report an improvement in their symptoms. A recent paper illustrating the placebo effect in action is this one comparing St. John's wort, an anti-depressant and a placebo in the treatment of mild depression. The results of the study by Rapaport and colleagues not only suggested that SJW and citalopram could not be separated by significance as the best treatment course for mild depression, but that a placebo, a sham intervention, a sugar pill, actually improved some of the symptoms of mild depression at a rate similar to that found in the more recognised treatment modalities.
Similar results from the placebo effect have been reported with regards to pain management, hypertension, asthma and even Parkinson's disease. Little wonder that the humble placebo has been touted as a potential treatment option for various things (not that I am recommending this option).
The question of how and why the placebo effect works is a little more challenging. There is a strong case for some brain-related changes following invokation of the placebo response. Having said that the precise areas involved (note the plural areas) remain under investigation. Mind over matter probably plays a hand, or at least the effects that a little knowledge and social expectation might bestow on reported health. Apparently the ideal placebo effect involves giving more than one placebo (two pills), branded by a well-known pharmaceutical company on the pill, for the treatment to be perceived as expensive, accompanied by information and direction, from a doctor wearing a white coat, on their proposed positive effects.
How does this all tie into autism?
Placebos have been used quite extensively as part of autism research. My post a few days back on the use of levocarnitine is a good example of placebo in action. With regards to the placebo effect in relation to autism, the information base is slightly lacking. Lisa Jo Rudy discussed the placebo effect in relation to autism in a post a few years back. As she pointed out, the placebo effect might be attenuated by lots of different factors such as age, and certainly might not be as strong in younger children with autism as older children as a result of differences in things like experience and expectation. I have to say that age independent of autism is still under investigation when it comes to the placebo effect. This meta-analysis of drug resistant epilepsy suggested that the placebo effect was actually magnified in children compared to adults.
I do wonder how such age differences might manifest themselves in relation to a developmental condition like autism. So, is any placebo effect moderated by cognitive-intellectual development or social development? Would any placebo effect be moderated by the presence of comorbid learning disability? Interestingly I have not been able to find very much looking experimentally at such issues. Assuming that there is a social aspect to the placebo effect ("this pill will reduce your symptoms"), young adults with high-functioning autism, are at least as likely as non-autistic controls to act on social cues as illustrated by this small study on magic and sleight of hand. So conceivably the placebo effect might be as strong in autism as that seen in not autism?
There are quite a few philosophical issues raised by the placebo effect. Placebo used as part of our yearning for an evidence-based medicine society is an important concept. Similarly however, one could question how much the placebo effect 'interferes' with results and could potentially lead to errors in our judgement of what does and does not provide potentially efficacious results.
Monday, 25 July 2011
Dune, water and autism
I like my Sci-Fi films. It all started round about Star Wars and just went (downhill) from there, particularly during that golden age of TV and cinema that was the 1980s. Why the 80s? Well where else can you find Gil Gerard as Buck Rogers or Jane Badler as Diana, leader of the Visitors. And that's just TV.
The latest film being rediscovered is that David Lynch classic, Dune. I won't bore you with the film details including a North-East son, Sting appearing amongst the star-studded cast, but those in the know might recognise the words 'never one drop of rain on Arrakis'. This very tenuous link from Dune to water leads me into the main event of this post, water drinking behaviour in relation to autism and a few other conditions.
It goes without saying that we all need water to survive. Indeed whereas we can survive without food or on minimal food for some time, a few days without water and its curtains pretty quickly. I've always been a little bit interested as to why H2O is so important, after reading a small part of the very large literature on why the body needs water, and what happens when we either drink too much or too little.
There are various conditions associated with water drinking behaviour. Diabetes insipidus is one of them; whereby the passing of large volumes of urine is accompanied by excessive and prolonged thirst (polydipsia) not suitably quenched by drinking water. Conditions such as schizophrenia have also been tied into fluid intake and thirst. Indeed whilst researching this part of the post, I came across that of the late Robert Cade, inventor of Gatorade and a man close to my own research heart following his work in autism and schizophrenia.
Various medications also carry side-effects associated with thirst. Lithium for example, used in the management of conditions such as bipolar disorder carries a risk of excessive thirst as a side-effect in some cases, possibly as a result of its impact on our thirst regulation. On the other side of the pharmacotherapy fence, the neuroleptic drug risperidone has shown some promise in treating 'psychogenic' polydipsia.
With autism in mind, water has been mentioned a few times. Outside of the possible environmental drinking water connection vis-a-vis my previous post on chlorination by-products including also speculation on things like fluoride in water, a lot of the research has focused on water drinking behaviour in autism, and in particular problems such as polydipsia or excessive thirst. I should point out that like many things related to autism, there is always the possibility that the behaviour we see is there as a consequence of the core areas associated with autism. One could therefore envisage a situation where excessive drinking habits are either a learned response or part of some routine or ritual rather than having any immediate somatic or physiological undertone. I dare say that there might even be a perceptual side to excessive water drinking in autism. Possible at least.
This paper found that polydipsia was more commonly reported in autism over learning disability, corroborating quite a few case studies and first- and second-person accounts on the web of this unusual behaviour. The possible biological mechanisms behind polydipsia are a little more of a mystery, assuming that conditions such as diabetes insipidus are not co-morbid and having an effect. I was interested by some comments made in this paper about polydipsia in a learning disability population potentially being co-morbid to pica and something called Kleine-Levin syndrome. Certainly pica has perhaps more than a passing relationship to autism, although at this point I wouldn't like to speculate too much as to whether pica and polydipsia might show any causal effect on one another outside of the effect of eating things like sand and earth which may well make one thirsty.
Whilst I have, once again, only paid lip service to excessive water intake and its possible relationship to autism, there are a few details which will get even less attention in this post. Conditions such as hyponatremia, and other disorders of electrolytes are perhaps possible risk factors as a result of excessive water consumption and the limited research so far suggests more work is needed specifically for autism. One might also expect that excessive water intake might have some effect on functional bowel patterns also; indeed one might assume that in moderation, increased water intake levels could be a useful complementary strategy at least in some cases. Finally, although polydipsia has received the most research attention in autism, I do wonder about those people with autism who might demonstrate the opposite behaviour... erm, low water intake (dont' know the Greek or Latin term) and the potential effects that this might have either on autistic symptoms or well-being in general.
To end a spot of Handel and some water music to jolly up anyone's day.
The latest film being rediscovered is that David Lynch classic, Dune. I won't bore you with the film details including a North-East son, Sting appearing amongst the star-studded cast, but those in the know might recognise the words 'never one drop of rain on Arrakis'. This very tenuous link from Dune to water leads me into the main event of this post, water drinking behaviour in relation to autism and a few other conditions.
It goes without saying that we all need water to survive. Indeed whereas we can survive without food or on minimal food for some time, a few days without water and its curtains pretty quickly. I've always been a little bit interested as to why H2O is so important, after reading a small part of the very large literature on why the body needs water, and what happens when we either drink too much or too little.
There are various conditions associated with water drinking behaviour. Diabetes insipidus is one of them; whereby the passing of large volumes of urine is accompanied by excessive and prolonged thirst (polydipsia) not suitably quenched by drinking water. Conditions such as schizophrenia have also been tied into fluid intake and thirst. Indeed whilst researching this part of the post, I came across that of the late Robert Cade, inventor of Gatorade and a man close to my own research heart following his work in autism and schizophrenia.
Various medications also carry side-effects associated with thirst. Lithium for example, used in the management of conditions such as bipolar disorder carries a risk of excessive thirst as a side-effect in some cases, possibly as a result of its impact on our thirst regulation. On the other side of the pharmacotherapy fence, the neuroleptic drug risperidone has shown some promise in treating 'psychogenic' polydipsia.
With autism in mind, water has been mentioned a few times. Outside of the possible environmental drinking water connection vis-a-vis my previous post on chlorination by-products including also speculation on things like fluoride in water, a lot of the research has focused on water drinking behaviour in autism, and in particular problems such as polydipsia or excessive thirst. I should point out that like many things related to autism, there is always the possibility that the behaviour we see is there as a consequence of the core areas associated with autism. One could therefore envisage a situation where excessive drinking habits are either a learned response or part of some routine or ritual rather than having any immediate somatic or physiological undertone. I dare say that there might even be a perceptual side to excessive water drinking in autism. Possible at least.
This paper found that polydipsia was more commonly reported in autism over learning disability, corroborating quite a few case studies and first- and second-person accounts on the web of this unusual behaviour. The possible biological mechanisms behind polydipsia are a little more of a mystery, assuming that conditions such as diabetes insipidus are not co-morbid and having an effect. I was interested by some comments made in this paper about polydipsia in a learning disability population potentially being co-morbid to pica and something called Kleine-Levin syndrome. Certainly pica has perhaps more than a passing relationship to autism, although at this point I wouldn't like to speculate too much as to whether pica and polydipsia might show any causal effect on one another outside of the effect of eating things like sand and earth which may well make one thirsty.
Whilst I have, once again, only paid lip service to excessive water intake and its possible relationship to autism, there are a few details which will get even less attention in this post. Conditions such as hyponatremia, and other disorders of electrolytes are perhaps possible risk factors as a result of excessive water consumption and the limited research so far suggests more work is needed specifically for autism. One might also expect that excessive water intake might have some effect on functional bowel patterns also; indeed one might assume that in moderation, increased water intake levels could be a useful complementary strategy at least in some cases. Finally, although polydipsia has received the most research attention in autism, I do wonder about those people with autism who might demonstrate the opposite behaviour... erm, low water intake (dont' know the Greek or Latin term) and the potential effects that this might have either on autistic symptoms or well-being in general.
To end a spot of Handel and some water music to jolly up anyone's day.
Saturday, 23 July 2011
Head size in autism is complicated
Size and growth are some pretty important concepts related to lots of different features of the human condition. Although universal connections related to health rarely (never?) exist, there are some interesting data linking small birth weight and later childhood intellectual development for example, as well as brain size and the intelligence quotient (at least to a degree). Size and growth tend to be determined by a variable combination of both genes and environment. This meta-analysis for example, showed how the physical environment affects various growth measures, height and weight, but perhaps not as much parameters such as head circumference. This leads me to the subject of this post - head size and autism - and some of the published research and its potential implications.
Macrocephaly is the technical term where head circumference is larger than about 2 standard deviations from the average (mean); the opposite condition being microcephaly, where head circumference is smaller. There are various reasons why a larger head may occur, such as an enlargement of the brain and cases of hydrocephalus (water on the brain). In most cases in infants and children, larger head size is thought to be governed by more genetic factors such as heredity or the presence of one or more various genetic disorders.
Macrocephaly has, down the years, been associated with some cases of autism spectrum conditions. Kanner first noted that some of his original cohort had larger heads (among other things). An observation which has subsequently been reported again and again and again with prevalence estimates of macrocephaly in autism ranging from approximately 10-30%. The data does suggest some degree of heritability linked to macrocephaly, although the relationship is not entirely straight forward and the heritability implications not immediately clear. In more recent years there has been some debate about macrocephaly and autism and how factors such as ethnicity might also show an effect. This study for example first published as an abstract at IMFAR 2009, based on an Israeli cohort found little evidence of elevated rates of macrocephaly in autism in comparison to asymptomatic controls.
Why might macrocephaly be important to autism? Well I mentioned that outside of heritability, generally macrocephaly is tied into one or more genetic conditions. The theory in autism is that such findings might indicate some genetic component and hence help point towards candidate areas of interest. To see this theory in action, readers may wish to have a look at these studies (here and here) on how macrocephaly from both a case study and group study point of view might help untangle a few research strands in such a heterogeneous condition. The 'endophenotypes' way of study is something which really is the future of autism research.
There are perhaps more immediate effects potentially tied into macrocephaly presenting in autism also. This study suggested specific autistic behaviours tend to be more severe in those with larger heads, including delays in acquiring language; the language side of things however seems to be the source of some speculation. Uta Frith joins a number of other researchers in saying that macrocephaly may imply abnormal neural connectivity. One might also expect that a larger head may indicate a larger brain and hence the maturational issue of brain growth could be implicated. Certainly studies of total brain volume in autism seem to suggest some discrepancy with control populations, driven by things like an increased cortical surface area. Such studies also seem to point to a 'brain overgrowth' as potentially being present, at least during early infancy with lots of different areas of the brain involved. Thinking about this, I was reminded of some work I have heard discussed quite a few years ago about synaptic pruning in relation to autism and the various instruments of such pruning including the MHC and endogenous opioid peptides. Indeed the work of Zagon and McLaughlin is I think absolutely fascinating, particularly their characterisation of the zeta opioid receptor and their various studies on the effects of opioid antagonists such as naltrexone on rat postnatal development. I don't know if and how it might tie into these latest findings on synaptic pruning.
I think it is important also to note that larger head size is not exclusive to autism spectrum conditions. This paper reported similar trends in head size and various other growth parameters from non-autism controls with a psychiatric disorder. Importantly however they indicated that there may be subtle differences in the timing of measurements between autism and controls which might provide some clues for the underlying processes involved.
What we can ascertain from this collected body of work is that larger heads show more than a passing association to autism spectrum conditions, and perhaps tie into some elements of the presented condition including some interesting findings on serotonin. Having said that, the recent meta-analysis of neonatal factors in connection to autism included as part of this post suggesting that the connection to head circumference might not be all it has been cracked up to be, perhaps needs to be taken on board. What I would like to see is more information on is any link to important autism co-morbidities such as epilepsy and if such 'overgrowth' is confined to early infancy, and whether it is controlled by genes or environment (or both)?
Regarding size matters...
Macrocephaly is the technical term where head circumference is larger than about 2 standard deviations from the average (mean); the opposite condition being microcephaly, where head circumference is smaller. There are various reasons why a larger head may occur, such as an enlargement of the brain and cases of hydrocephalus (water on the brain). In most cases in infants and children, larger head size is thought to be governed by more genetic factors such as heredity or the presence of one or more various genetic disorders.
Macrocephaly has, down the years, been associated with some cases of autism spectrum conditions. Kanner first noted that some of his original cohort had larger heads (among other things). An observation which has subsequently been reported again and again and again with prevalence estimates of macrocephaly in autism ranging from approximately 10-30%. The data does suggest some degree of heritability linked to macrocephaly, although the relationship is not entirely straight forward and the heritability implications not immediately clear. In more recent years there has been some debate about macrocephaly and autism and how factors such as ethnicity might also show an effect. This study for example first published as an abstract at IMFAR 2009, based on an Israeli cohort found little evidence of elevated rates of macrocephaly in autism in comparison to asymptomatic controls.
Why might macrocephaly be important to autism? Well I mentioned that outside of heritability, generally macrocephaly is tied into one or more genetic conditions. The theory in autism is that such findings might indicate some genetic component and hence help point towards candidate areas of interest. To see this theory in action, readers may wish to have a look at these studies (here and here) on how macrocephaly from both a case study and group study point of view might help untangle a few research strands in such a heterogeneous condition. The 'endophenotypes' way of study is something which really is the future of autism research.
There are perhaps more immediate effects potentially tied into macrocephaly presenting in autism also. This study suggested specific autistic behaviours tend to be more severe in those with larger heads, including delays in acquiring language; the language side of things however seems to be the source of some speculation. Uta Frith joins a number of other researchers in saying that macrocephaly may imply abnormal neural connectivity. One might also expect that a larger head may indicate a larger brain and hence the maturational issue of brain growth could be implicated. Certainly studies of total brain volume in autism seem to suggest some discrepancy with control populations, driven by things like an increased cortical surface area. Such studies also seem to point to a 'brain overgrowth' as potentially being present, at least during early infancy with lots of different areas of the brain involved. Thinking about this, I was reminded of some work I have heard discussed quite a few years ago about synaptic pruning in relation to autism and the various instruments of such pruning including the MHC and endogenous opioid peptides. Indeed the work of Zagon and McLaughlin is I think absolutely fascinating, particularly their characterisation of the zeta opioid receptor and their various studies on the effects of opioid antagonists such as naltrexone on rat postnatal development. I don't know if and how it might tie into these latest findings on synaptic pruning.
I think it is important also to note that larger head size is not exclusive to autism spectrum conditions. This paper reported similar trends in head size and various other growth parameters from non-autism controls with a psychiatric disorder. Importantly however they indicated that there may be subtle differences in the timing of measurements between autism and controls which might provide some clues for the underlying processes involved.
What we can ascertain from this collected body of work is that larger heads show more than a passing association to autism spectrum conditions, and perhaps tie into some elements of the presented condition including some interesting findings on serotonin. Having said that, the recent meta-analysis of neonatal factors in connection to autism included as part of this post suggesting that the connection to head circumference might not be all it has been cracked up to be, perhaps needs to be taken on board. What I would like to see is more information on is any link to important autism co-morbidities such as epilepsy and if such 'overgrowth' is confined to early infancy, and whether it is controlled by genes or environment (or both)?
Regarding size matters...
Wednesday, 20 July 2011
Methylmalonic acid and autism: baby and bathwater?
To 'throw the baby out with the bathwater' is perhaps one of more common mistakes we humans tend to make, alongside our tendency to generalise. The theory goes something like this: concept/product/idea X is put forward. It contains more than one element. One of the elements is found to be potentially wrong or show some error. Ergo, all of concept/product/idea X is wrong.
You can see such an idea at work nearly every day. Your TV stops working just after the warranty expires - your response: 'I'm never going to buy that brand of TV set again'. It couldn't just be that yours is [individually] a dodgy TV set? No, of course not; it has to be the whole brand at fault. Without wishing to get all political and certainly without offering any opinion, take also the recent Climategate arguments and the University of East Anglia and how this was used to in certain circles. Baby and bathwater.
In the post titled: should I mention gastrointestinal symptoms in autism? I talked briefly about co-morbid inflammatory bowel disease and autism, and the fact that such findings in some cases of autism have been reported by more than one team. The controversy around one paper, the original paper, has however raised debates after debates which have far extended beyond that one paper to have more wide-reaching effects on how we view autism and its various gastrointestinal (GI) co-morbidities - indeed how we manage (or don't) such co-morbidity when present. Baby and bathwater?
I have picked on the GI area because alongside the original (now retracted) bowel findings presented in the 1998 Lancet paper, there was another potentially important area of research: methylmalonic acid [and vitamin B12 (cobalamin)] which seems to have joined sulphate in its path towards autism research oblivion as a result of the various debates on the bowel findings and their suggested implications. A sort of death by association?
Methylmalonic acid (MMA) is quite an interesting compound. I am not for one minute suggesting that I am an expert on MMA, certainly nowhere near as in the same league as these chaps. Indeed Messers Bhatt and Linnell have quite an extensive history when it comes to MMA and vitamin B12, publishing in some pretty decent journals. I had the good fortune to meet with John Linnell many, many years ago and talk to him about some of his work at the vitamin B12 unit at the Chelsea & Westminster Hospital after its closure. He was a very nice chap and knew what he was talking about when it came to B12 and MMA.
Methylmalonic acidemia is another example of an inborn error of metabolism (alongside things like PKU). There is quite a good technical overview of the various possible reasons for the condition and the various phenotypes here. The basic effect of this condition is an increase in the levels of MMA in various biological fluids. Treatment is, depending on disease type, via dietary management, vitamin B12 injections and interestingly related to my previous post, supplementation with carnitine. In much the same way as with the management of PKU, a few adjustments can make a world of difference. Vitamin B12 (as methylcobalamin) has also received some interest in autism previously albeit not entirely efficaciously.
The retracted 1998 Lancet paper carries the only peer-reviewed published reference to the measurement of MMA in autism that I have found in the research literature; where all of the children included for study who were tested (n=8) showed elevated levels of urinary MMA against age-matched controls. Similar elevations of MMA have been reported in other conditions including schizophrenia. In amongst the various commentaries, one letter (from Ray Bhatt) questioned several aspects of the MMA findings in relation to autism, and certainly reading the detailed description of methylmalonic acidemia, some of them seem valid.
I would perhaps argue that MMA and cobalamin metabolism in general is still an unexplored avenue in relation to autism spectrum conditions. Knowing that our old friend homocysteine might show some link to at least some cases of autism, and the relationship between MMA and homocysteine, there is perhaps something that could be learned from a little more inquiry and a little less baby and bathwater.
You can see such an idea at work nearly every day. Your TV stops working just after the warranty expires - your response: 'I'm never going to buy that brand of TV set again'. It couldn't just be that yours is [individually] a dodgy TV set? No, of course not; it has to be the whole brand at fault. Without wishing to get all political and certainly without offering any opinion, take also the recent Climategate arguments and the University of East Anglia and how this was used to in certain circles. Baby and bathwater.
In the post titled: should I mention gastrointestinal symptoms in autism? I talked briefly about co-morbid inflammatory bowel disease and autism, and the fact that such findings in some cases of autism have been reported by more than one team. The controversy around one paper, the original paper, has however raised debates after debates which have far extended beyond that one paper to have more wide-reaching effects on how we view autism and its various gastrointestinal (GI) co-morbidities - indeed how we manage (or don't) such co-morbidity when present. Baby and bathwater?
I have picked on the GI area because alongside the original (now retracted) bowel findings presented in the 1998 Lancet paper, there was another potentially important area of research: methylmalonic acid [and vitamin B12 (cobalamin)] which seems to have joined sulphate in its path towards autism research oblivion as a result of the various debates on the bowel findings and their suggested implications. A sort of death by association?
Methylmalonic acid (MMA) is quite an interesting compound. I am not for one minute suggesting that I am an expert on MMA, certainly nowhere near as in the same league as these chaps. Indeed Messers Bhatt and Linnell have quite an extensive history when it comes to MMA and vitamin B12, publishing in some pretty decent journals. I had the good fortune to meet with John Linnell many, many years ago and talk to him about some of his work at the vitamin B12 unit at the Chelsea & Westminster Hospital after its closure. He was a very nice chap and knew what he was talking about when it came to B12 and MMA.
Methylmalonic acidemia is another example of an inborn error of metabolism (alongside things like PKU). There is quite a good technical overview of the various possible reasons for the condition and the various phenotypes here. The basic effect of this condition is an increase in the levels of MMA in various biological fluids. Treatment is, depending on disease type, via dietary management, vitamin B12 injections and interestingly related to my previous post, supplementation with carnitine. In much the same way as with the management of PKU, a few adjustments can make a world of difference. Vitamin B12 (as methylcobalamin) has also received some interest in autism previously albeit not entirely efficaciously.
The retracted 1998 Lancet paper carries the only peer-reviewed published reference to the measurement of MMA in autism that I have found in the research literature; where all of the children included for study who were tested (n=8) showed elevated levels of urinary MMA against age-matched controls. Similar elevations of MMA have been reported in other conditions including schizophrenia. In amongst the various commentaries, one letter (from Ray Bhatt) questioned several aspects of the MMA findings in relation to autism, and certainly reading the detailed description of methylmalonic acidemia, some of them seem valid.
I would perhaps argue that MMA and cobalamin metabolism in general is still an unexplored avenue in relation to autism spectrum conditions. Knowing that our old friend homocysteine might show some link to at least some cases of autism, and the relationship between MMA and homocysteine, there is perhaps something that could be learned from a little more inquiry and a little less baby and bathwater.
Tuesday, 19 July 2011
Even Superman had problems with lead
Whilst the Man of Steel was all but impervious to bullets and explosions, he was not without his weaknesses. Kryptonite was his primary problem, but when it came to using that X-ray vision of his, another obstacle stood in his way, lead.
Lead (Pb or plumbum) has popped up here and there in a few recent posts on this blog. It was one of the factors, the reduction of which, was put forward to partially account for the drop in crime levels in the US in this post; a factor no-one can rule out in relation to the risk of being diagnosed with ADHD in this post; and also exemplified as the archetypal behaviour-changer in this post on detox. Yes sir, lead might have quite a bit to answer for.
Lead exposure is a well-known effector of health. For children with their developing brain in particular, lead exposure is not good news and can affect both physical and cognitive development. It is perhaps with these quite important effects in mind, that lead exposure has been looked at with reference to quite a few childhood conditions, including those with a developmental aspect to them such as ADHD.
The possibility that lead exposure either pre-, peri- or post-natally might be implicated in the risk of being diagnosed with an autism spectrum condition has also been the topic of some research. Studies such as this one, this one and this one have all suggested some (varying) association between lead exposure and autism, either on the basis of treatment figures or based on biological measures of detected amounts. The literature has been joined by this recent paper suggesting chronic lead toxicity in a number of children with autism resident in Saudi Arabia.
I have blogged about the Saudi research group involved in this new study already, based on their excellent publication record this year in autism research which rivals that of the MIND Institute and Prof. Jim Adams. In this latest trial, for which I only have the abstract so far, it appears that they are signalling post-natal lead toxicity as, quote ".. could represent a causative factor in the pathogenesis of autism" on the basis of some very high levels of the lead ion being detected in plasma. Don't ask me how they made the detection because I don't have the full-text paper yet, but I would hazard a guess that based on their results they might have used our old friend ICP Mass Spectrometry or possibly via atomic absorption.
I don't want to go too overboard on this latest study yet. It is interesting to note that lead poisoning in the early years can affect various brain functions including synaptogenesis and the correct functioning of the blood-brain barrier. Both of which have been implicated, to varying degrees in cases of autism and related developmental conditions. Having said that, autism does not seem to have a monopoly on these issues outside of other conditions; whether such mechanisms could so fundamentally affect a person as to 'lead' (pardon the wordplay) to autism or autistic symptoms I don't know.
There are various potential implications from any association between lead and autism. Risk issues such as the environment, the prevalence of pica in autism and the various suggestions about the use of chelating agents to remove bioaccumulated lead all might figure in any discussions. What I would perhaps like to see initially is some guidance on ruling out lead poisoning in any and all cases of developmental diagnoses as a routine measure, bearing in mind what is known about the effects of lead and the developing brain.
Lead (Pb or plumbum) has popped up here and there in a few recent posts on this blog. It was one of the factors, the reduction of which, was put forward to partially account for the drop in crime levels in the US in this post; a factor no-one can rule out in relation to the risk of being diagnosed with ADHD in this post; and also exemplified as the archetypal behaviour-changer in this post on detox. Yes sir, lead might have quite a bit to answer for.
Lead exposure is a well-known effector of health. For children with their developing brain in particular, lead exposure is not good news and can affect both physical and cognitive development. It is perhaps with these quite important effects in mind, that lead exposure has been looked at with reference to quite a few childhood conditions, including those with a developmental aspect to them such as ADHD.
The possibility that lead exposure either pre-, peri- or post-natally might be implicated in the risk of being diagnosed with an autism spectrum condition has also been the topic of some research. Studies such as this one, this one and this one have all suggested some (varying) association between lead exposure and autism, either on the basis of treatment figures or based on biological measures of detected amounts. The literature has been joined by this recent paper suggesting chronic lead toxicity in a number of children with autism resident in Saudi Arabia.
I have blogged about the Saudi research group involved in this new study already, based on their excellent publication record this year in autism research which rivals that of the MIND Institute and Prof. Jim Adams. In this latest trial, for which I only have the abstract so far, it appears that they are signalling post-natal lead toxicity as, quote ".. could represent a causative factor in the pathogenesis of autism" on the basis of some very high levels of the lead ion being detected in plasma. Don't ask me how they made the detection because I don't have the full-text paper yet, but I would hazard a guess that based on their results they might have used our old friend ICP Mass Spectrometry or possibly via atomic absorption.
I don't want to go too overboard on this latest study yet. It is interesting to note that lead poisoning in the early years can affect various brain functions including synaptogenesis and the correct functioning of the blood-brain barrier. Both of which have been implicated, to varying degrees in cases of autism and related developmental conditions. Having said that, autism does not seem to have a monopoly on these issues outside of other conditions; whether such mechanisms could so fundamentally affect a person as to 'lead' (pardon the wordplay) to autism or autistic symptoms I don't know.
There are various potential implications from any association between lead and autism. Risk issues such as the environment, the prevalence of pica in autism and the various suggestions about the use of chelating agents to remove bioaccumulated lead all might figure in any discussions. What I would perhaps like to see initially is some guidance on ruling out lead poisoning in any and all cases of developmental diagnoses as a routine measure, bearing in mind what is known about the effects of lead and the developing brain.
Monday, 18 July 2011
Painkillers vs antipsychotics in dementia care
A very, very short post this one (I promise). The news here in the UK has been abuzz with lots of things today (that newspaper, that media baron, etc) but in amongst the talk of resignations, and Parliamentary hearings, a piece appeared on the BBC website about a new study published in the British Medical Journal (BMJ).
The study is here (full-text) and suggests that using various analgesics, including paracetamol (acetaminophen), with patients with dementia might decrease levels of 'agitation' over and above that which might be expected from the use of various antipsychotics, traditionally the first line of treatment for such issues. People with dementia can suffer pain (believe it or not!) and antipsychotics are not necessarily the best analgesic.
I am still digesting the study, its very comprehensive methodology and its findings, but already a few parallels are emerging with autism spectrum conditions. Principal among them is the notion that not every 'ill' that a person with autism might present with is necessarily due to their autism. I have hinted about this in a previous post on self-injurious behaviour (SIB) and the so-called challenging behaviours in autism. One could also conceivably see some relationship to the various bowel problems associated with some cases of autism and particularly Buie and colleagues' assertion about gastrointestinal problems, pain and 'aberrant behaviours' related to autism.
Worth a look.
The study is here (full-text) and suggests that using various analgesics, including paracetamol (acetaminophen), with patients with dementia might decrease levels of 'agitation' over and above that which might be expected from the use of various antipsychotics, traditionally the first line of treatment for such issues. People with dementia can suffer pain (believe it or not!) and antipsychotics are not necessarily the best analgesic.
I am still digesting the study, its very comprehensive methodology and its findings, but already a few parallels are emerging with autism spectrum conditions. Principal among them is the notion that not every 'ill' that a person with autism might present with is necessarily due to their autism. I have hinted about this in a previous post on self-injurious behaviour (SIB) and the so-called challenging behaviours in autism. One could also conceivably see some relationship to the various bowel problems associated with some cases of autism and particularly Buie and colleagues' assertion about gastrointestinal problems, pain and 'aberrant behaviours' related to autism.
Worth a look.
Second hand smoke and ADHD
Of all the modern day vices that society possesses like alcohol and drugs of abuse, tobacco smoking enjoys one the oddest relationships. Odd because despite a considerable body of evidence linking smoking to various health problems including those related to early mortality, combined with smoking being linked to a considerable health economics burden, people are still free to buy tobacco and smoke as much and as often as they choose to.
Yes, you might say that Governments have restricted various things in relation to smoking such as their taxed price, their availability to minors (supposedly), where a person can and cannot smoke, and even highlighting what smoking does to a person. The choice to smoke or not however still remains.
In recent times the health message on smoking has seemed to shift from emphasising the risk to the person smoking to the potential risks to those around the smoker with the rise of second-hand smoke. Here in the UK we have the recent 7-steps campaign, encouraging smoking parents for example to protect their kids by taking 7 steps outside from the backdoor when lighting up. I'm not sure how successful this initiative might be with the famous English weather whose default = rain.
I say all this because an article has appeared in the journal Pediatrics suggesting that second-hand smoke exposure might up the risk for various behavioural conditions, particularly attention-deficit hyperactivity disorder (ADHD). The full-text paper by Kabir and colleagues is available here. I don't want to go through all the papers methods and findings but the summary is here:
There are a few other details which have been picked up in the various media interest about this paper, but I have to say I am not altogether convinced that some of the reported points are the most important findings from this data. I would also add that as per the authors discussions, the data do not definitively show that smoke is the one and only risk factor; indeed adding a sentence which reads: "Other unmeasured potential confounders, such as lead exposure, cannot be ruled out". Mmm, takes me back to the US crime figures post.
I do think we have to be very careful when drawing firm conclusions from such fishing papers, particularly where 'risk' is used. Does this data alone make a case for banning smoking in homes where young children grow up? I'm afraid that I can't answer that question, although this is not the first study to suggest such an association between parental smoking and risk of ADHD. I would perhaps also add that such early exposure to tobacco smoke might also be one (of many) explanations why people with ADHD/ADD might be more prone to smoking themselves.
I would however think that data such as this on the link between second-hand smoke and potentially life-threatening conditions like asthma, perhaps makes for a more compelling public health message for Governments to work on about the dangers of second-hand smoke for children.
Yes, you might say that Governments have restricted various things in relation to smoking such as their taxed price, their availability to minors (supposedly), where a person can and cannot smoke, and even highlighting what smoking does to a person. The choice to smoke or not however still remains.
In recent times the health message on smoking has seemed to shift from emphasising the risk to the person smoking to the potential risks to those around the smoker with the rise of second-hand smoke. Here in the UK we have the recent 7-steps campaign, encouraging smoking parents for example to protect their kids by taking 7 steps outside from the backdoor when lighting up. I'm not sure how successful this initiative might be with the famous English weather whose default = rain.
I say all this because an article has appeared in the journal Pediatrics suggesting that second-hand smoke exposure might up the risk for various behavioural conditions, particularly attention-deficit hyperactivity disorder (ADHD). The full-text paper by Kabir and colleagues is available here. I don't want to go through all the papers methods and findings but the summary is here:
- From a total sample size of approximately 90,000 children aged from birth to 17 years old, data for 55,358 children (aged 0-11 years) were analysed based on their exposure to second-hand smoke and their receipt (or not) of various neurobehavioural diagnoses such as learning disability, ADHD and conduct disorders.
- Based on this 2007 data, approximately 6% of children were deemed to be exposed to second-hand tobacco smoke.
- Learning disability, as reported by parents, was present in 8.2% of participants, 5.9% had ADHD and 3.6% had a behavioural or conduct disorder.
- Adjusted prevalence figures showed that children exposed to tobacco smoke were quite a bit higher for all neurobehavioural conditions examined when compared with non-exposed children. The disparity in adjusted prevalence terms (exposed vs. not exposed) were: conduct disorder (8.7 vs. 2.8), ADHD/ADD (13.0 vs. 5.5), learning disability (15.1 vs. 7.2).
- Outside of second-hand smoke exposure, various other factors were 'predictive' of an increased prevalence of the neurobehavioural conditions included. Poverty seemed to be the largest influence, following on from the various research linking poverty to smoking.
There are a few other details which have been picked up in the various media interest about this paper, but I have to say I am not altogether convinced that some of the reported points are the most important findings from this data. I would also add that as per the authors discussions, the data do not definitively show that smoke is the one and only risk factor; indeed adding a sentence which reads: "Other unmeasured potential confounders, such as lead exposure, cannot be ruled out". Mmm, takes me back to the US crime figures post.
I do think we have to be very careful when drawing firm conclusions from such fishing papers, particularly where 'risk' is used. Does this data alone make a case for banning smoking in homes where young children grow up? I'm afraid that I can't answer that question, although this is not the first study to suggest such an association between parental smoking and risk of ADHD. I would perhaps also add that such early exposure to tobacco smoke might also be one (of many) explanations why people with ADHD/ADD might be more prone to smoking themselves.
I would however think that data such as this on the link between second-hand smoke and potentially life-threatening conditions like asthma, perhaps makes for a more compelling public health message for Governments to work on about the dangers of second-hand smoke for children.
Saturday, 16 July 2011
You are my sunshine: vitamin D and autism
Historically, England and Scotland have perhaps not enjoyed the best of relationships. Anyone who has watched the blood and guts of the film Braveheart, very, very, very loosely based on the life and times of Sir William Wallace, will get an idea of what the main problems were in terms of conquest, lands, identity and freedom. Down the years some degree of one-upmanship still survives as evidenced by little things like the 'anyone but England' slogan during the recent World Cup. Those who watched the 2010 World Cup will know that the English football (soccer) team did pretty well on their own in early-exiting the tournament without the help of the ABE campaign.
As an Englishman living fairly close to the Borders, I don't want to get too involved in the politics. My geographical proximity to Scotland does however give me a little bit of a flavour of the climate in Scotland and its relevance to this post on vitamin D.
I was intrigued by a comment made to me quite recently when discussing measuring levels of vitamin D. The comment included the term 'normal for Scotland' when interpreting some biochemical results on vitamin D levels in various patient groups. I found out that day that 'normal for Scotland' is usually taken to mean vitamin D results are not abnormal when compared to the Scottish population but neither do they show a particularly healthy level of vitamin D to be present assuming accuracy of the testing procedure. One of the possible reasons: well whilst the sun does shine in Scotland (sometimes), there is quite a bit of evidence to suggest that it doesn't necessarily translate into an all-year round adequate vitamin D level for many, many people living at certain geographical coordinates all of which cover Scotland; indeed also where I live.
I should perhaps back-up a little and provide a little more description of vitamin D first. Vitamin D is a fat-soluble vitamin. Although having multiple uses throughout the body, vitamin D is perhaps most famous for its role in aiding in the absorption of calcium; see my recent post on this subject. There are a few ways of getting vitamin D; through our modern fortified diet (assuming you eat breakfast cereals for example) and also by contact with sunshine, or more specifically via exposure to ultraviolet B light. I suppose a third way is via supplementation.
Vitamin D is a vitamin in the spotlight at the moment. There is quite a lot of research coming out telling us how much we need vitamin D for lots of different health reasons, ranging from cancer prevention to maintaining good cognitive health to potentially helping to tackle growing health problems like diabetes. Looking at childhood health in particular, there is some pretty good evidence that conditions classically associated with vitamin D like rickets might be making an unwelcome return here in the UK and beyond. Although not altogether clear as to what is driving our vitamin D deficiency, it seems as though lifestyle is a possible factor; so sitting reading blogs from a home PC indoors rather than reading them on an iPad outdoors, our use of barrier creams to prevent excessive sun exposure and its onward effects, but also physiological factors such as skin colour (although research in this area is not cut and dried).
There is also some suggestion that vitamin D might show some connection to various childhood developmental conditions including autism. Vitamin D and psychiatry have, what might be called, a blossoming relationship. PubMed lists over 100 entries based on the keywords vitamin D and schizophrenia, covering various angles of a possible connection from genes to biochemistry, even including psychology. I would not be so bold as to say that the link is in anyway definitive, but it makes for some interesting reading.
With autism in mind, vitamin D has also received more than passing mention. As with all dietary components, the possible influence of unusual eating habits and patterns attributed to many cases of autism, would perhaps predispose some people on the autism spectrum to a reduced intake of dietary-derived vitamin D. The research in this area does seem to corroborate this suggestion. One of the bigger names in all things vitamin D, Dr John Cannell, wrote an interesting paper about vitamin D and autism not so long ago (here). Putting the universality of the vitamin D-autism hypothesis to one side, there are some interesting points raised in his paper which are beginning to be borne out by the accumulated research in this area. In particular are the various research on autism in specific ethnic populations such as the Somali community, and the evidence put forward for some increase in autism prevalence in such groups when resident in more Northern climes. I would reiterate the old 'correlation does not imply causation' adage at this point also.
Another interesting area of research relates to the various work on the gastrointestinal (GI) co-morbidities noted alongside some cases of autism, and whether malabsorption as a result of coeliac disease or hyperpermeability of the gut might play a hand in hypovitaminosis D as has been suggested elsewhere. This research published on Egyptian children might be relevant to this side of the hypothesis given that I am sure that sunshine is at a premium in the land of the Pharaohs. Finally, although there is no contemporary epidemiological evidence to speak of, autism does not seem to be protective against the development of rickets as witnessed by this study (one of the study authors being also involved in this paper on iron deficiency and autism) and this study.
Taking into account the evidence currently available, I don't think that we can say that autism, or any one condition, has a monopoly on low levels of vitamin D. Many people from many different ethnic, geographic and symptomatic groups seem to be on the low side of what would be considered to be 'adequate' levels of vitamin D. There is also the 'chicken and egg' situation in terms of whether vitamin D levels are 'causative' of anything (outside of rickets or other classically related conditions) as complicated as autism or schizophrenia, etc. or just symptomatic of some other underlying mechanism or dysfunction. I will leave you to make your decision on this issue. Finally, vitamin D might be only one part of any association as can be seen by this editorial on how UVB sunlight might also have some other interesting effects.
To finish, this Sassenach wonders how many miles would you walk?
As an Englishman living fairly close to the Borders, I don't want to get too involved in the politics. My geographical proximity to Scotland does however give me a little bit of a flavour of the climate in Scotland and its relevance to this post on vitamin D.
I was intrigued by a comment made to me quite recently when discussing measuring levels of vitamin D. The comment included the term 'normal for Scotland' when interpreting some biochemical results on vitamin D levels in various patient groups. I found out that day that 'normal for Scotland' is usually taken to mean vitamin D results are not abnormal when compared to the Scottish population but neither do they show a particularly healthy level of vitamin D to be present assuming accuracy of the testing procedure. One of the possible reasons: well whilst the sun does shine in Scotland (sometimes), there is quite a bit of evidence to suggest that it doesn't necessarily translate into an all-year round adequate vitamin D level for many, many people living at certain geographical coordinates all of which cover Scotland; indeed also where I live.
I should perhaps back-up a little and provide a little more description of vitamin D first. Vitamin D is a fat-soluble vitamin. Although having multiple uses throughout the body, vitamin D is perhaps most famous for its role in aiding in the absorption of calcium; see my recent post on this subject. There are a few ways of getting vitamin D; through our modern fortified diet (assuming you eat breakfast cereals for example) and also by contact with sunshine, or more specifically via exposure to ultraviolet B light. I suppose a third way is via supplementation.
Vitamin D is a vitamin in the spotlight at the moment. There is quite a lot of research coming out telling us how much we need vitamin D for lots of different health reasons, ranging from cancer prevention to maintaining good cognitive health to potentially helping to tackle growing health problems like diabetes. Looking at childhood health in particular, there is some pretty good evidence that conditions classically associated with vitamin D like rickets might be making an unwelcome return here in the UK and beyond. Although not altogether clear as to what is driving our vitamin D deficiency, it seems as though lifestyle is a possible factor; so sitting reading blogs from a home PC indoors rather than reading them on an iPad outdoors, our use of barrier creams to prevent excessive sun exposure and its onward effects, but also physiological factors such as skin colour (although research in this area is not cut and dried).
There is also some suggestion that vitamin D might show some connection to various childhood developmental conditions including autism. Vitamin D and psychiatry have, what might be called, a blossoming relationship. PubMed lists over 100 entries based on the keywords vitamin D and schizophrenia, covering various angles of a possible connection from genes to biochemistry, even including psychology. I would not be so bold as to say that the link is in anyway definitive, but it makes for some interesting reading.
With autism in mind, vitamin D has also received more than passing mention. As with all dietary components, the possible influence of unusual eating habits and patterns attributed to many cases of autism, would perhaps predispose some people on the autism spectrum to a reduced intake of dietary-derived vitamin D. The research in this area does seem to corroborate this suggestion. One of the bigger names in all things vitamin D, Dr John Cannell, wrote an interesting paper about vitamin D and autism not so long ago (here). Putting the universality of the vitamin D-autism hypothesis to one side, there are some interesting points raised in his paper which are beginning to be borne out by the accumulated research in this area. In particular are the various research on autism in specific ethnic populations such as the Somali community, and the evidence put forward for some increase in autism prevalence in such groups when resident in more Northern climes. I would reiterate the old 'correlation does not imply causation' adage at this point also.
Another interesting area of research relates to the various work on the gastrointestinal (GI) co-morbidities noted alongside some cases of autism, and whether malabsorption as a result of coeliac disease or hyperpermeability of the gut might play a hand in hypovitaminosis D as has been suggested elsewhere. This research published on Egyptian children might be relevant to this side of the hypothesis given that I am sure that sunshine is at a premium in the land of the Pharaohs. Finally, although there is no contemporary epidemiological evidence to speak of, autism does not seem to be protective against the development of rickets as witnessed by this study (one of the study authors being also involved in this paper on iron deficiency and autism) and this study.
Taking into account the evidence currently available, I don't think that we can say that autism, or any one condition, has a monopoly on low levels of vitamin D. Many people from many different ethnic, geographic and symptomatic groups seem to be on the low side of what would be considered to be 'adequate' levels of vitamin D. There is also the 'chicken and egg' situation in terms of whether vitamin D levels are 'causative' of anything (outside of rickets or other classically related conditions) as complicated as autism or schizophrenia, etc. or just symptomatic of some other underlying mechanism or dysfunction. I will leave you to make your decision on this issue. Finally, vitamin D might be only one part of any association as can be seen by this editorial on how UVB sunlight might also have some other interesting effects.
To finish, this Sassenach wonders how many miles would you walk?
Thursday, 14 July 2011
What does detox mean?
Ever seen the original TV series 'V'?
I'm not talking about that new-fangled attempt with the fancy CGI effects; no, the 1980s one with the reptilian aliens, or at least the very plastic-mask looking reptilian aliens, wanting to turn humans into food. Even Freddy Krueger was a Visitor! (or the actor Robert Englund at least). Not a pretty thought I know, but if humans were ever to be sold as meat, by modern day standards, I question whether many of us would be fit to appear on the Visitors dinner table.
Sorry for the opening paragraph but what I wanted to suggest is that most people wouldn't disagree with the fact that modern day life, whilst presenting us with lots of comforts and labour-saving devices and technologies including those which have saved and extended our lives, also has it's downside. One downside of our romance with industrialisation is that we live in a very different environment from that only a few hundred years ago in terms of our exposure to lots of different things as a result of globalisation (viruses, bacteria, etc) and particularly our exposure to the various natural and man-made, synthetic chemicals. I kinda hinted at this in my last post on chlorination byproducts in the water.
I could write a whole thesis using the volumes of research done on what we could readily be exposed to on a daily basis from cradle to grave but I won't. Instead, here are a few references (here and here) to strengthen my point. Some of the compounds in question are pretty scary in terms of their potential biological activity and also their persistence in the environment. Asbestos, whilst being a natural product, is perhaps one of the archetypal industrial bad guys. For many compounds we just don't know what the long-term effects might be following either acute or chronic exposure and even worse, how they may interact with each other to potentially produce a more potent effect.
I read what I have written so far and think to myself, I don't live too near an incinerator or a chemical plant, I don't live too close to a busy road, I don't smoke, how would I be exposed? Well, easily. I need to drink, I need to eat, I need to breathe and I need to travel - traces of our industrial society are all around me (and you). In one way or another I will be exposed to many of them over the course of my lifetime. How my body handles them will depend on what the compounds are, the amount I am exposed to (and how frequently) and whether my genes-biology can metabolise them safely.
It is perhaps with all this in mind, that we have witnessed the rise of 'detoxification' as a suggested solution to relieving our chemical burden. I say chemical burden but detoxification has been put forward as an intervention for many different aspects of modern day life including that related to diet, medication and pollution.
Detox (to those in the know) means different things to different people. To some it is a trendy term which is used almost indiscriminately to denote some process of removing harmful compounds via 'natural' means. I remember people like Gillian McKeith using it in almost every second sentence coupled with words like 'superfoods', etc. To others, detoxification has a more 'scientific' meaning as related to things like the important function of the liver and its various enzymes for xenobiotic metabolism. Whatever your translation of the meaning, its use is part and parcel of the modern day dictionary.
A few months back I happened upon a very interesting article by Stephen Genuis. Some people might have heard his name before, particularly his recent work looking at the co-morbidity of coeliac disease in some selected cases of autism (and what happened to autistic symptoms when a gluten-free diet was implemented as part of the coeliac treatment regime). The article in question for this post is here* and is basically a review of what detoxification is and the various ways that is has been suggested to be useful.
I am sorry that I can't post a full-text copy of the paper (copyright y'know) because it is a very, very good review of detox which covers everything from description to the various challenges for toxicology research to summarising the various detox methods and their supporting evidence. I have supplied the reference at the foot of this post for anyone who is interested in popping through to their nearest academic library for a look. Genuis does not mince his words in this article in either his review of the evidence on the size of our chemical toxicity, the need for 'proof of safety not proof of harm', and his support for the budding environmental health sciences.
There is a case study included towards the end of his review paper about a previously healthy woman who developed many of the symptoms of psychosis. She was previously employed at a printing company which itself suggested several things in terms of potential environmental exposure. After various pharmacological treatments including antipsychotics, she was assessed by a separate physician who discovered high levels of bioaccumulated lead. Supervised chelation to bring down her lead levels correlated with an abatement of her psychiatric symptoms. I know this is only one case study and is limited to the findings of this n=1 but it does quite nicely illustrate our whole body relationship with contaminants. I made reference to lead in a previous post on the suggested reasons why the US crime figures are falling. I perhaps need to look at this with a more critical eye in the future.
There are a number of sensible take-home messages from Genuis and his review of other research being conducted in this area including:
To finish, a song from the Chemical Brothers - "the time has come to... galvanize".
*Genuis SJ. (2011) Elimination of persistent toxicants from the body. Human & Experimental Toxicology. 30: 3-18.
I'm not talking about that new-fangled attempt with the fancy CGI effects; no, the 1980s one with the reptilian aliens, or at least the very plastic-mask looking reptilian aliens, wanting to turn humans into food. Even Freddy Krueger was a Visitor! (or the actor Robert Englund at least). Not a pretty thought I know, but if humans were ever to be sold as meat, by modern day standards, I question whether many of us would be fit to appear on the Visitors dinner table.
Sorry for the opening paragraph but what I wanted to suggest is that most people wouldn't disagree with the fact that modern day life, whilst presenting us with lots of comforts and labour-saving devices and technologies including those which have saved and extended our lives, also has it's downside. One downside of our romance with industrialisation is that we live in a very different environment from that only a few hundred years ago in terms of our exposure to lots of different things as a result of globalisation (viruses, bacteria, etc) and particularly our exposure to the various natural and man-made, synthetic chemicals. I kinda hinted at this in my last post on chlorination byproducts in the water.
I could write a whole thesis using the volumes of research done on what we could readily be exposed to on a daily basis from cradle to grave but I won't. Instead, here are a few references (here and here) to strengthen my point. Some of the compounds in question are pretty scary in terms of their potential biological activity and also their persistence in the environment. Asbestos, whilst being a natural product, is perhaps one of the archetypal industrial bad guys. For many compounds we just don't know what the long-term effects might be following either acute or chronic exposure and even worse, how they may interact with each other to potentially produce a more potent effect.
I read what I have written so far and think to myself, I don't live too near an incinerator or a chemical plant, I don't live too close to a busy road, I don't smoke, how would I be exposed? Well, easily. I need to drink, I need to eat, I need to breathe and I need to travel - traces of our industrial society are all around me (and you). In one way or another I will be exposed to many of them over the course of my lifetime. How my body handles them will depend on what the compounds are, the amount I am exposed to (and how frequently) and whether my genes-biology can metabolise them safely.
It is perhaps with all this in mind, that we have witnessed the rise of 'detoxification' as a suggested solution to relieving our chemical burden. I say chemical burden but detoxification has been put forward as an intervention for many different aspects of modern day life including that related to diet, medication and pollution.
Detox (to those in the know) means different things to different people. To some it is a trendy term which is used almost indiscriminately to denote some process of removing harmful compounds via 'natural' means. I remember people like Gillian McKeith using it in almost every second sentence coupled with words like 'superfoods', etc. To others, detoxification has a more 'scientific' meaning as related to things like the important function of the liver and its various enzymes for xenobiotic metabolism. Whatever your translation of the meaning, its use is part and parcel of the modern day dictionary.
A few months back I happened upon a very interesting article by Stephen Genuis. Some people might have heard his name before, particularly his recent work looking at the co-morbidity of coeliac disease in some selected cases of autism (and what happened to autistic symptoms when a gluten-free diet was implemented as part of the coeliac treatment regime). The article in question for this post is here* and is basically a review of what detoxification is and the various ways that is has been suggested to be useful.
I am sorry that I can't post a full-text copy of the paper (copyright y'know) because it is a very, very good review of detox which covers everything from description to the various challenges for toxicology research to summarising the various detox methods and their supporting evidence. I have supplied the reference at the foot of this post for anyone who is interested in popping through to their nearest academic library for a look. Genuis does not mince his words in this article in either his review of the evidence on the size of our chemical toxicity, the need for 'proof of safety not proof of harm', and his support for the budding environmental health sciences.
There is a case study included towards the end of his review paper about a previously healthy woman who developed many of the symptoms of psychosis. She was previously employed at a printing company which itself suggested several things in terms of potential environmental exposure. After various pharmacological treatments including antipsychotics, she was assessed by a separate physician who discovered high levels of bioaccumulated lead. Supervised chelation to bring down her lead levels correlated with an abatement of her psychiatric symptoms. I know this is only one case study and is limited to the findings of this n=1 but it does quite nicely illustrate our whole body relationship with contaminants. I made reference to lead in a previous post on the suggested reasons why the US crime figures are falling. I perhaps need to look at this with a more critical eye in the future.
There are a number of sensible take-home messages from Genuis and his review of other research being conducted in this area including:
- Quite a lot more finance and resources need to be put into investigating the whole area of chemical exposure and detoxification. An interesting study is just starting in the States regarding the possible impact that the Deepwater Horizon fiasco might have had on human health. Whether the financial onus should be on Government or the chemical production sector, I don't know.
- We have a very close, yet very complicated relationship, with our environment (and our genes). Just look at the recent post on genes and environment in the autism research world.
- With particular reference to one of our most sensitive organs, the brain, one should never underestimate how much our behaviour (and mis-behaviour) might be influenced by our natural and synthetic chemical surroundings. I should also point out that studying such a relationship is not easy.
- Detox, a widely used (and abused) term, is a legitimate concept.
To finish, a song from the Chemical Brothers - "the time has come to... galvanize".
*Genuis SJ. (2011) Elimination of persistent toxicants from the body. Human & Experimental Toxicology. 30: 3-18.
Wednesday, 13 July 2011
Chlorinated byproducts and autism
Brick Township in New Jersey (USA) enjoys a few accolades. According to the 2003 FBI statistics, Brick Township was the 2nd safest place to live in America. It also features highly in terms of its educational provisions and is generally seen to be quite a nice place to live. Like every other place, Brick Township (BT) does however also enjoy a not-so-enviable part of its community. In the case of BT it is its history with landfill and in particular French's landfill.
Landfill is a world-wide issue in terms of the staggering amounts of waste we as a population produce and what we do with it. We, here in the UK, are unfortunately particularly wasteful still, having previously been dubbed the 'landfill dustbin of Europe'. We are getting better I might add, but still that label persists.
French's landfill in BT has been in the US Environmental Protection Agency's sights for quite a few years. So much so that there is a dedicated EPA entry on their website showing the various strategies and progress being made in cleaning up French's landfill. It makes for unpleasant reading in terms of the types of contaminants identified and the history of potential contamination from the site.
The reason for my interest is this paper which has recently appeared in the journal NeuroToxicology. The paper by Guariglia and colleagues appears to question the outcomes from a previous report on BT drinking water and the occurrence of autism (which can be read here). They undertook to examine how water treated with compounds similarly detected in the BT municipal drinking water supply might affect specific breeds of mice. The compounds in question were trihalomethanes (THMs) and perchloroethylenes (PCEs) which carry some pretty significant risks following continued exposure including being carcinogens. The mice (and their mothers) were given the contaminated water both whilst pregnant and post-natally.
The findings, bearing in mind that this is a study based on a mouse model:
I appreciate that undertaking such studies on mice is not really to anyone's taste. Even though mouse models are used widespread in science (including autism research) it doesn't necessarily make it right. Keeping the ethical aspects in mind, the results deliver some very interesting leads. Interesting because of the various associations made and how they link with quite a few aspects of autism including the gender preference. Of course, correlation does not imply causation.
This is not the first time that BT has cropped up on the autism research radar. Readers may remember this study from a decade ago which hinted that BT might be a 'hotspot' for autism diagnoses. I remember quite a lot of the media interest in this at the time, and the various links being made between environment, the superior schooling provisions in BT, etc. to account for the results. Nowadays, autism spectrum prevalence rates of 0.6% look positively low compared to the emerging data.
I would like to see a little more study undertaken based on the recent mice findings. Population sampling for similar metabolites present in humans might be a good start, particularly in BT; for which various methods for analysing various biological mediums are available (indeed some very sensitive methods available). Given the amount of data amassed by the EPA within BT, I would assume some very powerful results could be produced to contribute to any 'cause or association' discussions that could follow, if only to discount any relationship.
To end on a slightly happier note, Brick Township is dealing with French's landfill. Hopefully with the completion of these clean-up operations in future months, BT can focus on its more beautiful assets and turn the page on landfill and its potential environmental effects.
Landfill is a world-wide issue in terms of the staggering amounts of waste we as a population produce and what we do with it. We, here in the UK, are unfortunately particularly wasteful still, having previously been dubbed the 'landfill dustbin of Europe'. We are getting better I might add, but still that label persists.
French's landfill in BT has been in the US Environmental Protection Agency's sights for quite a few years. So much so that there is a dedicated EPA entry on their website showing the various strategies and progress being made in cleaning up French's landfill. It makes for unpleasant reading in terms of the types of contaminants identified and the history of potential contamination from the site.
The reason for my interest is this paper which has recently appeared in the journal NeuroToxicology. The paper by Guariglia and colleagues appears to question the outcomes from a previous report on BT drinking water and the occurrence of autism (which can be read here). They undertook to examine how water treated with compounds similarly detected in the BT municipal drinking water supply might affect specific breeds of mice. The compounds in question were trihalomethanes (THMs) and perchloroethylenes (PCEs) which carry some pretty significant risks following continued exposure including being carcinogens. The mice (and their mothers) were given the contaminated water both whilst pregnant and post-natally.
The findings, bearing in mind that this is a study based on a mouse model:
- Male mice seemed to be affected more by the cocktail given.
- Behaviours indicative of anxiety were increased.
- Vocalisations in response to being separated from mother mouse were decreased.
- Social behaviours were reduced.
I appreciate that undertaking such studies on mice is not really to anyone's taste. Even though mouse models are used widespread in science (including autism research) it doesn't necessarily make it right. Keeping the ethical aspects in mind, the results deliver some very interesting leads. Interesting because of the various associations made and how they link with quite a few aspects of autism including the gender preference. Of course, correlation does not imply causation.
This is not the first time that BT has cropped up on the autism research radar. Readers may remember this study from a decade ago which hinted that BT might be a 'hotspot' for autism diagnoses. I remember quite a lot of the media interest in this at the time, and the various links being made between environment, the superior schooling provisions in BT, etc. to account for the results. Nowadays, autism spectrum prevalence rates of 0.6% look positively low compared to the emerging data.
I would like to see a little more study undertaken based on the recent mice findings. Population sampling for similar metabolites present in humans might be a good start, particularly in BT; for which various methods for analysing various biological mediums are available (indeed some very sensitive methods available). Given the amount of data amassed by the EPA within BT, I would assume some very powerful results could be produced to contribute to any 'cause or association' discussions that could follow, if only to discount any relationship.
To end on a slightly happier note, Brick Township is dealing with French's landfill. Hopefully with the completion of these clean-up operations in future months, BT can focus on its more beautiful assets and turn the page on landfill and its potential environmental effects.
Tuesday, 12 July 2011
Coffee does not always mean coffee
The title of this post is based on an episode of Seinfeld. I wasn't a huge Seinfeld fan but happily bumped into the odd episode late night on BBC2 now and again. To quote:
Donna: Would you like to come upstairs for some coffee?
George: Oh, no, thanks. I can't drink coffee late at night, it keeps me up.
And with that comes George's realisation that 'coffee doesn't mean coffee, coffee means sex!'
I am hoping that this post manages to get through the many Internet filters and does not single this blog out as being one of 'those' kinds of blogs (which, in my best British prudish voice, 'it most certainly is not'). I want to talk about sex (education) in this post and how information about sex, sexuality and relationships are being transmitted to people with autism spectrum and related conditions. This is going to be quite a candid post, so please do not get too offended. It is quite a long post also.
I will readily admit that I am not an expert on this (or any) area of autism, merely an interested follower of the various discussions and research being carried out. I do know a few people in the psychology and autism research world who specialise in this topic in terms of either being research active or being at the coalface when it comes to teaching sex education to children and young adults with autism. Having seen one or two of them talk about this issue and present some data, I have to say it made for some interesting listening.
Parents the world over, whether with children with autism or not, will eventually be faced with the issue of 'the birds and the bees' and how to communicate an effective message about sex and relationships. Even where older children and adults present with profound difficulties in areas like cognitive skills or language, the chances are that sex or sexual behaviour will at some point emerge and need to be discussed. Of course such issues might be barriers to communicating about sex, but experience would tend to suggest not to under-estimate a person's capacity to receive such information.
In the more general world of sex education research, there is still quite a bit of discussion about how and when parents should communicate information about sex. I heard one speaker talk about this at a conference last year; some of her findings can be seen here. There are perhaps a few lessons from this research which are just as applicable to boys and girls with autism, as they are to everyone else. Things like:
I'd like to think that these same issues are pertinent the world over, and across things like autism and other developmental conditions. When specifically applied in the context of autism, there is perhaps an even greater requirement to ensure that sex education is imparted timely and properly given issues like the increased 'vulnerability' of some people on the spectrum when it comes to sex and the perhaps greater potential for abuse or being manipulated. Unfortunately this scenario does happen.
One of the best people I have heard talk about sex and autism is Lynne Moxon. Lynne is a bit of an expert in this area as well as being a resident here in the bracing North-East of England. You can download one of her (fairly) recent Powerpoint presentations here from a conference back in 2008 (scroll down the speaker list to download her talk titled: Issues within puberty and sexuality in people with autism spectrum disorders). I won't go through her presentation in rote fashion but would like to draw out a few important points that she raises.
Puberty (or should that be PUBERTY!). A previous post on this blog has discussed that most taxing of times for children and parents, puberty, in relation to autism. Bearing in mind the more generalised 'guidance' being suggested about the timing of sex education (earlier rather than later), I think most parents would have been confronted with sex education issues with their children before the start of puberty. I don't say this in such a way as to say 'it must have been discussed' because the situation is likely to be different between different children and different families. Given the physical changes associated with puberty, one could perhaps expect that this might be a good time to 'top-up' the knowledge about sex and relationships.
Communicating the message. There are a variety of ways of talking about sex and relationships. I know some parents have talked about how their child with autism liked to hear about it 'textbook' fashion - so getting out the pictures and going through the biological details one by one, using the proper names (not our social inventions) for the various bits and pieces, and importantly explaining that the pictures are representations, and different people come in different shapes and sizes. Techniques such as social stories might also come in handy in these descriptions to discuss tricky things like masturbation and the 'right' and 'wrong' times to do it. I would also draw attention to the fact that Lynne does also talk about other important issues: personal hygiene (making sure that everything is kept clean), how sex is portrayed in the media (and often does not reflect 'real life'), sexual diseases and the various types of contraception available.
Outside of Lynne's work, there are a few other valuable sources of information. The writings of Marc Segar have been linked to in a previous post. For those who don't know, Marc was a young man with Asperger syndrome who wrote a very useful 'survival guide' based on his life and experiences nearly 15 years ago now (it can be download for free here). Marc talks quite a bit about the various social nuances related to sex and relationships; more to do with the social situations where sex and relationships might crop up. So things like the use of chat-up lines (p.16), what to do when you like someone (pp.14-15) and even little details, such as when someone is a virgin, the various intricacies about not communicating this fact when in a social group of men in particular. I found Marc's writings to be insightful and worth a read.
I do hope that I have not offended anyone with some of the content used in this post, given that most [all] parents will have to discuss such issues at one time or another. I will restate my non-expertise in this area of autism; please do not take this as anything but a post on how people have talked about sex education and autism and the various issues involved. People with autism are as different, complicated and individual as anyone else, so it is unlikely that there is a 'one-size-fits-all' method for imparting advice on sex and relationships. Parents however know their children best and therefore should be in the driving seat as to when and how the message about sex is communicated.
Donna: Would you like to come upstairs for some coffee?
George: Oh, no, thanks. I can't drink coffee late at night, it keeps me up.
And with that comes George's realisation that 'coffee doesn't mean coffee, coffee means sex!'
I am hoping that this post manages to get through the many Internet filters and does not single this blog out as being one of 'those' kinds of blogs (which, in my best British prudish voice, 'it most certainly is not'). I want to talk about sex (education) in this post and how information about sex, sexuality and relationships are being transmitted to people with autism spectrum and related conditions. This is going to be quite a candid post, so please do not get too offended. It is quite a long post also.
I will readily admit that I am not an expert on this (or any) area of autism, merely an interested follower of the various discussions and research being carried out. I do know a few people in the psychology and autism research world who specialise in this topic in terms of either being research active or being at the coalface when it comes to teaching sex education to children and young adults with autism. Having seen one or two of them talk about this issue and present some data, I have to say it made for some interesting listening.
Parents the world over, whether with children with autism or not, will eventually be faced with the issue of 'the birds and the bees' and how to communicate an effective message about sex and relationships. Even where older children and adults present with profound difficulties in areas like cognitive skills or language, the chances are that sex or sexual behaviour will at some point emerge and need to be discussed. Of course such issues might be barriers to communicating about sex, but experience would tend to suggest not to under-estimate a person's capacity to receive such information.
In the more general world of sex education research, there is still quite a bit of discussion about how and when parents should communicate information about sex. I heard one speaker talk about this at a conference last year; some of her findings can be seen here. There are perhaps a few lessons from this research which are just as applicable to boys and girls with autism, as they are to everyone else. Things like:
- Children and adolescents generally want information about sex and relationships from their parents. Gone are the days (like mine) where boys and girls were separated off at school and taught about each others 'bits' by nervous biology teachers alone and without the aid of parental support. Children want parents to get involved.
- Mums in particular are seen to have an integral role in disclosing information and advice about sex to their children. Dads play a role but I assume that girls especially might perhaps feel a little more comfortable with a 'female' perspective. Whether this is due to societal conditioning (Dad's can't talk about menstruation apparently) or merely the fact that mums have been there and done that, I don't know. Both parents can contribute.
- Boys are perhaps more likely to use other 'sources' of information for their sex education particularly in the age of the Internet. This may or may not give a 'distorted' idea about certain 'normalities' (if there is such a concept) in sex and relationships depending on which sources are used. Not every plumber or gas engineer for example provides 'that kind of service' to lonely housewives.
- Parents generally want to be able to talk to their children about sex, but perhaps feel uncomfortable or lacking in the necessary schemes and plans to communicate such issues in an effective way. Starting the evening meal with the words 'let's talk about sex' is probably going to make for an interesting evening and some subsequent interesting playground conversations among young offspring.
I'd like to think that these same issues are pertinent the world over, and across things like autism and other developmental conditions. When specifically applied in the context of autism, there is perhaps an even greater requirement to ensure that sex education is imparted timely and properly given issues like the increased 'vulnerability' of some people on the spectrum when it comes to sex and the perhaps greater potential for abuse or being manipulated. Unfortunately this scenario does happen.
One of the best people I have heard talk about sex and autism is Lynne Moxon. Lynne is a bit of an expert in this area as well as being a resident here in the bracing North-East of England. You can download one of her (fairly) recent Powerpoint presentations here from a conference back in 2008 (scroll down the speaker list to download her talk titled: Issues within puberty and sexuality in people with autism spectrum disorders). I won't go through her presentation in rote fashion but would like to draw out a few important points that she raises.
Puberty (or should that be PUBERTY!). A previous post on this blog has discussed that most taxing of times for children and parents, puberty, in relation to autism. Bearing in mind the more generalised 'guidance' being suggested about the timing of sex education (earlier rather than later), I think most parents would have been confronted with sex education issues with their children before the start of puberty. I don't say this in such a way as to say 'it must have been discussed' because the situation is likely to be different between different children and different families. Given the physical changes associated with puberty, one could perhaps expect that this might be a good time to 'top-up' the knowledge about sex and relationships.
Communicating the message. There are a variety of ways of talking about sex and relationships. I know some parents have talked about how their child with autism liked to hear about it 'textbook' fashion - so getting out the pictures and going through the biological details one by one, using the proper names (not our social inventions) for the various bits and pieces, and importantly explaining that the pictures are representations, and different people come in different shapes and sizes. Techniques such as social stories might also come in handy in these descriptions to discuss tricky things like masturbation and the 'right' and 'wrong' times to do it. I would also draw attention to the fact that Lynne does also talk about other important issues: personal hygiene (making sure that everything is kept clean), how sex is portrayed in the media (and often does not reflect 'real life'), sexual diseases and the various types of contraception available.
Outside of Lynne's work, there are a few other valuable sources of information. The writings of Marc Segar have been linked to in a previous post. For those who don't know, Marc was a young man with Asperger syndrome who wrote a very useful 'survival guide' based on his life and experiences nearly 15 years ago now (it can be download for free here). Marc talks quite a bit about the various social nuances related to sex and relationships; more to do with the social situations where sex and relationships might crop up. So things like the use of chat-up lines (p.16), what to do when you like someone (pp.14-15) and even little details, such as when someone is a virgin, the various intricacies about not communicating this fact when in a social group of men in particular. I found Marc's writings to be insightful and worth a read.
I do hope that I have not offended anyone with some of the content used in this post, given that most [all] parents will have to discuss such issues at one time or another. I will restate my non-expertise in this area of autism; please do not take this as anything but a post on how people have talked about sex education and autism and the various issues involved. People with autism are as different, complicated and individual as anyone else, so it is unlikely that there is a 'one-size-fits-all' method for imparting advice on sex and relationships. Parents however know their children best and therefore should be in the driving seat as to when and how the message about sex is communicated.
Monday, 11 July 2011
Summarising birth risk factors for autism
Hot on the heels of the various evidence published last week on the rise and rise of variable gene-environment interactions in relation to autism aetiology, an entry on the Autism Speaks blog directed me to a study published in the Pediatrics today which takes an overview look at the collected data on birth factors in relation to risk of developing autism. The abstract to the paper can be found here.
Based on a meta-analysis of several studies looking at various perinatal and neonatal risk factors analysed in connection to autism, several issues are suggested to be potentially related by Gardener and colleagues, although like many things about autism, no one factor or pattern of factors seems to show a universal connection.
So, issues such as umbilical cord 'complications' (I assume this means things like knots and/or being wrapped around baby's head), low birth weight and small for dates are a few of the risks which seem to show some possible connection. Others which have already come up on this blog in one shape or form include: hyperbilirubinemia, neonatal anaemia, feeding difficulties, and being a summer birth. I note also a possible connection with blood or rhesus incompatibility which is something I perhaps will go into in a future entry. There were a few other conditions not found to be associated with any increased risk including head circumference and prematurity. I was a bit taken aback by prematurity not showing association when the data were joined. Having said that, studies like this one have perhaps indicated that such issues might be more related to any co-morbid cognitive problems attached to the autism diagnosis. The head circumference factor is something that is due to be discussed in a separate post in the coming weeks.
I don't want to jump on to any bandwagon with these findings because, as the authors note, they were often comparing oranges and apples with the array of research reviewed. I do however think that this paper provides some important data when starting to look at both 'risk' factors in developing autism and possibly mechanisms; building on what is known about some of the birth factors listed and the risk of other physical and behavioural developmental conditions outside of autism.
Based on a meta-analysis of several studies looking at various perinatal and neonatal risk factors analysed in connection to autism, several issues are suggested to be potentially related by Gardener and colleagues, although like many things about autism, no one factor or pattern of factors seems to show a universal connection.
So, issues such as umbilical cord 'complications' (I assume this means things like knots and/or being wrapped around baby's head), low birth weight and small for dates are a few of the risks which seem to show some possible connection. Others which have already come up on this blog in one shape or form include: hyperbilirubinemia, neonatal anaemia, feeding difficulties, and being a summer birth. I note also a possible connection with blood or rhesus incompatibility which is something I perhaps will go into in a future entry. There were a few other conditions not found to be associated with any increased risk including head circumference and prematurity. I was a bit taken aback by prematurity not showing association when the data were joined. Having said that, studies like this one have perhaps indicated that such issues might be more related to any co-morbid cognitive problems attached to the autism diagnosis. The head circumference factor is something that is due to be discussed in a separate post in the coming weeks.
I don't want to jump on to any bandwagon with these findings because, as the authors note, they were often comparing oranges and apples with the array of research reviewed. I do however think that this paper provides some important data when starting to look at both 'risk' factors in developing autism and possibly mechanisms; building on what is known about some of the birth factors listed and the risk of other physical and behavioural developmental conditions outside of autism.
Sunday, 10 July 2011
The fragile male
'It's a man's world' according to James Brown but 'would mean nothing without a woman or a girl'.
Mr Brown may well portray it as a man's world, but according to this paper from a few years back, us chaps are fighting an uphill struggle right from our very earliest days. The paper, from child and adolescent psychiatrist Sebastian Kraemer who is no stranger to gender research, reviews in quite some detail the many reasons why we men are more vulnerable than our female counterparts. 'Vulnerability' might seem a little at odds with our social models and conditioning of the genders (men not crying when watching Watership Down, but crying when your favourite football (soccer) team is relegated), but unfortunately men face a greater likelihood, throughout all stages of life, for adversity and an early death compared to women.
I touched briefly upon such gender discrepencies in a previous post on risk. I would in this post like to explore the male 'fragility' bit a little further and hopefully discuss some important issues along the way. It's funny but when I think about male fragility the first thing that comes to mind are our friends in the spider world, and those David Attenborough moments showing how female spiders tend to be bigger than males and after the je t'aime moment has finished have been known to eat their Mr Right too. Nature had possibly only a peripheral role for the male of the species in mind?
There are some interesting points raised in the Kraemer paper which I didn't know about previously. I have listed a few which include:
Added to the fact that males on average die quite a bit younger than females and show a greater risk of death throughout their lifetime than females and I get the distinct impression that our Maker might have a soft spot for women.
Searching the literature it does seem to be quite apparent that males are somehow 'hard-wired' for more serious potential issues than females. When I say 'hard-wired' I don't necessarily just mean genetics being the be all and end all, although genes may very well be a primary factor. From conception to early infancy, males fare significantly worse than females. Things don't really get any better from there afterwards. Men don't take to gastrointestinal surgery as well as women according to a recent paper described here. Take also for example the concept of addiction, and the gender splits on who is more likely to become addicted to things like alcohol and drugs of abuse. One could argue that alcohol addiction is to a large part mediated by social factors and the norms of society but still there might be some underlying tendency for men to more likely become addicted and show alcohol problems if not only because of overall gender differences in the way that alcohol is metabolised. I think back also to an older post on theory of mind and its links to things like alcoholism bearing in mind the gender and cognitive styles debates on-going in several domains including autism. It's potentially the same pattern when it comes to illicit drug use also, and opens up some potentially interesting research into brain differences and gender.
The male domination (but not exclusivity) of developmental and behavioural conditions is never more stark than when looking at the overall sex ratio in autism. Autism is perhaps the condition which shows the most gender disparity (maybe alongside ADHD) when it comes to development; the figures for reading disorder for example, tend to be slightly less skewed. A good overview comparing the various data on sex ratios in childhood developmental conditions can be found in this recent paper from Prof. Simon Baron-Cohen and colleagues. The precise reasons for the gender disparity are as yet unknown but likely multiple.
I think that there are some interesting issues raised from this area of research although as always, one has to treat such generalised associations with some caution. It does seem almost contradictory to the way modern society has modelled itself that males, as a group, may be the 'weaker' sex from a biological perspective. Kraemer in his conclusions makes some interesting comments about how many of the variables which contribute to the fragile male hypothesis may have had good evolutionary reasons at one time or another. He may be right although let's not get carried away with ourselves.
I opened with James Brown and his 'man's world'. After reading about the fragile male, and in the words of that dino-favourite Laura Dern, perhaps it is destiny that 'woman [not man] inherits the earth'?
Mr Brown may well portray it as a man's world, but according to this paper from a few years back, us chaps are fighting an uphill struggle right from our very earliest days. The paper, from child and adolescent psychiatrist Sebastian Kraemer who is no stranger to gender research, reviews in quite some detail the many reasons why we men are more vulnerable than our female counterparts. 'Vulnerability' might seem a little at odds with our social models and conditioning of the genders (men not crying when watching Watership Down, but crying when your favourite football (soccer) team is relegated), but unfortunately men face a greater likelihood, throughout all stages of life, for adversity and an early death compared to women.
I touched briefly upon such gender discrepencies in a previous post on risk. I would in this post like to explore the male 'fragility' bit a little further and hopefully discuss some important issues along the way. It's funny but when I think about male fragility the first thing that comes to mind are our friends in the spider world, and those David Attenborough moments showing how female spiders tend to be bigger than males and after the je t'aime moment has finished have been known to eat their Mr Right too. Nature had possibly only a peripheral role for the male of the species in mind?
There are some interesting points raised in the Kraemer paper which I didn't know about previously. I have listed a few which include:
- At conception, there are quite a few more male than female embryos but for one reason or another this advantage is cut when it comes to live births (the ratio being somewhere about 105 boys : 100 girls).
- A newborn girl is more physiologically advanced that a newborn boy.
- There is a male excess in most developmental and behavioural conditions. (OK I knew this one).
- There is a male excess in fatal and non-fatal accidents.
Added to the fact that males on average die quite a bit younger than females and show a greater risk of death throughout their lifetime than females and I get the distinct impression that our Maker might have a soft spot for women.
Searching the literature it does seem to be quite apparent that males are somehow 'hard-wired' for more serious potential issues than females. When I say 'hard-wired' I don't necessarily just mean genetics being the be all and end all, although genes may very well be a primary factor. From conception to early infancy, males fare significantly worse than females. Things don't really get any better from there afterwards. Men don't take to gastrointestinal surgery as well as women according to a recent paper described here. Take also for example the concept of addiction, and the gender splits on who is more likely to become addicted to things like alcohol and drugs of abuse. One could argue that alcohol addiction is to a large part mediated by social factors and the norms of society but still there might be some underlying tendency for men to more likely become addicted and show alcohol problems if not only because of overall gender differences in the way that alcohol is metabolised. I think back also to an older post on theory of mind and its links to things like alcoholism bearing in mind the gender and cognitive styles debates on-going in several domains including autism. It's potentially the same pattern when it comes to illicit drug use also, and opens up some potentially interesting research into brain differences and gender.
The male domination (but not exclusivity) of developmental and behavioural conditions is never more stark than when looking at the overall sex ratio in autism. Autism is perhaps the condition which shows the most gender disparity (maybe alongside ADHD) when it comes to development; the figures for reading disorder for example, tend to be slightly less skewed. A good overview comparing the various data on sex ratios in childhood developmental conditions can be found in this recent paper from Prof. Simon Baron-Cohen and colleagues. The precise reasons for the gender disparity are as yet unknown but likely multiple.
I think that there are some interesting issues raised from this area of research although as always, one has to treat such generalised associations with some caution. It does seem almost contradictory to the way modern society has modelled itself that males, as a group, may be the 'weaker' sex from a biological perspective. Kraemer in his conclusions makes some interesting comments about how many of the variables which contribute to the fragile male hypothesis may have had good evolutionary reasons at one time or another. He may be right although let's not get carried away with ourselves.
I opened with James Brown and his 'man's world'. After reading about the fragile male, and in the words of that dino-favourite Laura Dern, perhaps it is destiny that 'woman [not man] inherits the earth'?