Although I am not an expert, I think it was Nietzsche who famously said that "it is not enough to prove something, one has also to seduce or elevate people to it". Words which perhaps carry much more meaning in this age of information overload, where anyone can open their PC or laptop or phone and present their opinion or counter-opinion to the world in any number of ways. And quite a large percentage of the population exercise that right, including me.
But in the sea of opinions how do you find something that roughly equates as 'truth'? What criteria do people use to judge the quality of an opinion and can such judgements be 'manipulated'?
Well, the answer to the latter question is 'yes'; our judgement and opinion can be manipulated, whether we realise it or not. This can be done subtly through the use of things like nudge theory or it can be done more overtly by the use of 'expert' opinion.
In the world of autism research and opinion, there have been many expert opinions down the years. Many have attempted to 'tell' people what autism is and isn't, what causes and doesn't cause it, what works intervention-wise and what doesn't. Many opinions have seemingly been presented as fact on the basis of varying degrees of probability, despite the fact that few facts actually exist about autism. Indeed the fluidity of research findings in autism have led some people to question why so many certainties have been put as certainties.
One example, until fairly recently, autism was a genetic condition [sic]; the hunt was on the for the autism gene or genes and millions of pounds/dollars was committed. Now after some pretty heavy duty research findings, opinions are beginning to be modified; so maybe 'some' genetics but perhaps also 'some' environment as well, as per the Autism Spring post from Tom Insel of the NIMH. Some expert opinions in this area have been shaken.
A recent blogpost on the Psychology Today site might provide a solution for the authority figure and the communication of facts via expert opinions: don't be seen to be so certain, express some doubt. The post by Susan Cain is a short one, but interesting, as she discusses this study* by Karmarkar and Tormala also covered here. The main premise of the 'Bianco's restaurant' study is that a little less self-assurance and a little doubt might go quite some way to getting people to believe you and your message.
So the next time someone steps up and authoritatively tells you that diet has absolutely no connection to autism or schizophrenia, ask them to phrase it with a touch of doubt before you are ready to believe them.
* Karmarkar UR. & Tormala ZL. “Believe me, I have no idea what I’m talking about": The effects of source certainty on consumer involvement and persuasion. Journal of Consumer Research. April 2010.
Wednesday, 31 August 2011
Tuesday, 30 August 2011
Probiotics affect neurochemistry of mice
A short post this one on a piece of research picked up via the Science Daily website and also PopSci amogst others by Bravo and colleagues* published in PNAS on the role of probiotics in moderating behaviour in mice. The paper abstract is here.
I was immediately drawn to this paper because it seemed to tie in perfectly with some research discussed not so long ago on this blog concerning how gut bacteria can affect behaviour (and vice-versa). The difference in the Bravo paper being that not only did supplementation with a probiotic containing Lactobacillus rhamnosus JB-1 seem to affect gut bacterial populations, it also seemed to affect markers of stress and anxiety and the expression of receptors for the neurotransmitter GABA (at least in mice).
There are a few elements of this paper to, pardon the pun, digest.
L.rhamnosus is no stranger to probiotic research and speculation with various strains appearing in quite a few papers as a treatment for anything from dermatitis to diarrhoea (with varying degrees of clinical success). The current paper suggested that administration affected GABA receptors in parts of the mouse brain thought to be related to anxiety and depression, increasing receptors in some areas and reducing expression in others resulting in reduced anxiety-type behaviours being presented. It also seemed to affect levels of the stress hormone corticosterone involved in the stress response. The question of 'what did what' is a little more complex but at least the results tie in with similar findings using other preparations.
With human beings in mind, one can perhaps see the potential 'applicability' of these findings in both an intervention and exploratory capacity. GABA (and GABA receptors) like other neurotransmitters is found in the gut and as a result must serve some purpose in that vicinity and perhaps beyond. I don't have time to mention all the findings in relation to GABA and autism but there might be some connection there.
The authors in their description of the study describe this as a good example of communication of the gut-brain axis in light of effects only seen when the vagus nerve was intact. I would tend to agree that these findings offer some very, very interesting targets for research on how our gut and brain 'talk' to each other; something that has also been mentioned from time to time in autism and Asperger syndrome also.
The final words however really needs to go to the rising research star that is psychology potentially being mediated by what goes on in our gut and vice-versa.
* Bravo J. et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. PNAS. August 2011.
I was immediately drawn to this paper because it seemed to tie in perfectly with some research discussed not so long ago on this blog concerning how gut bacteria can affect behaviour (and vice-versa). The difference in the Bravo paper being that not only did supplementation with a probiotic containing Lactobacillus rhamnosus JB-1 seem to affect gut bacterial populations, it also seemed to affect markers of stress and anxiety and the expression of receptors for the neurotransmitter GABA (at least in mice).
There are a few elements of this paper to, pardon the pun, digest.
L.rhamnosus is no stranger to probiotic research and speculation with various strains appearing in quite a few papers as a treatment for anything from dermatitis to diarrhoea (with varying degrees of clinical success). The current paper suggested that administration affected GABA receptors in parts of the mouse brain thought to be related to anxiety and depression, increasing receptors in some areas and reducing expression in others resulting in reduced anxiety-type behaviours being presented. It also seemed to affect levels of the stress hormone corticosterone involved in the stress response. The question of 'what did what' is a little more complex but at least the results tie in with similar findings using other preparations.
With human beings in mind, one can perhaps see the potential 'applicability' of these findings in both an intervention and exploratory capacity. GABA (and GABA receptors) like other neurotransmitters is found in the gut and as a result must serve some purpose in that vicinity and perhaps beyond. I don't have time to mention all the findings in relation to GABA and autism but there might be some connection there.
The authors in their description of the study describe this as a good example of communication of the gut-brain axis in light of effects only seen when the vagus nerve was intact. I would tend to agree that these findings offer some very, very interesting targets for research on how our gut and brain 'talk' to each other; something that has also been mentioned from time to time in autism and Asperger syndrome also.
The final words however really needs to go to the rising research star that is psychology potentially being mediated by what goes on in our gut and vice-versa.
* Bravo J. et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. PNAS. August 2011.
Monday, 29 August 2011
He's not talking about magnetic fields is he?
Yes I am. But please hear me out before consigning this post to the 'what is he talking about' spam box.
I make no apology for the 'environmental' thread running through the various posts on this blog. I wouldn't say that I am particularly well-qualified to give a very detailed explanation of how our environment might modify our risk of developing lots of different things. I would like to think however that I know just about enough to be able to read about concepts such as environment and risk factors in the peer-reviewed literature so as to come to some informed opinion. As per the mantra of this blog, I am not trying to impart that opinion, merely passing a comment.
The study in question in this case is this one* by Li and colleagues: 'Maternal exposure to magnetic fields during pregnancy in relation to the risk of asthma in offspring' published in the journal Archives of Pediatrics & Adolescent Medicine. The first thing I thought of when reading the title was '...OK, right, magnetic fields...'. I would think that many people might have a similar reaction about this area of discussion. Looking more closely at this area, there is perhaps a little more to it.
Anyone who has visited or works/worked in an analytical chemistry lab containing an NMR spectrometer will know about strong magnetic fields and what they can potentially do to that magnetic strip on your bank card or perhaps more seriously to that pacemaker you may have been fitted with. OK, the magnetic fields generated by such equipment are pretty big in comparison to what you might be exposed to on a daily basis, but the introduction of what a magnetic field can potentially do is there.
Back to the asthma study. The authors prospectively looked at the effect of low-frequency electromagnetic field (EMF) exposure on a group of pregnant women between 1996 and 1998 for a 24-hour period. Women wore monitors which recorded their magnetic field exposure during that day and were questioned about how representative their behaviour that day was to their usual routine. Participants were monitored throughout the birth and growth of their child for a further 13 years, recording the number of cases of asthma present along the way.
They found that those women with the highest level of magnetic field exposure from things like microwaves, hairdryers, etc were at greatest risk of having a child with asthma in a dose-dependent relationship. The effect was particularly pronounced when other asthma risk factors were taken into consideration; so participants having asthma themselves or their child being the first-born. It is perhaps also important to say that high-frequency EMF exposure was not looked at in this study, so no effect from mobile phones or wireless broadband technologies can be inferred.
There are a few attractive aspects to this study and its findings but be warned, a lot more study is required before any firm conclusions can be made. Asthma, like autism, like many other diagnoses, is on the rise with no clear stand-out suspects as to why. If we assume that our low- and high-frequency magnetic field exposure is going to be greater now than say 25 or 50 years ago, it is easy to point the finger (Evil Monkey-style) at that TV or microwave as a potential culprit. Several other snippets of research have hinted at the effects of magnetic fields on things like immune function, although not necessarily in a bad way. The pathway from exposure to asthma is likely to be complex and dare I say, moderated by genetic effects?
This study was not a perfect one. Basing readings carried out on one day and extrapolating that to exposure patterns over the course of pregnancy and beyond does not instill a great amount of confidence in the results. The routines of a pregnant participant might also be slightly different from the same woman when not pregnant. The added fact that higher frequencies were not looked at also leaves the study findings open to some interpretation. I will post more on this topic as and when the research unfolds.
Dr Li seems to have done a fair bit of media courting as a result of this study. I will perhaps leave you with one of the more memorable pieces of advice for pregnant women: 'Don't stand in front of the microwave when its heating food'. Wise words indeed.
To end: Christoper Walken dances a 'weapon of choice'. Take it away...Chris.
* De-Kun Li. et al. Maternal exposure to magnetic fields during pregnancy in relation to the risk of asthma in offspring. Arch Pediatr Adolesc Med. 2011
I make no apology for the 'environmental' thread running through the various posts on this blog. I wouldn't say that I am particularly well-qualified to give a very detailed explanation of how our environment might modify our risk of developing lots of different things. I would like to think however that I know just about enough to be able to read about concepts such as environment and risk factors in the peer-reviewed literature so as to come to some informed opinion. As per the mantra of this blog, I am not trying to impart that opinion, merely passing a comment.
The study in question in this case is this one* by Li and colleagues: 'Maternal exposure to magnetic fields during pregnancy in relation to the risk of asthma in offspring' published in the journal Archives of Pediatrics & Adolescent Medicine. The first thing I thought of when reading the title was '...OK, right, magnetic fields...'. I would think that many people might have a similar reaction about this area of discussion. Looking more closely at this area, there is perhaps a little more to it.
Anyone who has visited or works/worked in an analytical chemistry lab containing an NMR spectrometer will know about strong magnetic fields and what they can potentially do to that magnetic strip on your bank card or perhaps more seriously to that pacemaker you may have been fitted with. OK, the magnetic fields generated by such equipment are pretty big in comparison to what you might be exposed to on a daily basis, but the introduction of what a magnetic field can potentially do is there.
Back to the asthma study. The authors prospectively looked at the effect of low-frequency electromagnetic field (EMF) exposure on a group of pregnant women between 1996 and 1998 for a 24-hour period. Women wore monitors which recorded their magnetic field exposure during that day and were questioned about how representative their behaviour that day was to their usual routine. Participants were monitored throughout the birth and growth of their child for a further 13 years, recording the number of cases of asthma present along the way.
They found that those women with the highest level of magnetic field exposure from things like microwaves, hairdryers, etc were at greatest risk of having a child with asthma in a dose-dependent relationship. The effect was particularly pronounced when other asthma risk factors were taken into consideration; so participants having asthma themselves or their child being the first-born. It is perhaps also important to say that high-frequency EMF exposure was not looked at in this study, so no effect from mobile phones or wireless broadband technologies can be inferred.
There are a few attractive aspects to this study and its findings but be warned, a lot more study is required before any firm conclusions can be made. Asthma, like autism, like many other diagnoses, is on the rise with no clear stand-out suspects as to why. If we assume that our low- and high-frequency magnetic field exposure is going to be greater now than say 25 or 50 years ago, it is easy to point the finger (Evil Monkey-style) at that TV or microwave as a potential culprit. Several other snippets of research have hinted at the effects of magnetic fields on things like immune function, although not necessarily in a bad way. The pathway from exposure to asthma is likely to be complex and dare I say, moderated by genetic effects?
This study was not a perfect one. Basing readings carried out on one day and extrapolating that to exposure patterns over the course of pregnancy and beyond does not instill a great amount of confidence in the results. The routines of a pregnant participant might also be slightly different from the same woman when not pregnant. The added fact that higher frequencies were not looked at also leaves the study findings open to some interpretation. I will post more on this topic as and when the research unfolds.
Dr Li seems to have done a fair bit of media courting as a result of this study. I will perhaps leave you with one of the more memorable pieces of advice for pregnant women: 'Don't stand in front of the microwave when its heating food'. Wise words indeed.
To end: Christoper Walken dances a 'weapon of choice'. Take it away...Chris.
* De-Kun Li. et al. Maternal exposure to magnetic fields during pregnancy in relation to the risk of asthma in offspring. Arch Pediatr Adolesc Med. 2011
Sunday, 28 August 2011
More autism and bowels and immune system
I'm sorry. Once again I am brought back to the topic of autism and gastrointestinal (GI) symptoms in this post. I am sure that some readers might be getting pretty fed up with the amount of times that I have talked about functional bowel symptoms or more persistent GI co-morbidity in relation to autism. It's not that I don't try and talk about other things, but the research just keeps pulling me back to this area, so please stay and humour me.
The research in question is this paper* by Harumi Jyonouchi and colleagues on autism, bowel symptoms and the immune system. I have quite a lot of time for Dr Jyonouchi and her various research efforts in autism down the years. A quick taste of some of the research she has been involved in is here, here and here. What she and her team provide in their various studies is a route through which elements such as diet, the immune system and GI dysfunction all congregate together, at least in some cases of autism spectrum conditions.
The recent paper adds to the collected works by suggesting some involvement for the way the innate immune system is able to cope with potential pathogens and how this might tie into behavioural presentation. I should perhaps back up a little and provide some information on the innate immune system which is basically our first line of defence against infection. I suppose one could suggest that the innate immune system is the first-line, bunker-buster that tries to smash infection as soon as it is detected, and the other branch, the adaptive immune system is the precision, laser-guided missile which targets specific pathogens (and importantly remembers them for next time). The memory bit however is still something under investigation as shown in this recent paper.
The main aims and results from the recent paper:
There are many more findings from this paper but I am fast approaching the outer limits of my competency. The authors summarise the main findings as being the identification of a distinct ASD phenotype, characterised by infection affecting/being affected by behavioural symptom presentation, the presence of functional bowel problems, abnormalities of the innate immune system indicated by functional and transcript profiling. It should be noted that the absolute numbers of children included in this study was relatively low. This will have obvious effects on how applicable the results might be to the wider autistic (and beyond?) population but that's why we have scientific replication.
Whilst some of the results sound pretty scary (immunodeficiency), I think there are a lot of positive to take from this work. I feel I am constantly talking about how autism is not autism but rather autisms and the concept of different phenotypes/sub-groups. What this work implies is that there may be several, measurable differences according to symptom presentation which provide some potentially tangible targets to focus on. The collected immune system findings in relation to autism are complicated and often at odds with each other (overactive vs. underactive). I don't see this as a problem; it suggests that just as we have a 'spectrum' of behavioural presentation, so we might also have a spectrum of biological/genetic presentation also. God knows with all the various genetic findings recently, we know that autism is just as complicated as not-autism. Although perhaps not the primary outcome, this recent paper also points to things which could be done to 'influence' some of the underlying biological issues. Whether these would have any knock-on effects for presented symptoms remains to be seen.
To end, completely and unashamedly nothing to do with this post, the genius of Elvis on what to do in Las Vegas.
* Jyonouchi H. et al. Children with autism spectrum disorders (ASD) who exhibit chronic gastrointestinal (GI) symptoms and marked fluctuation of behavioral symptoms exhibit distinct innate immune abnormalities and transcriptional profiles of peripheral blood (PB) monocytes. J Neuroimmunology. 2011
The research in question is this paper* by Harumi Jyonouchi and colleagues on autism, bowel symptoms and the immune system. I have quite a lot of time for Dr Jyonouchi and her various research efforts in autism down the years. A quick taste of some of the research she has been involved in is here, here and here. What she and her team provide in their various studies is a route through which elements such as diet, the immune system and GI dysfunction all congregate together, at least in some cases of autism spectrum conditions.
The recent paper adds to the collected works by suggesting some involvement for the way the innate immune system is able to cope with potential pathogens and how this might tie into behavioural presentation. I should perhaps back up a little and provide some information on the innate immune system which is basically our first line of defence against infection. I suppose one could suggest that the innate immune system is the first-line, bunker-buster that tries to smash infection as soon as it is detected, and the other branch, the adaptive immune system is the precision, laser-guided missile which targets specific pathogens (and importantly remembers them for next time). The memory bit however is still something under investigation as shown in this recent paper.
The main aims and results from the recent paper:
- Three groups of participants were recruited: ASD/Infection (children with a diagnosis of autism spectrum disorder confirmed by ADI-R and/or ADOS with 3 occurrences or more of behaviour change following infection, n=30), ASD/No Infection (no behaviour-infection relationship documented, n=28) and controls (asymptomatic, n=26).
- Various parameters were studied including: the presence of atopic disease (IgE-mediated), various cytokines, transcription profiling (I will come to this shortly).
- Chronic functional GI problems were more commonly found in the ASD/Infection group (63%). Such problems were not due to coeliac disease, inflammatory bowel disease or other known precursors which were looked for.
- Seven of the GI/Infection group (23%) were diagnosed with immunodeficiency (antibody deficiency syndrome). All were treated with intravenous immunoglobulin (IVIG).
- When sub-dividing the ASD/Infection group into whether GI symptoms were present or not, where present, measured levels of the cytokine IL-6 (when incubated with various agonists) were significantly lower when compared to controls. Various other cytokines (proinflammatory and counter-regulatory) were also altered.
- Transcription profiling, measuring the expression of genes, in peripheral blood monocytes, suggested that many more genes were up-regulated or down-regulated in the ASD group vs. controls. Indeed, where the ASD/Infection+GI symptoms group were examined, the greatest disparity was noted compared with both controls and those ASD/No infection. One of the more important up-regulated genes was that related to the chemokine, CCL2, potentially indicative of CNS inflammation. I wonder what effect this might have on that blood-brain barrier?
There are many more findings from this paper but I am fast approaching the outer limits of my competency. The authors summarise the main findings as being the identification of a distinct ASD phenotype, characterised by infection affecting/being affected by behavioural symptom presentation, the presence of functional bowel problems, abnormalities of the innate immune system indicated by functional and transcript profiling. It should be noted that the absolute numbers of children included in this study was relatively low. This will have obvious effects on how applicable the results might be to the wider autistic (and beyond?) population but that's why we have scientific replication.
Whilst some of the results sound pretty scary (immunodeficiency), I think there are a lot of positive to take from this work. I feel I am constantly talking about how autism is not autism but rather autisms and the concept of different phenotypes/sub-groups. What this work implies is that there may be several, measurable differences according to symptom presentation which provide some potentially tangible targets to focus on. The collected immune system findings in relation to autism are complicated and often at odds with each other (overactive vs. underactive). I don't see this as a problem; it suggests that just as we have a 'spectrum' of behavioural presentation, so we might also have a spectrum of biological/genetic presentation also. God knows with all the various genetic findings recently, we know that autism is just as complicated as not-autism. Although perhaps not the primary outcome, this recent paper also points to things which could be done to 'influence' some of the underlying biological issues. Whether these would have any knock-on effects for presented symptoms remains to be seen.
To end, completely and unashamedly nothing to do with this post, the genius of Elvis on what to do in Las Vegas.
* Jyonouchi H. et al. Children with autism spectrum disorders (ASD) who exhibit chronic gastrointestinal (GI) symptoms and marked fluctuation of behavioral symptoms exhibit distinct innate immune abnormalities and transcriptional profiles of peripheral blood (PB) monocytes. J Neuroimmunology. 2011
Friday, 26 August 2011
Aging in autism
Not so long ago I remember talking to a friend of mine about politics, the state of the country and a few other things as you do. Myself not being particularly political but nevertheless enjoying programmes like BBC Question Time, we happened to get on to the topic of Presidents and Prime Ministers and he came out with quite a memorable comment about wisdom and running countries. To quote: 'People who run countries should be at least 60 years old' he said. 'Only then does a person have both experience and wisdom'. Of course he is right. Indeed were his thoughts to be enshrined in various constitutional laws, I dare say we might all find ourselves in a slightly less chaotic world.
This point nicely brings me to a new paper recently published in the journal Gerontology by Francesca Happe (apologies for the lack of the acute accent on the final 'e') and Rebecca Charlton*. The paper is open-access and can be downloaded here and discusses the various research conducted on aging and autism.
I won't go into the paper point-by-point but there are some interesting findings and conclusions to be drawn from the collected works on aging in autism, some perhaps mirroring other conditions. What happens to symptoms (and comorbidities), how to ensure that services and support networks are properly positioned to meet the needs of older people with autism and probably most relevant to this blog, making sure that other conditions associated with aging are screened for and managed appropriately, to name but a few.
As the children of today move into adulthood, there is already growing interest in things like transition (school-college-big wide world), adult care and support for those who require it and the provision of suitable employment opportunities for people with autism. The Happe paper moves one step ahead of all that, to a time when people with autism are faced with the prospect that we all share, growing old, and the delights and challenges that brings.
I touched briefly on the issue of siblings and the role they will be asked to play for their brothers/sisters 'when mum and dad aren't around'. I know no-one likes to think about their own mortality; but nevertheless it is something everyone needs to plan for; parents, family, support organisations and State. Things like medicines management, mobility and access to services and quality of life are other themes that need to be considered. With the quite astounding rise in the numbers of cases of autism witnessed worldwide over the past few years, we perhaps need to start investigating and planning now how to ensure our lifelong commitment to people with autism spectrum conditions fulfills its promises.
* Happe F. & Charlton RA. Aging in autism spectrum disorders: a mini-review. Gerontology. August 2011.
This point nicely brings me to a new paper recently published in the journal Gerontology by Francesca Happe (apologies for the lack of the acute accent on the final 'e') and Rebecca Charlton*. The paper is open-access and can be downloaded here and discusses the various research conducted on aging and autism.
I won't go into the paper point-by-point but there are some interesting findings and conclusions to be drawn from the collected works on aging in autism, some perhaps mirroring other conditions. What happens to symptoms (and comorbidities), how to ensure that services and support networks are properly positioned to meet the needs of older people with autism and probably most relevant to this blog, making sure that other conditions associated with aging are screened for and managed appropriately, to name but a few.
As the children of today move into adulthood, there is already growing interest in things like transition (school-college-big wide world), adult care and support for those who require it and the provision of suitable employment opportunities for people with autism. The Happe paper moves one step ahead of all that, to a time when people with autism are faced with the prospect that we all share, growing old, and the delights and challenges that brings.
I touched briefly on the issue of siblings and the role they will be asked to play for their brothers/sisters 'when mum and dad aren't around'. I know no-one likes to think about their own mortality; but nevertheless it is something everyone needs to plan for; parents, family, support organisations and State. Things like medicines management, mobility and access to services and quality of life are other themes that need to be considered. With the quite astounding rise in the numbers of cases of autism witnessed worldwide over the past few years, we perhaps need to start investigating and planning now how to ensure our lifelong commitment to people with autism spectrum conditions fulfills its promises.
* Happe F. & Charlton RA. Aging in autism spectrum disorders: a mini-review. Gerontology. August 2011.
Obesity, obesity, obesity
Dear readers, please do not assume that the direction of this blog has changed as my posts start to include a little more than just musings on autism research. I assure you they have not and more autism research posts are scheduled within the next few days.
Today (Friday 26th August 2011) the Lancet carries a series of articles about obesity. The collected works can be viewed here. The BBC website also carries an item about this set of papers and summarises some of the main findings and suggestions to tackle our rising rates of the condition.
I'm not going to say too much more about this aside from the fact that the issue of obesity and the rising rates is probably not as simple as 'eat less, exercise more'. I have already covered this in previous posts (here and here). We need to look at the types of food which are being consumed in ever increasing quantities, why our thriving 'low-fat' food market does not seem to be 'cutting the mustard' and how messages about health and wellbeing are communicated to the masses.
Today (Friday 26th August 2011) the Lancet carries a series of articles about obesity. The collected works can be viewed here. The BBC website also carries an item about this set of papers and summarises some of the main findings and suggestions to tackle our rising rates of the condition.
I'm not going to say too much more about this aside from the fact that the issue of obesity and the rising rates is probably not as simple as 'eat less, exercise more'. I have already covered this in previous posts (here and here). We need to look at the types of food which are being consumed in ever increasing quantities, why our thriving 'low-fat' food market does not seem to be 'cutting the mustard' and how messages about health and wellbeing are communicated to the masses.
Thursday, 25 August 2011
Early nutrition shapes future health
The BBC website leads with a health headline: Future heart health 'shaped by diet'.
Whilst some people might look at this headline and say 'wow', I think many people would probably glance at it and say 'we know already'. Certainly those who might be interested in things like the Barker hypothesis recently explored by the BBC Horizon programme and the suggestion that right back to maternal nutrition during pregnancy, what is eaten (or not) can affect the future health of offspring, will know that diet throughout the lifespan is important.
The current study by Annet van Abeelen and colleagues* appears in the European Heart Journal. The crux of their study was to look at over 7,000 women survivors of the Dutch famine of 1944-1945 (the 'Hongerwinter') towards the endgame of WW2. Looking at women survivors who were aged up to 21 years old at the time of the famine, researchers found that those women who were categorised as being 'severely' exposed to the famine presented with a 27% greater risk of coronary heart disease than those unaffected. The risk increased to nearly 40% if girls were aged between 10-17 years at the start of the famine.
This is not the first time that this research group has looked at nutrition based on this sad, but unique period of recent history. In this paper they reviewed some of the studies undertaken on health following the Dutch famine. As per the recent post on the Barker hypothesis, they provide some interesting observations on maternal nutrition related to things like type-2 diabetes. Perhaps more interesting to me are the various studies indicating a potential association between famine babies and rates of schizophrenia and schizophrenia spectrum disorders as exemplified by this study. Indeed other studies of different famines have indicated similar elevated risk of schizophrenia; this paper detailing rates following prenatal exposure to the Chinese famine of 1959-1961.
Through these accumulated studies, there are perhaps a few points that require further investigation:
Whilst I don't want to make too many 'associations' from what is still quite limited data, already I start to think about the recent MIND study on the possible role of nutrition and SNPs suggested in relation to some autism spectrum conditions. Please don't assume that I am making any direct connection because I am not. I am wondering however whether a closer look at the nutritional value of our modern-day foods is in order and as this recent paper by Bakare and Munir ** inquired, what the rates of autism might be in areas more prone to famine, and why, in these times of plenty (for most of us), our food might not be delivering what it should.
* van Abeelen A. et al. Cardiovascular consequences of famine in the young. European Heart Journal. August 2011. doi:10.1093/eurheartj/ehr228
** Bakare MO & Munir KM. Autism spectrum disorders (ASD) in Africa: a perspective. African Journal of Psychiatry. August 2011.
Whilst some people might look at this headline and say 'wow', I think many people would probably glance at it and say 'we know already'. Certainly those who might be interested in things like the Barker hypothesis recently explored by the BBC Horizon programme and the suggestion that right back to maternal nutrition during pregnancy, what is eaten (or not) can affect the future health of offspring, will know that diet throughout the lifespan is important.
The current study by Annet van Abeelen and colleagues* appears in the European Heart Journal. The crux of their study was to look at over 7,000 women survivors of the Dutch famine of 1944-1945 (the 'Hongerwinter') towards the endgame of WW2. Looking at women survivors who were aged up to 21 years old at the time of the famine, researchers found that those women who were categorised as being 'severely' exposed to the famine presented with a 27% greater risk of coronary heart disease than those unaffected. The risk increased to nearly 40% if girls were aged between 10-17 years at the start of the famine.
This is not the first time that this research group has looked at nutrition based on this sad, but unique period of recent history. In this paper they reviewed some of the studies undertaken on health following the Dutch famine. As per the recent post on the Barker hypothesis, they provide some interesting observations on maternal nutrition related to things like type-2 diabetes. Perhaps more interesting to me are the various studies indicating a potential association between famine babies and rates of schizophrenia and schizophrenia spectrum disorders as exemplified by this study. Indeed other studies of different famines have indicated similar elevated risk of schizophrenia; this paper detailing rates following prenatal exposure to the Chinese famine of 1959-1961.
Through these accumulated studies, there are perhaps a few points that require further investigation:
- If famine / calorific restriction during childhood and particularly during the teenage years has the ability to increase the risk of future health problems, what does this potentially mean for those children presenting with feeding disorders such as anorexia nervosa?
- What are the implications of this work for populations where famine is still a fairly regular feature of modern life such as the on-going state in the Horn of Africa?
- If there is a link between prenatal exposure to famine and later psychiatric effects like schizophrenia, is the die cast or can we modify the risk of any association at various stages after birth? How?
- Does the shared physical and psychiatric effects of famine provide a template as to how diet can, long-term, affect body and mind? [There is considerable debate on the elevated risk of cardiovascular mortality in cases of schizophrenia].
Whilst I don't want to make too many 'associations' from what is still quite limited data, already I start to think about the recent MIND study on the possible role of nutrition and SNPs suggested in relation to some autism spectrum conditions. Please don't assume that I am making any direct connection because I am not. I am wondering however whether a closer look at the nutritional value of our modern-day foods is in order and as this recent paper by Bakare and Munir ** inquired, what the rates of autism might be in areas more prone to famine, and why, in these times of plenty (for most of us), our food might not be delivering what it should.
* van Abeelen A. et al. Cardiovascular consequences of famine in the young. European Heart Journal. August 2011. doi:10.1093/eurheartj/ehr228
** Bakare MO & Munir KM. Autism spectrum disorders (ASD) in Africa: a perspective. African Journal of Psychiatry. August 2011.
Tuesday, 23 August 2011
Screening for metabolic conditions in autism
I start with a question. It is not a question meant to offend anyone or provide a platform for extolling a particular view, merely a question that people probably come across quite regularly in relation to autism spectrum conditions.
What causes autism?
Your answer to this question will probably depend on lots of different factors: your relationship to autism, your interest in autism, your personal experiences of autism, your scientific/political/religious points of view and persuasions.
Some people might argue that this is not a question that needs answering and that autism, or at least a segment of the autism spectrum, is just neurodiversity. Other people might argue that autism, or again at least specific phenotypes of autism, is either genetically-controlled, a product of environment or lies somewhere in-between these concepts. Other people just sit on the fence.
I've thought long and hard about this question and the various answers given to it down the years. Those answers have really shaped the history of autism, from the dark times of the blame-game, to the hopefully more enlightened times we live in now. Whilst accepting that autism is in fact autisms, a heterogeneous group of conditions/perspectives/ways of thinking which span ability ranges from significant 'disability' to significant ability alongside the adage 'correlation does not imply causation', I am inclined to say that in some selected cases, science might be beginning to have some pretty good clues about how autism might come about. In much the same way that other behavioural, developmental conditions have been subject to such questioning, I reckon the evidence for causation in autism is probably on a par with things like ADHD.
Consider a few lines of inquiry (appreciating that this list may not be exhaustive).
First, the various research on Fragile X syndrome (which manifests autistic behaviours in some cases). Some might say Fragile X syndrome is not autism but rather autistic behaviours. Others might say, so what; autistic behaviours are autism - or at least autism spectrum. I note on the National Fragile X Foundation website, they use the word 'cause' to describe the relationship.
Second the growing evidence on things like the immune system, mitochondrial dysfunction, brain chemistry and architecture seen in some cases of autism: causative or coincidental?
Third are the various 'associations' between autism and environmental factors including that linking viral infections such as rubella and encephalitis. I did cover possible post-malarial autism in this post a while back. Whether there is any connection to other organisms (viral or bacterial) as there might be in some cases of schizophrenia remains unanswered.
Fourth, although taking a hit these past few weeks, the various genetic findings linked to cases of autism. You see them quite regularly in the scientific literature; this gene or that gene manifesting as autistic behaviours (we think).
Finally we have evidence from the various in-born errors of metabolism which forms the basis for this post.
I linked to a connection between PKU and autism when it came to listing inborn errors of metabolism simply because PKU is the archetypal metabolic condition and seems to show more than a passing relationship with autism. I suppose given the reports of dietary factors being also potentially linked to some cases of autism, it is perhaps all the more useful to list PKU as an example. When it comes to screening for inborn errors of metabolism, many parts of the world are actually getting quite good at this. Thanks to Robert Guthrie, who lent his name to the newborn heel prick test, several potentially life-changing conditions are screened for shortly after birth using the dried blood spot method. Importantly for some of these conditions, there are changes that can be made to off-set some of their effects on health and wellbeing.
My interest in metabolic conditions in relation to autism has been piqued recently following the publication of a couple of articles on the subject. This article by Schiff and colleagues reviewed a couple of hundred children with autism who passed through a French centre. They reviewed a variety of test results carried out including testing for disordered purine metabolism which has been discussed previously on this blog, and concluded that aside from 2 patients, there was no autism-specific relationship between indications of metabolic disorders and their cohort. At least one of their cohort who presented with abnormal results, one patient with elevated urinary creatine excretion, is interesting. Interesting because this is not the first time this has been reported either in the scientific literature or via a personal account.
A second article published in 2010 by Wang and colleagues suggested similar things with regards to there being no overall significant difference in the rates of creatine deficiency syndrome in autism vs. controls. That being said the authors did note elevated mean levels of urinary creatine in children with autism and their siblings as a result of several individuals in these groups showing elevated creatine levels. Importantly despite their 'negative' results, the authors do not rule out routine screening for such issues in autism.
There are various other 'associations' dotted around the autism research landscape. Glucose-6-phosphate dehydrogenase (G6PD) deficiency, L-2-hydroxyglutaric aciduria, and disorder of the urea cycle have all been mentioned. Autism and Smith-Lemli-Opitz syndrome is the topic of a blog post scheduled for the not-too-distant future on cholesterol and autism. Such conditions give us some interesting clues into the nature of autism (i.e. not necessarily 'caused' by only one factor) but also providing some interesting possibilities for management and intervention.
So back to the question of what causes autism, do we perhaps know more than we think?
What causes autism?
Your answer to this question will probably depend on lots of different factors: your relationship to autism, your interest in autism, your personal experiences of autism, your scientific/political/religious points of view and persuasions.
Some people might argue that this is not a question that needs answering and that autism, or at least a segment of the autism spectrum, is just neurodiversity. Other people might argue that autism, or again at least specific phenotypes of autism, is either genetically-controlled, a product of environment or lies somewhere in-between these concepts. Other people just sit on the fence.
I've thought long and hard about this question and the various answers given to it down the years. Those answers have really shaped the history of autism, from the dark times of the blame-game, to the hopefully more enlightened times we live in now. Whilst accepting that autism is in fact autisms, a heterogeneous group of conditions/perspectives/ways of thinking which span ability ranges from significant 'disability' to significant ability alongside the adage 'correlation does not imply causation', I am inclined to say that in some selected cases, science might be beginning to have some pretty good clues about how autism might come about. In much the same way that other behavioural, developmental conditions have been subject to such questioning, I reckon the evidence for causation in autism is probably on a par with things like ADHD.
Consider a few lines of inquiry (appreciating that this list may not be exhaustive).
First, the various research on Fragile X syndrome (which manifests autistic behaviours in some cases). Some might say Fragile X syndrome is not autism but rather autistic behaviours. Others might say, so what; autistic behaviours are autism - or at least autism spectrum. I note on the National Fragile X Foundation website, they use the word 'cause' to describe the relationship.
Second the growing evidence on things like the immune system, mitochondrial dysfunction, brain chemistry and architecture seen in some cases of autism: causative or coincidental?
Third are the various 'associations' between autism and environmental factors including that linking viral infections such as rubella and encephalitis. I did cover possible post-malarial autism in this post a while back. Whether there is any connection to other organisms (viral or bacterial) as there might be in some cases of schizophrenia remains unanswered.
Fourth, although taking a hit these past few weeks, the various genetic findings linked to cases of autism. You see them quite regularly in the scientific literature; this gene or that gene manifesting as autistic behaviours (we think).
Finally we have evidence from the various in-born errors of metabolism which forms the basis for this post.
I linked to a connection between PKU and autism when it came to listing inborn errors of metabolism simply because PKU is the archetypal metabolic condition and seems to show more than a passing relationship with autism. I suppose given the reports of dietary factors being also potentially linked to some cases of autism, it is perhaps all the more useful to list PKU as an example. When it comes to screening for inborn errors of metabolism, many parts of the world are actually getting quite good at this. Thanks to Robert Guthrie, who lent his name to the newborn heel prick test, several potentially life-changing conditions are screened for shortly after birth using the dried blood spot method. Importantly for some of these conditions, there are changes that can be made to off-set some of their effects on health and wellbeing.
My interest in metabolic conditions in relation to autism has been piqued recently following the publication of a couple of articles on the subject. This article by Schiff and colleagues reviewed a couple of hundred children with autism who passed through a French centre. They reviewed a variety of test results carried out including testing for disordered purine metabolism which has been discussed previously on this blog, and concluded that aside from 2 patients, there was no autism-specific relationship between indications of metabolic disorders and their cohort. At least one of their cohort who presented with abnormal results, one patient with elevated urinary creatine excretion, is interesting. Interesting because this is not the first time this has been reported either in the scientific literature or via a personal account.
A second article published in 2010 by Wang and colleagues suggested similar things with regards to there being no overall significant difference in the rates of creatine deficiency syndrome in autism vs. controls. That being said the authors did note elevated mean levels of urinary creatine in children with autism and their siblings as a result of several individuals in these groups showing elevated creatine levels. Importantly despite their 'negative' results, the authors do not rule out routine screening for such issues in autism.
There are various other 'associations' dotted around the autism research landscape. Glucose-6-phosphate dehydrogenase (G6PD) deficiency, L-2-hydroxyglutaric aciduria, and disorder of the urea cycle have all been mentioned. Autism and Smith-Lemli-Opitz syndrome is the topic of a blog post scheduled for the not-too-distant future on cholesterol and autism. Such conditions give us some interesting clues into the nature of autism (i.e. not necessarily 'caused' by only one factor) but also providing some interesting possibilities for management and intervention.
So back to the question of what causes autism, do we perhaps know more than we think?
Monday, 22 August 2011
Barker hypothesis and thin-fat bodies
Viewers here in the UK can, for a limited time, watch this weeks edition of Horizon on BBC2. It is a really interesting programme this week on our first nine months of being, including the theory postulated by Prof. David Barker - the Barker hypothesis of how our birth weight might predict our health later in life. The long and short of theory is simply that low birth weight might increase our risk of various conditions such as coronary heart disease and type 2 diabetes. The reasons why are perhaps slightly more complicated.
It is an interesting theory with a number of lines of evidence potentially supportive. The programme highlighted the studies conducted in Pune, India including this one by Yajnik and colleagues* which suggested that low birth weight children showed a greater level of impaired glucose tolerance, a potential early indicator of future diabetes complications. The paradox is that in India, most of the population are living pretty healthy lives by Western standards: thin bodies, a diet following and exceeding the Western 5-a-day slogan in terms of fruits and vegetable intake and good standards of physical activity, yet have quite high rates of more 'Western' diseases like heart disease and type 2 diabetes considered to be related to our more sedentary lifestyles.
Having said that when you look closer at those 'thin' people, looking at things like the percentage of body fat, these are in fact thin people with fat people bodies: normal body mass index (BMI) but higher percentages of body fat. The programme highlighted one potentially important factor related to birth weight; micronutrients and particularly ideas that low maternal vitamin B12 and low folic acid might make offspring more prone to the thin-fat body and the onward health effects suggested.
A second line of evidence was that derived from the studies on the wartime famine in Holland (sorry, the Netherlands) and the suggested effects on children born to mothers who experienced the famine. This study by Ravelli and colleagues** kinda sums it up: mums exposed to famine especially during the later stages of pregnancy resulted in offspring with decreased glucose tolerance as adults.
I don't claim to understand all the concepts highlighted in the programme and relevant to the Barker hypothesis and there is some evidence to the contrary. What is perhaps most interesting is that we live in a world where our access to food has never been better, certainly over the past 60 years or so, yet ironically the food we eat, or rather the food our mother's or grandmothers ate, might be so deficient in certain nutrients that our physical health and longevity may be at risk. The challenge is to know more about potential mechanisms (including things like the efficiency of the placenta) and make the necessary dietary changes for the sake of future generation health.
* Yajnik CS. et al. Fetal growth and glucose and insulin metabolism in four-year old Indian children. Diabetic Medicine. April 1995.
** Ravelli ACJ. et al. Glucose tolerance in adults after prenatal exposure to famine. Lancet. January 1998.
It is an interesting theory with a number of lines of evidence potentially supportive. The programme highlighted the studies conducted in Pune, India including this one by Yajnik and colleagues* which suggested that low birth weight children showed a greater level of impaired glucose tolerance, a potential early indicator of future diabetes complications. The paradox is that in India, most of the population are living pretty healthy lives by Western standards: thin bodies, a diet following and exceeding the Western 5-a-day slogan in terms of fruits and vegetable intake and good standards of physical activity, yet have quite high rates of more 'Western' diseases like heart disease and type 2 diabetes considered to be related to our more sedentary lifestyles.
Having said that when you look closer at those 'thin' people, looking at things like the percentage of body fat, these are in fact thin people with fat people bodies: normal body mass index (BMI) but higher percentages of body fat. The programme highlighted one potentially important factor related to birth weight; micronutrients and particularly ideas that low maternal vitamin B12 and low folic acid might make offspring more prone to the thin-fat body and the onward health effects suggested.
A second line of evidence was that derived from the studies on the wartime famine in Holland (sorry, the Netherlands) and the suggested effects on children born to mothers who experienced the famine. This study by Ravelli and colleagues** kinda sums it up: mums exposed to famine especially during the later stages of pregnancy resulted in offspring with decreased glucose tolerance as adults.
I don't claim to understand all the concepts highlighted in the programme and relevant to the Barker hypothesis and there is some evidence to the contrary. What is perhaps most interesting is that we live in a world where our access to food has never been better, certainly over the past 60 years or so, yet ironically the food we eat, or rather the food our mother's or grandmothers ate, might be so deficient in certain nutrients that our physical health and longevity may be at risk. The challenge is to know more about potential mechanisms (including things like the efficiency of the placenta) and make the necessary dietary changes for the sake of future generation health.
* Yajnik CS. et al. Fetal growth and glucose and insulin metabolism in four-year old Indian children. Diabetic Medicine. April 1995.
** Ravelli ACJ. et al. Glucose tolerance in adults after prenatal exposure to famine. Lancet. January 1998.
Sunday, 21 August 2011
Battling Clostridia difficile
Perhaps second only to MRSA, the bacteria Clostridia difficile (C.difficile) is on various 'wanted' posters in many hospitals around the world. I say 'wanted' but in this instance do not refer to a welcome invitation, rather the $10,000 reward variety of wanted. Wanted dead or alive as Bon Jovi once asked? Dead in this case.
Why? Well because C.difficile whilst being present in a proportion of the population, and not seemingly involved in anything untoward in many cases, has the propensity to do some pretty nasty things to a person under the right conditions - usually associated with antibiotic use. One of the most widely presented links is with something called pseudomembranous colitis. I am interested in C.difficile and the colitis angle because of the link to gastrointestinal hyperpermeability (the leaky gut) which has had its speculations for some cases of autism and other conditions.
There is some hope on the horizon for tackling C.difficile as represented by this article* by Savidge and colleagues published in Nature Medicine. Don't be too put off by the title and abstract because the BBC website carries quite a good layman version of the findings. The long and short of it is that the compound S-nitrosoglutathione (GSNO), a nitric oxide donor, may be a key component in inhibiting the ability of the bacteria to enter cells and exert its damaging effect. Tests on mice (sorry!) suggested that GSNO helped survival rates in cases of clostridial infection.
The authors are cautious in their findings and application to treating C.difficile infection. Lots more research is required before this compound goes from peer-reviewed paper to practice not least to make sure additional supplementation is actually safe. I am however intrigued about this compound and its potential effects including its proposed effects on things like nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) which might show more than a passing connection to some cases of autism spectrum conditions. More than that though is the potential to treat C.difficile, which at the moment might (and I do stress 'might') show some connection to autism and some intervention measures previously described.
Your days might be numbered C.difficile infection...
* Savidge TC. et al. Host S-nitrosylation inhibits clostridial small molecule-activated glucosylating toxins. Nature Medicine. August 2011.
Why? Well because C.difficile whilst being present in a proportion of the population, and not seemingly involved in anything untoward in many cases, has the propensity to do some pretty nasty things to a person under the right conditions - usually associated with antibiotic use. One of the most widely presented links is with something called pseudomembranous colitis. I am interested in C.difficile and the colitis angle because of the link to gastrointestinal hyperpermeability (the leaky gut) which has had its speculations for some cases of autism and other conditions.
There is some hope on the horizon for tackling C.difficile as represented by this article* by Savidge and colleagues published in Nature Medicine. Don't be too put off by the title and abstract because the BBC website carries quite a good layman version of the findings. The long and short of it is that the compound S-nitrosoglutathione (GSNO), a nitric oxide donor, may be a key component in inhibiting the ability of the bacteria to enter cells and exert its damaging effect. Tests on mice (sorry!) suggested that GSNO helped survival rates in cases of clostridial infection.
The authors are cautious in their findings and application to treating C.difficile infection. Lots more research is required before this compound goes from peer-reviewed paper to practice not least to make sure additional supplementation is actually safe. I am however intrigued about this compound and its potential effects including its proposed effects on things like nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) which might show more than a passing connection to some cases of autism spectrum conditions. More than that though is the potential to treat C.difficile, which at the moment might (and I do stress 'might') show some connection to autism and some intervention measures previously described.
Your days might be numbered C.difficile infection...
* Savidge TC. et al. Host S-nitrosylation inhibits clostridial small molecule-activated glucosylating toxins. Nature Medicine. August 2011.
Saturday, 20 August 2011
Schizophrenia and milk
Only two posts ago I was extolling the virtues of milk and dairy produce and yet here I am again plunging the reputation of the white stuff into disrepute. Michael MacIntyre highlighted such a paradox best in one of his comedy sketches about his children: you love them when they are sleeping ('the little darlings') but seem to find other emotions and words when you want to get them to go to sleep.
The paper in question is this one* from David Niebuhr and colleagues published in Schizophrenia Research. I admit that I am a little late getting to this paper. The main finding from the study is that from looking through quite a few hundred, nay thousand, serum samples for the presence of IgG antibodies to cow milk derived casein, there was a reported association between the risk of schizophrenia and elevated serum levels of casein antibodies before symptoms onset.
I will come back to the findings in more detail momentarily but first there are a few other important things to bring into this. Those who follow this blog will know that schizophrenia in relation to gluten and casein has been discussed before. The original work of the late Curt Dohan on schizophrenia and grains has been talked about (here) alongside the more recent work from people like Faith Dickerson and colleagues detailing findings in relation to gluten antibodies (here). Dohan is perhaps the key person here, following his suggestions over 40 years ago, that some cases of schizophrenia might be tied into diets which contain gluten and casein, and using such diets might actually be quite beneficial to some people with schizophrenia in terms of ameliorating some of their symptoms.
Back to the Niebuhr study, reading through their paper I get the impression that whilst there was great scientific interest in looking at casein antibodies in relation to schizophrenia risk, there was a more practical perspective also. The study was carried out on soldiers, and in particular soldiers who were later diagnosed with schizophrenia and hence medically-discharged from the military as a result. Aside from having a large bank of 'volunteers' and all the accompanying controls in terms of accurate diagnosis and tests for military discharge, I assume that screening serum samples provided by new recruits might eventually provide some further information about those soldiers who might be prone to developing schizophrenia (assuming that the casein hypothesis holds up)?
Anyway, a summary of the methods and findings:
With the number of participants included in this study, I don't think anyone can say that the study authors did not recruit enough people to conduct an adequately powered study. Indeed most researchers could only wish of having such a large and well-defined patient group as this. As the authors point out, the military treat their personnel well. That means that with some confidence, they knew that their patient group were not initially presenting with schizophrenia or bipolar disorder at recruitment alongside the comprehensive investigations carried out post-symptom onset prior to and as part of their medical discharge from the military.
As to why such results were found is more of a mystery. This study was based on levels of circulating IgG antibodies to casein. I have tried to go through the various immunoglobulin isotypes in a previous post. IgG does not seem to imply 'allergy' in the way that IgE (type 1 hypersensitivity) implies. Rather IgG is perhaps better described as demonstrating some degree of immunologic sensitisation, in this case to casein. As per the authors' comments on the opioid-excess hypothesis, I do wonder if such findings are potentially present as a result of an increase in circulating neuroactive casein peptide species. Speculation at least.
All in all, a well-designed, well-performed study. I should perhaps end with an apology to milk, or rather casein, for this post. In future posts I will try and say something more positive about milk and casein again, this time without the sting in the tail. To end a song about apology and regret from the very Beautiful South.
* Niebuhr D. et al. Association between bovine casein antibody and and new onset schizophrenia among US military personnel. Schizophrenia Research. May 2011.
The paper in question is this one* from David Niebuhr and colleagues published in Schizophrenia Research. I admit that I am a little late getting to this paper. The main finding from the study is that from looking through quite a few hundred, nay thousand, serum samples for the presence of IgG antibodies to cow milk derived casein, there was a reported association between the risk of schizophrenia and elevated serum levels of casein antibodies before symptoms onset.
I will come back to the findings in more detail momentarily but first there are a few other important things to bring into this. Those who follow this blog will know that schizophrenia in relation to gluten and casein has been discussed before. The original work of the late Curt Dohan on schizophrenia and grains has been talked about (here) alongside the more recent work from people like Faith Dickerson and colleagues detailing findings in relation to gluten antibodies (here). Dohan is perhaps the key person here, following his suggestions over 40 years ago, that some cases of schizophrenia might be tied into diets which contain gluten and casein, and using such diets might actually be quite beneficial to some people with schizophrenia in terms of ameliorating some of their symptoms.
Back to the Niebuhr study, reading through their paper I get the impression that whilst there was great scientific interest in looking at casein antibodies in relation to schizophrenia risk, there was a more practical perspective also. The study was carried out on soldiers, and in particular soldiers who were later diagnosed with schizophrenia and hence medically-discharged from the military as a result. Aside from having a large bank of 'volunteers' and all the accompanying controls in terms of accurate diagnosis and tests for military discharge, I assume that screening serum samples provided by new recruits might eventually provide some further information about those soldiers who might be prone to developing schizophrenia (assuming that the casein hypothesis holds up)?
Anyway, a summary of the methods and findings:
- 6106 serum samples from 855 cases and 1165 controls were analysed alongside a few thousand samples from cases of bipolar disorder (some participants provided more than one sample).
- Three time periods were examined: 2-4 years before diagnosis, 2 years before diagnosis and 2 years after diagnosis.
- There was a significant differences between schizophrenia cases and controls for casein antibody levels for the 2-4 years before diagnosis period.
- There was a significant difference between schizophrenia cases and bipolar cases for both the 2-4 years period before and 2 year period before diagnosis.
- Those cases with a high initial level of casein antibodies at first sampling who also showed an increase in antibody levels on subsequent samples were faced with an 18% increased risk of developing schizophrenia per standard value increase in casein IgG level (this trend not seen in bipolar disorder cases).
With the number of participants included in this study, I don't think anyone can say that the study authors did not recruit enough people to conduct an adequately powered study. Indeed most researchers could only wish of having such a large and well-defined patient group as this. As the authors point out, the military treat their personnel well. That means that with some confidence, they knew that their patient group were not initially presenting with schizophrenia or bipolar disorder at recruitment alongside the comprehensive investigations carried out post-symptom onset prior to and as part of their medical discharge from the military.
As to why such results were found is more of a mystery. This study was based on levels of circulating IgG antibodies to casein. I have tried to go through the various immunoglobulin isotypes in a previous post. IgG does not seem to imply 'allergy' in the way that IgE (type 1 hypersensitivity) implies. Rather IgG is perhaps better described as demonstrating some degree of immunologic sensitisation, in this case to casein. As per the authors' comments on the opioid-excess hypothesis, I do wonder if such findings are potentially present as a result of an increase in circulating neuroactive casein peptide species. Speculation at least.
All in all, a well-designed, well-performed study. I should perhaps end with an apology to milk, or rather casein, for this post. In future posts I will try and say something more positive about milk and casein again, this time without the sting in the tail. To end a song about apology and regret from the very Beautiful South.
* Niebuhr D. et al. Association between bovine casein antibody and and new onset schizophrenia among US military personnel. Schizophrenia Research. May 2011.
Friday, 19 August 2011
Dog poo bacteria in the air
I apologise for the somewhat childish title to this post. It refers to a piece of research which most definitely fits into my 'other musings' category.
Here in the UK we are known as a nation of dog lovers. We do of course host the annual Crufts competition so as to celebrate our devoted four-legged friends. Whilst being man's best friend, there is some unpleasantness attached to dog ownership; things like cleaning up after their, ahem.. mess.
A new study by Robert Bowers and colleagues* published in the journal Applied & Environmental Microbiology suggests that such mess whilst not exactly great for the local pavement (US = sidewalk) might also be bad news for the local air quality at particular times of the year also. The study has received some coverage (here).
OK, apologies to any residents of Cleveland and Detroit, but apparently bacteria most likely derived from dog feces constitutes the dominant source of airborne bacteria in the Winter months in such places. Deep breath, mouth firmly closed (not that this will do much good).
I, like most people, never thought that bacteria in dog dirt on the ground might have the ability to become airborne. Indeed, bacteria are generally thought as being something present on floors, walls, doors and other surfaces rather than something we breathe in. Not so though as this report highlighted. As if to reiterate the point have a look at a report of a study on the fecal transport system here in the UK, including my locality; hence the age-old phrase 'now wash your hands'.
Of course the authors point out that much more research is needed to confirm the pooch as primary perpetrator and any onward effects to human health from such exposures. Whilst not wishing to force any connection to autism or anything else, I do find it interesting that our seasonal environment from a bacterial point of view might be quite fluid, and how this might perhaps tie into differing exposures and differing risk.
* Bowers RM. et al. Sources of bacteria in outdoor air across cities in the Midwestern United States. Applied & Environmental Microbiology. August 2011.
Here in the UK we are known as a nation of dog lovers. We do of course host the annual Crufts competition so as to celebrate our devoted four-legged friends. Whilst being man's best friend, there is some unpleasantness attached to dog ownership; things like cleaning up after their, ahem.. mess.
A new study by Robert Bowers and colleagues* published in the journal Applied & Environmental Microbiology suggests that such mess whilst not exactly great for the local pavement (US = sidewalk) might also be bad news for the local air quality at particular times of the year also. The study has received some coverage (here).
OK, apologies to any residents of Cleveland and Detroit, but apparently bacteria most likely derived from dog feces constitutes the dominant source of airborne bacteria in the Winter months in such places. Deep breath, mouth firmly closed (not that this will do much good).
I, like most people, never thought that bacteria in dog dirt on the ground might have the ability to become airborne. Indeed, bacteria are generally thought as being something present on floors, walls, doors and other surfaces rather than something we breathe in. Not so though as this report highlighted. As if to reiterate the point have a look at a report of a study on the fecal transport system here in the UK, including my locality; hence the age-old phrase 'now wash your hands'.
Of course the authors point out that much more research is needed to confirm the pooch as primary perpetrator and any onward effects to human health from such exposures. Whilst not wishing to force any connection to autism or anything else, I do find it interesting that our seasonal environment from a bacterial point of view might be quite fluid, and how this might perhaps tie into differing exposures and differing risk.
* Bowers RM. et al. Sources of bacteria in outdoor air across cities in the Midwestern United States. Applied & Environmental Microbiology. August 2011.
Dairy and casein: some positive PR
Remember the campaign 'milk has gotta lotta bottle'?
It was a bit of a daft advert but I doubt many people who saw it forgot the tune and the public relations (PR) message: milk = good, so drink lots of it. The advert was made on behalf of the UK Milk Marketing Board who perhaps had an interest in making sure that we all bought as much milk as possible to be healthy (and also support our dairy market). As per a previous post, through my childhood, I had a slightly different opinion of school milk.
Milk, and its protein casein, has played and continues to be play, quite a large role in my professional life alongside its dietary partner, gluten. To save any confusion, I will state for the record that I hold no personal grudge or ill-will against these ubiquitous compounds despite the various suggestions that they may play some role, either directly or peripherally in some cases of autism and perhaps a few other conditions outside of their classical links. For the majority of people milk (and bread) are staple foods and provide countless nutritional benefits particularly for those who are economically less fortunate than ourselves.
So as to demonstrate my impartiality in relation to milk and casein, I first offer a few lines of evidence suggesting some positive effects linked to the ingestion of said foodstuff outside of the quite well known calcium link. There is this fairly comprehensive meta-analysis demonstrating a possible protective effect of milk and dairy products on the risk of developing colorectal cancer. Replacing carbohydrates with a milk protein supplement might also lower blood pressure according to this study; although I do perhaps question what might be having the effect, given the carb-health associations which seem to be emerging daily. Milk has recently also been suggested to be better at hydrating children than water (despite who funded the study). This study also suggested that a certain type of fermented goats milk might serve as an alternative to all those ever-so modern probiotic drinks which seem to be all the rage, with its positive mucosal effects.
The paper on fermented goats milk is an interesting one. Interesting because it asks a few questions, not least, are all dairy products the same? It is well known that different mammals, even different animals of the same species produce different types of milk structurally. This is none the more evident than when looking at the recent A1 vs. A2 milk debate (I will leave this for a future post). Even based on the same core product, the way that milk is processed might also affect its various properties. A recent large epidemiological study has been completed and published based in Sweden trying to ascertain whether milk consumption was in any way related to risk of cardiovascular disease (CVD). The abstract is here. The main findings were that when dairy products were divided up into specific categories (fermented dairy products like yoghurt vs. regular, non-fermented milk), higher intake of fermented dairy products was associated with a lower risk of CVD. This might suggest that not all dairy products are the same and their impact on health might similarly vary according to what type and what form of dairy is consumed.
Similar work on fermented milk products such as kefir has also provided some interesting data. This paper for example suggested that kefir might aid the so-called leaky gut, at least in mice, which has been implicated in quite a few conditions including autism. Kefir is an interesting product in that its effects could be due to lots of things. It could be due to the various bacteria present (traditionally using sheep's intestinal flora, don't ask me how); it could be due to the various yeasts present, it could be due to the fermentation of lactose, one reason why kefir has been suggested as an alternative for lactose intolerant individuals. This last effect might be particularly relevant in light of the fairly-recent Harvard findings.
We are still very much at the early stage of dietary intervention research for conditions like autism, despite the fact that it has taken almost 30 years for research to get this far. I would like to think that as our scientific interest and understanding increases in this area (accompanied by a few more research pounds and dollars), more investigations can be undertaken to determine exactly how dairy (and gluten) specifically affects some cases of autism. Whether also a dairy-free diet should automatically mean a total dairy-free diet for some or all is another question posed.
To finish, was it something about the 1980s and milk- and wheat-based products which lead to such annoying adverts being aired?
It was a bit of a daft advert but I doubt many people who saw it forgot the tune and the public relations (PR) message: milk = good, so drink lots of it. The advert was made on behalf of the UK Milk Marketing Board who perhaps had an interest in making sure that we all bought as much milk as possible to be healthy (and also support our dairy market). As per a previous post, through my childhood, I had a slightly different opinion of school milk.
Milk, and its protein casein, has played and continues to be play, quite a large role in my professional life alongside its dietary partner, gluten. To save any confusion, I will state for the record that I hold no personal grudge or ill-will against these ubiquitous compounds despite the various suggestions that they may play some role, either directly or peripherally in some cases of autism and perhaps a few other conditions outside of their classical links. For the majority of people milk (and bread) are staple foods and provide countless nutritional benefits particularly for those who are economically less fortunate than ourselves.
So as to demonstrate my impartiality in relation to milk and casein, I first offer a few lines of evidence suggesting some positive effects linked to the ingestion of said foodstuff outside of the quite well known calcium link. There is this fairly comprehensive meta-analysis demonstrating a possible protective effect of milk and dairy products on the risk of developing colorectal cancer. Replacing carbohydrates with a milk protein supplement might also lower blood pressure according to this study; although I do perhaps question what might be having the effect, given the carb-health associations which seem to be emerging daily. Milk has recently also been suggested to be better at hydrating children than water (despite who funded the study). This study also suggested that a certain type of fermented goats milk might serve as an alternative to all those ever-so modern probiotic drinks which seem to be all the rage, with its positive mucosal effects.
The paper on fermented goats milk is an interesting one. Interesting because it asks a few questions, not least, are all dairy products the same? It is well known that different mammals, even different animals of the same species produce different types of milk structurally. This is none the more evident than when looking at the recent A1 vs. A2 milk debate (I will leave this for a future post). Even based on the same core product, the way that milk is processed might also affect its various properties. A recent large epidemiological study has been completed and published based in Sweden trying to ascertain whether milk consumption was in any way related to risk of cardiovascular disease (CVD). The abstract is here. The main findings were that when dairy products were divided up into specific categories (fermented dairy products like yoghurt vs. regular, non-fermented milk), higher intake of fermented dairy products was associated with a lower risk of CVD. This might suggest that not all dairy products are the same and their impact on health might similarly vary according to what type and what form of dairy is consumed.
Similar work on fermented milk products such as kefir has also provided some interesting data. This paper for example suggested that kefir might aid the so-called leaky gut, at least in mice, which has been implicated in quite a few conditions including autism. Kefir is an interesting product in that its effects could be due to lots of things. It could be due to the various bacteria present (traditionally using sheep's intestinal flora, don't ask me how); it could be due to the various yeasts present, it could be due to the fermentation of lactose, one reason why kefir has been suggested as an alternative for lactose intolerant individuals. This last effect might be particularly relevant in light of the fairly-recent Harvard findings.
We are still very much at the early stage of dietary intervention research for conditions like autism, despite the fact that it has taken almost 30 years for research to get this far. I would like to think that as our scientific interest and understanding increases in this area (accompanied by a few more research pounds and dollars), more investigations can be undertaken to determine exactly how dairy (and gluten) specifically affects some cases of autism. Whether also a dairy-free diet should automatically mean a total dairy-free diet for some or all is another question posed.
To finish, was it something about the 1980s and milk- and wheat-based products which lead to such annoying adverts being aired?
Thursday, 18 August 2011
Rats attracted to cats?
I'm not really obsessed with Toxoplasma gondii but you have to admire this organism. Read on to see why.
I discussed T.gondii in a previous post on schizophrenia in light of work like this one from Faith Dickerson and colleagues. Now a new study has come to quite a startling conclusion: T.gondii might make rats sexually attracted to cats (or at least cat urine).
The study in question is this one* from Patrick House and colleagues from Stanford University. They looked at what happens to certain parts of the brain of infected rats and found increased activity in parts of the limbic system. The limbic system is also known as the paleomammalian brain by people like Paul D. MacLean (the father of Evolutionary Psychiatry) and includes quite a few structures known to be involved in emotions and hormone regulation.
In the current study, various alterations of limbic response were noted in infected rats in response to cat urine. The authors suggest that T.gondii may modulate behaviour by shifting the 'defensive' neural pathway of infected rats to the 'reproductive' pathway; in effect rather than running away, the rats are sexually attracted to cat urine.
Conditions like schizophrenia and obsessive-compulsive disorder (OCD) indicate perhaps more than a passing association with exposure to T.gondii as represented by elevated antibodies to the organism. Indeed even some cases of suicide might also be linked to T.gondii. What studies like the one from House et al suggest is that neural targets, areas of the brain, likely to be affected by infection should be the subject of much more investigation. Once again environment shows its hand.
* House PK. et al. Predator cat odors activate sexual arousal pathways in brains of Toxoplasma gondii infected rats. PLoS ONE. August 2011.
I discussed T.gondii in a previous post on schizophrenia in light of work like this one from Faith Dickerson and colleagues. Now a new study has come to quite a startling conclusion: T.gondii might make rats sexually attracted to cats (or at least cat urine).
The study in question is this one* from Patrick House and colleagues from Stanford University. They looked at what happens to certain parts of the brain of infected rats and found increased activity in parts of the limbic system. The limbic system is also known as the paleomammalian brain by people like Paul D. MacLean (the father of Evolutionary Psychiatry) and includes quite a few structures known to be involved in emotions and hormone regulation.
In the current study, various alterations of limbic response were noted in infected rats in response to cat urine. The authors suggest that T.gondii may modulate behaviour by shifting the 'defensive' neural pathway of infected rats to the 'reproductive' pathway; in effect rather than running away, the rats are sexually attracted to cat urine.
Conditions like schizophrenia and obsessive-compulsive disorder (OCD) indicate perhaps more than a passing association with exposure to T.gondii as represented by elevated antibodies to the organism. Indeed even some cases of suicide might also be linked to T.gondii. What studies like the one from House et al suggest is that neural targets, areas of the brain, likely to be affected by infection should be the subject of much more investigation. Once again environment shows its hand.
* House PK. et al. Predator cat odors activate sexual arousal pathways in brains of Toxoplasma gondii infected rats. PLoS ONE. August 2011.
Wednesday, 17 August 2011
What does the Internet tell us about autism?
The recent 'discussions' (and continuing saga) between Dorothy Bishop and Baroness Susan Greenfield on any possible connection between Internet use and autism got me slightly hot under the collar, and no, not in a good way. The suggestion from Greenfield that our embracing of the digital world might somehow be linked to the rise in autism prevalence has been quite widely questioned, and perhaps rightly so.
Reading her piece in the New Scientist, I did however see some interesting points that Greenfield was trying to raise about how we need to have more dialogue on how technology might potentially be involved in our 'adapting' biology as it definitely is on our social and cultural world (see the recent London riots as one example). If one accepts a Darwinian version of evolution, one must accept that we are constantly adapting to the environment presented to us and that environment, physical and cultural, has changed pretty substantially over the past 100 years or so, even during the past 30 years coinciding with the technological age. A recent programme on BBC Radio 4 discussed a similar issue. Correlation however does not imply causation.
Away from that particular duel, in this post I want to briefly discuss the role of the Internet in relation to autism, from the perspective of this paper* by Reichow and colleagues recently published in JADD which sought to tell us about the characteristics and quality of autism websites. MJ over at Autism Jabberwocky has already covered this paper and I would strongly direct readers to the post (here).
Anyone who uses the Internet knows that whilst it is an incredible source of information for good, one can find misinformation and bad in equal, dare I say greater, measure. According to Google Insights for Search, the top search term for autism (aside from just 'autism') in 2011 so far is the term 'symptoms of autism'. Try typing it in and see what you get. OK, now try and type in something like 'autism causes' and see what you get. I would wager that you probably might not be in total agreement with all the information presented to you from this particular query.
So it was with the Reichow paper, where Government sources denoted by a .gov web address were generally determined to offer the more accurate information about autism. This paper offered similar advice when using Google for more general healthcare advice. When I say accurate, I mean accurate from the point-of-view of what the professionally-accepted opinion of autism might be. Indeed this is perhaps one of the problems when information is 'graded' according to accuracy: who decides what is accurate and what is not and how do they do it?
One could perhaps see that in a widely heterogeneous condition like autism, where presentation is so varied and aetiology potentially also different in different phenotypes, universal constants might be few and far between. Combined with increasingly large volumes of research constantly being produced and perhaps overturning some of our widely-held beliefs about things like genes and environment or sibling recurrence of autism for example, you can see that accuracy is perhaps a more fluid concept than many people realise.
Whilst I am all for accuracy and science being communicated properly, I wouldn't necessarily suggest that information about autism or lots of other things be solely derived from Government or professional sources. Why? Well one need only read through the blog list at the foot of this blog to see that many other sources of information, first-person, second-person, research-based, lay opinion, can provide accurate (yes accurate) and up-to-date information which one would never get from merely towing the party line. Moreover in previous posts I have come across information which whilst from professional sources was nevertheless inaccurate and how accuracy and opinion aren't necessarily built on overwhelming evidence. No-one is infallible is perhaps the key take-home message.
One resource that I would hope will help at least here in the UK are the upcoming streams of advice to be provided by NICE. For those who are interested, here is a link to my 'NICE to see you' post from a few months back on exactly what is being looked at and how far a long things have progressed.
A feel-good tune now from the Carpenters who are on top of the World (feel free to sing along).
* Reichow B. et al. Characteristics and quality of autism websites. JADD. August 2011
Reading her piece in the New Scientist, I did however see some interesting points that Greenfield was trying to raise about how we need to have more dialogue on how technology might potentially be involved in our 'adapting' biology as it definitely is on our social and cultural world (see the recent London riots as one example). If one accepts a Darwinian version of evolution, one must accept that we are constantly adapting to the environment presented to us and that environment, physical and cultural, has changed pretty substantially over the past 100 years or so, even during the past 30 years coinciding with the technological age. A recent programme on BBC Radio 4 discussed a similar issue. Correlation however does not imply causation.
Away from that particular duel, in this post I want to briefly discuss the role of the Internet in relation to autism, from the perspective of this paper* by Reichow and colleagues recently published in JADD which sought to tell us about the characteristics and quality of autism websites. MJ over at Autism Jabberwocky has already covered this paper and I would strongly direct readers to the post (here).
Anyone who uses the Internet knows that whilst it is an incredible source of information for good, one can find misinformation and bad in equal, dare I say greater, measure. According to Google Insights for Search, the top search term for autism (aside from just 'autism') in 2011 so far is the term 'symptoms of autism'. Try typing it in and see what you get. OK, now try and type in something like 'autism causes' and see what you get. I would wager that you probably might not be in total agreement with all the information presented to you from this particular query.
So it was with the Reichow paper, where Government sources denoted by a .gov web address were generally determined to offer the more accurate information about autism. This paper offered similar advice when using Google for more general healthcare advice. When I say accurate, I mean accurate from the point-of-view of what the professionally-accepted opinion of autism might be. Indeed this is perhaps one of the problems when information is 'graded' according to accuracy: who decides what is accurate and what is not and how do they do it?
One could perhaps see that in a widely heterogeneous condition like autism, where presentation is so varied and aetiology potentially also different in different phenotypes, universal constants might be few and far between. Combined with increasingly large volumes of research constantly being produced and perhaps overturning some of our widely-held beliefs about things like genes and environment or sibling recurrence of autism for example, you can see that accuracy is perhaps a more fluid concept than many people realise.
Whilst I am all for accuracy and science being communicated properly, I wouldn't necessarily suggest that information about autism or lots of other things be solely derived from Government or professional sources. Why? Well one need only read through the blog list at the foot of this blog to see that many other sources of information, first-person, second-person, research-based, lay opinion, can provide accurate (yes accurate) and up-to-date information which one would never get from merely towing the party line. Moreover in previous posts I have come across information which whilst from professional sources was nevertheless inaccurate and how accuracy and opinion aren't necessarily built on overwhelming evidence. No-one is infallible is perhaps the key take-home message.
One resource that I would hope will help at least here in the UK are the upcoming streams of advice to be provided by NICE. For those who are interested, here is a link to my 'NICE to see you' post from a few months back on exactly what is being looked at and how far a long things have progressed.
A feel-good tune now from the Carpenters who are on top of the World (feel free to sing along).
* Reichow B. et al. Characteristics and quality of autism websites. JADD. August 2011
Pole position in autism research
Many research groups are at work in the autism research arena. I have blogged about a few of them over the past few months, and in some cases readily admit to being a bit of fan of some of their ideas and produce. One group has kinda crept up on my autism research radar with no or only little media publicity for their research findings, some of which actually might be quite important.
The group in question is a team based at the Technical University of Lodz in Poland (hence the 'Poles') and the author who keeps cropping up is Dr Joanna Kaluzna-Czaplinska (apologies for the lack of Latin characters in her name). I posted an entry about some research from this group recently and their interesting findings related to the big 'H' - homocysteine - which seems to also potentially tie into quite a few other areas.
A recent paper from this Polish group also piqued my interest; this one* looking at what happened to urinary levels of various dicarboxylic acids in children with autism in response to a supplementation regime which included magnesium and vitamins B6 (pyridoxine) and B2 (riboflavin). I should perhaps back up a little and explain what exactly dicarboxylic acids are and which ones were examined in this study. Dicarboxylic acids are organic acids which, chemically, have two carboxyl functional groups (hence the di-).
The paper describes results based on the application of gas chromatography mass spectrometry (GC-MS) to analyse for several dicarboxylic acids in urine including succinic, adipic and suberic acids. Some of these dicarboxylic acids are involved in things like the Krebs cycle among other things.
Anyhow, the results suggested that the supplementation protocol (listed in the paper) seemed to have had quite an effect on the quantities of the dicarboxylic acids measured; adjusting of course for our old friend urinary creatinine. This is not really startling news considering that elevated urinary levels of compounds such as succinic acid for example, might (might!) indicate a deficiency of vitamin B2 [or coenzyme Q10] among other things.
Some caution needs to be attached to these findings as they stand. There were only 30 participants included for study and no control group used. Having said that the main thrust of the paper seems to be about what happened to detected compound levels in children with autism following supplementation, so maybe I should not be so critical at this stage.
There are perhaps a few ways that this collected data can be interpreted. Elevated levels of such organic acids as markers of some kind of disorder of metabolism is perhaps one way. Another is the possibility that a proportion of people with an autism spectrum condition might actually be deficient in various vitamins and minerals and what is being seen are the knock-on effects of that. I stand back at this point preferring not to speculate which option might be most applicable, bearing in mind that metabolic disorders involving such parameters might show 'overlap' with some of the characteristics seen in autism.
* Kaluzna-Czaplinska J. et al. B vitamin supplementation reduces excretion or urinary dicarboxylic acids in autistic children. Nutrition Research. August 2011.
The group in question is a team based at the Technical University of Lodz in Poland (hence the 'Poles') and the author who keeps cropping up is Dr Joanna Kaluzna-Czaplinska (apologies for the lack of Latin characters in her name). I posted an entry about some research from this group recently and their interesting findings related to the big 'H' - homocysteine - which seems to also potentially tie into quite a few other areas.
A recent paper from this Polish group also piqued my interest; this one* looking at what happened to urinary levels of various dicarboxylic acids in children with autism in response to a supplementation regime which included magnesium and vitamins B6 (pyridoxine) and B2 (riboflavin). I should perhaps back up a little and explain what exactly dicarboxylic acids are and which ones were examined in this study. Dicarboxylic acids are organic acids which, chemically, have two carboxyl functional groups (hence the di-).
The paper describes results based on the application of gas chromatography mass spectrometry (GC-MS) to analyse for several dicarboxylic acids in urine including succinic, adipic and suberic acids. Some of these dicarboxylic acids are involved in things like the Krebs cycle among other things.
Anyhow, the results suggested that the supplementation protocol (listed in the paper) seemed to have had quite an effect on the quantities of the dicarboxylic acids measured; adjusting of course for our old friend urinary creatinine. This is not really startling news considering that elevated urinary levels of compounds such as succinic acid for example, might (might!) indicate a deficiency of vitamin B2 [or coenzyme Q10] among other things.
Some caution needs to be attached to these findings as they stand. There were only 30 participants included for study and no control group used. Having said that the main thrust of the paper seems to be about what happened to detected compound levels in children with autism following supplementation, so maybe I should not be so critical at this stage.
There are perhaps a few ways that this collected data can be interpreted. Elevated levels of such organic acids as markers of some kind of disorder of metabolism is perhaps one way. Another is the possibility that a proportion of people with an autism spectrum condition might actually be deficient in various vitamins and minerals and what is being seen are the knock-on effects of that. I stand back at this point preferring not to speculate which option might be most applicable, bearing in mind that metabolic disorders involving such parameters might show 'overlap' with some of the characteristics seen in autism.
* Kaluzna-Czaplinska J. et al. B vitamin supplementation reduces excretion or urinary dicarboxylic acids in autistic children. Nutrition Research. August 2011.
Tuesday, 16 August 2011
Hoarding
A very, very quick post this one. I am just watching the BBC programme 'My hoarder mum and me' in which the presenter Jasmine Harman discusses in quite some depth the various issues raised by her mum, Vasoulla and her extreme hoarding behaviour. Both mum and daughter are quite brave to allow such candid access to perhaps a most secretive condition.
I don't know a lot about hoarding other than that which I have come across in the odd research article and so this programme is a real eye-opener on just how how much material can be accumulated and how there is genuine pain and anguish when it comes to clearing such collections. What perhaps strikes me from watching the programme is the focus on 'functionality' by the hoarder. A perfect example being the question raised by one of Vasoulla's sons on why she has kept some old stereo speaker; the reply being because of the 'magnets' and how useful they could be for picking up paperclips.
I don't know a lot about hoarding other than that which I have come across in the odd research article and so this programme is a real eye-opener on just how how much material can be accumulated and how there is genuine pain and anguish when it comes to clearing such collections. What perhaps strikes me from watching the programme is the focus on 'functionality' by the hoarder. A perfect example being the question raised by one of Vasoulla's sons on why she has kept some old stereo speaker; the reply being because of the 'magnets' and how useful they could be for picking up paperclips.
Ideal or minimum standard?
A short 'other musings' post this one.
Let's face it, when it comes to health advice (healthy eating, lifestyle, exercise, etc) most people tend to follow a chain of reactions which goes something like this:
I am not saying that everyone does this, because in the case of smoking for example, a lot of people do quit and do not go back to tobacco again. What I am saying is that our initial 'shock' followed by 'enthusiasm' to fundamentally change things related to our health is generally short-lived barring any significant 'scare' to us as individuals or those close to us.
In such cases I have often thought that the best way to effect a change is to provide people with a rough idea of what the 'bare minimum' constitutes. So, rather than setting goals to attain - the so called 'ideal', draw a line below which things should not fall. A recent article appearing in the Lancet did just that. The paper by Chi Pang Wen and colleagues* based in Taiwan provided a benchmark for physical activity in Taiwanese populations about what the minimum requirement is for physical activity for reduced mortality and extending life expectancy. They reported that, based on various statistics and reports of risk (there's that word again), 15 minutes of activity of moderate intensity a day at least helps in reducing the risk of various life-limiting complaints.
Already this study has invoked opinion after opinion on the results, as well as some quite sensational headlines suggesting things like 'every hour of TV watching takes 22 minutes of your life' (this is from the same paper which described an 'Asperger gene' and a man with Asperger syndrome as being a pathological liar which are concepts I am still trying to comprehend).
Health is of course important to all. It is not until you don't have good health that you realise just how important it is. Communicating health and healthy practices is always going to be a challenge for Governments and other agencies, not least when the evidence is not necessarily just straight-forward for all people. The decision facing the various health authorities can be essentially boiled down to this: do they communicate the 'ideal' standards or should they communicate the 'minimum standard'?
* Chi Pang Wen et al. Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study. Lancet. August 2011
Let's face it, when it comes to health advice (healthy eating, lifestyle, exercise, etc) most people tend to follow a chain of reactions which goes something like this:
- Advice given (through personal contact, TV, media, etc),
- Initial thoughts about health and mortality,
- Short-term attempt at making some changes (which lasts from a few days to a few weeks/months),
- Fading memory of initial advice,
- Back to pre-advice default position
I am not saying that everyone does this, because in the case of smoking for example, a lot of people do quit and do not go back to tobacco again. What I am saying is that our initial 'shock' followed by 'enthusiasm' to fundamentally change things related to our health is generally short-lived barring any significant 'scare' to us as individuals or those close to us.
In such cases I have often thought that the best way to effect a change is to provide people with a rough idea of what the 'bare minimum' constitutes. So, rather than setting goals to attain - the so called 'ideal', draw a line below which things should not fall. A recent article appearing in the Lancet did just that. The paper by Chi Pang Wen and colleagues* based in Taiwan provided a benchmark for physical activity in Taiwanese populations about what the minimum requirement is for physical activity for reduced mortality and extending life expectancy. They reported that, based on various statistics and reports of risk (there's that word again), 15 minutes of activity of moderate intensity a day at least helps in reducing the risk of various life-limiting complaints.
Already this study has invoked opinion after opinion on the results, as well as some quite sensational headlines suggesting things like 'every hour of TV watching takes 22 minutes of your life' (this is from the same paper which described an 'Asperger gene' and a man with Asperger syndrome as being a pathological liar which are concepts I am still trying to comprehend).
Health is of course important to all. It is not until you don't have good health that you realise just how important it is. Communicating health and healthy practices is always going to be a challenge for Governments and other agencies, not least when the evidence is not necessarily just straight-forward for all people. The decision facing the various health authorities can be essentially boiled down to this: do they communicate the 'ideal' standards or should they communicate the 'minimum standard'?
* Chi Pang Wen et al. Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study. Lancet. August 2011
Monday, 15 August 2011
Sibling risk of autism
It has been known for quite some time that autism spectrum conditions, whilst not being a wholly genetically based set of condition, does seem to occur more often in siblings of affected children. The research base in this area is fairly large and the 'amount' of risk potentially present varies according to study sample sizes and diagnostic methods and criteria used.
One of the more comprehensive studies carried out fairly recently (2010) hinted that the sibling re-occurrence rate for autism spectrum condition could be anything up to 10%; indeed even higher if one were to start looking at the broader phenotype presentation to include things like speech and language problems. You are probably thinking 10%.. that sounds pretty high. Well a recent study suggests that in some cases it might actually be much higher.
The study by Ozonoff and colleagues* published in the journal Pediatrics estimated that the risk of sibling re-occurrence of an autism spectrum condition might be as high as 18%. There are quite a few descriptions of the study on the web. Geraldine Dawson from Autism Speaks provides a brief overview here and the BBC have also covered the study. I have not yet seen the full-text so can't provide too detailed an overview yet. From these collected and other sources, there are however a few details which can be reported from the data:
[Update: the full-text of the paper can be viewed here]
Whilst appreciating that risk is not necessarily eventuality, these are some quite startling figures from a research point of view as once again some of our commonly held views on autism are starting to be overturned. It started with the sex ratio, then it was the rates in MZ-DZ siblings and now the recurrence rates.
The current study is a strong one methodologically. Given that it was part of the High Risk Baby Siblings Research Consortium and hence relied on data from more than one location, the generalisability of the data outside of just one geographical area is strong. The use of ADOS and clinical opinion similarly means that diagnostic verification is high.
Looking at this new data and the previous studies 15-20 years ago I am struck by one question: did they really get it so wrong back then or is the autism of today, the same as it was in yesteryear?
* Ozonoff S. et al. Recurrence risk for autism spectrum disorders: a baby siblings research consortium study. Pediatrics. August 2011.
One of the more comprehensive studies carried out fairly recently (2010) hinted that the sibling re-occurrence rate for autism spectrum condition could be anything up to 10%; indeed even higher if one were to start looking at the broader phenotype presentation to include things like speech and language problems. You are probably thinking 10%.. that sounds pretty high. Well a recent study suggests that in some cases it might actually be much higher.
The study by Ozonoff and colleagues* published in the journal Pediatrics estimated that the risk of sibling re-occurrence of an autism spectrum condition might be as high as 18%. There are quite a few descriptions of the study on the web. Geraldine Dawson from Autism Speaks provides a brief overview here and the BBC have also covered the study. I have not yet seen the full-text so can't provide too detailed an overview yet. From these collected and other sources, there are however a few details which can be reported from the data:
[Update: the full-text of the paper can be viewed here]
- This was a prospective study whereby 664 infants who had a sibling with an autism spectrum condition were followed for the first 3 years of their lives.
- Children were assessed for autism using the ADOS (one of the gold-standards for assessing autism) and by expert clinical diagnosis.
- Of the original 664 infants, 132 children met the cut-off criteria for an autism spectrum condition. Of these, 54 exceeded the cut-offs from autism and 78 infants for the wider autism spectrum.
- Male siblings were more likely to be diagnosed with autism in all its forms (26%) compared with females (9%). This translates as 1 in 4 younger brothers were diagnosed with an autism spectrum condition compared with 1 in 9-10 younger sisters.
- Where there was more than one older sibling with autism, the risk to younger siblings presenting with an autism spectrum condition was also increased (to an average of 32%).
Whilst appreciating that risk is not necessarily eventuality, these are some quite startling figures from a research point of view as once again some of our commonly held views on autism are starting to be overturned. It started with the sex ratio, then it was the rates in MZ-DZ siblings and now the recurrence rates.
The current study is a strong one methodologically. Given that it was part of the High Risk Baby Siblings Research Consortium and hence relied on data from more than one location, the generalisability of the data outside of just one geographical area is strong. The use of ADOS and clinical opinion similarly means that diagnostic verification is high.
Looking at this new data and the previous studies 15-20 years ago I am struck by one question: did they really get it so wrong back then or is the autism of today, the same as it was in yesteryear?
* Ozonoff S. et al. Recurrence risk for autism spectrum disorders: a baby siblings research consortium study. Pediatrics. August 2011.
Sunday, 14 August 2011
Not lying, I am puzzled
I am puzzled by this story which has appeared in the UK Daily Mail on-line. Puzzled because the article about sperm donation by a man purported to have Asperger syndrome carries a few details which quite frankly puzzle me.
The person in question lives in the Netherlands and offered his services to several women wishing to have a child. Apparently a few of these women did a little digging around after some of their offspring were diagnosed with Asperger syndrome and found out a few things about their donor.
Puzzle 1: the article makes mention of an 'Asperger gene' and an 'autism gene'. Strange.. I didn't know there was one.
Puzzle 2: the chap in question has been named (by a newspaper) as being a 'pathological liar'. I admit that I have not looked comprehensively at the literature on telling fibs and autism spectrum conditions such as Asperger syndrome. A quick look at some of the first-hand accounts suggests that people with Asperger syndrome don't lack the capacity to be able to lie as everyone else, but to be pathological liars? I don't know, I suppose it depends on the situation and other personal factors. Maybe one for another post some time and how to lie.
Still I am puzzled about this article (and I'm not lying).
The person in question lives in the Netherlands and offered his services to several women wishing to have a child. Apparently a few of these women did a little digging around after some of their offspring were diagnosed with Asperger syndrome and found out a few things about their donor.
Puzzle 1: the article makes mention of an 'Asperger gene' and an 'autism gene'. Strange.. I didn't know there was one.
Puzzle 2: the chap in question has been named (by a newspaper) as being a 'pathological liar'. I admit that I have not looked comprehensively at the literature on telling fibs and autism spectrum conditions such as Asperger syndrome. A quick look at some of the first-hand accounts suggests that people with Asperger syndrome don't lack the capacity to be able to lie as everyone else, but to be pathological liars? I don't know, I suppose it depends on the situation and other personal factors. Maybe one for another post some time and how to lie.
Still I am puzzled about this article (and I'm not lying).
Saturday, 13 August 2011
Edible colloids to reduce food fat content
A brief post. The August 2011 edition of Chemistry World carries an interesting article about the use of edible colloids as an alternative way of reducing the fat in foods (full-text here). I don't want to get into any debate about whether dietary fat is good or bad because (a) I don't know enough about it and (b) it is not the main aim of this post.
Being Chemistry World, the text is quite heavily chemistry-orientated but I was quite interested in some of the various ways that chemistry is approaching the issue of fat in food and our modern-day obsession with diet and fat reduction. The article lists a few interesting possibilities under investigation. Things like the incorporation of gel-coated air bubbles into foods behaving like fat droplets in the mouth, and the addition of emulsions to food which survive our stomach and areas of our gastrointestinal (GI) tract to make us feel fuller for longer. I know some people might gasp in horror as chemistry contemplates toying with our foods, and obviously a lot more research and investment needs to go into such areas. Having said that hands up if your diet solely consists of food which has not been manipulated in one way or another already?
All of these options must be better than the 'no food diet'?
Being Chemistry World, the text is quite heavily chemistry-orientated but I was quite interested in some of the various ways that chemistry is approaching the issue of fat in food and our modern-day obsession with diet and fat reduction. The article lists a few interesting possibilities under investigation. Things like the incorporation of gel-coated air bubbles into foods behaving like fat droplets in the mouth, and the addition of emulsions to food which survive our stomach and areas of our gastrointestinal (GI) tract to make us feel fuller for longer. I know some people might gasp in horror as chemistry contemplates toying with our foods, and obviously a lot more research and investment needs to go into such areas. Having said that hands up if your diet solely consists of food which has not been manipulated in one way or another already?
All of these options must be better than the 'no food diet'?
Polybrominated diphenyl ethers (PBDEs) and autism
The beautiful game of football (soccer) is a bit of national obsession here in the UK. In the bracing North-East of England, we have a particularly loyal following of fans who, every Saturday (or thereabouts) dress up in either red and white or black and white depending on their affinity to the Black Cats or the Magpies, and brave the elements to watch 90 minutes of sporting battle. Derby days when the two teams meet are something else!
I myself, whilst an interested follower of one of these teams (not saying which!), have never been as overly enthusiastic as some of my fellow North-Easterners, instead preferring to follow a different kind of sport, research. Funny you might think that he equates research with football, but it follows very similar principles: competition, goals, star players, money, esteem. Some would say that football is a matter of life or death; research is perhaps in some cases even more about life or death.
Within the autism research football division, several teams compete. At the moment, I would probably say that the team based at the UC Davis MIND Institute are the Manchester United of the Premier League. Indeed various papers from the MIND Institute have been covered on this blog. Their focus on the environmental as well as the genetic is perhaps what makes the MIND Institute stand out from the rest.
Why the long-winded introduction?
Well a paper has appeared recently which whilst outside of autism research could potentially tie into some areas covered by the MIND Institute team. The paper by Zota and colleagues* reports on a study looking at polybrominated diphenyl ethers (PBDEs) and related metabolites used as flame retardant materials alongside markers of thyroid function in pregnant mums based in California.
Many things contain PBDEs despite such compounds being banned in several parts of the world. Plastics, wire insulation, old furniture foam - much like asbestos, being banned does not necessarily mean that people are not exposed to such compounds (and for years after). Zota and colleagues sought to measure serum concentrations of PBDEs in mums-to-be who were in the second trimester of pregnancy. They found some of the highest concentrations of PBDE-related metabolites ever reported in pregnant women. Added to that they reported associations between PBDE findings and moderators of thyroid function such as thyroid-stimulating hormone (TSH).
Whilst it is not possible to say what specific effects such serum PBDE levels might have on the developing foetus bearing in mind their toxicity profile, it is fair to say that any potential disruption to maternal thyroid function caused by alterations in TSH levels is not likely to be good for the child. Foetal premature birth, low birth weight and even miscarriage and stillbirth have been noted in cases of gestational maternal hyper- and hypothyroidism.
So how does this relate back to the MIND Institute and autism research?
Levels of PBDEs and related metabolites in cases of autism have been examined by our intrepid UC Davis team. This paper from Hertz-Piciotto and colleagues measured serum PBDE levels in children with autism vs. developmental delay vs. asymptomatic controls. They did not report any significant differences among the groups, the groups made up of participants from California, but noted high levels of PBDEs in all. OK, you might say so there was no difference, but wait.. what if there might be some difference in the way that such compounds affect a person, a person with autism perhaps? During preliminary study this is what was hinted at in this paper by Ashwood and colleagues, who suggested an altered sensitivity to a specific PBDE, BDE-47 resulting in an increased inflammatory response in cells from people with autism spectrum conditions compared with controls. This finding follows other research suggestive of a potential association between BDE-47 and attention problems.
As with any environmental agent, it is nearly impossible to ascribe an effect in isolation because people do not live in a vacuum. As a population, we potentially face hundreds if not thousands of other exposures which might be contributory to any effect. Unless you measure them all, there is always doubt. Having said that, I don't want to take away from the findings of the study by Zota and colleagues. Findings which require replication and follow-up of infants born to mothers with such high levels, and if deemed necessary, urgent action to minimise any associated health or developmental risks.
I leave you with a song by a footballer which many North-Easterners will know well. It's probably not going to win a Grammy but harks back to happier times for the gentleman in question.
* Zota AR. Polybrominated diphenyl ethers (PBDEs), hydroxylated PBDEs (OH-PBDEs), and measures of thyroid function in second trimester pregnant women in California. Environmental Science & Technology. August 2011.
I myself, whilst an interested follower of one of these teams (not saying which!), have never been as overly enthusiastic as some of my fellow North-Easterners, instead preferring to follow a different kind of sport, research. Funny you might think that he equates research with football, but it follows very similar principles: competition, goals, star players, money, esteem. Some would say that football is a matter of life or death; research is perhaps in some cases even more about life or death.
Within the autism research football division, several teams compete. At the moment, I would probably say that the team based at the UC Davis MIND Institute are the Manchester United of the Premier League. Indeed various papers from the MIND Institute have been covered on this blog. Their focus on the environmental as well as the genetic is perhaps what makes the MIND Institute stand out from the rest.
Why the long-winded introduction?
Well a paper has appeared recently which whilst outside of autism research could potentially tie into some areas covered by the MIND Institute team. The paper by Zota and colleagues* reports on a study looking at polybrominated diphenyl ethers (PBDEs) and related metabolites used as flame retardant materials alongside markers of thyroid function in pregnant mums based in California.
Many things contain PBDEs despite such compounds being banned in several parts of the world. Plastics, wire insulation, old furniture foam - much like asbestos, being banned does not necessarily mean that people are not exposed to such compounds (and for years after). Zota and colleagues sought to measure serum concentrations of PBDEs in mums-to-be who were in the second trimester of pregnancy. They found some of the highest concentrations of PBDE-related metabolites ever reported in pregnant women. Added to that they reported associations between PBDE findings and moderators of thyroid function such as thyroid-stimulating hormone (TSH).
Whilst it is not possible to say what specific effects such serum PBDE levels might have on the developing foetus bearing in mind their toxicity profile, it is fair to say that any potential disruption to maternal thyroid function caused by alterations in TSH levels is not likely to be good for the child. Foetal premature birth, low birth weight and even miscarriage and stillbirth have been noted in cases of gestational maternal hyper- and hypothyroidism.
So how does this relate back to the MIND Institute and autism research?
Levels of PBDEs and related metabolites in cases of autism have been examined by our intrepid UC Davis team. This paper from Hertz-Piciotto and colleagues measured serum PBDE levels in children with autism vs. developmental delay vs. asymptomatic controls. They did not report any significant differences among the groups, the groups made up of participants from California, but noted high levels of PBDEs in all. OK, you might say so there was no difference, but wait.. what if there might be some difference in the way that such compounds affect a person, a person with autism perhaps? During preliminary study this is what was hinted at in this paper by Ashwood and colleagues, who suggested an altered sensitivity to a specific PBDE, BDE-47 resulting in an increased inflammatory response in cells from people with autism spectrum conditions compared with controls. This finding follows other research suggestive of a potential association between BDE-47 and attention problems.
As with any environmental agent, it is nearly impossible to ascribe an effect in isolation because people do not live in a vacuum. As a population, we potentially face hundreds if not thousands of other exposures which might be contributory to any effect. Unless you measure them all, there is always doubt. Having said that, I don't want to take away from the findings of the study by Zota and colleagues. Findings which require replication and follow-up of infants born to mothers with such high levels, and if deemed necessary, urgent action to minimise any associated health or developmental risks.
I leave you with a song by a footballer which many North-Easterners will know well. It's probably not going to win a Grammy but harks back to happier times for the gentleman in question.
* Zota AR. Polybrominated diphenyl ethers (PBDEs), hydroxylated PBDEs (OH-PBDEs), and measures of thyroid function in second trimester pregnant women in California. Environmental Science & Technology. August 2011.
Thursday, 11 August 2011
Amyloid precursor protein and autism
A cobbler should stick to his last. Meaning that people should generally stick to what they know and do best. I think most people would feel comfortable with this phrase. We would after all never (knowingly or willingly) go for surgery at a bakery or have our teeth fixed by a plumber. Likewise I probably wouldn't want my doctor to butcher my pork chops, even if she was handy with a scalpel.
I hope that I am not getting too out of my depth with this quite biochemistry-heavy post on some new findings on the amyloid precursor protein in relation to autism spectrum conditions. I have consulted with a few people who know a little more about this than I, just to check a few facts, but please do not assume I am an expert in this area. We will see if I do the science and research justice.
I start with some definition and description. Those with a medical or scientific background or possibly some family experience will probably already have heard of amyloid precursor protein (APP) in relation to Alzheimer's disease (AD). AD is the most common cause of dementia and the condition's profile is being elevated by people such as Sir Terry Pratchett (he of the Discworld novels). Without going too deeply into AD, the characteristic brain pathology of the condition is noted by the presence of neurofibrillary tangles and amyloid plaques. The plaques are made up of certain accumulated breakdown products of APP.
Nobody really knows how such pathology comes about in terms of genes and environment, but amongst the various investigations being undertaken into AD, one of the more widely suggested hypotheses involves APP and in particular, its peptide fragments, beta-amyloid, which are the main constituent of the plaques found in AD. Like any peptide, beta-amyloid is formed as a result of enzymatic processes involving a protease acting on APP, specifically the beta- and gamma-secretases. There are various other processes involved in this chain of events potentially related to AD but that's as far as I am going for now. I would perhaps also mention about the various pharmacotherapeutic measures currently available to tackle AD, based around two main classes of drug: the acetylcholinesterase inhibitors, which increase acetylcholine (often depleted in AD) and the glutamate-blocker, memantine. I have talked about acetylcholinesterase inhibitors previously in relation to autism (here). I note that memantine has also been trialled in cases of autism with some indications of positive symptom response.
A recent paper by Ray and colleagues* (open access copy available here) looked at some of the products of amyloid precursor protein (APP) in plasma from people with autism. The paper is a quite complicated one and not the easiest piece to follow, hence my use of bullet-points to break the methods and selected findings down:
These are interesting findings. Plasma levels of beta-amyloid peptides (particularly 42) are associated with cognitive decline and onset of AD. I would however caution before making too many statements about the study results and risk of AD based on things like the small participant numbers included in the current study, and also their young age.
This is not the first time that this particular research group have published in this area. Indeed in a previous study based on even smaller participant numbers, they reported increased total sAPP in severe autism relative to other groups and controls; contrasting with no overall difference in the current study. Perhaps more interesting however was the confirmation from the recent study of higher levels of non-plaque related sAPP combined with lower levels of plaque-related beta-amyloid-40 peptide in severe autism. Likewise another group has confirmed some of theses findings.
I would like to believe that there may be some good sense in conducting further, large-scale study of levels of sAPP-alpha in autism which some have suggested might be a potential biomarker for autism. There are also a few other potential tie-ins to sAPP-alpha which might also necessitate some further investigation including a peripheral nicotinic effect, the use of statins, and the effect of selected neuropeptides.
As per my initial caveat, I would perhaps advise interested readers to do a little confirmatory reading before taking my observations as any kind of truth. If on the other hand you need someone to name your Star Wars villains, well I'm yer man..
* Ray B. et al. Increased secreted amyloid precursor protein-α (sAPPα) in severe autism: proposal of a specific, anabolic pathway and putative biomarker. PLoS ONE. 2011: 6:6
I hope that I am not getting too out of my depth with this quite biochemistry-heavy post on some new findings on the amyloid precursor protein in relation to autism spectrum conditions. I have consulted with a few people who know a little more about this than I, just to check a few facts, but please do not assume I am an expert in this area. We will see if I do the science and research justice.
I start with some definition and description. Those with a medical or scientific background or possibly some family experience will probably already have heard of amyloid precursor protein (APP) in relation to Alzheimer's disease (AD). AD is the most common cause of dementia and the condition's profile is being elevated by people such as Sir Terry Pratchett (he of the Discworld novels). Without going too deeply into AD, the characteristic brain pathology of the condition is noted by the presence of neurofibrillary tangles and amyloid plaques. The plaques are made up of certain accumulated breakdown products of APP.
Nobody really knows how such pathology comes about in terms of genes and environment, but amongst the various investigations being undertaken into AD, one of the more widely suggested hypotheses involves APP and in particular, its peptide fragments, beta-amyloid, which are the main constituent of the plaques found in AD. Like any peptide, beta-amyloid is formed as a result of enzymatic processes involving a protease acting on APP, specifically the beta- and gamma-secretases. There are various other processes involved in this chain of events potentially related to AD but that's as far as I am going for now. I would perhaps also mention about the various pharmacotherapeutic measures currently available to tackle AD, based around two main classes of drug: the acetylcholinesterase inhibitors, which increase acetylcholine (often depleted in AD) and the glutamate-blocker, memantine. I have talked about acetylcholinesterase inhibitors previously in relation to autism (here). I note that memantine has also been trialled in cases of autism with some indications of positive symptom response.
A recent paper by Ray and colleagues* (open access copy available here) looked at some of the products of amyloid precursor protein (APP) in plasma from people with autism. The paper is a quite complicated one and not the easiest piece to follow, hence my use of bullet-points to break the methods and selected findings down:
- A total of 39 participants were included for study: 15 diagnosed with severe autism (CARS score of 37+), 6 with mild-moderate autism (CARS: 30-36.5) and 18 asymptomatic controls. There was no significant difference across the mean ages of the groups.
- Various measures of the residues and peptides derived from APP in plasma were analysed alongside levels of brain-derived neurotrophic factor (BDNF). The main reason seems to be the study's focus on BDNF and specific APP breakdown products being neurotrophic (related to neuronal growth or survival) on the back of the data looking at head circumference in autism.
- There was no significant difference across the groups in terms of the mean total of total secreted amyloid precursor protein (sAPP) (that is the combined species based on the actions of the various forms of the secretase on APP).
- Levels of sAPP-alpha, the residue of the non-plaque associated form of APP, were elevated in the more severely affected autism group compared with controls.
- Levels of sAPP-beta, the residue associated with plaques from APP, were reduced in the more severely affected autism group compared with controls.
- Levels of the beta-amyloid peptides involved in plaque formation, including the most insoluble and toxic peptide, beta-amyloid-42, were also reduced in the more severely affected autism group compared with controls.
These are interesting findings. Plasma levels of beta-amyloid peptides (particularly 42) are associated with cognitive decline and onset of AD. I would however caution before making too many statements about the study results and risk of AD based on things like the small participant numbers included in the current study, and also their young age.
This is not the first time that this particular research group have published in this area. Indeed in a previous study based on even smaller participant numbers, they reported increased total sAPP in severe autism relative to other groups and controls; contrasting with no overall difference in the current study. Perhaps more interesting however was the confirmation from the recent study of higher levels of non-plaque related sAPP combined with lower levels of plaque-related beta-amyloid-40 peptide in severe autism. Likewise another group has confirmed some of theses findings.
I would like to believe that there may be some good sense in conducting further, large-scale study of levels of sAPP-alpha in autism which some have suggested might be a potential biomarker for autism. There are also a few other potential tie-ins to sAPP-alpha which might also necessitate some further investigation including a peripheral nicotinic effect, the use of statins, and the effect of selected neuropeptides.
As per my initial caveat, I would perhaps advise interested readers to do a little confirmatory reading before taking my observations as any kind of truth. If on the other hand you need someone to name your Star Wars villains, well I'm yer man..
* Ray B. et al. Increased secreted amyloid precursor protein-α (sAPPα) in severe autism: proposal of a specific, anabolic pathway and putative biomarker. PLoS ONE. 2011: 6:6
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