I apologise in advance to readers that this is one of my more indulgent posts.
2011 has been an interesting year for lots of people including me. Not only did I embrace the wonders of Blogger and the joys of discussing and conversing with lots of interesting people about autism research and more, but I also went full-on with social media such as Facebook and Twitter. This from a man who not so long ago had only one bookmark in his chosen internet browser (PubMed naturally) and thought social media was just for teenagers discussing Justin Bieber and the X-Factor.
Although I only started blogging in February 2011, I thought it would be a good idea to write a post summarising some of the things that I found interesting in the research world this year. Some of these studies have already been shared across other blogs. I know that this is not a novel idea for an end of year post, but at least it offers readers a condensed version of 'what I done discussing'. I will be as brief as I can so as not to take any time away from your forthcoming renditions of Auld Lang Syne.
January
Not on blogger and haven't got the time to go trawling back through PubMed to see the relevant research highlights. I probably am cheating a little and also showing a little too much self-promotion if I provide a link to a paper I was involved with which was published in December 2010 detailing some of the possible reasons why a gluten- and casein-free diet may or may not work when used as an intervention for autism spectrum conditions. Open-access.. yes. Speculative... yes.
February
Saturday 19 February 2011: joined blogger. I can remember the day well. Didn't see my second post? The first was an introduction and some 'keep it civil' guidance; the second was on autism, gut bacteria and urine. Two other posts caught my eye in this month: Food and ADHD and those DSM-V suggestions about autism.
March
Worms. Parasitic worms and the immune system to be precise. That and the new paper from Tim Buie and colleagues on disaccharidases and autism and the stark message that lactose intolerance might be more prevalent in cases of autism than many people may have thought. Leo Kanner also figured quite a lot in March as per this post on his original descriptions and also remembering the 30th anniversary of his passing away.
April
Looking at the evidence for autism 'treatments' and more closely at interventions and autism. Gut bacteria was also still on the menu.
May
A busy month. The numbers of adults with autism estimated in the UK alongside the Utah data on prevalence and that South Korean study. Not forgetting the SNPs and vits study.
June
Autism prevalence across the DSMs is a favourite of mine. An introduction to copy number variations (CNVs) and autism in this post and not forgetting autism and the technological phenotype and evolutionary autism.
July
Quite a lot of interest in the whole twins and heritability. I know that since the publication of this paper lots of people have talked about the figures and the way the statistics were applied to the dataset but it still remains an interesting finding. Chlorination by-products and autism also cropped up in a part of the US (Brick Township) which had been a talking point about autism a few years back.
August
The maternal immune profile and autism in offspring raised some interesting questions as did the link between casein and schizophrenia and the Barker hypothesis and thin-fat bodies.
September
A taster of some of the first results from the Autism Phenome Project featured but perhaps the highlight of the year for me were the preliminary findings on carbs, dysbiosis and autism from Brent Williams and colleagues. Here in the UK we also had the publication of the first strand guidance from NICE on pathways to diagnosis in autism. We'll wait to see how implementation is rolled out in these austere times.
October
Quite a lot of interest in the facial characteristics of autism but for me the suggested prevalence of coeliac (celiac) disease in cases of ADHD was a highlight alongside the possibility that the diagnosis of schizophrenia might, just might, be possible by biochemical analysis. Happy birthday to the seven billionth person on the planet by the way.
November
Nature did autism and created quite some discussions. CNVs appeared again in relation to ADHD (or maybe not) and also intellectual disability. The prefrontal cortex in relation to autism also got more than one mention in the research literature.
December
Formal publication of the biological phenotypes data on head size and regression in autism. The large extent to which autism is genetically, a very complicated condition and why MRI findings on high-functioning autism aren't neccessarily all that different from not-autism. The results of a double-blind, placebo-controlled trial of a vitamin and mineral supplement for autism spectrum conditions should really be creating a lot more interest than it has so far bearing in mind the dearth of methodologically top-class studies into autism.
So there you have it. An interesting year for sure. I know that I am not yet a year into blogging but rather than waiting for the first anniversary, I offer my thanks and best wishes to all readers for their insightful comments and thoughts, and wishes of health and happiness to all for 2012 (hoping that the prophecies don't come true).
To finish, the festive season just wouldn't be the same without the Pogues and Kirsty MacColl (starring Matt Dillon as the arresting officer). This sassenach wishes all a very happy Hogmanay.
Monday, 26 December 2011
Thursday, 22 December 2011
Beans, beans, penny a lump..
A final light-hearted post before Christmas classified under the 'other musings' heading as I approach probably one of the more unusual papers that I have read in a while.
There is no easy way to say this but beans (legumes) have a slightly unfortunate reputation for erm, causing flatulence. If like me you grew up watching the Mel Brooks classic 'Blazing Saddles' you will remember that quite memorable scene around the campfire.
Here comes the science. Donna Winham and Andrea Hutchins* report results following a study looking at whether bean consumption increases the reports of flatulence. The summary:
Joking aside, there are a few important points to take from this research. We now for example know that beans can cause flatulence. I know this is probably not new news to many consumers, particularly male consumers, but at least science has made its input. Having said that the reported rates of flatulence seemed to decrease as time eating beans consistently went on. I like the idea that some kind of adaptive process is at work, bearing in mind the study findings already indicated on bean consumption and biochemical and bacterial parameters. The authors also ask a few questions about the psychological effects of expectation with regards to flatulence and beans.
I hope I didn't offend anyone with this post. Science is science after all; and I suppose a study like this is a good way of bringing science to the masses. As it is Christmas, the BMJ have their usual 'interesting' studies which this year, rather un-Christmasly(?) includes how fast/slow the Grim Reaper walks and comparing grip strength and intelligence across different medical disciplines.
Happy Christmas!
* Winham DM. & Hutchins AM. Perceptions of flatulence from bean consumption among adults in 3 feeding studies. Nutrition Journal. November 2011.
There is no easy way to say this but beans (legumes) have a slightly unfortunate reputation for erm, causing flatulence. If like me you grew up watching the Mel Brooks classic 'Blazing Saddles' you will remember that quite memorable scene around the campfire.
Here comes the science. Donna Winham and Andrea Hutchins* report results following a study looking at whether bean consumption increases the reports of flatulence. The summary:
- A questionnaire was completed by participants already involved in various studies on beans and health (here and here and here) based on various parameters of flatulence, stool changes and bloating.
- Controlling for various other dietary factors and compared against a control portion of carrots, various types of beans differentially increased reported episodes of flatulence. It wasn't necessarily a uniform increase in reports of wind following bean consumption but nevertheless 1 week of pinto bean consumption correlated with 50% of people reporting flatulence, vegetarian baked beans (47%) and black-eyed peas (19%). Flatulence abated slightly in subsequent weeks.
- Reported flatulence was not necessarily followed by changes to stools, whether in consistency or frequency despite some slight alterations reported. Participant reports on individual beans were also not necessarily due to the fibre content of individual beans although black-eyed peas are reported to have the lower fibre content.
Joking aside, there are a few important points to take from this research. We now for example know that beans can cause flatulence. I know this is probably not new news to many consumers, particularly male consumers, but at least science has made its input. Having said that the reported rates of flatulence seemed to decrease as time eating beans consistently went on. I like the idea that some kind of adaptive process is at work, bearing in mind the study findings already indicated on bean consumption and biochemical and bacterial parameters. The authors also ask a few questions about the psychological effects of expectation with regards to flatulence and beans.
I hope I didn't offend anyone with this post. Science is science after all; and I suppose a study like this is a good way of bringing science to the masses. As it is Christmas, the BMJ have their usual 'interesting' studies which this year, rather un-Christmasly(?) includes how fast/slow the Grim Reaper walks and comparing grip strength and intelligence across different medical disciplines.
Happy Christmas!
* Winham DM. & Hutchins AM. Perceptions of flatulence from bean consumption among adults in 3 feeding studies. Nutrition Journal. November 2011.
Tuesday, 20 December 2011
May I draw your attention to...
A very quick post, designed to draw your attention to two very interesting blog posts recently appearing.
The first is by MJ over at Autism Jabberwocky detailing the results of a meta-analysis of the collected studies looking at a potential role for food in cases of ADHD. Bottom-line: based on the available research, dietary intervention (either a restricted diet or a diet devoid of various food colours) might be useful for some people with ADHD in terms of effects on symptom presentation. I know this is probably not a huge surprise to many but lets see where this goes.
The second post features on the Autism Speaks blog summarising the top 10 autism research achievements in 2011. I have an end of year post scheduled in the next week or so which covers quite a few of the studies detailed so won't go too much into that for now. What I would perhaps say, echoing the ADHD-food link, is that much like the final coming together of the Ross-Rachel relationship from Friends (remember that!) or the reuniting of Take That, the natural order of genetics and environment (variably) working in tandem seems to be a recurrent theme in quite a few of the studies included.
Who knows, next year we might even see words like 'epigenetics' and 'endophenotypes' appearing; well I can hope can't I?
The first is by MJ over at Autism Jabberwocky detailing the results of a meta-analysis of the collected studies looking at a potential role for food in cases of ADHD. Bottom-line: based on the available research, dietary intervention (either a restricted diet or a diet devoid of various food colours) might be useful for some people with ADHD in terms of effects on symptom presentation. I know this is probably not a huge surprise to many but lets see where this goes.
The second post features on the Autism Speaks blog summarising the top 10 autism research achievements in 2011. I have an end of year post scheduled in the next week or so which covers quite a few of the studies detailed so won't go too much into that for now. What I would perhaps say, echoing the ADHD-food link, is that much like the final coming together of the Ross-Rachel relationship from Friends (remember that!) or the reuniting of Take That, the natural order of genetics and environment (variably) working in tandem seems to be a recurrent theme in quite a few of the studies included.
Who knows, next year we might even see words like 'epigenetics' and 'endophenotypes' appearing; well I can hope can't I?
Monday, 19 December 2011
C-sections and obesity
This is an extension post to a topic previously discussed on this blog and its sister blog in relation to your route of entry into the world potentially being correlated with later health and ill-health risk.
The header in the UK Sunday Times on 20 November 2011 was 'caesarean babies have greater risk of obesity'. We are told through this article that babies born through planned c-sections are more likely to become obese. The reason: higher levels of fats in the liver as a result of a malfunction of the metabolic processes which allows people to handle fats according to one of the authors, Prof. Neena Modi of Imperial College, London. It appears that the often traumatic journey from snug warm cocoon to big wide world via the birth canal, and all the hormones and chemicals involved in this process, might have lots of different lasting effects on baby. That's before you even reach the stage of cord clamping and when to do it.
I can't post a link to the study in question reporting these findings because I can't find it (yet). What we do know is that scanning livers of 62 babies and correlating with maternal body mass index (BMI) and birth route (vaginal, emergency c-section, planned c-section) revealed some interesting trends. So, mum's weight seemed to have an effect on liver fat content but only when birth was by planned c-section. This might have some interesting implications for the message being put out about larger mums predisposing to larger offspring.
The Imperial team (no, not that Imperial) are no strangers to this type of research as evidenced by a recent paper of theirs suggesting that fat in liver (intrahepatocellular lipid) of babies might be correlated with maternal body mass index (BMI). I assume that this latest research is an extension of their tried and tested investigative techniques.
Going back to my previous posts on c-sections, it is interesting that a few trends seem to be appearing. Labour and all the biochemical changes a woman's body makes when it is time to give birth seem to be important when it comes to a baby's subsequent risk of obesity (fatty liver anyway) and coeliac disease. Distinguishing emergency c-sections from planned c-sections, where one would assume that many of those biochemical changes are already starting to take place despite the fact that entry into the world is via a different port, also seems to be important.
I do also wonder about that favourite topic of mine 'bacteria' and whether babies who need to be delivered by emergency c-section might have already taken a few mouthfuls of the good stuff as a result of their partial journey down the birth canal? Does this mean that a good dose of mum's bacteria should accompany all planned c-sections? (Not that I'm offering any clinical advice!)
The header in the UK Sunday Times on 20 November 2011 was 'caesarean babies have greater risk of obesity'. We are told through this article that babies born through planned c-sections are more likely to become obese. The reason: higher levels of fats in the liver as a result of a malfunction of the metabolic processes which allows people to handle fats according to one of the authors, Prof. Neena Modi of Imperial College, London. It appears that the often traumatic journey from snug warm cocoon to big wide world via the birth canal, and all the hormones and chemicals involved in this process, might have lots of different lasting effects on baby. That's before you even reach the stage of cord clamping and when to do it.
I can't post a link to the study in question reporting these findings because I can't find it (yet). What we do know is that scanning livers of 62 babies and correlating with maternal body mass index (BMI) and birth route (vaginal, emergency c-section, planned c-section) revealed some interesting trends. So, mum's weight seemed to have an effect on liver fat content but only when birth was by planned c-section. This might have some interesting implications for the message being put out about larger mums predisposing to larger offspring.
The Imperial team (no, not that Imperial) are no strangers to this type of research as evidenced by a recent paper of theirs suggesting that fat in liver (intrahepatocellular lipid) of babies might be correlated with maternal body mass index (BMI). I assume that this latest research is an extension of their tried and tested investigative techniques.
Going back to my previous posts on c-sections, it is interesting that a few trends seem to be appearing. Labour and all the biochemical changes a woman's body makes when it is time to give birth seem to be important when it comes to a baby's subsequent risk of obesity (fatty liver anyway) and coeliac disease. Distinguishing emergency c-sections from planned c-sections, where one would assume that many of those biochemical changes are already starting to take place despite the fact that entry into the world is via a different port, also seems to be important.
I do also wonder about that favourite topic of mine 'bacteria' and whether babies who need to be delivered by emergency c-section might have already taken a few mouthfuls of the good stuff as a result of their partial journey down the birth canal? Does this mean that a good dose of mum's bacteria should accompany all planned c-sections? (Not that I'm offering any clinical advice!)
Friday, 16 December 2011
Autism and gastroenteritis
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| Somethin' fishy @ Paul Whiteley 2010 |
Gastroenteritis is another quite nebulous diagnosis in terms of what exactly it is and indeed how it is managed. The medical terminology refers to inflammation of the gastrointestinal tract caused by either a virus or bacteria. Having said that, its a little like saying you have a cold, in terms of what a cold covers and the numerous causes of it. One of the more recent studies on infectious intestinal illness here in the UK by Tam and colleagues* (open-access) estimated that case numbers are high and contribute quite substantially to the overall healthcare burden.
Gastroenteritis is not normally a serious condition. I say not normally but don't be under any disillusion that many thousands, hundreds of thousands of people around the world contract gastroenteritis and, particularly in developing countries, it ends their days especially young children. Even in our 'developed' societies, gastroenteritis for very young children or for the very elderly can be dangerous as a result of things like the dehydration it can bring. The causes of gastroenteritis as I said are numerous; ranging from various bacteria to various viruses.
NHS Choices lists a separate entry for gastroenteritis in children. It talks about the near certainty that children will come into contact with the pathogens which can cause viral gastroenteritis, particularly the Norovirus and rotavirus and sapoviruses, as a function of children being children, mixing with one another and not always having ideal handwashing practices. Perhaps one of the only redeeming features is that generally speaking, immunity is built up to the viruses after multiple childhood contacts and subsequent reinfections often tend to be fairly minor.
OK, descriptions finished, how does this relate to autism spectrum conditions?
I should perhaps make a distinction here when I talk about gastroenteritis and autism, in that I am not talking about chronic gastroenteritis as detailed in one of my previous posts, but rather the more transient type present particularly in early childhood. Having said that see a little later in the post. Gastroenteritis has been mentioned in the case histories of quite a few people with autism involved in research. This paper for example (which was discussed in this post), discusses hospitalisation of one child for dehydration following gastroenteritis. Indeed, Kanner is his description of autism in 1943 noted bouts of gastroenteritis in the early histories of some of his cohort. OK, I hear you say, individual cases do not a relationship make. That is true.
There is some evidence that episodes of gastroenteritis, viral gastroenteritis, 'might' be slightly more common in autism than other populations. This paper reported a non-significant increase in reported viral gastroenteritis in autism cases in the first 2 years of life using a case-control study design. The prevalence was non-significant but the authors saw fit to discuss it, perhaps because of some increase in frequency when looking at the children in their cohort who were more severely affected with autism.
Without trying to make too many connections that might not be there, this recent paper on prolonged viral gastroenteritis potentially being related to inflammatory enteropathy in immuno-deficient hosts makes me wonder about any possible link between episodic gastroenteritis and more long term issues. This in light of previous research talking about immune system issues in some cases of autism.
The case has not yet been made to suggest that episodic gastroenteritis is anything but a coincidence in cases of autism, caused by the same risk factors as that noted in everyone else. Having said that, the various other research examining a more chronic inflammatory bowel condition associated with some cases of autism, does perhaps incline us to start looking more closely at episodic gastroenteritis in cases of autism and whether there is any more direct connection to be had.
* Tam CC. et al. Longitudinal study of infectious intestinal disease in the UK (IID2 study): incidence in the community and presenting to general practice. BMJ. June 2011
Tuesday, 13 December 2011
Vitamins and autism: double-blind, placebo-controlled RCT
It is the gold-standard of experimental trial designs, second only to the meta-analysis on the hierarchy of evidence-based practice: the double-blind, placebo-controlled, randomised controlled trial. To you and me it means that neither participants nor investigators knew who was taking what during the trial, the 'what' experimental treatment was compared against a placebo or sham treatment option, and when it came to deciding who got 'what' or placebo, it was a very random affair.
So it was with a new study by Jim Adams and colleagues* looking at the effects of an individually titrated vitamin and mineral supplement for children and adults with autism spectrum conditions. Regular readers will know that Jim Adams has cropped up more than once on this blog with his various research into the more nutritional aspects to autism, or at least linked to some cases of autism. Indeed the current paper rounds off quite a research publication intensive year for him.
The study. Well it is the best kind of study (open-access) with results which are difficult to ignore or put down purely to methodological issues given the study design and participant group size. To summarise:
I have already made a few active links in the above summary to posts previously made on this blog in relation to the current findings. Without trying to repeat myself, the interesting things from my point of view were that glutathione and sulphate (sulfate) levels went up, homocysteine and methylmalonic acid levels went down; that and an overall 'normalisation' of various vitamin and mineral levels so important for lots of things including being co-factors for various enzymes. The accompanying behavioural changes also reported for supplemented participants reiterates the fact that participants physical health might just tie into behavioural presentation.
This is a big paper both in terms of content and results and also in terms of potential implications to autism. I know some people might look at the competing interests statement at the end of the paper and see that there are various connections between the supplement suppliers, testing companies and some of the authors. I have to say that this does not worry me so much knowing what it means to register a trial with the NIH and the requirement to publish your results whatever they show. That and the gold-standard trial design instills quite a bit of faith that the results are accurate, at least in the group examined. The next questions: finding out which people with autism might be 'best' responders to such a supplement and looking at the longer term profile of supplementation with regards to safety and outcome. A definite watch this space.
* Adams JB. et al. Effect of a vitamin/mineral supplement on children and adults with autism. BMC Pediatrics. December 2011.
So it was with a new study by Jim Adams and colleagues* looking at the effects of an individually titrated vitamin and mineral supplement for children and adults with autism spectrum conditions. Regular readers will know that Jim Adams has cropped up more than once on this blog with his various research into the more nutritional aspects to autism, or at least linked to some cases of autism. Indeed the current paper rounds off quite a research publication intensive year for him.
The study. Well it is the best kind of study (open-access) with results which are difficult to ignore or put down purely to methodological issues given the study design and participant group size. To summarise:
- The trial was registered with the NIH Clinical Trials directory (here). Recruited participants diagnosed with an autism spectrum condition formed either an Arizona or National group reflecting geographic status but also whether or not a series of medical exams looking at nutrition and metabolism were carried out. 72 participants split between the Arizona and National groups were allocated to a vitamin-mineral supplement group and compared with 69 participants receiving a placebo designed to look and taste the same as the active supplement.
- The supplement itself contained quite a bit including things like MSM. Most vitamins and minerals were within current RDA guidelines where data on the typical and upper-limit values were available. A few exceptions were things like vitamin D[3], biotin, chromium, iodine, molybdenum, manganese and zinc which were all at the upper ranges in terms of concentration.
- The study analysed data from baseline upto 12 weeks on supplement (or placebo) based on a variety of psychometric and biological parameters. The ATEC is mentioned (and its growing popularity). I've talked about the relative lack of good measures to analyse behavioural 'change' in autism before and it looks like the authors used more than one source schedule for their measurements to perhaps compensate for this void in the research literature.
- The findings. Well there are quite a few of them and it is slightly difficult to say what individual component did what, but here goes: (a) quite a few of the levels of vitamins, the 'b vitamins' in particular, were increased in the experimental group who underwent nutritional testing when assayed for in blood or urine, (b) a general 'normalisation' of minerals compared to control values was observed; most interesting that physiological levels of lithium (+485%) and calcium (+43%) went up alongside levels of iodine (+54%) and molybdenum (+48%), whereas iron levels seemed to drop (-9%), (c) levels of sulphate (total and free), that dusty compound under the bed compound, increased (+83% & +17% respectively) as did levels of glutathione (reduced) (+17%), (d) levels of ATP, NADH and coenzyme Q10 all increased, (e) levels of methylmalonic acid seemed to show improvement (-41%), and homocysteine levels also dropped (-34%), (f) behaviourally, positive effects were noted in areas of hyperactivity, number of tantrums, receptive language and play compared to the placebo.
- The attrition rates were slightly unexpected in that more participants dropped out of the placebo group (n=11) than the experimental group (n=8) even when comparing drop-outs due to adverse effects (n=5, n=3 respectively). Temporary adverse effects were also reported during the early days of getting the dosages right but these seemed to be short-lived for the majority of participants.
I have already made a few active links in the above summary to posts previously made on this blog in relation to the current findings. Without trying to repeat myself, the interesting things from my point of view were that glutathione and sulphate (sulfate) levels went up, homocysteine and methylmalonic acid levels went down; that and an overall 'normalisation' of various vitamin and mineral levels so important for lots of things including being co-factors for various enzymes. The accompanying behavioural changes also reported for supplemented participants reiterates the fact that participants physical health might just tie into behavioural presentation.
This is a big paper both in terms of content and results and also in terms of potential implications to autism. I know some people might look at the competing interests statement at the end of the paper and see that there are various connections between the supplement suppliers, testing companies and some of the authors. I have to say that this does not worry me so much knowing what it means to register a trial with the NIH and the requirement to publish your results whatever they show. That and the gold-standard trial design instills quite a bit of faith that the results are accurate, at least in the group examined. The next questions: finding out which people with autism might be 'best' responders to such a supplement and looking at the longer term profile of supplementation with regards to safety and outcome. A definite watch this space.
* Adams JB. et al. Effect of a vitamin/mineral supplement on children and adults with autism. BMC Pediatrics. December 2011.
Monday, 12 December 2011
Genes, SNPs, CNVs and autism
I open this post with a quote from a relatively new article:
"We show that as many as 2193 genes, 2806 SNPs/VNTRs, 4544 copy number variations (CNVs) and 158 linkage regions have been associated with ASD by GWAS, genome-wide CNV studies, linkage analyses, low-scale genetic association studies, expression profiling and other low-scale experimental studies".
The paper in question is this one (open-access) from Li-Ming Xu and colleagues*.
The first thing that struck me when I read this abstract is wow... autism is complicated. OK, nothing new in that statement and for those regular readers who quite often see me gently tugging at the loose threads of various genetic findings, I suppose summaries like this go to show that the concept of an 'autism gene' is pretty well past distant memory seemingly heading the same direction as Voyager 1. In fact reading through this quite complicated paper, perhaps too complicated for me, several things popped into my mind. Stop me if you heard these before:
Still today some people talk about an autism gene as if right on chromosome X [fill in the blank], findings are going to emerge to say that 100% of people with autism will show issues with gene X compared with 0% of the non-autism population (however you define this as) and that genetic tests for autism are only years away. The problem is that there is no evidence of this either happening now or going to happen any time soon. Indeed as with everything, the more you look at it, the more complicated technology you apply to it, the less you seem to know about it and the more questions start to be asked. Yes, our genes are a big part of us and control lots and lots and lots of different things. But they don't do it in isolation. Crikey, even our gut bacteria might be involved in some processes!
To end a song for Mrs Robinson.
* Li-Ming Xu. et al. AutismKB: an evidence-based knowledge base of autism genetics. Nucleic Acids Research. December 2011.
"We show that as many as 2193 genes, 2806 SNPs/VNTRs, 4544 copy number variations (CNVs) and 158 linkage regions have been associated with ASD by GWAS, genome-wide CNV studies, linkage analyses, low-scale genetic association studies, expression profiling and other low-scale experimental studies".
The paper in question is this one (open-access) from Li-Ming Xu and colleagues*.
The first thing that struck me when I read this abstract is wow... autism is complicated. OK, nothing new in that statement and for those regular readers who quite often see me gently tugging at the loose threads of various genetic findings, I suppose summaries like this go to show that the concept of an 'autism gene' is pretty well past distant memory seemingly heading the same direction as Voyager 1. In fact reading through this quite complicated paper, perhaps too complicated for me, several things popped into my mind. Stop me if you heard these before:
- If there was a prize for really knuckling down, collecting and collating data, Li-Ming Xu and colleagues might very well be in the running for it. I say this not only for their paper but also the database they developed on the genetic findings related to autism which is quite brilliant (here). If you have a few hours free (don't we all!), I would definitely recommend browsing the dataset which covers everything including population differences, gender differences and even how the diagnosis of autism was arrived at.
- Yep, lots of genetic findings related to lots of different autisms. When you see the the various studies all laid out and summarised like this, I tend to wonder what similar analyses might look like for other developmental conditions like ADHD, dyslexia, learning disability, etc. How about if researchers conducted genome wide analyses of a group of children randomly selected from your average town or city, how would they compare with these results? How much overlap would there be and how many genes might be associated with this random group? I would wager that there would be quite a bit of overlap in terms of the number of genes, SNPs, CNVs et al related to our random group simply because we are all the product of mutation.
- Heterogeneity is something most people with a connection to autism will know about. If you've met one person with autism, you've met one person with autism is a common saying. Further complicating that heterogeneity is the issue of comorbidity; so like everyone else, people with autism carry varying risks for other conditions. Whether these conditions are more or less likely to be related to some of the collected genetic findings... [fill in the blank].
- Given the wide range of genetic findings in "autism", is this perhaps a sign that the field of genetics needs to start (continue) diversifying; looking at sub-groups or phenotypes for example, a little more closely if it wishes to more ably describe autism or at least certain types of autism. There are already some signs of this happening as exemplified by the paper a few years back looking at paraoxonase gene SNPs in Italian vs. US cohorts.
- As per previous posts, there is a new sheriff coming to town with regards to genetics; epigenetics: changes to gene function not due to changes to DNA. "Hey Pilgrim, you forgot your pop-gun".
Still today some people talk about an autism gene as if right on chromosome X [fill in the blank], findings are going to emerge to say that 100% of people with autism will show issues with gene X compared with 0% of the non-autism population (however you define this as) and that genetic tests for autism are only years away. The problem is that there is no evidence of this either happening now or going to happen any time soon. Indeed as with everything, the more you look at it, the more complicated technology you apply to it, the less you seem to know about it and the more questions start to be asked. Yes, our genes are a big part of us and control lots and lots and lots of different things. But they don't do it in isolation. Crikey, even our gut bacteria might be involved in some processes!
To end a song for Mrs Robinson.
* Li-Ming Xu. et al. AutismKB: an evidence-based knowledge base of autism genetics. Nucleic Acids Research. December 2011.
Friday, 9 December 2011
MRI and (high-functioning) autism
I've nattered before about trends in autism research and how even across a relatively short period of time, the focus of autism research can change as interests and funding priorities change. The concept of an 'autism gene' for example seems like a increasingly distant memory as the heterogeneity of autism and its comorbidities combines with the complexity of the human genome to illustrate that one gene does not equal one condition but rather multiple genes work together over several processes and also show some connection to the environment of their 'user'. We are all a product of our genes and their mutations and we all carry our own individual genetic nuances.
Whilst genetic research into autism and lots of other conditions is still on-going, one of the other big areas of research focus currently is that of the application of imaging technologies to autism spectrum conditions. I assume most people have heard about MRI (Magnetic Resonance Imaging) and seen the pictures of those Star Trek body scanners and the spectacularly clear images they produce of our inner bodily workings. The application of MRI and its counterpart (functional) fMRI to conditions like autism where the brain is an important area of interest is seemingly growing by the day as evidenced by the large numbers of papers being published in this area. If you were to apply all these findings universally, you might well think that autism is absolutely, undoubtedly, 100% linked to structural issues in the brain. Heck, why don't we just diagnose autism by MRI?
Well, hold that thought for a moment.
An interesting paper was recently published by Vasa and colleagues* at the Kennedy Krieger Institute. The paper is open-access until 31st December 2011 (here). The main message from the study is that after reviewing the neuroradiological findings from quite a large proportion of children with autism (high-functioning autism) gathered over a 9 year period, about 90% of children showed no significant brain abnormality. That's right, you heard correctly, roughly 1 in 10 children with high-functioning autism had something picked up on their MRI, which was actually the same ratio for typically developing controls and slightly less than the figure for children with ADHD.
Assuming that you either did not want to or could not access the full-text of this paper, here is a summary:
The main strength of this study is that it includes data for quite a large group of children including control samples. Ages were matched but gender once again was more male-skewed in the autism group than the other groups which could potentially be a confounding variable. One should also bear in mind that this was a study looking at children towards the more able end of the autism spectrum so we can't generalise too much to those with a more severe presentation or with learning disability as a comorbidity. Bearing in mind that operational criteria were set for where and what to look for via MRI, there are some interesting points to take from this trial.
First, brain findings from MRI in relation to high-functioning autism don't yet appear to be particularly useful as objective diagnostic markers. That's not to say that they won't in future as the hardware and software get more complex and sensitive, but for now we wait. I was interested to see that focal white matter lesions came up given the link (and my obsession) between such features and coeliac (celiac) disease (CD) and other inflammatory bowel conditions; I wonder how many kids in this study were screened for potential 'dietary' issues particularly with the recent CD-ADHD paper in mind?
Second, much like the old one-gene hypothesis of autism, a picture seems to be emerging whereby no one brain area or MRI findings seems to be tied into the presentation of autism - all cases of autism. Yes, I take your point about the recent profrontal cortex study by Eric Courchesne and that deserves further work given that it was based on a very small participant sample. As far as I am aware however MRI scans cannot currently count neurons(?) so we are perhaps looking at different things in relation to brain findings in autism. Again with the biological phenotypes study fresh in my mind, it is not inconceivable that various brain areas might be involved in certain types of autism or at least contributory to certain presented features.
Finally, the brain is a pretty remarkable piece of kit. One of the best things about the brain is its adaptability; so when one part of it malfunctions for whatever reason, other parts of it are often able to take up the reins. Potential examples of this process are abound in the literature. What this might imply is that even though there may be structural issues detected, that does not necessarily translate into aberrant functioning. The recent remarkable comeback shown by Congresswoman Giffords is probably the best example of just how resilient the brain can be. Combined also with the fact that brain biochemistry might be an important feature to look at, we perhaps need to take a more holistic look at the brain with imaging technologies as part of the repertoire for autism research but not necessarily the sole agent of this important area of investigation.
To finish, a link to a band who just got a worthy entry into the Brit pop hall of fame.. Blur.
* Vasa RA. et al. Normal rates of neuroradiological findings in children with high functioning autism. JADD. November 2011.
Whilst genetic research into autism and lots of other conditions is still on-going, one of the other big areas of research focus currently is that of the application of imaging technologies to autism spectrum conditions. I assume most people have heard about MRI (Magnetic Resonance Imaging) and seen the pictures of those Star Trek body scanners and the spectacularly clear images they produce of our inner bodily workings. The application of MRI and its counterpart (functional) fMRI to conditions like autism where the brain is an important area of interest is seemingly growing by the day as evidenced by the large numbers of papers being published in this area. If you were to apply all these findings universally, you might well think that autism is absolutely, undoubtedly, 100% linked to structural issues in the brain. Heck, why don't we just diagnose autism by MRI?
Well, hold that thought for a moment.
An interesting paper was recently published by Vasa and colleagues* at the Kennedy Krieger Institute. The paper is open-access until 31st December 2011 (here). The main message from the study is that after reviewing the neuroradiological findings from quite a large proportion of children with autism (high-functioning autism) gathered over a 9 year period, about 90% of children showed no significant brain abnormality. That's right, you heard correctly, roughly 1 in 10 children with high-functioning autism had something picked up on their MRI, which was actually the same ratio for typically developing controls and slightly less than the figure for children with ADHD.
Assuming that you either did not want to or could not access the full-text of this paper, here is a summary:
- Structural data from MRI scans for children with autism (n=73) were compared with data from children with ADHD (n=107) and asymptomatic controls (n=144). When I say 'autism' these were children who were either diagnosed with high-functioning autism (32/73) or Asperger syndrome (41/73) and lumped together partly "because of on-going discussions that these two disorders may not exist as separate entities" (their words not mine). I should also add that quite a few comorbidities were also isolated in the autism group including ADHD(?), OCD and things like conduct disorder.
- I can't pretend to be able to give you the authoritative low-down on the MRI methods employed. My Mr Men reading suggests that scans were not necessarily done all on the same instrument but certain protocols on where to look were followed for each case. These included a set of 11 predefined lesion categories taken from the research literature alongside systematic ways to code for these lesions. Going back to the notion of physicians as artists, this also seemingly applies to neuroradiologists in terms of their coding of what may or may not be considered 'normal' and 'abnormal'. Consensus was reached on cases where the findings were a little bit fuzzy.
- Results: when looking at the sample groups as a whole, nearly 90% of participants either showed nothing at all in terms of 'abnormal' features or showed only normal variant findings. For the autism group, 11% showed one or more abnormal finding; for the ADHD group this was 12.1% and the control group, 11.1%. The most frequent finding for the autism group was in the category of focal white matter lesions (n=3, 4.1%). Having said that similar focal white matter lesions were found in 3 children with ADHD (2.8%) and 8 of the control group children (5.6%) also. As per the lack of statistical difference, the results in all areas seemed to be very similar across the groups.
The main strength of this study is that it includes data for quite a large group of children including control samples. Ages were matched but gender once again was more male-skewed in the autism group than the other groups which could potentially be a confounding variable. One should also bear in mind that this was a study looking at children towards the more able end of the autism spectrum so we can't generalise too much to those with a more severe presentation or with learning disability as a comorbidity. Bearing in mind that operational criteria were set for where and what to look for via MRI, there are some interesting points to take from this trial.
First, brain findings from MRI in relation to high-functioning autism don't yet appear to be particularly useful as objective diagnostic markers. That's not to say that they won't in future as the hardware and software get more complex and sensitive, but for now we wait. I was interested to see that focal white matter lesions came up given the link (and my obsession) between such features and coeliac (celiac) disease (CD) and other inflammatory bowel conditions; I wonder how many kids in this study were screened for potential 'dietary' issues particularly with the recent CD-ADHD paper in mind?
Second, much like the old one-gene hypothesis of autism, a picture seems to be emerging whereby no one brain area or MRI findings seems to be tied into the presentation of autism - all cases of autism. Yes, I take your point about the recent profrontal cortex study by Eric Courchesne and that deserves further work given that it was based on a very small participant sample. As far as I am aware however MRI scans cannot currently count neurons(?) so we are perhaps looking at different things in relation to brain findings in autism. Again with the biological phenotypes study fresh in my mind, it is not inconceivable that various brain areas might be involved in certain types of autism or at least contributory to certain presented features.
Finally, the brain is a pretty remarkable piece of kit. One of the best things about the brain is its adaptability; so when one part of it malfunctions for whatever reason, other parts of it are often able to take up the reins. Potential examples of this process are abound in the literature. What this might imply is that even though there may be structural issues detected, that does not necessarily translate into aberrant functioning. The recent remarkable comeback shown by Congresswoman Giffords is probably the best example of just how resilient the brain can be. Combined also with the fact that brain biochemistry might be an important feature to look at, we perhaps need to take a more holistic look at the brain with imaging technologies as part of the repertoire for autism research but not necessarily the sole agent of this important area of investigation.
To finish, a link to a band who just got a worthy entry into the Brit pop hall of fame.. Blur.
* Vasa RA. et al. Normal rates of neuroradiological findings in children with high functioning autism. JADD. November 2011.
Tuesday, 6 December 2011
Brain enlargement and regression in autism
I will warn you that I have blogged about this research before. By 'this research' I mean the latest paper from Christine Wu Nordahl and colleagues* from the MIND Institute and Harvard University. The paper suggested that brain enlargement, a feature mentioned more than once in autism research, might be tied into a specific type of autism characterised by symptom onset with regression of previously acquired skills. The blog post in question was on the presentation of possible biological phenotypes in autism; that is sub-groups of people with autism with shared, homogeneous biological findings. Homogeneous is not normally a word used in autism and even now I use it very sparingly.
OK lets take a step back. Regression associated with the onset of autistic symptoms is a topic previously covered on this blog. The summary of that post was that for a long time, the general idea was that regression (a loss in previously acquired skills) seemed not to be possible in cases of autism. This then changed to 'of course its possible' and the detailing of quite a few different kinds of regression including the concept of delays + regression. There is still some debate on how widespread regression is in autism and the best criteria to score regression (language, behaviour, adaptive skills, etc). Having said that with the rise of the digital age and the fact that most parents these days have a photographic and video archive of their child's growth and development from very early ages, the process is made slightly easier to examine.
Head size and growth have also been discussed in relation to autism. The general consensus being that larger heads and early accelerated brain growth shows more than a passing connection to cases of autism but with some interesting ethnic variables and certainly, by no means, an exclusive phenomenon to just autism.
So putting head size and regression together, Nordahl and colleagues present the results of a small, but quite important study which in my humble opinion charts the future course for autism research, looking at smaller sub-groups with shared commonalities. The paper itself is open-access but here is a brief summary:
Allowing for the relatively small participant numbers and the reliance on stock items from the ADI-R to denote regression or not, this is an interesting paper. If we add these findings to that of the recent neuron counting in the prefrontal cortex data allowing for difference in things like age, a very fuzzy picture starts to emerge of when and possibly where brain overgrowth might occur in some cases of autism.
More of this phenotype research please.
* Nordahl et al. Brain enlargement is associated with regression in preschool-age boys with autism spectrum disorders. PNAS. November 2011.
OK lets take a step back. Regression associated with the onset of autistic symptoms is a topic previously covered on this blog. The summary of that post was that for a long time, the general idea was that regression (a loss in previously acquired skills) seemed not to be possible in cases of autism. This then changed to 'of course its possible' and the detailing of quite a few different kinds of regression including the concept of delays + regression. There is still some debate on how widespread regression is in autism and the best criteria to score regression (language, behaviour, adaptive skills, etc). Having said that with the rise of the digital age and the fact that most parents these days have a photographic and video archive of their child's growth and development from very early ages, the process is made slightly easier to examine.
Head size and growth have also been discussed in relation to autism. The general consensus being that larger heads and early accelerated brain growth shows more than a passing connection to cases of autism but with some interesting ethnic variables and certainly, by no means, an exclusive phenomenon to just autism.
So putting head size and regression together, Nordahl and colleagues present the results of a small, but quite important study which in my humble opinion charts the future course for autism research, looking at smaller sub-groups with shared commonalities. The paper itself is open-access but here is a brief summary:
- Participants were enrolled as part of the Autism Phenome Project and included 114 children with autism. Controls (n=66) were matched for age and gender (well perhaps not so much for gender).
- Children with autism were divided into two groups: regression (n=61) and non-regression (n=53) with regards to their symptom onset history using the ADI-R. Before you say ADI-R...mmm, there was some other follow-up to determine the presence of regression or not.
- Imaging scans were conducted to ascertain total cerebral (brain) volume which was accompanied by inspection of infant records charting head circumference.
- Results suggested a few things: brain enlargement is not consistent across all cases of autism but perhaps showing slightly more connection to those cases where regression in onset was cited. Having said that brain enlargement seemed to be more of a boy than girl thing and there was a large amount of overlap between the autism and control groups. Head circumference measurements showed that head enlargement in cases of autism appeared to become more pronounced after about 4 months of age and between 6-13 months of age, there was some clear water in measurements comparing the autism-regression vs. the autism-non-regression and control groups. The regression group showing larger measurements.
Allowing for the relatively small participant numbers and the reliance on stock items from the ADI-R to denote regression or not, this is an interesting paper. If we add these findings to that of the recent neuron counting in the prefrontal cortex data allowing for difference in things like age, a very fuzzy picture starts to emerge of when and possibly where brain overgrowth might occur in some cases of autism.
More of this phenotype research please.
* Nordahl et al. Brain enlargement is associated with regression in preschool-age boys with autism spectrum disorders. PNAS. November 2011.
Saturday, 3 December 2011
Interconnectedness: depression and heart disease
Today's topic is slightly off the beaten track when it comes to autism research but some of the themes coming out of the research in question may link back to a few issues discussed previously.
Whilst a term often used as a catch-all for lots of different signs and symptoms, there are a few things to say about depression. First and foremost, depression is a real condition. We all feel down from time to time as a result of lots of different things; work, money, family, football team being relegated, etc. but depression represents something more persistent, all-encompassing and can appear alongside other symptoms. Second, depression appears for many different reasons and is linked to lots of different circumstances. Most people would probably have heard of post-natal depression or the baby blues thought to be tied into the hormonal and chemical changes which occur to new mums after their new arrival has 'left the building'. One example, but there are others. Finally it is pretty well known that depression puts a person at greater risk of developing quite a few different ailments.
Shah and colleagues* recently reported on depression and a history of suicide attempts as being risk factors for cardiovascular disease (CHD) and ischemic heart disease (IHD). Analysing data from over 7500 people, aged 17-39, following up after 15 years as part of the Third National Health and Nutrition Examination Survey and correcting for various lifestyle variables such as smoking and poor diet, the authors reported an increased risk of death associated with CHD and IHD where depression / suicide attempts were historically present. The risk was particularly marked in women; a history of suicide attempts being associated with a 14-fold adjusted risk for IHD. I might add that this is not the first time that an association between depression and heart health outcomes has been reported.
The authors suggested that these findings might be evidence for a physiological effect from depression; so lower heart rate variability, increased stress hormones or inflammation. Indeed on the topic of inflammation, other evidence and commentators have reported some interesting effects relating to depression and inflammatory markers which might tie in. My recent post on the inflammatory consequences of caring might also link to some effect also.
Cumulatively what the research in this area seems to be pointing to is that our psychological health and wellbeing might not only be linked to physiological health but also might be an important driver of risk for quite a few somatic health complaints. Trauma, such as abuse, might also produce a similar effect. There may very well be more peripheral routes from depression to physiological health problems. Without trying to sound like a stuck record, I wonder about the whole gut bacteria angle as potentially being involved also; realising that 'inter-connectedness' is a word that really should be used a lot more with regards to psychology-physiology and health-disease.
* Shah AJ. et al. Depression and history of attempted suicide as risk factors for heart disease mortality in young individuals. Archives of General Psychiatry. 2011: 68: 1135-1142.
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| First tulips @ Paul Whiteley 2011 |
Shah and colleagues* recently reported on depression and a history of suicide attempts as being risk factors for cardiovascular disease (CHD) and ischemic heart disease (IHD). Analysing data from over 7500 people, aged 17-39, following up after 15 years as part of the Third National Health and Nutrition Examination Survey and correcting for various lifestyle variables such as smoking and poor diet, the authors reported an increased risk of death associated with CHD and IHD where depression / suicide attempts were historically present. The risk was particularly marked in women; a history of suicide attempts being associated with a 14-fold adjusted risk for IHD. I might add that this is not the first time that an association between depression and heart health outcomes has been reported.
The authors suggested that these findings might be evidence for a physiological effect from depression; so lower heart rate variability, increased stress hormones or inflammation. Indeed on the topic of inflammation, other evidence and commentators have reported some interesting effects relating to depression and inflammatory markers which might tie in. My recent post on the inflammatory consequences of caring might also link to some effect also.
Cumulatively what the research in this area seems to be pointing to is that our psychological health and wellbeing might not only be linked to physiological health but also might be an important driver of risk for quite a few somatic health complaints. Trauma, such as abuse, might also produce a similar effect. There may very well be more peripheral routes from depression to physiological health problems. Without trying to sound like a stuck record, I wonder about the whole gut bacteria angle as potentially being involved also; realising that 'inter-connectedness' is a word that really should be used a lot more with regards to psychology-physiology and health-disease.
* Shah AJ. et al. Depression and history of attempted suicide as risk factors for heart disease mortality in young individuals. Archives of General Psychiatry. 2011: 68: 1135-1142.
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