I'm wandering a little outside of my area of primary interest with this post on possible dietary correlates attached to the risk of psychosis. I therefore tread carefully and hopefully succinctly with this post based on two independent pieces of research recently published by Gracious and colleagues* (full-text) and Karlsson and colleagues**.
Perhaps best to start with a very brief description of what psychosis is and isn't. Psychosis is more of a symptom rather than a stand-alone condition involving a loss of contact with reality where a person is described as not being able to distinguish between what is real and what is imagination. Symptoms include hallucinations, delusions, confused and disturbed thoughts and a lack of insight and self-awareness. I say not a condition in its own right but there had been some discussion in the preparations for DSM-5 to include a new category called 'attenuated psychosis syndrome' which seems to have been dropped from the latest manifestiation. I should also point out that psychosis does not mean psychopath or anything similar.
The causes of psychosis are still the source of some speculation but generally speaking, three main areas have been put forward as reasons for psychosis including: (i) psychotic episodes linked to an underlying mental health conditions such as schizophrenia or bipolar disorder, (ii) episodes linked to more somatic health conditions such as hypoglycemia (low blood sugar) or dementia, and (iii) episodes following the taking of various drugs of abuse or in rare cases, more 'mainstream' pharmacotherapy. These areas are not exhaustive as per the suggestions about stress and social adversity also being risk factors.
The paper by Gracious and colleagues* suggested that vitamin D deficiency and insufficiency seemed to be quite a common occurrence in cases of adolescents presenting with mental health problems, and was particularly marked where psychosis was a feature of the expression of those problems. Their data also suggested that ethnicity and vitamin D levels seemed to be important factors. Similar data based on the examination of adult psychosis has suggested a related connection to the sunshine vitamin and indeed a potential 'protective' effect from adequate vitamin D intake. Takes me back to the whole vitamin D-autism debate acknowledging that autism is not psychosis and psychosis is not autism.
The paper by Karlsson and colleagues** was slightly different insofar as reporting on a possible connection between maternal circulating levels of IgG anti-gliadin antibodies and the presence of non-affective psychosis in offspring. To some degree this work ties into the wheat and schizophrenia link posited by people like the late Curt Dohan and followed up in the recent paper by Emily Severence and colleagues on food antigens and gastrointestinal inflammation in cases of schizophrenia. I'm also reminded of the very interesting work being done by Drs Marios Hadjivassiliou and David Sanders from right here in Blighty on the extra-intestinal manifestations of issues with gluten (see here and here).
Both the Gracious and Karlsson papers caught my eye given that both suggest an association between dietary components and mental health. Before you ask, yes, these were studies of association and let's face it, associations are abound in lots of areas nowadays so some caution needs to be applied. One could also argue that vitamin D whilst partially dietary-derived has a strong link with sunlight exposure and you would of course be right. Having said that don't underestimate how important dietary vitamin D might be especially in places where sunlight, the right kind of sunlight, is not necessarily always at a premium.
Diet potentially mediating behavioural symptom presentation - now where have we heard that before? Accepting that any link between food and mental health is likely to be complicated and influenced by lots of other factors, there are several potentially important points to make from these and other studies not least on how gut biology may very well have an influence on brain and behaviour with diet as an important factor. One does also wonder whether before reaching for the 'treatment' of these symptoms, medical science perhaps needs to have a more detailed look at how we might be able to influence the 'onset' of such symptoms via adequate dietary and nutritional means. Food for the body, food for the mind? (bearing in mind my caveats about not giving medical advice).
To finish, UK viewers might be tuning into The Voice on the BBC. I like Jesse J and will.i.am but lets face it, Sir Tom (Jones) is the main event when it comes to a voice (sorry guys). So here he is with The Stereophonics (he looks much better with grey hair).
* Gracious BL. et al. Vitamin D deficiency and psychotic features in mentally ill adolescents: A cross-sectional study. BMC Psychiatry. May 2012.
DOI: 10.1186/1471-244X-12-38
** Karlsson H. et al. Maternal antibodies to dietary antigens and risk for nonaffective psychosis in offspring. American Journal of Psychiatry. April 2012.
DOI: 10.1176/appi.ajp.2012.11081197
Thursday, 10 May 2012
Tuesday, 8 May 2012
Carnitine & autism: genes, biochemistry & intervention ideas
Carnitine. Mention of carnitine has graced this blog before with regards to how a deficiency in carnitine might show some relationship with some cases of autism spectrum conditions and the knock-on effects with regards to areas such as mitochondrial dysfunction. The whole relationship between carnitine and autism is still very much a work in progress but the data so far opens up some interesting avenues.
A recent study by Celestino-Soper and colleagues* (full-text) continues the interest in carnitine and autism with the suggestion that issues with a gene, trimethyllysine hydroxylase, epsilon (TMLHE) involved in the biosynthesis of carnitine, might be associated with some cases of autism.
I was drawn to this paper on several levels, not least further evidence that amino acid chemistry might show some involvement to cases of autism and the authors' suggestion of another in-born error of metabolism to be added to a growing list in general medicine. The authorship content of the current paper is a veritable who's who in autism genetic research (here and here for example) bearing in mind some overlap with the recent Nature de novo papers.
The paper is full-text but here are a few highlights:
As per just about every genetics paper that I have ever attempted to read, this is quite a complex story to follow if you are not a molecular biologist or at least with some detailed interest in the ways and means of genetics research. It's not quite the dark art of EEG reading, but pretty close.
The authors make some interesting remarks in the manuscript discussion relating to their findings.
First, they talk about the disparity in their results when it came to simplex and mulitplex family findings. Without making too sweeping a generalisation, the argument goes something like this: having more than one child with autism in the family is more likely to represent a stronger genetic component to aetiology as being involved than those cases of a simplex child, bearing in mind the snapshot and 'what if' scenarios of future offspring attached to looking at simplex families. I can see the logic in this argument about single and multiple instances, and how, when it comes to the eternal question of genes vs. environment as per Trading Places and the $1 bet, the heterogeneity of autism might, to some degree become more homogeneous if autism research were to start looking at simplex vs. multiplex autism rather than bundling it all together.
Second, the authors talk about whether or not the 'risk' of autism could potentially be modified by dietary carnitine intake from birth in the early years, perhaps even prenatally and during gestation when it comes to mum's diet. With some degree of caution, I find myself interested in this suggestion, particularly with all the recent interest in epigenetics and how issues like maternal diet might have the propensity to modify offspring risk for lots of different conditions not just autism. I know epigenetic modification is not a large part of the current study but still, genetics is an awfully complicated business where genes being switched on or off by means other than mutation or deletion might be pertinent.
Finally, this is probably not the last we are going to hear about this area of research by this group. Two studies are being initiated we are told, one looking at carnitine metabolites in cerebrospinal fluid (CFS) of infants with autism with or without TMLHE deficiency; a second following on from other research by Geier and colleagues** on the supplementation of L-carnitine or γBB for cases of autism again with and without TMLHE deficiency. A case of watch this space.
Regular readers to this blog will perhaps know that the genetics of autism are becoming more and more complicated as more research emerges. The concept of an 'autism gene' is becoming an ever more distant memory as a result of the cumulative findings and a realisation that autism is an extremely nebulous condition. What I do like about the current paper is that not only does it detail results based on genetic findings, but more than that, it goes through how those findings relate to biochemistry (expression of the gene) and, in this case, the possibility that there may be ways to 'rescue' some of that biological functioning. I also wonder if through epigenetic means, issues with carnitine biosynthesis might also be present in cases of autism without the underlying genetic structural issues and what those all-important modifying variables might be. All that and the need to screen cases for those ever-so important in-born errors of metabolism, I'll be keeping a look out for further results from this group.
To finish something a little less mind-boggling but nevertheless with some bite: The Clash (the law won y'know and don't they keep telling us).
* Celestino-Soper PBS. et al. A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism. PNAS. May 2012.
DOI: 10.1073/pnas.1120210109
** Geier DA. et al. A prospective double-blind, randomized clinical trial of levocarnitine to treat autism spectrum disorders. Medical Science Monitor. 2011; 17: 15-23
A recent study by Celestino-Soper and colleagues* (full-text) continues the interest in carnitine and autism with the suggestion that issues with a gene, trimethyllysine hydroxylase, epsilon (TMLHE) involved in the biosynthesis of carnitine, might be associated with some cases of autism.
I was drawn to this paper on several levels, not least further evidence that amino acid chemistry might show some involvement to cases of autism and the authors' suggestion of another in-born error of metabolism to be added to a growing list in general medicine. The authorship content of the current paper is a veritable who's who in autism genetic research (here and here for example) bearing in mind some overlap with the recent Nature de novo papers.
The paper is full-text but here are a few highlights:
- Based on previous findings of potential issues with TMLHE in cases of autism (here), the frequency of mutations in TMLHE was analysed in cases of autism and controls. Various sources were used to acquire participants including the Simons Simplex Collection (SSC) and the Autism Genetic Resource Exchange (AGRE) covering both simplex (one child in the family with autism) and multiplex families (more than one child diagnosed with autism).
- Deletions of exon 2 seemed to be relatively common in both autism and control groups. So of the control male participants examined, roughly 1 in 366 showed deletions of exon 2. Looking at simplex participants in the autism group, the rate was 1 in 323 presenting with a deletion. When it came to looking at multiplex families, the rate of deletions in the autism group became stronger, estimated at 1 in 130.
- Based on this cumulative data, the authors write "The frequency of TMLHE deficiency is startling" suggesting that this in-born error of metabolism is relatively common, approximately 20 times more frequent than phenylketonuria (PKU) in males.
- When it came to looking at the functional biological effects of exon 2 deletions, based on the activity of 6-N-trimethyllysine dioxygenase (TMLD), enzyme activity was low or undetectable for those carrying the deletion.
- Urinary and plasma analysis for related metabolites, 6-N-trimethyllysine (TML) 3-hydroxy-6-N-trimethyllysine (HTML) and 4-N-trimethylaminobutyric acid [γ-butyrobetaine (γBB)] suggested alterations in the levels detected according to the presence of TMLHE exon 2 deletions. Some of these metabolites were even suggested to have 'diagnostic potential' for TMLHE deficiency.
- Cognitive function did not seem to determine TMLHE deletions, varying widely among those with deletions.
- The authors conclude that TMLHE deficiency is likely to be a risk factor for autism although with low genetic penetrance.
As per just about every genetics paper that I have ever attempted to read, this is quite a complex story to follow if you are not a molecular biologist or at least with some detailed interest in the ways and means of genetics research. It's not quite the dark art of EEG reading, but pretty close.
The authors make some interesting remarks in the manuscript discussion relating to their findings.
First, they talk about the disparity in their results when it came to simplex and mulitplex family findings. Without making too sweeping a generalisation, the argument goes something like this: having more than one child with autism in the family is more likely to represent a stronger genetic component to aetiology as being involved than those cases of a simplex child, bearing in mind the snapshot and 'what if' scenarios of future offspring attached to looking at simplex families. I can see the logic in this argument about single and multiple instances, and how, when it comes to the eternal question of genes vs. environment as per Trading Places and the $1 bet, the heterogeneity of autism might, to some degree become more homogeneous if autism research were to start looking at simplex vs. multiplex autism rather than bundling it all together.
Second, the authors talk about whether or not the 'risk' of autism could potentially be modified by dietary carnitine intake from birth in the early years, perhaps even prenatally and during gestation when it comes to mum's diet. With some degree of caution, I find myself interested in this suggestion, particularly with all the recent interest in epigenetics and how issues like maternal diet might have the propensity to modify offspring risk for lots of different conditions not just autism. I know epigenetic modification is not a large part of the current study but still, genetics is an awfully complicated business where genes being switched on or off by means other than mutation or deletion might be pertinent.
Finally, this is probably not the last we are going to hear about this area of research by this group. Two studies are being initiated we are told, one looking at carnitine metabolites in cerebrospinal fluid (CFS) of infants with autism with or without TMLHE deficiency; a second following on from other research by Geier and colleagues** on the supplementation of L-carnitine or γBB for cases of autism again with and without TMLHE deficiency. A case of watch this space.
Regular readers to this blog will perhaps know that the genetics of autism are becoming more and more complicated as more research emerges. The concept of an 'autism gene' is becoming an ever more distant memory as a result of the cumulative findings and a realisation that autism is an extremely nebulous condition. What I do like about the current paper is that not only does it detail results based on genetic findings, but more than that, it goes through how those findings relate to biochemistry (expression of the gene) and, in this case, the possibility that there may be ways to 'rescue' some of that biological functioning. I also wonder if through epigenetic means, issues with carnitine biosynthesis might also be present in cases of autism without the underlying genetic structural issues and what those all-important modifying variables might be. All that and the need to screen cases for those ever-so important in-born errors of metabolism, I'll be keeping a look out for further results from this group.
To finish something a little less mind-boggling but nevertheless with some bite: The Clash (the law won y'know and don't they keep telling us).
* Celestino-Soper PBS. et al. A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism. PNAS. May 2012.
DOI: 10.1073/pnas.1120210109
** Geier DA. et al. A prospective double-blind, randomized clinical trial of levocarnitine to treat autism spectrum disorders. Medical Science Monitor. 2011; 17: 15-23
Monday, 7 May 2012
Urinary phthalate metabolites and autism
I don't know if it is just me but investigations on the potential role of certain environmental factors in relation to at least some cases of autism spectrum conditions seem to be coming in thick and fast recently. I speak for example about the paper suggesting a role for high-fructose corn syrup (HFCS) and other factors; alongside other interesting papers published at the same time as the 'top 10 environmental factors' editorial discussed recently.
Appreciating that there are some gaps in the whole environmental area of investigation with regards to cause-and-effect, mixed in with the question of what might do what and to who, there is some interesting reading in amongst the various studies. This includes discussions around the concept of 'risk' and how autism research seems to be (partially) reinventing itself into a slightly more complicated hypothesis where environment and genes (variably) might play a role in aetiology rather than just genes, genes, genes. I get to say that word again.. 'epigenetics'.
Add then this paper by Testa and colleagues* (full-text) to the list of environmental question marks which was very quietly published recently looking at a possible connection between phthalate excretion and autism.
Phthalates (assuming I have spelled the word correctly) according to the US EPA, are a class of compounds called plasticisers as a result of their ability to make things more 'plastic' in terms of properties such as flexibility and durability. Whilst moves are underway to remove / limit phthalates in the industrial chain, their use is pretty widespread in products as diverse as cosmetics to food packaging, flooring to detergents.
As mentioned, there are moves to reduce the use of phthalates in the production of certain types of product as a result of growing evidence associating their exposure and unwelcome effects such as their endocrine disrupting potential. Just before you start looking around at what products you are surrounded by which might contain phthalates, the answer is probably quite a few; and in terms of exposure to these compounds, generally speaking we all have some of them circulating (or at least traces of them as per the analysis of biofluids like urine). Modern man and woman it seems are probably not going to grace the Visitors table as per an older post.
To the Testa paper:
As far as I can see, the authors are correct in their statement that this is the first time that phthalates have been directly looked for in the biological fluids of people with autism compared to controls. The research literature contains a couple of more speculative papers looking for example at in-door environment and autism (with accompanying reporting here) or reviewing the very limited available evidence on lots of endocrine disrupting compounds in relation to autism but not much else. There is other work in areas such as ADHD for example, again suggesting the possibility of some connection between reported ADHD symptoms and urinary phthalate content. Even executive functions get a look-in with regards to prenatal exposure. But that's your lot.
Where to go from here?
Well, we have to be slightly cautious in making too many assumptions from this current data. Yes, children with autism were better excretors of phthalates and yes, better to the degree that certain metabolites might even serve some identifying feature in comparison to control samples. But, and it is quite a large but(!), this paper does not provide a cause-and-effect role for phthalates in cases of autism. So for example, only urine was looked at and only individual spot samples at that. I could be a little bit pedantic and start asking whether circulating plasma levels of phthalates were any different or asking about levels in other tissues?
The authors did undertake some routine correlational analysis between phthalate metabolite levels and things like CARS scores, finding a positive association between MEHP and CARS scores such that increasing levels of one was correlated to increasing levels of the other. I do find this 'severity' relationship to be interesting although I perhaps would have liked to have seen confirmatory analysis from other tools including the ADOS.
Despite my queries about the results, what this study does offer is another potential target area to include when looking at environmental pollutants and any relationship to autism - add it to the list. Without wishing to seem like I'm too obsessed, I do wonder also about a gut bacterial connection as per other data, very preliminary data, on pesticides and bacteria. Sideways thinking is always advised.
To finish, a spot of New Order. Indeed since I am reminiscing about the Manchester scene, how about some Stone Roses too.
* Testa C. et al. Di(2-ethylhexyl)phthalate and autism spectrum disorders. ASN Neuro. April 2012.
DOI: 10.1042/AN20120015
Appreciating that there are some gaps in the whole environmental area of investigation with regards to cause-and-effect, mixed in with the question of what might do what and to who, there is some interesting reading in amongst the various studies. This includes discussions around the concept of 'risk' and how autism research seems to be (partially) reinventing itself into a slightly more complicated hypothesis where environment and genes (variably) might play a role in aetiology rather than just genes, genes, genes. I get to say that word again.. 'epigenetics'.
Add then this paper by Testa and colleagues* (full-text) to the list of environmental question marks which was very quietly published recently looking at a possible connection between phthalate excretion and autism.
Phthalates (assuming I have spelled the word correctly) according to the US EPA, are a class of compounds called plasticisers as a result of their ability to make things more 'plastic' in terms of properties such as flexibility and durability. Whilst moves are underway to remove / limit phthalates in the industrial chain, their use is pretty widespread in products as diverse as cosmetics to food packaging, flooring to detergents.
As mentioned, there are moves to reduce the use of phthalates in the production of certain types of product as a result of growing evidence associating their exposure and unwelcome effects such as their endocrine disrupting potential. Just before you start looking around at what products you are surrounded by which might contain phthalates, the answer is probably quite a few; and in terms of exposure to these compounds, generally speaking we all have some of them circulating (or at least traces of them as per the analysis of biofluids like urine). Modern man and woman it seems are probably not going to grace the Visitors table as per an older post.
To the Testa paper:
- Based on the assumption that phthalates might be able to affect aspects of child development (particularly boys), the authors looked at urinary levels of primary and secondary metabolites of di(2-ethylhexyl)phthalate (DEHP) in a small-ish group of Italian children with autism (n=48) compared with an asymptomatic age- and gender-matched group (n=45). I say gender-matched but the authors use the word 'sex comparable' given that the autism group seemed to have a greater ratio of boys than the control group.
- The autism group were all DSM-IV diagnosed with autism and importantly all had ADOS and/or other data as some kind of confirmation of autism.
- First morning, spot urine samples were analysed by a favourite method, mass spectrometry, tandem mass spectrometry, preceded by quite a complicated extraction procedure based on the use of solid-phase extraction (SPE) to clean the sample up. I'm not going to go through the total list of metabolites they looked at but rather pick out the results that were significantly different.
- Results: levels of secondary metabolites, 5-OH-MEHP, 5-oxo-MEHP and MEHP were significantly increased in the autism group as a whole compared with controls. That being said, these metabolites were not detected in every sample from children in the autism group (52% & 46% & 79% respectively) bearing in mind the sensitivity of the assay used and lower limits of detection reported. Further comparison with a separate group of people diagnosed with Rett syndrome (RS) (n=10) - no age range described - suggested that the autism group excreted more secondary metabolites of DEHP (MEHP) than RS participants.
- One secondary metabolite, 5-oxo-MEHP, was suggested to show over 90% specificity when it came to identifying participants with autism.
As far as I can see, the authors are correct in their statement that this is the first time that phthalates have been directly looked for in the biological fluids of people with autism compared to controls. The research literature contains a couple of more speculative papers looking for example at in-door environment and autism (with accompanying reporting here) or reviewing the very limited available evidence on lots of endocrine disrupting compounds in relation to autism but not much else. There is other work in areas such as ADHD for example, again suggesting the possibility of some connection between reported ADHD symptoms and urinary phthalate content. Even executive functions get a look-in with regards to prenatal exposure. But that's your lot.
Where to go from here?
Well, we have to be slightly cautious in making too many assumptions from this current data. Yes, children with autism were better excretors of phthalates and yes, better to the degree that certain metabolites might even serve some identifying feature in comparison to control samples. But, and it is quite a large but(!), this paper does not provide a cause-and-effect role for phthalates in cases of autism. So for example, only urine was looked at and only individual spot samples at that. I could be a little bit pedantic and start asking whether circulating plasma levels of phthalates were any different or asking about levels in other tissues?
The authors did undertake some routine correlational analysis between phthalate metabolite levels and things like CARS scores, finding a positive association between MEHP and CARS scores such that increasing levels of one was correlated to increasing levels of the other. I do find this 'severity' relationship to be interesting although I perhaps would have liked to have seen confirmatory analysis from other tools including the ADOS.
Despite my queries about the results, what this study does offer is another potential target area to include when looking at environmental pollutants and any relationship to autism - add it to the list. Without wishing to seem like I'm too obsessed, I do wonder also about a gut bacterial connection as per other data, very preliminary data, on pesticides and bacteria. Sideways thinking is always advised.
To finish, a spot of New Order. Indeed since I am reminiscing about the Manchester scene, how about some Stone Roses too.
* Testa C. et al. Di(2-ethylhexyl)phthalate and autism spectrum disorders. ASN Neuro. April 2012.
DOI: 10.1042/AN20120015
Friday, 4 May 2012
When poo tells a story (and I'm not talking about Winnie)
 |
| If you sprinkle while you tinkle, be a sweetie and wipe the seatie. |
When was the last time you watched a film and saw any of the protagonists pop into the toilet for a 'number two'? Seriously now. Did James Bond ever stop to think about the yummy Brussels sprout curry he ate last night washed down with a vodka martini or two? Come to think about it, does anyone know where the toilets were on the Millenium Falcon, to the sound of Han Solo telling everyone to 'give it about 10 minutes' to air? (May the 4th be with you by the way).
I know it is a bit gross to think about poo, stools, kaka, whatever you want to call it. But move past the sight, smell and visualising of people, well-known people, sat on the 'throne' and think a little about how our poo might actually be able to tell quite a bit about us. While that thought remains, have a look at this paper by Wang and colleagues* (full-text) on the analysis of fecal bacteria from children with autism.
I am discussing this paper for several reasons: the growing interest in gut bacteria and autism, the potential link with gut barrier dysfunction - the so-called 'leaky gut' - and the Australian research group who conducted this study who are fast becoming part of the Premier League of autism research to match the MIND Institute and the very impressive Saudi researchers.
The details of the Wang study:
- Similar to their study on short chain fatty acids and ammonia, the participant group comprised 23 children with an autism spectrum condition, 22 siblings and 9 asymptomatic controls.
- A number of fecal - poo - specimens were collected from each participant over 48 hours, bagged, tagged and shipped out for PCR analysis of various types of target bacteria.
- Results: well, there were quite a few interesting results such as a lower relative abundance of Bifidobacterium spp. in samples from children with autism compared to controls. A similar finding was also reported for Akkermansia muciniphila, a bacterium that I have never come across before but as the authors note, is a mucin degrading bacterium and seemingly quite abundant in samples from other groups.
- The lower concentrations of A. muciniphila were potentially indicative of a thinner gastrointestinal mucus barrier and onwards to impaired gut permeability aka the leaky gut.
The findings whilst unique so far in autism research do seem to mirror, to some degree, other areas of research such as this paper on weight gain during pregnancy. I'm not exactly sure how and why women who gain excessive weight during pregnancy and children with autism might be biologically and microbiologically similar, unless one assumes that there might be a link from mum's bacteria to child's bacteria (see this full-text paper by a very interestingly named person called Fåk and colleagues**) and dare I mention that other recent study which received so much attention. That and the possibility of ethnic differences as a function of factors such as breastfeeding (or not) complicate matters somewhat. I'm not really qualified enough to go any further into these areas.
If one however does assume that gut bacteria is involved in some cases of autism in whatever way, shape or form, all those 'wacky suggestions' about things like probiotics and bacterial transplantations might turn out to be not so daft after all (even the stool transplant science is gaining research ground!). No medical advice intended.
To finish and to erase all those harrowing mental images of toilets and poo, something altogether different from Sparks and Good morning. Indeed, good morning if you are reading this in the morning.
* Wang L. et al. Low relative abundances of the mucolytic bacterium Akkermansia muciniphila and Bifidobacterium spp. in feces of children with autism. Applied & Environmental Microbiology. 2011; 77: 6718-6721
DOI: 10.1128/AEM.05212-11
** Fåk F et al. Microbial manipulation of the rat dam changes bacterial colonization and alters properties of the gut in her offspring. American Journal of Physiology: Gastrointestinal & Liver Physiology. 2008; 294: G148-G154.
DOI: 10.1152/ajpgi.00023.2007
Wednesday, 2 May 2012
'You know what boys are like' and the autism pre-diagnostic experience
"Slugs and snails, And puppy dog tails" is apparently a good description of the young male. Slightly less appealing in comparison to "Sugar and spice, And all things nice" for young ladies.
I'm not necessarily one for sweeping generalisations about gender, particularly on the back of interesting discussions like this one as part of the Cordelia Fine vs. Simon Baron-Cohen academic MTV Celebrity Deathmatch. That being said, there are some generalities about development between the sexes which seem to crop up time and time again.
So it was with this paper by Ryan & Salisbury* and their research piece titled: 'You know what boys are like': pre-diagnosis experiences of parents of children with autism spectrum conditions. I was drawn to comment on this paper for quite a few reasons outside of just the quote in the title. This was a qualitative paper looking at the pre-diagnosis experiences of 24 UK parents of children who were subsequently diagnosed with an autism spectrum condition. The aim was to look at how contact with primary care health professionals such as general practitioners, GPs, might be improved for parents and their children.
The results are interesting bearing in mind the small participant group:
A few things struck me about this latest research.
Whilst this was a qualitative study, something which the BJGP seem to publish quite a lot of, this is a fascinating insight into the whole medical / lay relationship when it comes to child development and expressions of parental concern. As any child development expert / parent will tell you, kids don't generally develop in a single, standardised, uniform way precisely as per the various developmental milestone books, but rather with lots of stopping and starting of new and existing skills. Although reluctant to use the word 'bloomers' in this context, some children seem to do everything really quickly, others can be content to just let the world and its skills come to them. Such is the heterogeneity of child development.
The active concern group and the reports of premature reassurance highlighted in this paper are however a point of real concern. There is an old adage in medicine circles: when in doubt, examine the patient. I'd like to think that now at least here in the UK, with the guidance from NICE on pathways to diagnosis (see here for full document), and the realisation that parental opinions can be a very accurate source of information about their child (remember this study on bowel symptoms and autism?), less premature reassurance and more focus on testing assumptions will be forthcoming. Not least because of how, when such situations occur, they can cloud what will be a fairly vital relationship between patient (or patients parents) and physician once a diagnosis is given.
Probably the most important thing revealed in this latest research is the continued state of 'not-knowing' when it comes to autism onset and the sole reliance on observation and developmental history for the screening and assessment of autism. It's been mentioned more than once on this blog, how despite various screening instruments, there is (a) currently no objective measure of autism, and (b) the time taken from developmental concern to getting a diagnosis is often quite a long period of time. Obviously a degree of 'wait and see' is to be expected given the very important requirements to make diagnoses as accurate as possible, taking other differential diagnoses and comorbidities into consideration and reducing the possibility of 'false-positive' results, particularly with the emergence of research suggesting that autism might not necessarily be as 'fixed' as was originally thought (here).
But all that needs to be balanced against things like the growing body of evidence on the impact of early intervention in cases of autism.
To finish, for any persons with the surname 'Shufflebottom', you might be interested to read that Shufflebottoms are not necessarily any more likely to bottom shufflers as toddlers. Please file under 'eh?'
* Ryan S. & Salisbury H. 'You know what boys are like': pre-diagnosis experiences of parents of children with autism spectrum conditions. British Journal of General Practice. 2012; 62: 378-383
I'm not necessarily one for sweeping generalisations about gender, particularly on the back of interesting discussions like this one as part of the Cordelia Fine vs. Simon Baron-Cohen academic MTV Celebrity Deathmatch. That being said, there are some generalities about development between the sexes which seem to crop up time and time again.
So it was with this paper by Ryan & Salisbury* and their research piece titled: 'You know what boys are like': pre-diagnosis experiences of parents of children with autism spectrum conditions. I was drawn to comment on this paper for quite a few reasons outside of just the quote in the title. This was a qualitative paper looking at the pre-diagnosis experiences of 24 UK parents of children who were subsequently diagnosed with an autism spectrum condition. The aim was to look at how contact with primary care health professionals such as general practitioners, GPs, might be improved for parents and their children.
The results are interesting bearing in mind the small participant group:
- Three groups of parents emerged from the semi-structured interviews undertaken: (i) parents who noted no issues with their child's development before a diagnosis was suggested and received, (ii) parents who had seen something a little bit different in their children but nothing that warranted communication with health care professionals (labelled 'passive concern') and (iii) parents who saw something in their child's development and spoke up about it (labelled 'active concern').
- Where parents showed passive concern, one of the primary reasons for not raising the issue with their GP or related medical type, was the inability to put their finger on precisely what was 'not right' with their child's development.
- Where parents showed active concern which led them to expressing some opinion to a healthcare professional, a degree of being 'fobbed off' (they call it 'prematurely reassured') seems to have been evident among at least some health care professionals; hence the title "you know what boys are like".
- The final sentence of the abstract is also an interesting one: "Parents may be the best resource in identifying ASC".
A few things struck me about this latest research.
Whilst this was a qualitative study, something which the BJGP seem to publish quite a lot of, this is a fascinating insight into the whole medical / lay relationship when it comes to child development and expressions of parental concern. As any child development expert / parent will tell you, kids don't generally develop in a single, standardised, uniform way precisely as per the various developmental milestone books, but rather with lots of stopping and starting of new and existing skills. Although reluctant to use the word 'bloomers' in this context, some children seem to do everything really quickly, others can be content to just let the world and its skills come to them. Such is the heterogeneity of child development.
The active concern group and the reports of premature reassurance highlighted in this paper are however a point of real concern. There is an old adage in medicine circles: when in doubt, examine the patient. I'd like to think that now at least here in the UK, with the guidance from NICE on pathways to diagnosis (see here for full document), and the realisation that parental opinions can be a very accurate source of information about their child (remember this study on bowel symptoms and autism?), less premature reassurance and more focus on testing assumptions will be forthcoming. Not least because of how, when such situations occur, they can cloud what will be a fairly vital relationship between patient (or patients parents) and physician once a diagnosis is given.
Probably the most important thing revealed in this latest research is the continued state of 'not-knowing' when it comes to autism onset and the sole reliance on observation and developmental history for the screening and assessment of autism. It's been mentioned more than once on this blog, how despite various screening instruments, there is (a) currently no objective measure of autism, and (b) the time taken from developmental concern to getting a diagnosis is often quite a long period of time. Obviously a degree of 'wait and see' is to be expected given the very important requirements to make diagnoses as accurate as possible, taking other differential diagnoses and comorbidities into consideration and reducing the possibility of 'false-positive' results, particularly with the emergence of research suggesting that autism might not necessarily be as 'fixed' as was originally thought (here).
But all that needs to be balanced against things like the growing body of evidence on the impact of early intervention in cases of autism.
To finish, for any persons with the surname 'Shufflebottom', you might be interested to read that Shufflebottoms are not necessarily any more likely to bottom shufflers as toddlers. Please file under 'eh?'
* Ryan S. & Salisbury H. 'You know what boys are like': pre-diagnosis experiences of parents of children with autism spectrum conditions. British Journal of General Practice. 2012; 62: 378-383
Tuesday, 1 May 2012
Autism and saliva
This is a little bit of an unusual post in that I want to discuss some of the collected data looking at a bit of a forgotten biological fluid, saliva, specifically with autism spectrum conditions in mind. The idea for doing this post stemmed in part from a quite recent paper by Soukup and colleagues* (full-text) which suggested that monitoring salivary uric acid might be a good idea in terms of cardiometabolic risk. Exactly how this finding itself might translate to some work on purines and autism linked to uric acid is food for thought.
Whilst pretty essential for lots of things, saliva or spit is not exactly dinner table conversation so I promise to try and keep this scientific. I hasten to add that I am not covering things like the excessive production of saliva (and onward things like drooling) or anything like that, accepting that such issues have been reported primarily as a side-effect to certain medications.
Certain areas on the autism research landscape have examined saliva as a functional biofluid. So looking at levels of cortisol in saliva is a bit of a favourite, as is some interest in salivary testosterone levels. A very recent paper by Rai and colleagues suggested that salivary antioxidant levels in autism were significantly reduced compared to asymptomatic controls which might tie in with some other findings on important markers of antioxidant health. Molecular biologists out there will already know about the value of buccal (cheek) samples as a way of collecting DNA but cheek cells are slightly different from plain old saliva.
Whilst pretty essential for lots of things, saliva or spit is not exactly dinner table conversation so I promise to try and keep this scientific. I hasten to add that I am not covering things like the excessive production of saliva (and onward things like drooling) or anything like that, accepting that such issues have been reported primarily as a side-effect to certain medications.
Certain areas on the autism research landscape have examined saliva as a functional biofluid. So looking at levels of cortisol in saliva is a bit of a favourite, as is some interest in salivary testosterone levels. A very recent paper by Rai and colleagues suggested that salivary antioxidant levels in autism were significantly reduced compared to asymptomatic controls which might tie in with some other findings on important markers of antioxidant health. Molecular biologists out there will already know about the value of buccal (cheek) samples as a way of collecting DNA but cheek cells are slightly different from plain old saliva.
The study I want to focus on is this one from Castagnola and colleagues** published in 2008. They reported results for a group of children diagnosed with an autism spectrum condition (n=27) compared to controls (n=23) based on a chemical analysis of naturally occurring salivary peptides. With my metabolomics hat on, this kind of study makes so much sense. Here you have a biofluid which most people produce in pretty copious amounts (during waking hours), easily available and relatively non-invasive to capture which contrasts against other research on blood as an analyte medium for example. The technology nowadays is such that you can get a lot of information from a spit sample.
Evidence suggests that little if any difference is present in the basic salivary parameters between people with autism and asymptomatic controls. The results produced by Castagnola, based on mass spectrometric analysis, suggested that hypo-phosphorylation (reduced) of certain salivary peptides was more common in the samples from children with autism compared to controls. Phosphorylation means the addition of a phosphate group to a molecule which can have various effects on a compound and its actions. The authors speculated that such hypo-phosphorylation might be a marker for other issues with phosphorylation in other tissues, using Rett syndrome as an example. Interestingly, they also draw a comparison with some of their other work on phosphorylation in preterm and term babies, suggesting that delayed peptide phosphorylation in the early days ".. may cause asynchrony or timing deregulation in some process involved in neuronal maturation, development or differentiation resulting in ASD phenotype". A few ideas there to digest possibly.
I'd like to think that as the technology gets more sensitive, analysis of saliva might be a growth area for at least some parameters related to autism currently only measurable via invasive collection of blood and plasma. Let's face it children in particular don't like having blood drawn, and children with autism are no exception to that rule. I note that studies have already reported in the area of vitamin D - measuring salivary 25-hydroxyvitamin D(3), for example; vitamin D having cropped up more than once in relation to autism. One wonders how many more biological parameters might also be measurable from a humble sample of spit.
To finish, how about a red hot chilli pepper to get us all salivating?
Evidence suggests that little if any difference is present in the basic salivary parameters between people with autism and asymptomatic controls. The results produced by Castagnola, based on mass spectrometric analysis, suggested that hypo-phosphorylation (reduced) of certain salivary peptides was more common in the samples from children with autism compared to controls. Phosphorylation means the addition of a phosphate group to a molecule which can have various effects on a compound and its actions. The authors speculated that such hypo-phosphorylation might be a marker for other issues with phosphorylation in other tissues, using Rett syndrome as an example. Interestingly, they also draw a comparison with some of their other work on phosphorylation in preterm and term babies, suggesting that delayed peptide phosphorylation in the early days ".. may cause asynchrony or timing deregulation in some process involved in neuronal maturation, development or differentiation resulting in ASD phenotype". A few ideas there to digest possibly.
I'd like to think that as the technology gets more sensitive, analysis of saliva might be a growth area for at least some parameters related to autism currently only measurable via invasive collection of blood and plasma. Let's face it children in particular don't like having blood drawn, and children with autism are no exception to that rule. I note that studies have already reported in the area of vitamin D - measuring salivary 25-hydroxyvitamin D(3), for example; vitamin D having cropped up more than once in relation to autism. One wonders how many more biological parameters might also be measurable from a humble sample of spit.
To finish, how about a red hot chilli pepper to get us all salivating?
* Soukup M. et al. Salivary uric acid as a noninvasive biomarker of metabolic syndrome. Diabetology & Metabolic Syndrome. April 2012.
DOI: 10.1186/1758-5996-4-14
DOI: 10.1186/1758-5996-4-14
** Castagnola M. et al. Hypo-phosphorylation of salivary peptidome as a clue to the molecular pathogenesis of autism spectrum disorders. Journal of Proteome Research. 2008; 7: 5237-5232.
Subscribe to:
Posts (Atom)