Monday, 30 November 2015

Health service use, autism and preventative medicine

Appreciating that the title of this post potentially offers the opportunity to write a long (very long) post, today I'm specifically focusing on two papers. The first by Janet Cummings and colleagues [1] discussing health service use "among youth with and without an autism spectrum disorder (ASD)" concluded that yes, young people with autism were more likely to experience health service use than not-autism control populations. Importantly however, was the suggestion that this group were "less likely to receive important preventive services including flu shots and other vaccinations."

The second paper to bring into discussions is that from Paul Carbone and colleagues [2] who examined "the prevalence of hospitalizations for ambulatory care sensitive conditions (ACSC) in children with and without autism spectrum disorder (ASD)." ACSC in case you did not click on the highlighted link, refers to chronic conditions "for which it is possible to prevent acute exacerbations and reduce the need for hospital admission through active management, such as vaccination; better self-management, disease management or case management; or lifestyle interventions."

Based on data derived from a '2009 Kids' Inpatient Database' researchers concluded that hospitalisations for ACSC were quite a bit more frequent than for those with either other chronic conditions outside of autism or those without any chronic conditions at all. Indeed compared with that 'no chronic conditions at all' group, those with autism were more likely to be admitted for a variety of issues including "a mental health condition, epilepsy, constipation, pneumonia, dehydration, vaccine-preventable diseases, underweight, and nutritional deficiencies."

Without over-analysing the results of these collected investigations, the primary issues presented seem to be: (a) that people diagnosed on the autism spectrum are more likely to use healthcare services than non-autism controls, and (b) although many of the 'ailments' for which treatment is sought have been previously recognised in the research and clinical literature, the idea of preventative medicine, and the potential benefits that it can bring, is still to some degree missing when looking at the wider picture of health and wellbeing with autism in mind.

Preventative medicine casts a wide net in terms of what is covered. Having previously discussed important lifestyle issues such as diet and exercise when it comes to the autism spectrum on this blog (see here and see here for example) I've been particularly interested in how science can offer some solutions for issues such as getting people more physically active or recognising the value of a balanced diet (and where certain dietary extremes can eventually lead). Discussions about bowel issues in relation to autism have also been ramped up in recent years as science cottons on to what many people have been saying: functional and pathological bowel issues are over-represented when it comes to a diagnosis on the autism spectrum (see here).

The associated findings that rates of "vaccine-preventable diseases" may be increased in some of the analysed cohorts with autism and/or that immunisation as part of a strategy of preventative medicine might be diminished are worrying trends. I know this area still attracts some discussion alongside more general debates about vaccines for example [3] but as part of the arsenal of initiatives to improve public and 'personal' health, one might see such findings as part of a wider issue with health inequality when it comes to autism. Indeed, if one looks to the future and the idea that autism is not generally a life-limiting condition (at least not for many), one wonders what the long-term future holds for older adults with autism in light of the potential seriousness of something like influenza for older populations (see here) for example?

Music to close and Axis of Awesome talk number 1 hits...


[1] Cummings JR. et al. Health Services Utilization Among Children With and Without Autism Spectrum Disorders. J Autism Dev Disord. 2015 Nov 7.

[2] Carbone PS. et al. A Comparison of Ambulatory Care Sensitive Hospitalizations Among Children With and Without Autism Spectrum Disorder. Acad Pediatr. 2015 Nov-Dec;15(6):626-635.

[3] Suryadevara M. et al. Pediatric provider vaccine hesitancy: An under-recognized obstacle to immunizing children. Vaccine. 2015 Oct 31. pii: S0264-410X(15)01552-2.

---------- Cummings JR, Lynch FL, Rust KC, Coleman KJ, Madden JM, Owen-Smith AA, Yau VM, Qian Y, Pearson KA, Crawford PM, Massolo ML, Quinn VP, & Croen LA (2015). Health Services Utilization Among Children With and Without Autism Spectrum Disorders. Journal of autism and developmental disorders PMID: 26547921 Carbone PS, Young PC, Stoddard GJ, Wilkes J, & Trasande L (2015). A Comparison of Ambulatory Care Sensitive Hospitalizations Among Children With and Without Autism Spectrum Disorder. Academic pediatrics, 15 (6), 626-635 PMID: 26547543

Saturday, 28 November 2015

Acetylcysteine and autism: another case report

I don't want to spend too long on the findings reported by Danielle Stutzman & Julie Dopheide [1] talking about how: "Treatment with acetylcysteine improved ASD [autism spectrum disorder] symptoms, including irritability and aggression, in a teenage patient" but it is a blog-worthy paper.

Describing the experiences of a "7-year-old Hispanic male with ASD and intellectual disability" who was hospitalised due to some rather 'challenging behaviours', the authors noted how the addition of acetylcysteine (often called N-acetlycysteine or NAC for short) seemed to have some pretty interesting positive effects on this young boy's behaviour. Not least also that the use of NAC "was well tolerated, with no observed or reported adverse effects." The authors go on to speculate that within the context of other reports on the use of NAC either alone or as an adjunct medicine, there may be quite a bit more to see with autism in mind, as well as providing some important information about relevant biological pathways in relation to specific 'types' of autism.

I've talked about NAC and autism before on this blog, both within the context of group studies (see here) and under more individual 'N=1' conditions (see here) including with the word 'adjunct' in mind (see here). Within the context of issues that seem to come under the heading of 'challenging behaviours' (bearing in mind the variety of factors that such a description covers) there does appear to be some promising stories coming out of the use of NAC which might have all the be more importance given the lack of good therapeutic interventions for such behaviours.

I'm not at this point going to speculate too much about exactly how and why NAC seems to 'help' when it comes to some challenging behaviours for some people on the autism spectrum. I will suggest that set within the context of studies on glutathione and some autism (see here) there may be some further research to do. That, and not being afraid to look at NAC in relation to something like schizophrenia (see here), and I dare say that there could be surprises for NAC in relation to some autism in future times...

Music to close, and in amongst some recent discussions about 'Where are all the climate change songs?' a gem from The Pixies about a monkey...


[1] Stutzman D. & Dopheide J. Acetylcysteine for treatment of autism spectrum disorder symptoms. Am J Health Syst Pharm. 2015 Nov 15;72(22):1956-9.

---------- Stutzman D, & Dopheide J (2015). Acetylcysteine for treatment of autism spectrum disorder symptoms. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 72 (22), 1956-9 PMID: 26541950

Friday, 27 November 2015

Premature mortality and autism continued

"Premature mortality was markedly increased in ASD [autism spectrum disorder] owing to a multitude of medical conditions."

So said the study by Tatja Hirvikoski and colleagues [1] and findings that although making uncomfortable reading, highlight how we have some way to go when it comes to addressing important health inequalities as and when a label of autism or ASD is given.

Drawing on Swedish data including over 27,000 people diagnosed with an ASD between 1987 and 2009 compared against population information for some 2.6 million "gender-, age- and county of residence-matched controls", researchers examined the frequency of all-cause and cause-specific mortality rates across the groups. During their observation period some 0.9% of controls died compared with 2.6% of those on the autism spectrum. As per the opening sentence, this difference was described as "markedly increased" by the authors. Other important details are also provided as per the idea that gender and "general intellectual ability" might be moderating factors when it comes to the mortality patterns described with autism in mind.

Realising that behind every statistic is a person and a family and a wider social group, I was not surprised by the Hirvikoski findings. Increased rates of early mortality when discussed in the context of autism have been talked about before on this blog (see here). In that previous case it was the findings reported by Deborah Bilder and colleagues [2] as the headline paper and their results based on data from the 1980s Utah/UCLA autism epidemiologic study. Then, as this time, "the presence of comorbid medical conditions and intellectual disability" played their part.

There is an obvious need for continued need for research in this important area. Preferential screening is also perhaps implied based on the known over-representation of conditions like epilepsy or seizures disorder(s) when it comes to autism (see here) and onwards the potential for states such as SUDEP. Indeed, recognising that a diagnosis of autism may place someone at elevated risk of various medical comorbidity (see here) really needs to be talked about a lot more as per what seems to be happening when it comes to schizophrenia (see here) in the context of health inequalities leading to early mortality.

Just before I go, I'd also like to refer you back to a post I wrote previously talking about 'issues' with screening and diagnosing certain medical comorbidity (see here) with autism in mind and how attending physicians might need to show a little medical creativity to ensure that diagnosis is both timely and accurate...


[1] Hirvikoski T. et al. Premature mortality in autism spectrum disorder. Br J Psychiatry. 2015 Nov 5.

[2] Bilder D. et al. Excess mortality and causes of death in autism spectrum disorders: a follow up of the 1980s Utah/UCLA autism epidemiologic study. J Autism Dev Disord. 2013 May;43(5):1196-204.

---------- Hirvikoski T, Mittendorfer-Rutz E, Boman M, Larsson H, Lichtenstein P, & Bölte S (2015). Premature mortality in autism spectrum disorder. The British journal of psychiatry : the journal of mental science PMID: 26541693

Thursday, 26 November 2015

The continued rise of autism research metabolomics

For anyone that has followed this blog down the years you'll probably have noticed that I'm quite a big fan of the inclusion of the science of metabolomics on to the autism research menu (see here for example).

Looking at the myriad of chemical footprints left behind by an almost incomprehensible number of cellular processes, metabolomics offers some real promise to autism in terms of teasing apart phenotypes and as a valuable partner to other -omics sciences in ascertaining the relevance or not of specific biological pathways. All of this set within the context of the plural autisms and the important role of comorbidity (see here).

It is therefore with metabolomics again in mind that I bring to your attention the paper by Binta Dieme and colleagues [1] who weren't joking when they talk about a "multiplatform analytical methodology" with autism in mind. That multiplatform approach included "1H- and 1 H-13C-NMR-based approaches and LC-HRMS-based approaches (ESI+ and ESI- on a HILIC and C18 chromatography column)." If all that sounds like gibberish, the watchwords are NMR - Nuclear magnetic resonance spectroscopy - and LC-HRMS - Liquid chromatography–high resolution mass spectrometry - two of the gold-standard analytical techniques for detecting and identifying compounds of interest in this realm of biology. Some of the other details such as HILIC columns are all to do with how one goes about separating out the individual components of a complicated biological medium like urine as well as some further details about what the authors did to detect them. I might add that this authorship group have some previous form in this area of the autism research landscape (see here).

Based on the analysis of urine samples initially from 22 children with autism and 24 not-autism controls (a training group), researchers talked about the results they obtained from the various metabolomic approaches employed including processing of results by OPLS-DA (orthogonal partial least squares discriminant analysis). I don't want to bore you with the ins-and-outs of what OPLS-DA means (yeah, as if I know!) but suffice to say its all about how one classifies the multitude of data one generates via such analytical methods. This data and analyses were then used to generate a set of compounds (pattern of compounds) potentially predictive of whether or not it could classify a urine sample from someone with autism from a urine sample from someone without autism. Samples from a separate group of participants - "8 autistic children and 8 controls" - were used to 'test' the predictions generated. The authors report that the OPLS-DA model generated "showed an enhanced performance... compared to each analytical modality model, as well as a better predictive capacity (AUC=0.91, p-value 0.006)." AUC by the way, refers to area under the curve and is a term associated with a ROC (receiver operating characteristic). In this respect, the Dieme paper seemed to do pretty well at classifying samples according to autism or not-autism status bearing in mind the relatively small participant group numbers.

Just in case you're not confused enough, there are a few other details about the Dieme paper and findings that are worthy of comment. So: "Metabolites that are most significantly different between autistic and control children (p<0.05) are indoxyl sulfate, N-〈-Acetyl-L-arginine, methyl guanidine and phenylacetylglutamine." Indoxyl sulfate is a particularly interesting compound for quite a few reasons. Not only is the source material for this compound one of the those oh-so-interesting aromatic amino acids, tryptophan (y'know serotonin, melatonin and all that jazz) but the compound itself is described as a uremic toxin [2]. Without wishing to make connections where none may exist, uremic compounds in relation to autism have been discussed before on this blog as per the Elaine Hsiao findings on bacteria and leaky gut in a mouse model of autism (see here) and some chatter about p-cresol and autism (see here and see here). If there is an overlapping factor potentially uniting these findings, it would have to be a possible role for those trillions of wee beasties that call our gut home - the gut microbiome. I might also briefly mention the arginine finding too in relation to a related tryptophan observation for some autism... BH4 (see here).

As I mentioned at the start of this post I am a fan of this area of research area and its potential for furthering knowledge about autism. Larger datasets and perhaps a focus outside of just zooming in on the label of autism are perhaps elements that are needed to aid investigations in this area, alongside a more general combinatorial -omic initiative with a systems biology slant (see here).

Music and I've played this before but here it is again... Weapon Of Choice by Fatboy Slim (a favourite video of my brood).


[1] Dieme B. et al. Metabolomics study of urine in autism spectrum disorders using a multiplatform analytical methodology. J Proteome Res. 2015 Nov 5.

[2] Vanholder R. et al. The uremic toxicity of indoxyl sulfate and p-cresyl sulfate: a systematic review. J Am Soc Nephrol. 2014 Sep;25(9):1897-907.

---------- Dieme B, Mavel S, Blasco H, Tripi G, Bonnet-Brilhault F, Malvy J, Bocca C, Andres CR, Nadal-Desbarats L, & Emond P (2015). Metabolomics study of urine in autism spectrum disorders using a multiplatform analytical methodology. Journal of proteome research PMID: 26538324

Wednesday, 25 November 2015

The Autism-Spectrum Quotient (AQ) and the media: a few thoughts

"Are you on the autistic spectrum? Take the test" read a recent media headline.

Commenting on the findings reported by Emily Ruzich and colleagues [1], the headline is followed by some pretty bizarre text about how the study "has confirmed that men are more likely to be autistic than women."

I have to take some exception to this sentence, as I quote from the Ruzich findings: "In a sample of nearly half a million individuals, we found a moderate effect of sex on AQ [Autism-Spectrum Quotient], with males scoring higher than females by an average of 2.5 points." As per other discussions about the Ruzich research (see here) scores on the AQ reflect the presentation of autistic traits not the likelihood of 'being diagnosed autistic'. That and the fact that their findings were geared towards the idea that sex/gender and occupational path might be correlated with AQ scores and I'm not entirely sure that accuracy is at the forefront of that particular headline and media article.

Stepping back a little, some people might know that the AQ represents something of a potential 'screening' instrument when it comes to autism and Asperger syndrome (AS) [2]. I have emphasised the word 'screening' because screening is something quite independent from 'assessment' when it comes to autism and the often detailed investigation(s) needed to arrive at an accurate diagnosis of something like autism or an autism spectrum disorder (ASD). If you want a little more information about how assessment for autism might run here in the UK, take a look at the NICE guidance on the topic specifically with adults in mind (see here), paying particular attention to the sentence: "Comprehensive (diagnostic, needs and risks) assessment of suspected autism."

I've been interested in the AQ for a while on this blog and the large, and growing, peer-reviewed evidence base that has utilised the instrument (see here). Appreciating the strengths of the AQ, I am still a little wary about what is being measured by the AQ especially when one considers research such as that from Lugnegård and colleagues [3] (discussed in this post) and the idea that: "significant overlap of AQ scores... reduces the discriminating power of the AQ in the separation of schizophrenia from AS." In other words, with the requirement for further study, does a high score on the AQ denote something like Asperger syndrome or could it be also picking up people who might be more readily considered to be on the schizophrenia spectrum (to coin a phrase) bearing in mind how said spectrums might be colliding?

Hopefully without coming across as having a 'bee in my bonnet' I was similarly taken to comment on the findings reported by Heather Westwood and colleagues [4] (open-access) and their systematic review and meta-analysis of the available peer-reviewed literature when it came to AQ in cases of the eating disorder, anorexia nervosa (AN). As per previous research (see here), there is something of a growing recognition that some of the signs and symptoms of autism might also cross over into AN following a trend in looking at autistic traits crossing diagnostic labels (see here and see here). Westwood et al surveyed the literature and reported that those with AN may indeed present with: "significant difficulties with social skills, communication and flexibility that present in a manner characteristic of autistic traits." Importantly, and bearing in mind their acknowledgement of the Lugnegård findings, they conclude however that: "the results do not allow for conclusions to be drawn regarding whether a proportion of those with AN also have an underlying ASD [autism spectrum disorder]" as a function of the sole reliance on the AQ among other factors.

I appreciate that in these days of pop psychology and the increased use of 'Dr Google' people want to find out as much as they can about themselves and their behaviour and/or health. I'm no exception to that trend in some of my googling habits either. Media headlines however about how simple screening instruments can 'tell' if someone is on the autism spectrum can seriously undervalue what it means to be on the autism spectrum and to have a clinical label of autism, with all the strengths and struggles that includes. Of course there is cross-over when it comes to the presentation of autistic traits in the general population and the blurred boundaries that distinguish between clinically relevant (as in clinically affecting a person's life) and something a little less life-changing. I do think however that we all need to be a little more cautious using the term autism or autistic spectrum, save any charges of diluting its impact...

Music: Muppets and giant crumpets? "Mad for it!"


[1] Ruzich E. et al. Sex and STEM Occupation Predict Autism-Spectrum Quotient (AQ) Scores in Half a Million People. PLoS One. 2015 Oct 21;10(10):e0141229.

[2] Baron-Cohen S. et al. The autism-spectrum quotient (AQ): evidence from Asperger syndrome/high-functioning autism, males and females, scientists and mathematicians. J Autism Dev Disord. 2001 Feb;31(1):5-17.

[3] Lugnegård T. et al. Asperger syndrome and schizophrenia: Overlap of self-reported autistic traits using the Autism-spectrum Quotient (AQ). Nord J Psychiatry. 2015 May;69(4):268-74.

[4] Westwood H. et al. Using the Autism-Spectrum Quotient to Measure Autistic Traits in Anorexia Nervosa: A Systematic Review and Meta-Analysis. Journal of Autism and Developmental Disorders. 2015; Nov 5.

---------- Westwood, H., Eisler, I., Mandy, W., Leppanen, J., Treasure, J., & Tchanturia, K. (2015). Using the Autism-Spectrum Quotient to Measure Autistic Traits in Anorexia Nervosa: A Systematic Review and Meta-Analysis Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-015-2641-0

Tuesday, 24 November 2015

Secondary conditions impacting on obesity stats in autism?

"Decision makers, clinicians, and researchers developing interventions for children with ASDs [autism spectrum disorders] should consider how secondary conditions may impact obesity and related activities."

That was the conclusion reached in the study by Kathryn Corvey and colleagues [1] looking to: "examine obesity, overweight, physical activity, and sedentary behavior among children and youth with and without ASD using nationally representative data and controlling for secondary conditions, including intellectual and learning disabilities, ADHD, developmental delay, and other mental, physical, and medical conditions, as well as medication use."

Detailing results based on information gathered from the 2011-2012 National Survey of Children's Health whereby households of some 65,000 children between the ages of 6 and 17 years were quizzed about various physical and emotional health related matters, researchers specifically focused on some 1300 children with a reported diagnosis of ASD. Various confounding variables including those 'secondary conditions' were taken into account in their quite detailed analyses.

Results: following a trend noted in other peer-reviewed research (see here), the authors reported that a diagnosis of ASD was associated with elevated odds of being obese. But... when it came to adjusting their analyses for the presence of some of those secondary conditions "ASD diagnosis was no longer associated with obesity."

This is interesting stuff. In line with some of the shifts in thinking about autism these days - including plurality, comorbidity clusters and the idea of differing developmental trajectories - the Corvey results imply that more care is needed before making sweeping generalisations about how 'all' autism is linked to obesity or related issues. This comes at a time when other research has talked about the timing of weight issues when it comes to autism [2]. Allied to previous research more generally looking at obesity in learning disability [3] the message is becoming a little clearer that a variety of factors 'around' autism might be the important risk issues for something like obesity or being overweight including various social factors linked to physical activity levels too (see here).

Quite recently I've also become rather interested in the peer-reviewed research related to ADHD (attention-deficit hyperactivity disorder) and obesity (see here) and some of the clues emerging there that are potentially relevant to some autism. Allied to what is known about the 'anthropometric' effects of certain types of medication used by some on the autism spectrum (see here), and it appears that risk of obesity and being overweight in relation to autism is at last getting the 'no sweeping generalisations needed' handling that it truly deserves.

Music: Pick A Part That's New - Stereophonics.


[1] Corvey K. et al. Obesity, Physical Activity and Sedentary Behaviors in Children with an Autism Spectrum Disorder. Matern Child Health J. 2015 Oct 29.

[2] Hill AP. et al. Obesity and Autism. Pediatrics. 2015. Nov 2.

[3] de Winter CF. et al. Overweight and obesity in older people with intellectual disability. Res Dev Disabil. 2012 Mar-Apr;33(2):398-405.

---------- Corvey K, Menear KS, Preskitt J, Goldfarb S, & Menachemi N (2015). Obesity, Physical Activity and Sedentary Behaviors in Children with an Autism Spectrum Disorder. Maternal and child health journal PMID: 26515467

Monday, 23 November 2015

Does eczema increase the risk of childhood speech disorder?

Nativity Kylo?
The question posed in the title of this post reflects some interesting data published by Mark Strom & Jonathan Silverberg [1] who reported that: "Pediatric eczema may be associated with increased risk of speech disorder" on the basis of their analysis of data for some 350,000 children "from 19 US [United States] population-based cohorts."

Taking into account various variables such as "sociodemographics and comorbid allergic disease" authors determined that among the 19 cohorts, the majority (12) showed some kind of connection between eczema and elevated odds of speech disorder. Further, when pooled together, the prevalence of speech disorder among those children with eczema was 4.7% compared with a figure of 2.2% for those children without eczema.

One other detail to impart from the Strom/Silverberg study was how eczema plus other labels was also linked to risk of speech disorder as per the sentence: "children with both eczema and attention deficit disorder with or without hyperactivity or sleep disturbance had vastly increased risk of speech disorders than either by itself."

Allowing for the fact that correlation is not necessarily the same as causation and that as the authors admit: "Further, prospective studies are needed to characterize the exact nature of this association" these are interesting data strengthened by the large number of participants included for study. A quick trawl of the research literature in this area suggests that childhood speech disorders may very well be associated with additional health problems [2] although not necessarily just rooted in something like eczema.

The possibility that a physical ailment like eczema might have implications for a developmental condition like childhood speech disorder is a tantalising one. I've covered the preliminary idea of a 'skin-brain axis' before on this blog (see here) on the basis of data like that reported by Yaghmaie and colleagues [3] talking about atopic dermatitis and various developmental/psychiatric labels. More generally, allergic disease in infancy has been linked to various neurodevelopmental outcomes (see here) with again, the requirement for quite a bit more investigation of this possible association. Indeed, even the 'big data' of Taiwan has something to say on this topic (see here).

As to any mechanism, well, outside of the suggestion of shared genetic risk between something like eczema and speech (and language) issues, the idea that the immune function (a cardinal mechanism of eczema) might play a much greater role in our health and wellbeing than merely the somatic is becoming more mainstream in these days of immune system and psychiatry intersecting (see here). The more general idea that immune features such as inflammation might be able to 'interact' with psychology is a whole new frontier of medicine (see here) and one that should be incorporated into any future research strategy. The other potentially important question outside of any aetiological association is whether or not early treatment of eczema including attending to some of the possible triggers [3] might also have important implications for the risk of developing speech disorders?

Music: Blur - Trimm Trabb.


[1] Strom MA. & Silverberg JI. Eczema Is Associated with Childhood Speech Disorder: A Retrospective Analysis from the National Survey of Children's Health and the National Health Interview Survey. J Pediatr. 2015 Oct 28. pii: S0022-3476(15)01140-3.

[2] Keating D. et al. Childhood speech disorders: reported prevalence, comorbidity and socioeconomic profile. J Paediatr Child Health. 2001 Oct;37(5):431-6.

[3] Yaghmaie P. et al. Mental health comorbidity in patients with atopic dermatitis. J Allergy Clin Immunol. 2013 Feb;131(2):428-33.

---------- Strom MA, & Silverberg JI (2015). Eczema Is Associated with Childhood Speech Disorder: A Retrospective Analysis from the National Survey of Children's Health and the National Health Interview Survey. The Journal of pediatrics PMID: 26520915