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...

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[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.

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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

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...

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[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.

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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

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...

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[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.

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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

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).

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[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.

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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

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!"

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[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.

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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

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.

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[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.

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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

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.

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[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.

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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

Subthreshold autism signs in childhood OCD

OCD in the title of this post, refers to obsessive compulsive disorder and the intriguing observation put forward by Arildskov and colleagues [1] suggesting that: "Pediatric OCD patients were found to exhibit elevated rates of ASD [autism spectrum disorder] symptoms compared to a norm group of school-age children."

Taking advantage of data collected as part of the Nordic Long-term OCD Treatment Study and specifically where "parents of 257 children and adolescents with OCD aged 7-17 completed the Autism Spectrum Screening Questionnaire", researchers looked at the possible manifestations of autism traits in their participant group. As per the opening paragraph, there was potentially more to see in this area. The authors added: "ASD symptoms were concentrated in a subgroup with a prevalence of 10-17 %" and further: "This subgroup was characterized by a male preponderance."

Bearing in mind the authors' use of the term 'subclinical' when it came to the description of autism traits in their OCD group, this is interesting research. Quite a few moons ago I took to writing about OCD and autism on this blog (see here) and the question of whether overlap between OCD and autism is just that or rather the two labels should be seen as more discrete conditions. I don't think I actually arrived at a specific answer in that previous post; just that papers such as the one from Francisca van Steensel and colleagues [2] reporting that ~17% of their cohort with autism met criteria for OCD mean that clinicians should be aware of the possibility of a connection.

Alongside other research suggesting that autistic traits are probably over-represented in quite a few clinical labels (see here for example) there are some important lessons that can be perhaps learned from such work. Invoking the paradigm of ESSENCE (see here) and specifically that the signs and symptoms of autism rarely appear in some sort of diagnostic vacuum (even clusters) I'd be minded to suggest that when it comes to assessments for autism for example, inclusion of various other screening instruments pertinent to other diagnoses might be something to consider...

Music: Gomez - 78 Stone Wobble.

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[1] Arildskov TW. et al. Subclinical autism spectrum symptoms in pediatric obsessive-compulsive disorder. Eur Child Adolesc Psychiatry. 2015 Oct 30.

[2] Van Steensel FJA. et al. Anxiety Disorders in Children and Adolescents with Autistic Spectrum Disorders: A Meta-Analysis. Clinical Child and Family Psychology Review. 2011;14(3):302-317.

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Arildskov, T., Højgaard, D., Skarphedinsson, G., Thomsen, P., Ivarsson, T., Weidle, B., Melin, K., & Hybel, K. (2015). Subclinical autism spectrum symptoms in pediatric obsessive–compulsive disorder European Child & Adolescent Psychiatry DOI: 10.1007/s00787-015-0782-5

Vitamin D levels and autism meta-analysed

A quote to begin: "Levels of serum 25(OH) D in participants with ASD [autism spectrum disorder] were significantly lower than controls, suggesting that lower vitamin D level might be a risk factor for ASD."

That was the bottom line finding reported by Tiantian Wang and colleagues [1] following their systematic review and meta-analysis of the existing peer-reviewed science literature looking at whether serum concentrations of 25-hydroxy vitamin D - the typically measured compound reflective of vitamin D status - might be something to look at when it comes to autism.

Of course these results are nothing new to this blog and the various occasions that I've covered research suggesting that lower vitamin D levels may be 'associated' with autism (see here and see here for example). That body of work also includes the idea that some of the genetics of the vitamin D receptor might also be implicated in some autism (see here).

There is still quite a bit more to do in this area notwithstanding the idea that screening for vitamin D issues in cases of autism should be rather more prevalent than it already is. The use of vitamin D supplements in cases of insufficiency / deficiency with autism is mind is a bit of a growth area as per other research from the Wang research group (see here). The idea that vitamin D issues in autism might also overlap with various other data from other conditions / labels is also of interest (see here) given that quite a few of those labels seem to be over-represented when it comes to a diagnosis of autism or ASD (see here and see here for example). With such multiple associations in mind, one wonders whether quite a bit more 'integrated' research taking a wider view of autism and labels such as depression might be in order...

Music: The Chemical Brothers - Block Rockin' Beats.

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[1] Wang T. et al. Serum concentration of 25-hydroxyvitamin D in autism spectrum disorder: a systematic review and meta-analysis. Eur Child Adolesc Psychiatry. 2015 Oct 29.

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Wang T, Shan L, Du L, Feng J, Xu Z, Staal WG, & Jia F (2015). Serum concentration of 25-hydroxyvitamin D in autism spectrum disorder: a systematic review and meta-analysis. European child & adolescent psychiatry PMID: 26514973

Heavy metals, heavy conflicts and autism?

Two papers are presented for your reading delight today, both based on the often contentious issue of heavy metals and autism.

The first paper is from Farida El Baz Mohamed and colleagues [1] (open-access available here) and further substantiates the claim that for whatever reason(s) the levels of various heavy metals seem to be increased or raised in some children diagnosed with an autism spectrum disorder (ASD). The second paper by Janet Kern and colleagues [2] (open-access available here) provides results based on a systematic review of the literature on one specific heavy metal, mercury (Hg), with autism in mind and concludes that: "of the studies with public health and/or industry affiliation, 86 % reported no relationship between Hg and ASD" whilst "among studies without public health and/or industry affiliation, only 19 % find no relationship between Hg and ASD."

The Mohamed paper continues a theme that for some on the autism spectrum (remember: the autisms) there may be quite a bit more to see when it comes to the burden of heavy metals (see here). Based on hair analysis for various heavy metals - "mercury, lead, and aluminum" - researchers looked at samples from 100 children diagnosed with ASD compared with 100 age- and gender-matched controls. "Comparison between cases and controls as regards heavy metal levels shows that the mean levels of the three toxic heavy metals in hair were significantly higher among the studied ASD cases than the controls" was the primary finding. The authors further report that said heavy metal findings correlated with "maternal fish consumptions, living nearby gasoline stations, and the usage of aluminum pans" and that: "Environmental exposure to these toxic heavy metals, at key times in development, may play a causal role in autism."

I know that to talk about issues with mercury for example, can be a contentious topic with autism in mind but as uncomfortable as it might be to accept, there is some evidence of a 'connection' between elevated levels of the stuff and at least some autism (see here). The link is not, I might add, seemingly generalisable to all autism (see here) but for those children/adults presenting with elevated levels of this heavy metal, further inspection is warranted save any further health inequalities appearing when the label of autism is discussed. As to the suggestion of a connection between some autism and lead (Pb) exposure, well, again this is not the first time that this has been mentioned in the peer-reviewed literature following a more general assertion that there is nothing very good to come from when lead and children in particular meet (see here).

The paper by Kern and colleagues pours further fuel on to something of an on-going debate in some autism circles about how much factors such as conflicts of interest and research transparency may impact on autism research. Focused specifically on the issue of mercury and autism (again), the authors argue that public health or pharmaceutical industry affiliation seems to show something of a potential relationship with study outcomes when it comes to mercury and autism research. So: "over 80 % of the studies without public health or industry affiliation found evidence a relationship between Hg exposure and ASD." This contrasted with something quite a bit less when it came to studies with a public health or industry affiliation slant. Further: "The dramatic discrepancy in these results... provides evidence of biased outcomes, indicative of a conflict of interest."

The authorship group involved in the Kern paper have something of a peer-reviewed research history when it comes to this topic [3] including independent findings that hair levels of mercury might show an association with autism [4]. Their mention of mercury related compounds found in certain vaccines [5] as potentially showing a correlation with risk of autism makes for controversy in some quarters in view of the 'hot potato' that such as association has become down the years.

Appreciating that whilst the Kern findings report something of a connection between affiliations and research outcomes, I'm hard-pressed to suggest that this is hard evidence of some sort of deliberate scheme to exonerate mercury of any potential role in the very wide autism spectrum. Taking for example one paper that is cited in the Kern analysis - the paper by Barry Wright and colleagues [6] - which I've discussed before on this blog (see here) who found no overall connection between urinary mercury levels and autism, they did also call for further research in this area in light of 'outliers' being reported in their autism and their learning disability group. To quote: "further research is warranted to better understand whether a subgroup with autism or learning disabilities have mercury poisoning or excretion difficulties." In these days of plural autism (see here) one can see the logic in such a suggestion.

Music: Radiohead - Lucky.

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[1] Mohamed Fel B. et al. Assessment of Hair Aluminum, Lead, and Mercury in a Sample of Autistic Egyptian Children: Environmental Risk Factors of Heavy Metals in Autism. Behav Neurol. 2015;2015:545674.

[2] Kern JK. et al. Systematic Assessment of Research on Autism Spectrum Disorder and Mercury Reveals Conflicts of Interest and the Need for Transparency in Autism Research. Sci Eng Ethics. 2015 Oct 27.

[3] Geier DA. et al. Thimerosal: Clinical, epidemiologic and biochemical studies. Clinica Chimica Acta. 2015; 444: 212-220.

[4] Geier DA. et al. Hair toxic metal concentrations and autism spectrum disorder severity in young children. Int J Environ Res Public Health. 2012 Dec 6;9(12):4486-97.

[5] Geier DA. et al. A two-phase study evaluating the relationship between Thimerosal-containing vaccine administration and the risk for an autism spectrum disorder diagnosis in the United States. Translational Neurodegeneration. 2013;2:25.

[6] Wright B. et al. A Comparison of Urinary Mercury between Children with Autism Spectrum Disorders and Control Children. PLoS ONE. 2012;7(2):e29547.

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Mohamed, F., Zaky, E., El-Sayed, A., Elhossieny, R., Zahra, S., Salah Eldin, W., Youssef, W., Khaled, R., & Youssef, A. (2015). Assessment of Hair Aluminum, Lead, and Mercury in a Sample of Autistic Egyptian Children: Environmental Risk Factors of Heavy Metals in Autism Behavioural Neurology, 2015, 1-9 DOI: 10.1155/2015/545674




Kern JK, Geier DA, Deth RC, Sykes LK, Hooker BS, Love JM, Bjørklund G, Chaigneau CG, Haley BE, & Geier MR (2015). Systematic Assessment of Research on Autism Spectrum Disorder and Mercury Reveals Conflicts of Interest and the Need for Transparency in Autism Research. Science and engineering ethics PMID: 26507205

The kynurenine pathway and some autism

"Our data indicated that there were alterations to the KP [kynurenine pathway] in ASD [autism spectrum disorder]. Specifically, increased production of the downstream metabolite, quinolinic acid, which is capable of enhancing glutamatergic neurotransmission was noted."

Those were some of the rather interesting results reported by Chai Lim and colleagues [1] suggesting that when it comes to tryptophan metabolism in relation to autism, the continued sole focus on serotonin and melatonin (see here) might not be the best overall research strategy.

Detailing results based on the examination of an: "Immunological profile and the KP metabolic signature" for a small group of Omani children diagnosed with autism (n=15) and their "age-matched healthy siblings" (n=12), researchers reported their findings. That specific detail about "increased production of the downstream metabolite, quinolinic acid" may indeed be an important one given connections with things like activated microglia for example [2] and the rise and rise of the 'constant gardener' with autism in mind (see here).

Obviously further studies are required to confirm the Lim findings in light of converse findings [3] (albeit reported in cerebrospinal fluid). Mention that their results might "help rationalize the efficacy of sulforaphane treatment in ASD" (yes, broccoli sprouts and autism) is another aspect in need of further investigation in these days of plural autisms (see here) and a focus on 'best' and 'non' responders to the various intervention strategies put forward with autism in mind (see here). One might also need to further expand the links between autism and schizophrenia on the basis of any kynurenine-glutamatergic link (see here).

I might finally add that as quite a fan of the need for more research into the aromatic amino acids (tryptophan, tyrosine and phenylalanine) when it comes to a label like autism (see here), I'm also of the opinion that what goes on in our deepest, darkest recesses might also be a place to look when it comes to this research. Those trillions of wee beasties that call our gut home - the gut microbiota - may seemingly have quite an effect on some of the processes involved in something like tryptophan metabolism (see here) an onwards the (bio)chemistry of how the kynurenine pathway might tie into at least some autism. Investigation of the mechanism pertinent to such processes and whether 'changing' the gut microbiota environment might impact on them, seem to be important areas of further work. Oh and speaking of tryptophan metabolites, I'll be coming to the findings reported by Dieme and colleagues [4] quite soon...

Music: Oliver Cheatham - Get Down Saturday Night (although I was slightly underwhelmed by the film Ex Machina).

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[1] Lim CK. et al. Altered kynurenine pathway metabolism in autism: Implication for immune-induced glutamatergic activity. Autism Res. 2015 Oct 24.

[2] Heyes MP. et al. Human microglia convert l-tryptophan into the neurotoxin quinolinic acid. Biochemical Journal. 1996;320(Pt 2):595-597.

[3] Zimmerman AW. et al. Cerebrospinal fluid and serum markers of inflammation in autism. Pediatr Neurol. 2005 Sep;33(3):195-201.

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

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Lim CK, Essa MM, de Paula Martins R, Lovejoy DB, Bilgin AA, Waly MI, Al-Farsi YM, Al-Sharbati M, Al-Shaffae MA, & Guillemin GJ (2015). Altered kynurenine pathway metabolism in autism: Implication for immune-induced glutamatergic activity. Autism research : official journal of the International Society for Autism Research PMID: 26497015

Sex, STEM careers and the 'big data' of the Autism-Spectrum Quotient (AQ)

I'm a fan of 'big data' on this blog (see here) and the particular idea that large participant numbers can offer up some really important results or patterns of results relevant to our knowledge of labels like autism.  I do also believe there is a balance to be struck between big data and somewhat smaller data - specifically the value of the N=1 when it comes to a heterogeneous condition like autism - but big data is a nice way of introducing or confirming more general trends and/or correlations.

When I therefore came across the paper by Emily Ruzich and colleagues [1] (open-access available here) talking about "Autism-Spectrum Quotient (AQ) scores in a 'big data' sample" it was music to my ears. Describing how researchers tapped into data connected to a medical TV show - "Embarrassing Bodies: Live from the Clinic" - specifically AQ scores and other data for over 450,000 people living in the UK, results are presented on the value of the AQ with autistic traits in mind and the idea that sex and occupation type might influence such self-reported characteristics.

I've been particularly interested in the AQ on this blog and its various research uses down the years. Ranging from autistic traits in those adults diagnosed with epilepsy (see here) through to autistic traits in older adults diagnosed with depressive disorders (see here), this simple to use self-report instrument is proving to be a research choice for many. I still have some reservations about the instrument; specifically, it's discriminating power when it comes to autism and schizophrenia (see here) for example, but as a rough-and-ready 'screening' instrument we have little else currently on offer and importantly, the instrument is open-access to all.

Ruzich et al reported results examining "correlations between the AQ and age, sex, occupation, and UK geographic region" as a function of the airing of a particular episode of the Embarrassing Bodies program "that included a brief TV segment following an individual with Asperger Syndrome." I hasten to add that the program title in no way describes Asperger syndrome or any other part of the autism spectrum as being 'embarrassing', merely reflecting the program content that at other times can be rather 'personal' in nature. Researchers reported that whilst age and geographic area of AQ completers did not seem to correlate with total AQ scores, there was something statistically to see when it came to scores across the sexes/genders and when taking into account the career option selected by participants. So: "[A] Career in a STEM [science, technology, engineering, and mathematics] area of work is associated in an increase in AQ scores in both genders" and "on average, males (m = 21.55, SD = 8.82) scored higher than females (m = 18.95; SD = 8.52)."

The authors interpret this data as further evidence "that traits commonly associated with autism are strongly linked to traits associated with being male and with STEM occupations, regardless of other factors." Those with some appreciation of the research literature in this area might know about the discussions on how parental career choice might tie into offspring outcomes specifically with autism in mind [2]. Indeed, how concepts such as 'hyper-systemising' [3] have been suggested to represent a core cognitive style in relation to autism.

These are interesting data allowing for the fact that various caveats are included in the Ruzich paper when it comes to the data collected and the participant group included. Investigations remain about how such results might generalise to the autism spectrum in terms of career paths (see here) and performance data (see here) and indeed, whether one might consider the wider schizophrenia spectrum as potentially being relevant also to the current results (see here) as part of any comorbidity.

I do think we also need to exercise a little caution in how the results are presented; the generalised idea for example, that 'extreme maleness' might be somehow connected to a career in STEM and what that might mean for the issue of women in science and specifically recruiting more women into such career paths needs to be handled with due care and respect. I'd also suggest that media headlines like: 'Are you on the autistic spectrum? Take the test' related to the Ruzich results need to be taken with a pinch of salt in light of the difference between a self-report screening instrument and a detailed assessment for autism (I'll be posting about this soon enough...)

Music: Portishead - Wandering Star.

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[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] Wheelwright S. & Baron-Cohen S. The link between autism and skills such as engineering, maths, physics and computing: a reply to Jarrold and Routh. Autism. 2001 Jun;5(2):223-7.

[3] Baron-Cohen S. The extreme male brain theory of autism. Trends Cogn Sci. 2002 Jun 1;6(6):248-254.

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Ruzich E, Allison C, Chakrabarti B, Smith P, Musto H, Ring H, & Baron-Cohen S (2015). Sex and STEM Occupation Predict Autism-Spectrum Quotient (AQ) Scores in Half a Million People. PloS one, 10 (10) PMID: 26488477

Symptom profiles of chronic fatigue syndrome across borders

To quote from the paper by Maria Zdunek and colleagues [1] (open-access available here): "These findings suggest that there may be important differences in illness characteristics across individuals with CFS [chronic fatigue syndrome] in the US [United States] and the UK [United Kingdom], and this has implications for the comparability of research findings across these two countries."

Looking at how symptom profiles and the "functional differences experienced by patients with chronic fatigue syndrome (CFS) across cultures" might differ, researchers set about analysing data from two cohorts of participants meeting criteria for CFS as described by the 1994 case definition (see here).

Two cohorts, based in the US (n=154) (termed the DePaul sample as a function of their previous participation in studies at DePaul University) and in the UK (n=73) (clinically referred to the RVI in Newcastle-Upon-Tyne), completed various measures of functioning related specifically to fatigue symptoms and also more general health. Results were then compared across the groups.

Quite a few group differences were noted across the study instruments used. So: "The UK sample was significantly more impaired with regard to role emotional and mental health functioning, multiple symptoms, experienced a more gradual onset of illness, and believed the cause of the illness to be both physical and psychological." In contrast: "The US sample experienced more sudden onset of illness, more frequently believed their illness to be physical, and more often were on disability."

Digging into the data with a little more detail, authors reported that quite a few more people in the DePaul sample were likely to look to the cause of their symptoms as being 'definitely physical' over the UK sample results (78% vs. 57%). Quite a few more participants in the US sample were also more likely to have been diagnosed and/or treated for conditions like fibromyalgia compared to the UK sample. What this could imply outside of more physical factors indeed being linked to symptom onset in the US sample, is something of a greater tendency to medicalise CFS in this group rather than explain it in terms of psychological and physical factors mixed together. I wonder if this might hark back to the unfortunate 'tradition' here in Blighty (UK) of viewing CFS/ME as more of a psychological issue than a physical condition and the various controversy that has surrounded this view in recent times (see here). The authors likewise suggest that: "those who believe their illness is partly psychological may have had previous experience with a psychological illness such as depression, which may influence their perception of the illness." Indeed.

Following on: "These results suggest there may be differences between the UK and US in relation to impairment in functioning, where the UK is more impaired in terms of mental health." The idea that within the constellation of symptoms that surround ME/CFS there may be a mix of physical and psychological aspects is not a new one. As per the previous paragraph, the perception of medical illness may indeed play a role in how one might define the illness. That being said, I'm generally favouring a model whereby the psychological effects noted in CFS are indeed 'effects' that stem from the initial physical/somatic nature of the condition as per other ramblings on this topic (see here). That for example, health-related quality of life is pretty much at the bottom of rankings compared with other conditions (see here) and combined with the impact of various physical ailments not normally noted in the diagnostic criteria as they stand for CFS (see here) and it's little wonder that emotional and mental health also suffer as per other research on psychiatric comorbidity accompanying such somatic complaints (see here). I don't say this to belittle the mental health aspect to CFS but rather to emphasise the continued growth of the view that CFS/ME represent a very real 'medical' condition(s) requiring 'medical' treatment/intervention (see here). Psychological intervention has some way to go in this area [2] despite other results [3] (and their criticism).

The Zdunek study is by no means perfect in terms of applicability to all ME/CFS in either the US or UK so one has to be a little cautious about extrapolating results. That the label itself is undergoing a bit of an overhaul in recent times (see here) is perhaps moving the description of the condition (at least in the US) into a more medical domain matched by the considerable efforts being put into treating it as a physical condition (see here for example). What the Zdunek study does imply, is that alongside such medical research, quite a bit more might need to be done to focus views and opinions on CFS according to geography as a physical condition in both patient and professional circles.

Debates continue in CFS/ME realms and indeed, one of the co-authors on the Zdunek paper is very much part of that debate...

To close, a Dalek relaxation tape anyone?

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[1] Zdunek M. et al. A Cross Cultural Comparison of Disability and Symptomatology Associated with CFS. Int J Psychol Behav Sci. 2015;5(2):98-107.

[2] Loades M. et al. he Cognitive Behavioral Treatment of Depression and Low Self-Esteem in the Context of Pediatric Chronic Fatigue Syndrome (CFS/ME): A Case Study. J Child Adolesc Psychiatr Nurs. 2015 Oct 16.

[3] Sharpe M. et al. Rehabilitative treatments for chronic fatigue syndrome: long-term follow-up from the PACE trial. Lancet Psychiatry. 2015 Oct 27. pii: S2215-0366(15)00317-X.

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Zdunek M, Jason LA, Evans M, Jantke R, & Newton JL (2015). A Cross Cultural Comparison of Disability and Symptomatology Associated with CFS. International journal of psychology and behavioral sciences, 5 (2), 98-107 PMID: 26478826