A 'frank' presentation of autism?

"Many individuals with ASD [autism spectrum disorder] have a distinctive behavioral presentation that is recognizable within moments, a phenomenon we call "frank" ASD." So said the paper by Ashley de Marchena & Judith Miller [1] who carried out an "empirical study of frank ASD" and by the looks of my Twitter feed when I initially posted about this study, there are quite a few varied opinions about the concept of 'frank' autism.

Although 'frank autism' makes up a significant portion of the chatter about the de Marchena/Miller paper, the authors do provide an alternative description using the term "classic autism" and how "there is no unitary "classic" presentation, and classic autism does not seem to correspond to level of functioning." On that basis, they set about surveying just over 150 clinicians involved in the diagnostic assessment of autism/ASD using a "13-item questionnaire about frank ASD" and report results on just how many people in their cohort were familiar with this term, how widespread they thought it might be as well as how it might be comprised.

Results: "Ninety-seven percentage of respondents were familiar with the phenomenon. Respondents estimated that 40% of the ASD population has a frank presentation." The sorts of behaviours respondents thought were most frequently associated with frank autism were things like eye contact issues, the "presence of motor mannerisms, and atypical gait or posture" and communicative styles. Surprisingly: "respondents reported detecting frank features rapidly, with the majority forming their impressions within the first ten minutes of interaction or observation." Ten minutes, eh?

"We discuss these findings within the context of diagnostic decision-making and behavioral phenotyping of ASD" said the authors, as some important insights into clinical decisions about autism assessments are potentially revealed in this paper.

In line with the comments received about this paper on social media, there are a few things to note. First and foremost is the idea that clinicians might be pretty good at spotting [some] autism fairly quickly. I don't think this should surprise anyone given that autism is diagnosed by behaviour (and developmental history) and whilst nothing beats a comprehensive assessment, experienced clinicians are always going to have 'hunches' or mental tick-boxes based on their previous experiences of diagnosing autism (or not). I might add that one needs only read some of the literature behind the development of the ICF core sets for autism (which are due out in the not-so-distant-future) to see such expertise in action (see here).

But... experts whilst being experts aren't always correct as we've seen on other occasions when it comes to experts and autism screening/diagnosing (see here). There is also the suspicion that bias could be creeping into clinical decision-making too which could potentially affect diagnostic rates for specific groups for example (see here). Indeed, with all the changes being applied to some of the diagnostic criteria for autism as per the introduction of DSM-5, one wonders how such 'bias' is going to affect groupings such as the SCD 'catch-all' description (see here) for example?

I would also be a little concerned that behaviours "absent from diagnostic criteria (e.g., atypical gait or posture)" are being potentially used to form clinical opinions/decisions. Yes, I appreciate that motor issues - potentially linked to gait and posture - are in the ascendancy again when it comes to autism (see here for example) but in light of known comorbidity accompanying autism such as dyspraxia for example [2] I think we have to be quite cautious about the mindset being applied here and how comorbidity is potentially being grouped into core autism. I might also add that the growing interesting in tic disorder(s) being 'over-represented' in autism is something else that could potentially be affected by such 'frank' thinking (see here).

I'm a great believer in appropriate screening and detailed diagnostic assessment when it comes to autism on the basis of many variables, not least that autism rarely comes as a stand-alone diagnosis (see here) and that autistic traits are seemingly present across various other different labels too (see here and see here). Whilst it is not unexpected that those assessing and diagnosing day-after-day may build up a mental picture of what autism is (and isn't), there are cautions attached to the idea that clinical impressions are being formed seemingly so early during 'interaction or observation' and what this could mean for the heterogeneity of autism and the presentation of its important over-represented comorbidities.

Music to close and something a little relaxed to ease your 2016 worries: Erik Satie - Gymnopédie No.1.

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[1] de Marchena A. & Miller J. "Frank" presentations as a novel research construct and element of diagnostic decision-making in autism spectrum disorder. Autism Res. 2016 Oct 21.

[2] MacNeil LK. & Mostofsky SH. Specificity of dyspraxia in children with autism. Neuropsychology. 2012 Mar;26(2):165-71.

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de Marchena, A., & Miller, J. (2016). “Frank” presentations as a novel research construct and element of diagnostic decision-making in autism spectrum disorder Autism Research DOI: 10.1002/aur.1706

Language and motor skills: preschool predictors of academic achievement in autism

A fairly quick post for your reading delight today as I bring the paper by Miller and colleagues [1] to your attention suggesting that: "Early intervention targeting language and motor skills may improve later achievement in this population."

'This population' referred to a small cohort (N=26) of children diagnosed with an autism spectrum disorder (ASD) who were examined "at the approximate ages of two, four, and ten" years with regards to their academic achievement and the variables that might be important to 'successful' achievements.

Including some familiar names when it comes to the concept of 'outcome' in relation to autism ('optimal outcome' that is), researchers determined a few potentially important relationships from their collected data: "Preschool verbal abilities significantly predicted school-age reading comprehension" and "early motor functioning predicted later math skills."

I'm not entirely surprised that infancy verbal (talking) abilities might play a role in later reading comprehension but I was rather more intrigued by the observation potentially linking motor skills to later maths abilities. Yes, I get that children learn to count on their fingers (and toes) and no doubt this and other scenarios might influence the connection between the two, but it strikes me that this connection requires quite a bit more study [2]. Indeed, welcoming the idea that motor skills are an important issue with regards to autism (see here) and that maths ability is 'as varied as the label of autism is itself' (see here) the idea that the archetypal all-rounder that is the occupational therapist (OT) might have a key role here is rather interesting (see here).

I'm also minded to suggest that a certain sport/discipline that I'm particularly fond of on this blog (the martial arts) might have some rather far-reaching 'mathematical' effects if one considers it's application to autism and motor functioning...

To close, Marvel are going full-strength with their next Wolverine film instalment titled 'Logan'...

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[1] Miller LE. et al. Preschool predictors of school-age academic achievement in autism spectrum disorder. Clin Neuropsychol. 2016 Oct 5:1-22.

[2] Pitchford NJ. et al. Fine Motor Skills Predict Maths Ability Better than They Predict Reading Ability in the Early Primary School Years. Front Psychol. 2016 May 30;7:783.

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Miller LE, Burke JD, Troyb E, Knoch K, Herlihy LE, & Fein DA (2016). Preschool predictors of school-age academic achievement in autism spectrum disorder. The Clinical neuropsychologist, 1-22 PMID: 27705180

Taekwondo training and balance in autism

"TKD [Taekwondo] training can help children with ASD [autism spectrum disorder] improve their balance."

Go on.

"Our findings suggest that TKD can be a fun, feasible, and effective therapeutic option for balance improvement of children with ASD."

So said the results of the study by Yumi Kim [1] (open-access) looking at whether the Korean martial art might be able to help with aspects of some of the very important movement issues that can be associated with a diagnosis of autism.

Based on quite a small participant group (N=14) where 8 children diagnosed with an ASD "completed the TKD intervention twice per week for eight weeks (50 min per session)" and 6 served as a 'no intervention' control group, researchers looked at various measures of balance using the "NeuroCom Balance Master."

Again keeping in mind the small participant groups, there did appear to be some short-term benefit on aspects of balance following the use of TKD training. Specifically: "Following the TKD intervention, children with ASD showed balance improvement during right single leg stance under eyes closed condition compared to those who did not participate in the intervention." Also: "Children with ASD in the TKD group also improved their balance during left single leg stance under eyes open condition compared to their baseline performance" bearing in mind that there were some changes to balance variables for the control group too (albeit not significant). Insofar as what happened to autistic traits/symptoms as a consequence of the intervention (or not), well the words "we did not have any clinical measures of symptom severity of ASD" tell you all you need to know.

Regular readers to this blog might have already know that I am a bit of a fan of how participation in the martial arts might be something suited to at least some people on the autism spectrum (see here for example). Several components of the martial arts might be useful outside of just 'knowing how to handle yourself' including: (a) the focus on repetition and routine (certainly in karate there is a lot of this with respect to kata and kumite) all bound to 'specific rules', (b) the combination of aerobic and anaerobic exercise being pretty good for keeping physically and mentally active (important for some autism or at least some comorbidities) and (c) the 'motor' advantages of the martial arts; something that is being talked about a lot more these days with autism in mind. As a sport or pastime, the martial arts have some significant draws for many groups of people.

There is more research to do in this area not least to work on improving the research methodologies of studies on the use of martial arts when it comes to autism. So say for example, rather than just having a 'treatment as usual' arm, how about pitting some of the martial arts against each other (for science of course) or even comparing them with some of the 'softer edges' of the arts (see here) to provide some more detailed information. As per some of the various studies looking at karate training and autism, I'd also be minded to say that monitoring the presentation of autism (or comorbidities) over the course of training might be a good thing too as is some further inspection on whether particular movement diagnoses potentially accompanying autism might also be important [2]. There is lots more to see and do in this area.

To close, some karate kata set to music and a question: how many kata can you name? I'll start you off.. Enpi.

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[1] Kim Y. et al. Effects of Taekwondo intervention on balance in children with autism spectrum disorder. J Exerc Rehabil. 2016 Aug 31;12(4):314-9.

[2] McAuliffe D. et al. Dyspraxia in ASD: Impaired coordination of movement elements. Autism Res. 2016 Sep 21.

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Kim Y, Todd T, Fujii T, Lim JC, Vrongistinos K, & Jung T (2016). Effects of Taekwondo intervention on balance in children with autism spectrum disorder. Journal of exercise rehabilitation, 12 (4), 314-9 PMID: 27656628

The force is strong with autism?

"Tablet and phone games could help diagnose autism, study suggests" went the BBC headline covering the paper by Anna Anzulewicz and colleagues [1] (open-access). The idea being that the way that touch screens are used on tablet and smart phones could potentially 'separate out' those with autism from those with not-autism.

Based on a small participant number of "37 children 3–6 years old with autism and 45 age- and gender-matched children developing typically" researchers set about examining "autism-specific motor patterns in the gameplay of children as they engaged with a smart tablet computer (iPad mini) under natural conditions and with minimal instructions." Motor issues accompanying autism are something gaining some renewed (and welcomed) research attention in recent times (see here). Specifically, researchers were utilising the astounding technology that goes into all those swipes and taps that we're also used to these days, and whether under 'serious' game conditions, aspects like force impact and gesture pressure could differentiate the two groups.

As per the headline and the rather cheesy title to this post, there were some differences picked up between the autism and control groups based on touch and swiping responses being put through their machine-learning paces (something else that has a growing following in autism research circles). So: "The inertial data indicate children with autism engaged in gameplay with greater force of impact than those developing typically." This and other potential differences led researchers to conclude that: "children with autism applied a significantly different distribution of forces into the device during gameplay than the typically developing children did."

Whilst interesting research there is quite a bit more to do before anyone starts using taps and swipes as a means to diagnose autism (or anything else). I don't really need to say that this was a study including a relatively small participant group nor that whilst "All participants had normal or corrected-to-normal vision and no other sensory or motor deficits" this does not preclude the possibility that subtle issues might also be at work (see here). That also recent discussions have suggested moving away from the singular diagnosis of autism as a research starting point is also worth reiterating (see here).

Still, I can see some opportunities arising from this area of research and how perhaps combined with other innovative areas of screening and diagnosis there may be much more to see including how subtle differences in movement might also influence variables such as interaction [2]. Yes indeed, "smart tablet technology offers an attractive, new paradigm for clinical autism assessment and bio-behavioural research of pre-school children, enabling engaging, ecological testing of children’s motor behaviour in a fun, accessible format fit for precise computational analysis of neuropsychological function."

To close: Danny Boy (from the Proms 2013 although this years version was pretty good too).

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[1] Anzulewicz A. et al. Toward the Autism Motor Signature: Gesture patterns during smart tablet gameplay identify children with autism. Scientific Reports. 2016; 6: 31107.

[2] Edey R. et al. Interaction Takes Two: Typical Adults Exhibit Mind-Blindness Towards Those With Autism Spectrum Disorder. J Abnorm Psychol. 2016 Sep 1.

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Anzulewicz A, Sobota K, & Delafield-Butt JT (2016). Toward the Autism Motor Signature: Gesture patterns during smart tablet gameplay identify children with autism. Scientific reports, 6 PMID: 27553971

Physical activity in children and youth: themes and consensus

'Physical activity boosts kids' brain power and academic prowess' went the press release accompanying the consensus statement published by Jens Bangsbo and colleagues [1] (open-access).

The consensus statement brought together researchers from around the world "and from a variety of academic disciplines" to emphasise how undertaking all-manner of different kinds of exercise "are still a good investment in academic achievement" when it comes to children aged between 6-18 years of age.

The statement is open-access but a few choice passages are particularly worthy of highlighting including the idea that there are various positive physical effects from exercise (as if you needed telling): "Frequent moderate-intensity and, to a lesser extent, low-intensity exercise improves cardiometabolic fitness in children and youth." I might at this point also refer you to the findings by Ekelund and colleagues [2] that made some headlines recently suggesting that about 65-70 minutes of "moderate intensity physical activity" a day might be something to aim for across different age groups. Yes, move more.

Perhaps just as important are the various associations being made between exercise and other important areas of health and well-being including that: "Physical activity before, during and after school promotes scholastic performance in children and youth" and: "Mastery of fundamental movement skills is beneficial to cognition and scholastic performance in children and youth." Being careful not to fall into the trap that is 'those who exercise are more 'smarter' than those who don't' the idea that mastering movement skills might be another positive from exercise is an important point to make. As I've said before on this blog (see here) one particular pastime ticks a lot of boxes in terms of exercise and a particular focus on fine and gross motor skills: the martial arts. Added to the fact that some important life skills can be gained from disciplines such as karate (e.g. self-confidence) and I'd be the first to advocate more children and young adults getting involved in such activities. Indeed, this is something else covered in the Bangsbo article: "Physical activity-based positive youth development programmes that have an intentional curriculum and deliberate training are effective at promoting life skills (eg, interpersonal, self-regulation skills) and core values (eg, respect and social responsibility) in children and youth."

Finally, I leave you with another important point raised in the consensus statement: "Social inclusion can be promoted by providing equal access to opportunities within physical activity and sports settings regardless of children and young people's social, cultural, physical and demographic characteristics." Wearing my autism research hat, I might agree with the tenets of this point (see here) applied to the autism spectrum and how participation in sports and exercise can be a really important part of social inclusion strategies.

Now, added to exercise potentially improving academic outcomes, how about some outdoor learning too and importantly, making sure that children and young people get enough [quality] sleep?

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[1] Bangsbo J. et al. The Copenhagen Consensus Conference 2016: children, youth, and physical activity in schools and during leisure time. Br J Sports Med. 2016 Jun 27. pii: bjsports-2016-096325.

[2] Ekelund U. et al. Does physical activity attenuate, or even eliminate, the detrimental association of sitting time with mortality? A harmonised meta-analysis of data from more than 1 million men and women. Lancet. 2016. July 27.

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Bangsbo J, Krustrup P, Duda J, Hillman C, Andersen LB, Weiss M, Williams CA, Lintunen T, Green K, Hansen PR, Naylor PJ, Ericsson I, Nielsen G, Froberg K, Bugge A, Lundbye-Jensen J, Schipperijn J, Dagkas S, Agergaard S, von Seelen J, Østergaard C, Skovgaard T, Busch H, & Elbe AM (2016). The Copenhagen Consensus Conference 2016: children, youth, and physical activity in schools and during leisure time. British journal of sports medicine PMID: 27354718

Siblings of probands with autism: preferential screening suggested?

"Psychiatric and neurodevelopmental disorders cluster among siblings of probands with ASD [autism spectrum disorder]."

That was the research bottom line presented in the paper by Elina Jokiranta-Olkoniemi and colleagues [1] who extracted data from the Finnish Prenatal Study of Autism and Autism Spectrum Disorders (FIPS-A). FIPS-A has been mentioned previously on this blog (see here) but this time around the aim was to look not at the various risk factors potentially associated with receipt of an autism diagnosis, but rather how siblings of those with autism might require some preferential screening for a variety of potential psychiatric and/or neurodevelopmental labels. I know that might not make great reading but burying ones head in the sand is not likely to do anyone any good.

With a starting participant sample in the thousands - "31, 2005, who received a diagnosis of ASD" - researchers matched cases with asymptomatic (not autism) controls to a ratio of 4:1. "This nested case-control study included 3578 cases with ASD with 6022 full siblings and 11 775 controls with 22 127 siblings from Finnish national registers." Various psychiatric and behavioural diagnoses were searched for among siblings of those with autism and compared with rates among control participant siblings. An adjusted risk ratio was generated; authors also taking into account the various ASD sub-diagnoses (many of which have been subsumed under the latest DSM-5 definition of autism).

Results: as per the opening sentence, siblings of those diagnosed with autism were at a significantly increased risk of various psychiatric and neurodevelopmental outcomes. Around 10% of siblings of those with autism were diagnosed with an ASD tallying with what has been previously reported in the peer-reviewed literature on familial recurrence (see here). This compared with the similarly standard 1% of siblings of asymptomatic controls who were diagnosed with an ASD. Actually, 1% might not be the standard any longer...

Other associations were also noted; so learning and coordination disorders were reported in around 15% of siblings of those with autism compared with 6% in control siblings. Similar patterns were noted with regards to attention-deficit hyperactivity disorder (ADHD) and interestingly, tic disorders too (a particular interest to this blog). The bottom line again being that siblings of those with autism might have something of an increased risk of receiving various developmental or behavioural diagnoses.

The authors conclude that when it comes to discussions about aetiology, there may be some common risk factors that predispose to the various labels included for study. Of course this is not necessarily new news as per other research looking at 'overlapping' structural genetics for example (see here) and the realisation that a diagnosis of autism is by no means protective against other conditions occurring (see here). Indeed, other research published in the same journal hints at some important genetic overlap when it comes to autism and other diagnoses [2] which may be particularly relevant (see here). If there is anything that I would add to any future research agenda it would be some way of incorporating the concept of the broader autism phenotype (BAP) into proceedings (see here) and also the inclusion of more somatic diagnoses (see here) as well as neurodevelopmental and psychiatric as a means to search for overlapping variables. As for clinical practice, well to reiterate again, the implication is to potentially offer preferential screening for a variety of neurodevelopmental and/or psychiatric labels when autism appears in the family...

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[1] Jokiranta-Olkoniemi E. et al. Risk of Psychiatric and Neurodevelopmental Disorders Among Siblings of Probands With Autism Spectrum Disorders. JAMA Psychiatry. 2016. May 4.

[2] Goes FS. et al. Exome Sequencing of Familial Bipolar Disorder. JAMA Psychiatry. 2016. April 27.

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Jokiranta-Olkoniemi, E., Cheslack-Postava, K., Sucksdorff, D., Suominen, A., Gyllenberg, D., Chudal, R., Leivonen, S., Gissler, M., Brown, A., & Sourander, A. (2016). Risk of Psychiatric and Neurodevelopmental Disorders Among Siblings of Probands With Autism Spectrum Disorders JAMA Psychiatry DOI: 10.1001/jamapsychiatry.2016.0495

ICF core sets for autism continued: what do experts think about autism?

Consider this post an extension of a previous discussion thread (see here) continuing the voyage of developing "International Classification of Functioning, Disability and Health (ICF; and Children and Youth version, ICF(-CY)) Core Sets for Autism Spectrum Disorder (ASD)."

This time around it is another paper by Elles de Schipper and colleagues [1] (open-access available here) providing the blogging fodder and specifically the stage two of their four stage project building up those core sets for how we might conceptualise functioning and health when it comes to the autism spectrum. So: "The objective of this study was to survey the opinions and experiences of international experts on functioning and disability in ASD."

Those experts included responses from over 200 professionals ranging from physicians (22%) to nurses (3%) and everyone in-between including some really worthwhile representation from the all-rounder that is the occupational therapist (OT) (20%). They were asked various questions pertinent to the development of the core sets for autism including aspects designed to cover the "bio-psycho-social of the ICF(-CY)" and questions around "the possible functional strengths in ASD and the... possible gender differences in functioning and disability."

The data presented provides a fascinating insight into what experts think about [childhood] autism derived from the extracted "8792 meaningful concepts." I don't want to plagiarise the whole document but some key points emerge:

• As perhaps expected, social interaction issues feature heavily when it comes to defining important items for the ICF; "complex interpersonal interactions" comes top in one category of definable codes followed not so far behind by "basic interpersonal interactions." Communication issues are also mentioned as, importantly, are motor issues e.g. "fine hand use." I've talked about motor issues and autism before (see here).
• When asked about "ASD-related skills and functional strengths", the notion of "attention to detail" was prominent as was: "A preference to work on repeated or monotonous tasks." Experts also recognised that a "Strong sense of morality (e.g., honesty, lack of judgmental attitude, etc.)" was also a functional strength with other keywords such as "Trustworthiness" and "Loyalty" following suit. I was also interested to see that "Mathematical abilities" and "Technical abilities (computer skills, engineering)" were also reported in this section (see Table 6). Personally I think we have to be quite careful about sweeping generalisations of people on the autism all being 'maths geniuses' given data suggesting the contrary (see here) even when information might "mainly [be] associated with higher functioning individuals." Likewise, technical abilities in computing or engineering although important for quite a few people on the autism spectrum should not necessarily define all autism or all future job prospects (see here).
• When it came to opinions about 'body structures' potentially pertinent to autism, it is interesting that although most experts heavily endorsed involvement of the brain - "structures of the nervous system" - quite a few also saw other body structures as being important. So: "structure of intestine" was mentioned by about 15% of experts and "structure of stomach" by a smaller percentage. Bearing in mind the array of experts quizzed about these core sets and their varied areas of work and expertise, the inclusion of the gastrointestinal (GI) tract will be a welcome one for quite a few people (see here).
• Gender differences in the presentation of autism also created some discussion. Of the 60% or so of experts who "reported gender-related differences in ASD" quite a few focused on the idea that "more externalizing behaviors among males and more internalizing behaviors in females" were notable. Indeed, that females may be more likely to be 'overlooked' as being on the autism spectrum as a function of being "better socially adjusted, showing more prosocial behaviors, communication skills and friendships than males." This perhaps accords with other findings in the research literature (see here) onwards to the idea of a female phenotype or more.

I would encourage readers to take some time to read through the latest article from de Schipper et al for the important information that it holds. As and when the development of the core sets is eventually finished, autism research and practice will probably be hearing a lot about them. I dare say that one day they may become fundamental to autism research and practice. In the meantime, I'll be keeping my eyes open for further peer-reviewed publications from this group on this topic; the expected next stage I think being 'a patient and caregiver qualitative study' and thereafter a 'clinical cross-sectional study'. Interesting times lie ahead for the core sets for autism as indeed applied to other labels too [2].

Music and something from arguably one of the most well-educated singers/bands ever... Stranger Than Fiction.

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[1] de Schipper E. et al. Functioning and disability in autism spectrum disorder: A worldwide survey of experts. Autism Res. 2016 Jan 8.

[2] de Schipper E. et al. Towards an ICF core set for ADHD: a worldwide expert survey on ability and disability. Eur Child Adolesc Psychiatry. 2015 Dec;24(12):1509-21.

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de Schipper E, Mahdi S, de Vries P, Granlund M, Holtmann M, Karande S, Almodayfer O, Shulman C, Tonge B, Wong VV, Zwaigenbaum L, & Bölte S (2016). Functioning and disability in autism spectrum disorder: A worldwide survey of experts. Autism research : official journal of the International Society for Autism Research PMID: 26749373

Karate and autism continued: Kiai!

Gichin Funakoshi

"We concluded that teaching Karate techniques to children with ASD [autism spectrum disorder] leads to significant reduction in their communication deficit."

That was the [research] bottom line from Fatimah Bahrami and colleagues [1] continuing their very interesting voyage into looking at how aspects of the martial arts might well benefit some people on the autism spectrum. I mention the word 'continuing' because this authorship group from Iran have some research form in this area previously covered on this blog (see here).

In their latest paper, the authors took to looking at how another core area of autism - communication issues - may also be impacted by kata training (that is, the various structured movements against an invisible opponent(s) practised as part of karate). This time as previously, the kata in question was Heian Shodan, the kata normally used to grade transition from orange belt to red belt in Shotokan karate. Helpfully, the authors also provide their own video of the kata used as supplementary material to their paper.

Their results, based on a similarly small group of children with autism assigned to kata training (n=15) or a control (n=15) as in previous papers, suggested that after 14 weeks of training the "Exercise group showed significant reduction in communication deficit compared to control group." Such gains seemingly persisted at 1 month follow-up too.

Appreciating that there is quite a bit more science to do in this area, including that taking on board how issues with simulative skills with autism in mind [2] might interact with the practise of martial arts training (being careful about over-generalisation [3]), I continue to find this an area of real interest. Associated research hinting that regular exercise and motor skills training might benefit quite a few aspects of autism (see here) emphasises how something like practising kata could represent a 'good fit' for quite a few children and adults diagnosed on the autism spectrum. This alongside the wider potential benefits to be had from martial arts training (see here), bearing in mind aspects like kumite might not be to everyone's taste. Dare I also even start to talk about the more 'spiritual' side of some of the martial arts (Zen played a role apparently) intersecting with some interesting case reports with autism in mind (see here)? (being careful not to fall into the bull**** trap [4]).

To close, I note that one of the national governing bodies for the martial arts here in Blighty has already come around to the idea of further opening up the sport to those on the autism spectrum.

Why not give it a try? Kiai!

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[1] Bahrami F. et al. The Effect of Karate Techniques Training on Communication Deficit of Children with Autism Spectrum Disorders. J Autism Dev Disord. 2015 Nov 17.

[2] Conson M. et al. Body Constraints on Motor Simulation in Autism Spectrum Disorders. J Autism Dev Disord. 2015 Nov 16.

[3] Torres EB. Atypical signatures of motor variability found in an individual with ASD. Neurocase. 2013 Apr;19(2):150-65.

[4] Pennycook G. et al. On the reception and detection of pseudo-profound bullshit. Judgment and Decision Making. 2015; 10: 549-563.

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Bahrami F, Movahedi A, Marandi SM, & Sorensen C (2015). The Effect of Karate Techniques Training on Communication Deficit of Children with Autism Spectrum Disorders. Journal of autism and developmental disorders PMID: 26577688

Regular exercise and motor skills training for autism?

I approach the study results presented by Serge Brand and colleagues [1] (open-access available here) with some caution given the preliminary nature of the findings suggesting that: "regular AET [aerobic exercise training] and MST [motor skill training] impact positively on sleep, MSs, and mood among children with ASD [autism spectrum disorder]." The caution is due to the fact that the Brand results report on an uncontrolled pilot study (we've all done them) and included only 10 children diagnosed with an autism spectrum disorder (ASD).

Researchers report how "an individual training plan was created" for each participant, consisting of three sessions weekly including "a 30-minute bicycle workout (AET) followed by 30 minutes of training in coordination and especially in balance (MST)." Cycle training was chosen because it: "is easily adapted to individual motor abilities and allows specific progressive steps" and "allows training in the endurance zone." Further: "The intervention was executed in a highly structured manner and was based on the “Applied Behavioral Analysis” (ABA) method."

Whilst the intervention was running, various measures were employed to primarily look at aspects of sleep. This included sleep EEGs and sleep polygraphs. More subjective data were also obtained from sleep schedules and "the Insomnia Severity Index (ISI), a screening tool for insomnia."

Results: perhaps unsurprisingly, some aspects of sleep were 'unusual' for quite a few of the small participant group. So: "Mild-to-moderate insomnia was reported in 70% of children." Further: "a 3-week intervention involving AET and MST improved specific MSs and led to improved objectively assessed sleep on nights following PA as compared to nights not preceded by PA. Mood also improved over time." I might reiterate that this was an uncontrolled pilot study and, as the authors suggest: "future studies might also add control groups such as children with ASD on a waiting list and healthy controls."

This is not the first time that physical activity and sleep patterns in relation to autism have been looked at in the peer-reviewed literature (see here). As per the results from Wachob & Lorenzi [2] using a similarly 'preliminary' study design, there may be quite a bit more to see in this area subject to more robust research strategies. As to how far this will go, well others have their own views on this [3]. That physical fitness might not necessarily be the deciding factor here (see here) but rather the level of physical activity is something else to consider in this area.

One final note that I might make in this whole area of physical activity with autism in mind, is the idea that there may be more than one way to get kids/adults up and active. Martial arts is something that I'm particularly keen on seeing more research done on in light of some initial research in this area with autism in mind (see here) and other potentially 'over-represented' comorbidity such as attention-deficit hyperactivity disorder (ADHD) (see here). I know it's probably not going to be suitable for everyone (avoiding sweeping generalisations!) but given the emphasis on motor skills and aerobic exercise that disciplines such as karate offers, it could be one option to consider...

To close, Alan Whicker on karate - "so deadly that most of the Japanese are frightened of it" (apparently).

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[1] Brand S. et al. Impact of aerobic exercise on sleep and motor skills in children with autism spectrum disorders - a pilot study. Neuropsychiatr Dis Treat. 2015 Aug 5;11:1911-20.

[2] Wachob D. & Lorenzi DG. Brief Report: Influence of Physical Activity on Sleep Quality in Children with Autism. J Autism Dev Disord. 2015; 45: 2641-2646.

[3] Archer T. Exercise Alleviates Autism Spectrum Disorder Deficits. Autism Open Access 2015; 5:146.

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Brand S, Jossen S, Holsboer-Trachsler E, Pühse U, & Gerber M (2015). Impact of aerobic exercise on sleep and motor skills in children with autism spectrum disorders - a pilot study. Neuropsychiatric disease and treatment, 11, 1911-20 PMID: 26346856

Parkinsonism in adults with autism

"We find a high frequency of parkinsonism among ASD [autism spectrum disorder] individuals older than 39 years."

So said the paper by Sergio Starkstein and colleagues [1] (open-access) and Q & A with authors who, during a "a hypothesis-generating, pilot study" with extras looked for parkinsonism motor signs in a small group of adults diagnosed with an autism spectrum disorder.

Parkinsonism is an umbrella term that refers to any condition that leads to a combination of symptoms noted in Parkinson's disease including tremor, slow movement (bradykinesia) speech issues and/or muscle stiffness. Parkinsonism does not necessarily mean just Parkinson's disease (PD) as per the number of conditions that have been mentioned under this umbrella (see here).

Starkstein and colleagues describe their results within the context of a research initiative looking to examine ASD in older individuals. They report: "As the project progressed, we observed what appeared to be high rates of parkinsonian signs in our ASD subjects" (n=19) that was then extended into a more systematic assessment of parkinsonian signs in a different cohort (n=37). In that latter group: "The frequency of occurrence of the cardinal signs for parkinsonism were 46 % (N = 17) with bradykinesia, 19 % (N = 7) with resting tremor, 19 % (N = 7) with rigidity, and 19 % (N = 7) with postural instability." Assessment by the way, was via the Movement Disorders Society-Unified Parkinson’s disease Rating Scale (MDS-UPDRS) with a slight modification whereby "final clinical judgment on the presence of bradykinesia was based on scores rating limb bradykinesia... and/or scores rating global spontaneity of movement."

Because medication, particularly certain neuroleptic pharmacotherapy, can impact on parkinsonism, researchers also looked at the 20 participants from both cohorts combined who were not currently on neuroleptics. So: "After excluding subjects currently on neuroleptic medications, the frequency of occurrence of parkinsonism was 20 % in the combined sample and 17 and 25 %, in each sample, respectively." Oh, and 4 participants (7% of the combined sample) were "diagnosed with PD by community neurologists."

"The possibility that individuals with autism are at increased risk for Parkinson’s disease as adults has important implications for detection and assessment, clinical practice, systems of care, training, and public policy." That's an important sentence from the authors about their findings and the implications for screening and care of adults on the autism spectrum. Added to the idea that various other medical comorbidity might be 'over-represented' when it comes to autism (adult autism) (see here and see here and more recently in the paper by Fortuna and colleagues [2]) and how the symptoms of autism can sometimes affect the delivery of appropriate screening and healthcare (see here), and quite a research agenda continues to emerge.

As to the mechanism(s) potentially pertinent to parkinsonism being associated with autism... well, all I can really say is that it is likely to be a complicated relationship insofar as the plurality of autism and all that elevated risk of other comorbidity allied to the label. To single out one area where the possibility of overlap might occur, I'll draw your attention to the findings reported by Cheng and colleagues [3] who, based on that ever-so useful resource called the Taiwan National Health Insurance Research Database (see here), reported that: "Patients with asthma had an elevated risk of developing Parkinson's disease later in life." Given something of an emerging connection between asthma and autism (see here) one might speculate that this could be just one avenue for further investigation.

Music: Florence + The Machine - Rabbit Heart (Raise it Up).

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[1] Starkstein S. et al. High rates of parkinsonism in adults with autism. Journal of Neurodevelopmental Disorders 2015, 7:29.

[2] Fortuna RJ. et al. Health Conditions and Functional Status in Adults with Autism: A Cross-Sectional Evaluation. J Gen Intern Med. 2015 Sep 11.

[3] Cheng CM. et al. Risk of developing Parkinson's disease among patients with asthma: a nationwide longitudinal study. Allergy. 2015 Aug 27.

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Starkstein, S., Gellar, S., Parlier, M., Payne, L., & Piven, J. (2015). High rates of parkinsonism in adults with autism Journal of Neurodevelopmental Disorders, 7 (1) DOI: 10.1186/s11689-015-9125-6

Effects of prenatal organophosphate pesticide exposure on a mouse model of autism

Pesticides and autism is a topic previously covered on this blog (see here for example). The idea that some of the various preparations that we use to control the pests which have an ability to blight our crops or cause serious health issues could be linked to an increased risk of autism is an area likely to invoke some divisions within elements of the autism and wider scientific community.


Part of the problem with the available evidence suggesting a link between autism and pesticide exposure is that it is, to a large extent, observational and correlational. As per the paper from Janie Shelton and colleagues [1], results are based on variables such as looking at what types and amounts of pesticides are used in a specific area and correlating proximity to that area as a function of a diagnosis of autism or not. Similar to the work looking at other environmental factors linked (or not) to autism such as air pollution (see here), it's all about where and when you were, followed by calculations on your probable exposure being tied into risk.

The paper from Alessia De Felice and colleagues [2] (open-access) approaches the research area of pesticide exposure and autism (a model of autism) from a slightly different angle. Their findings were based on the use of a mouse model of autism and what happened to mouse offspring when mother mice were exposed to a particular pesticide "at doses devoid of maternal or systemic toxicity."

The mouse model in question was a favourite in autism research circles, the BTBR T+tf/J strain (see here). The pesticide used was "the organophosphate insecticide chlorpyrifos (CPF)." Organophosphate (OP) by the way, refers to the chemical make-up of the compound and its particular effects on the enzyme acetylcholinesterase working in a similar fashion to certain warfare agents.

The De Felice paper is open-access but as ever, a few details are provided:

• Recognising that pesticide exposure already has quite a long history in terms of adverse health effects (pesticide applicators of the world take note), the authors set about looking to "evaluate in the offspring of both sexes the effect of the gestational CPF exposure on spontaneous locomotion, ultrasonic vocalization and neurodevelopment during the first two weeks of postnatal life, to evidence early changes in behavioral profile." Further they decided to "evaluate the long-term effects of CPF on selected markers of the peculiar behavioral repertoire of this mouse strain." You'll note that the word autism does not appear in either of those aims.
• Male and female BTBR mice were allowed to 'get it on' in breeding cages. Females mice were regularly inspected for evidence of carrying a baby mouse and 14 days into the pregnancy were either given peanut oil (vehicle) or CPF dissolved in peanut oil by oral gavage for 4 days. This was given as a single dose.
• Baby mice were born ("Twenty-four litters (13 Vehicle-treated and 11 CPF-treated"). Various behavioural assessments were conducted including an analysis of ultrasonic vocalisations and spontaneous movements. Various other behavioural measures were also made when the baby mice grew into adult mice.
• Results: "prenatal CPF exposure significantly modifies spontaneous motor activity in BTBR pups, delaying their motor development and further enhancing the abnormally high vocalization rates." The authors also reported reduced weight gain in CPF exposed offspring during the early days. 
• Looking into adulthood, CPF exposure seemed to show more pronounced effects for males over females with an "altered pattern of investigation of a sexual partner." This finding has however been downplayed by the authors to a certain extent. They conclude with the need for further research in this area "to evaluate the role of environmental chemicals in the etiology of neurodevelopment disorders."

Taking a few steps back, one has to remember that this was a study of mouse exposure to pesticides not humans. Indeed, other similar work from some of the authors has also recently seen the light of day [3]. As per other discussions, mice might be good 'models' of something like autism but they are never ever going to reflect autism (and its important comorbidities) in their entirety. Given also that the BTBR mouse "exhibit a 100% absence of the corpus callosum and a severely reduced hippocampal commissure" according to suppliers, one has to be careful about any sweeping generalisations to all autism. The timing and route of CPF exposure described by De Felice et al might also be seen as potentially important variables insofar as their focus some time into pregnancy and sole reliance on the oral route of exposure. 

That all being said, these are potentially important results not least because of their focus on how both genes and environment might be implicated in [models of] cases of autism. As I've mentioned, this was a study of offspring BTBR mice thus implying that there may be some familial predisposition to mimicking the effects of autism anyway. The idea that in predisposed individuals there may be additional effects from an environmental factor is an important one and perhaps complements the whole 'air pollution effects modified by genotype' suggestion (see here) with autism in mind. Certainly, I think there is quite a bit more research to see and do in this area.

Music: Buddy Holly - Rave on!

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[1] Shelton JF. et al. Neurodevelopmental disorders and prenatal residential proximity to agricultural pesticides: The CHARGE study. Environ Health Perspect. 2014: June 23.

[2] De Felice A. et al. Prenatal Exposure to a Common Organophosphate Insecticide Delays Motor Development in a Mouse Model of Idiopathic Autism. PLoS One. 2015 Mar 24;10(3):e0121663.

[3] Venerosi A. et al. Effects of maternal chlorpyrifos diet on social investigation and brain neuroendocrine markers in the offspring – a mouse study. Environmental Health 2015, 14:32.

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De Felice, A., Scattoni, M., Ricceri, L., & Calamandrei, G. (2015). Prenatal Exposure to a Common Organophosphate Insecticide Delays Motor Development in a Mouse Model of Idiopathic Autism PLOS ONE, 10 (3) DOI: 10.1371/journal.pone.0121663

Physical activity and fitness levels and autism

Although at present having to be slightly more cautious following some recent surgery (general anaesthetic is awesome by the way!), I normally consider myself to be quite an active person. Through previous discussions on this blog covering topics on the positive effects of walking (see here) and the physical+ benefits of the martial arts (see here) I'd like to think that there are quite a few ways and means that the population at large can easily increase their daily physical activity levels. That physical activity might have quite a few knock-on effects for mental health and wellbeing is another angle to which I subscribe.

"'A storm is coming,' Frank says"

With my autism research blogging hat on, I've talked about how quite a bit of the peer-reviewed literature looking at autism and physical activity levels seems to imply 'more to do' when it comes to decreasing sedentary behaviours and getting people up and active (see here). A recent paper from Kiley Tyler and colleagues [1] (open-access) confirms this assertion.

The Tyler paper in open-access but a few pointers might be useful...

• Small groups of children and young adults with autism (n=17) and asymptomatic controls (n=12) were included for study and following an assessment looking at diagnostic and developmental factors were investigated using "a series of physical fitness assessments in aerobic fitness, muscular strength, flexibility, and anthropometric measures (height and weight)". We are also told that: "Physical activity was measured through accelerometry".
• If, like me, measures like aerobic fitness mean very little to you, this particular assessment involved something called the 20-metre multistage shuttle run [2] used to "determine the estimated maximal aerobic power (VO2max) for that individual". Basically, run back and forth across 20m to an ever frequent pinging sound until you can do no more and measure your maximum rate of oxygen consumption. 
• Muscular strength was measured "using a handgrip strength assessment". Reading about this assessment brought to mind some other autism research in this area which I read about recently from Janet Kern and colleagues [3].
• Physical activity levels were assessed using an accelerometer worn over 7 days. 
• Results: well, most of the physical fitness parameters did not significantly differ between the autism and not-autism groups. Strength did come out as reduced in the autism group as per the findings from Kern et al but that's about it. 
• But... physical activity levels were different between the groups across the various gradings describing sedentary, light and moderate activity levels. "Children with ASD spent less time in light, moderate, and moderate-to-vigorous physical activity and spent more time in sedentary behavior when compared to typically developing peers".
• The authors conclude that: "more research is needed on the physical activity determinants specific to children with ASD [autism spectrum disorder]". But also that their results were "encouraging as they indicate that children and youth with an ASD show capacity to meet daily guidelines for physical fitness and activity".

So basically, this particular cohort of children and young adults with autism do not lack the capacity to engage in physical activity but for whatever reason, physical activity levels are down compared to those not in receipt of a diagnosis of autism. I should also say that I summarise this without pointing any fingers of blame.

A quick trawl of some of the related research literature in this area provides one or two clues as to what might be influencing those activity levels. Schenkelberg and colleagues [4] talked about features of the social environment potentially influencing physical activity levels of children with autism. It is perhaps an under-appreciated aspect of the social side of autism that solitary play for example, is probably not going to include any great degree of physical activity as compared to what you might see in shared play with peers for example. Schenkelberg et al kinda hint at this with their observation of no significant differences in physical activity levels between their small group with autism vs. asymptomatic controls when engaged in "organized activity".

I mentioned previously that capacity to engage in physical activity did not seem to be affected in the participants of the Tyler study but one should also not assume this is pertinent to all on the autism spectrum. Motor issues have been talked about previously on this blog (see here) and, as per the findings from Christensen and colleagues [5] there is a growing appreciation that an autism diagnosis might increase the risk for conditions potentially affecting motor function: "The higher frequency of ASD in non-spastic than in spastic subtypes of CP [cerebral palsy] calls for closer examination". Again, something discussed on this blog before (see here). Rather more speculatively, I'm also minded to point you to a gap in the research base looking at something like comorbidity of Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS / ME) with autism (see here) as another area to potentially investigate.

Physical inactivity is pretty endemic these days across all walks of life. Autism is not unique in its general relationship to relative inactivity although does seem to rank up there when it comes to the available data [6]. Allied to the data on levels of obesity in cases (see here) and the corresponding issues circling things like eating habits for example (see here), there are some important factors to tackle here to ensure that such physical inactivity does not further 'disable' or disadvantage many people who are perhaps already subject to significant health inequality...

Oh, and just in case you were wondering, it's as easy as 10,000 steps [7].

Music then. Fill My Little World by The Feeling.

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[1] Tyler K. et al. Physical Activity and Physical Fitness of School-Aged Children and Youth with Autism Spectrum Disorders. Autism Research and Treatment. 2014; Article ID 312163.

[2] Léger LA. et al. The multistage 20 metre shuttle run test for aerobic fitness. J Sports Sci. 1988 Summer;6(2):93-101.

[3] Kern JK. et al. Handgrip strength in autism spectrum disorder compared with controls. J Strength Cond Res. 2013 Aug;27(8):2277-81.

[4] Schenkelberg MA. et al. Social Environmental Influences on Physical Activity of Children With Autism Spectrum Disorders. J Phys Act Health. 2014 Aug 7. [Epub ahead of print]

[5] Christensen D. et al. Prevalence of cerebral palsy, co-occurring autism spectrum disorders, and motor functioning - Autism and Developmental Disabilities Monitoring Network, USA, 2008. Dev Med Child Neurol. 2014 Jan;56(1):59-65.

[6] Mangerud WL. et al. Physical activity in adolescents with psychiatric disorders and in the general population. Child Adolesc Psychiatry Ment Health. 2014 Jan 22;8(1):2.

[7] LaLonde KB. et al. Increasing physical activity in young adults with autism spectrum disorders. Research in Autism Spectrum Disorders. 2014; 8: 1679-1684.

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Tyler, K., MacDonald, M., & Menear, K. (2014). Physical Activity and Physical Fitness of School-Aged Children and Youth with Autism Spectrum Disorders Autism Research and Treatment, 2014, 1-6 DOI: 10.1155/2014/312163

Scurvy, vitamin C and autism

I'd been thinking about writing this post on scurvy, vitamin C and autism for quite a while. The paper by Kitcharoensakkul and colleagues [1] really made the decision for me, following their discussions on three young children with walking difficulties who were eventually diagnosed with scurvy, one of whom was diagnosed with autism. The authors concluded: "These clinical manifestations and radiologic findings highlight the importance for rheumatologists to have a higher index of suspicion for scurvy in nonambulatory children". Nonambulatory by the way, means not able to walk about (independently). "Interestingly, all patients had concomitant vitamin D deficiency" was another important point made in the Kitcharoensakkul study which is something I'm always a little interested in on this blog (see here).

Limes... @ Fludkov @ Wikipedia 

Scurvy, as some people might already know, is a condition characterised by a lack of sufficient vitamin C (ascorbic acid). It can manifest in a variety of ways including fatigue, lack of appetite, irritability alongside various functional gastrointestinal (GI) symptoms. Gingival swelling or bleeding (the gums) is perhaps one of the best known [oral] signs of the disease. Nowadays it is quite a rare condition.

In other blog entries I've referred to myself as a Limey reflective of a slang phrase for someone from these hallowed Isles called Great Britain (Britain, Britain, Britain..), which seems to derive from the practice of giving lime juice to British sailors way back when, to prevent scurvy.

Suffice to say however that the Kitcharoensakkul paper is not the first time that scurvy has appeared alongside the word autism or words autism spectrum disorder (ASD) as I'll attempt to show you...

• Case studies describing scurvy concurrent to a diagnosis of autism can be found in the peer-reviewed research literature [2]. The description by Mawson [3] is typical although some symptoms reported in that particular case as being perhaps complicated by "treatment with indomethacin, which lowers vitamin C levels" is an important addition. I do think it is important to raise the point that some medicines can interfere with the availability of things like vitamins and minerals similar to such nutraceuticals affecting some medicines.
• Cole and colleagues [4] talked about the continued presence of scurvy "among susceptible populations" which includes "certain unique populations-particularly the elderly subjects, patients with neurodevelopmental disabilities or psychiatric illnesses, or others with unusual dietary habits" in their report on a "10-year-old autistic child". 'Unusual' dietary patterns are no stranger to autism [5] (open-access here) over and above any special dietary regimes being implemented (see here).
• Congidi and colleagues [6] described another case of scurvy in "an autistic child with food-avoidant behavior". They also described MRI findings for their patient. Indeed, this is something also described in the report by Tetsu and colleagues [7] who reported that the: "imaging findings of the thigh showed diffuse signal abnormality in the bone marrow, periosteum, and the femoral muscle". Further: "A biopsy specimen of the femur showed hematoma, proliferative fibroblasts, and few collagen fibers, which suggested a deficiency of vitamin C".
• Slightly outside of the issue of scurvy is the study presented by Dolske and colleagues [8] "exploring the effectiveness of ascorbic acid (8g/70kg/day) as a supplemental pharmacological treatment for autistic children in residential treatment". Although this was a small trial in terms of participant numbers, it was a "double-blind, placebo-controlled trial" lasting 30 weeks. The authors reported "a reduction in symptom severity associated with the ascorbic acid treatment" making specific mention of "sensory motor scores". Obviously I'm not making any recommendations about these findings (no medical or clinical advice given or intended) but do find them to be interesting and perhaps overlapping with other research where vitamin C supplementation has been included. So, think back to the Jim Adams trial data (see here) based on some older research [9]. As to the hows and whys, well, unlike the chatter about vitamin C therapy potentially impacting on Epstein-Barr antibodies no biological measure was used in the Dolske study so we are left speculating...

As you've probably realised, most of the research evidence surrounding the presence of scurvy in cases of autism is based on individual case reports. I can't for example, provide you with any population estimates of how prevalent scurvy might be in cases of autism because no-one has really looked at this issue with any great assiduity. I can point you in the direction of other work talking again about cases of scurvy appearing alongside schizophrenia for example [10] but will only say that a poor diet lacking in sources of vitamin C is as much to blame in those examples as it probably is where cases of autism are discussed.

Just before I go, there are a few other things to note about vitamin C and autism which may also be pertinent to other issues. I've talked about iron before on this blog and how there is some data suggesting issues with iron for some on the autism spectrum (although certainly not all). It's quite long been recognised that vitamin C also plays a role in the absorption of iron [11] particularly non-heme iron sources and a deficiency in vitamin C is probably not going to be conducive to 'optimal' function. Quite a while back I also talked about autism and oxalates (see here) but will say no more than re-iterating the study by Chai and colleagues [12] with the requirement for lots more investigation in this area.

To close, I was saddened to hear of the death of Prof. Paul Patterson this week, a real research pioneer who's studies on autism and schizophrenia were frequently discussed on this blog (see here and see here). One of his final research contributions was the very important study fronted by Elaine Hsiao supporting a "gut-microbiome-brain connection in a mouse model of ASD". My condolences go to his family and those who knew him.

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[1] Kitcharoensakkul M. et al. Scurvy revealed by difficulty walking: three cases in young children. J Clin Rheumatol. 2014 Jun;20(4):224-8.

[2] Monks G. et al. A case of scurvy in an autistic boy. J Drugs Dermatol. 2002 Jul;1(1):67-9.

[3] Mawson AR. Bone pain, growth failure, and skin rash after an upper respiratory illness in a boy with autism: possible association with altered retinoid metabolism. Clin Pediatr (Phila). 2009 Jan;48(1):21-5.

[4] Cole JA. et al. Scurvy in a 10-year-old boy. Pediatr Dermatol. 2011 Jul-Aug;28(4):444-6

[5] Bandini LG. et al. Food selectivity in children with autism spectrum disorders and typically developing children. J Pediatr. 2010 Aug;157(2):259-64.

[6] Gongidi P. et al. Scurvy in an autistic child: MRI findings. Pediatr Radiol. 2013 Oct;43(10):1396-9.

[7] Tetsu N. et al. curvy in a Child With Autism: Magnetic Resonance Imaging and Pathological Findings. Journal of Pediatric Hematology/Oncology. 2012; 34: 484-487.

[8] Dolske MC. et al. A preliminary trial of ascorbic acid as supplemental therapy for autism. Prog Neuropsychopharmacol Biol Psychiatry. 1993 Sep;17(5):765-74.

[9] Adams JB. & Holloway C. Pilot study of a moderate dose multivitamin/mineral supplement for children with autistic spectrum disorder. J Altern Complement Med. 2004 Dec;10(6):1033-9.

[10] Dubé M. Scurvy in a man with schizophrenia. CMAJ. Aug 9, 2011; 183(11): E760.

[11] Hallberg L. et al. The role of vitamin C in iron absorption. Int J Vitam Nutr Res Suppl. 1989;30:103-8.

[12] Chai W. et al. Oxalate absorption and endogenous oxalate synthesis from ascorbate in calcium oxalate stone formers and non-stone formers. AJKD. 2004; 44: 1060-1069.

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Kitcharoensakkul M, Schulz CG, Kassel R, Khanna G, Liang S, Ngwube A, Baszis KW, Hunstad DA, & White AJ (2014). Scurvy revealed by difficulty walking: three cases in young children. Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 20 (4), 224-8 PMID: 24847751