Friday, 14 June 2019

Nighttime body movements and autism

I was rather interested in the findings reported by Nobushige Naito and colleagues [1] talking about how atypical body movements during the night seemed to be more frequently observed in children diagnosed with an autism spectrum disorder (ASD) compared to not-autism controls. Interested because, sleep is a long-running 'issue' in relation to autism (see here) and because, researchers relied on the use of actigraphy in their study: "a movement-based index measured by an accelerometer" rather than just second-hand observational questioning.

So: "Seventeen TD [typically developing] children and 17 children with ASD participated in this study (5 to 8 years old)." Importantly (see here) we are told that: "Considering the frequent co-occurrence of ASD and ADHD [attention-deficit hyperactivity disordersymptoms, we did not exclude ASD patients with ADHD symptoms." Authors relied on data from a waistband accelerometer worn by participants over at least 3 nights. Using a waistband was seen as preferable to the more typical wristband. Data was collected and analysed. It included something called a movement index (MI): "the ratio of the body movement period in 20 minutes was calculated continuously for 9 hours using the sliding window method."

Results: "a higher rate of body movement 2 to 3 hours after the first onset of body stillness was more prominent in children with ASD than in TD children." Importantly authors also mention how the objective data provided by the waistband accelerometer showed a different "time course of body movements during night in young children with ASD" despite parents/carers reporting no "apparent" problems with sleeping. They also talk some of the differences in body movements seen in those children with ASD potentially *related* to some awake behaviours - "a lower social ability and more frequent maladaptive behaviour."

The Naito results represent a good start at looking at these important behaviours. I'm a little bit hesitant to go all-in with the suggestion from the authors that "atypical nocturnal body movement could be an ASD state and trait marker in young children with ASD" but can see the importance of further investigations in this area.

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[1] Naito N. et al. Atypical body movements during night in young children with autism spectrum disorder: a pilot study. Sci Rep. 2019 May 6;9(1):6999.

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Wednesday, 12 June 2019

Childhood dietary patterns and ADHD?

The findings of the systematic review and meta-analysis published by Bianca Del-Ponte and colleagues [1] provide the blogging fodder today, and the suggestion that: "a diet high in refined sugar and saturated fat can increase the risk, whereas a healthy diet, characterized by high consumption of fruits and vegetables, would protect against ADHD [attention-deficit hyperactivity disorder] or hyperactivity."

The starting point: "The diet during childhood has been investigated as a factor potentially involved in the ADHD etiology." Yes it has, and Del-Ponte et al managed to find 14 studies looking at this issue published in the peer-reviewed literature. The data were boiled down and results obtained suggesting that "healthy dietary patterns were protective against ADHD (OR: 0.65; 95% CI: 044 – 0.97), while unhealthy dietary patterns were found as risk to ADHD (OR: 1.41; 95% CI: 1.15–1.74)."

The authors admit that the science upon which they made their observation is "weak" insofar as cause and effect not being proved. This is an important point (see here) that follows other research in this area too (see here and see here) together with an understanding that many different variables *might* influence the risk of something like ADHD as a diagnosis or in behaviour (see here and see here for examples).

Still, if there is even the remotest possibility that diet might be something to consider in respect of ADHD, adding it to the intervention arsenal that already exists (see here) can only be a good thing...

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[1] Del-Ponte B. et al. Dietary patterns and attention deficit/hyperactivity disorder (ADHD): A systematic review and meta-analysis. Journal of Affective Disorders. 2019; 252: 160-173.

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Tuesday, 11 June 2019

SHANK3, gut issues and (mouse) autism continued

"We conclude that apart from its well-known role in the CNS [central nervous system], SHANK3 plays a specific role in the GI [gastrointestinal] tract that may contribute to the ASD [autism spectrum disorder] phenotype by extracerebral mechanisms."

So said the findings reported by Ann Katrin Sauer and colleagues [1], and yet more evidence that issues with SHANK3 mentioned in relation to 'some' autism, may well (partly) explain much more than just behaviour (see here and see here).

The Sauer study was yet another mouse study. They specifically focused on the "Shank3αβ KO" mouse, where KO means knock-out, referring to the engineering of this mouse strain to mimic issues with the functioning and availability of SHANK3, "a known scaffolding protein of the postsynaptic density (PSD) of glutamatergic excitatory synapses." Said knock-out mice have been "reported to display ASD-like behavior with abnormal ultrasonic vocalization, repetitive self-grooming, and reduced interest in novel mice." I say this being careful to reiterate that we're talking about a mouse not human beings (see here).

On the basis of the observation that SHANK3 is expressed in the gut as well as brain and that GI issues are no stranger to autism (see here), researchers set about looking at how SHANK3 issues might also manifest as gut issues, and what this *could* mean for some autism. They observed some interesting things:

  • "analysis of the GI tract of Shank3αβ KO mice revealed significantly altered gut morphology" which included, among other things, increased levels of ZONULIN1 ("a modulator of tight junctions and alterations"). Zonulin is something that I'm particularly interested in on this blog (see here and see here) on the basis of its *connection* to intestinal barrier function and the misnomer that is 'leaky gut' (see here).
  • "The Microbiome of Shank3 KO Mice Is Altered." Bearing in mind the increasing importance of the gut microbiome to autism (see here), researchers reported some interesting difference between "Shank3αβ KO mice" and controls with regards to several different bacterial species. 
  • Researchers describe how those gut morphology and gut bacterial differences seemed to be linked to alterations in the "expression of inflammatory markers" too as they talked about "signs of increased immune activation in the periphery and the brain." A familiar cytokine is mentioned - IL-6 - and quite a few avenues for further investigation.

The net result of all this work is to say that, yes, the SHANK3 mouse model *potentially* mimicking some of the behavioural signs and symptoms of autism does also appear to show some significant gut-related issues. No, this does not directly translate into issues for 'all human autism', but it does add further credence to the idea that the gut-brain axis is likely important to at least 'some autism'. Where also SHANK3 issues are identified as coinciding with 'human autism', one might also entertain the idea that gut issues should be screened and treated/managed. And there might be lots of ways to manage them (see here for one example)...


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[1] Sauer AK. et al. Altered Intestinal Morphology and Microbiota Composition in the Autism Spectrum Disorders Associated SHANK3 Mouse Model. Int. J. Mol. Sci. 2019; 20: 2134.

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Monday, 10 June 2019

Constipation and autism is not an uncommon combination

For those who know (or think they know) anything about autism, the title of this post - "Constipation and autism is not an uncommon combination" - is unlikely to be new or novel. Indeed, I've talked again and again and again about how functional gastrointestinal (GI) symptoms are very well over-represented when it comes to a diagnosis of autism (see here for example).

Enter then two further recent articles - one from Bradley Ferguson and colleagues [1] and one from María José Penzol and colleagues [2] - which further add to the evidence base in this area. Both papers are open-access, so please peruse at your leisure. The long-and-short of them can be quickly summarised:


  • The Ferguson paper set out to examine the "relationships among GI [gastrointestinal] problems, problem behaviors, and internalizing symptoms in a sample of 340 children and adolescents with ASD [autism spectrum disorder]." Caregivers/parents reported on their child's GI issues. Bottom line: "The majority of the sample experienced constipation (65%)." Various other functional GI issues were also reported.
  • The Penzol paper "reviewed the medical records of all patients admitted to the Comprehensive Medical Program for ASD (AMITEA) at Gregorio Marañón University General Hospital from January 2012 to December 2015." They analysed records for nearly 850 patients diagnosed with ASD. Their data were collected and transcribed by physicians including the "presence of fGID [functional gastrointestinal disorders] (gastrointestinal reflux, aerophagia, functional diarrhea, functional constipation, functional abdominal pain, cyclic vomiting)." Bottom line: "At least one fGID was present in 30.5% of patients, constipation being the most prevalent (47.4% of fGID patients)." They also observed that GI issues *seemed* to be related to the presence of intellectual (learning) disability, sleep issues and behavioural problems. These are not novel associations (see here and see here).


Of course there are strengths and weaknesses to those studies. No-one would dispute the fact that these are not perfect data. But, set within the context of a mountain of peer-reviewed science suggesting that something like constipation is over-represented when it comes to a diagnosis of autism, the collected results add a further layer of evidence. They also ask the question 'why', why oh why have we not got a greater handle on how to successfully treat/manage such symptoms?

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[1] Ferguson BJ. et al. The Relationship Among Gastrointestinal Symptoms, Problem Behaviors, and Internalizing Symptoms in Children and Adolescents With Autism Spectrum Disorder. Front Psychiatry. 2019 Apr 9;10:194.

[2] Penzol MJ. et al. Functional Gastrointestinal Disease in Autism Spectrum Disorder: A Retrospective Descriptive Study in a Clinical Sample. Front Psychiatry. 2019 Apr 10;10:179.

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Friday, 7 June 2019

Preventing, yes preventing, elopement in kids with autism

I know the word 'prevention' is a dirty word for some in relation to some aspects of autism. When however 'prevention' is used in the context of elopement or wandering and autism, the word(s) take on an altogether different meaning...

The word prevention is used in the study findings reported by Silvia Pereira‐Smith and colleagues [1] and their focus on "the use of preventive measures that target elopement" in relation to autism. They add that "elopement can lead to dire consequences." Seldom have truer words been spoken in relation to this issue with autism in mind (see here).

For those of you who might know too much about this topic, wandering is an important issue in both autism research and practice (see here and see here). Figures suggest that around 1 in 4 children diagnosed with an autism spectrum disorder (ASD) will consistently wander from home or school or other place, but this issue does not seem to be as widely talked about or parents/caregivers consistently given as much information about it as they should.

Pereira-Smith and colleagues asked nearly 400 parent-caregivers of children and young people diagnosed with an autism spectrum disorder (ASD) about their [child's] experience of wandering/elopement. They asked questions about who did it, "preventive measure use, and sociodemographic characteristics" of their cohort.

Results: "Two hundred and sixty-seven caregivers (68%) reported elopement by their child." That figure is way over the 1 in 4 estimate that has been previously banded around. Researchers also found that wandering was not confined to any one "sociodemographic characteristics, nor with any specific comorbidity or neurobehavioral medication." Kids and young people across the autism spectrum wandered. That being said: "Children with limited communication skills were more likely to have a history of elopement." As for that word 'prevention', most families used "lock(s) at top of doors" with other families utilising "handicap permits, signs/visual markers, or tracking devices" albeit to a lesser degree than locks. Researchers conclude that "use of specific preventive measures can help guide recommendations for this dangerous comorbid symptom, and provide information needed for future studies to assess the efficacy of various preventive measures." Who would argue with that?

Oh, and just to let you know that there are some autism organisations who have really taken a lead in this area (see here)...

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[1] Pereira-Smith S. et al. Preventing elopement in children with autism spectrum disorder. Autism Res. 2019 Apr 29.

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Thursday, 6 June 2019

That 'gut bacteria transplant provokes autistic signs in mice' paper is not perfect but...

The paper by Gil Sharon and colleagues [1] has certainly created headlines and discussion in equal measure (see here and see here and see here and see here). Concluding that: "Mice harboring human ASD [autism spectrum disorder], but not TD [typically developing], microbiomes exhibit ASD-like behaviors", the idea of a gut-brain connection in relation to autism (see here) potentially gains some research traction.

The Sharon study involved transplanting gut bacteria - the gut microbiome - from a small number of participants - "from 5 control volunteers and 11 patients diagnosed with autism spectrum disorder" - into mice lacking a microbiome and breeding said mice. They then analysed the behaviour and other biological parameters of those offspring mice according to whether their mother mice had received a transplant from controls or participants with various 'degrees' of autism. They also looked at 'metabolite profiles' based on "analyses of colon contents from oTD [offspring typically developing] and oASD [offspring autism spectrum disorder] mice."

Results: "colonization with ASD microbiota is sufficient to induce hallmark autistic behaviors." By 'hallmark autistic behaviors' researchers observed that said mice showed "increased repetitive behavior, decreased locomotion, and decreased communication... compared to mice colonized with samples from TD controls (oTD), as tested by marble burying (MB), open-field testing (OFT), and ultrasonic vocalization (USV), respectively." Researchers also observed specific differences across the mouse group gut microbiomes, some of which were consistent with that noted in other independent studies.

Also: "Twenty-seven out of 313 detected metabolites were significantly different in the colon contents of oASD mice, compared to oTD mice." They specifically focused in on two metabolites - taurine and 5-aminovaleric acid (5-AV) - both of which were reported in lower levels in the oASD mice, and how these compounds show a *connection* to GABA, a compound potentially important to autism (see here). Further they showed that supplementation of 5-AV and taurine to another strain of mouse that serves as a 'mouse model of autism' (BTBR T+ tf/J (BTBR) mouse model) resulted in "improved repetitive and social behaviors." I should add the word 'mouse' into the sentence "improved repetitive and social behaviors."

Insofar as the limitations of the Sharon studies and paper, various people have been keen to point out that the results should be viewed cautiously and as preliminary. This on the basis of the number of animals included for study, the reliance on mouse models of autism (and the logical fallacies that can sometimes follow) and some of the generalisations made in the study write-up by the authors. I wouldn't disagree with such cautions, bearing in mind that some mouse models of autism - the valproic acid autism mouse model for example - actually seem to be pretty good at mimicking some facets of (induced) autism. I'd also point out that the metabolomics work undertaken by Sharon and colleagues looks to be pretty wide-ranging (GC-MS and NMR are discussed) and findings related to taurine have also been noted in other independent study (see here). I also observed that there was a research tie-up with Arizona State University in the Sharon study, as the name Dae-Wook Kang is mentioned and 'poo transplants for [some] autism' makes yet another appearance (see here and see here).

"While ours is a limited study, with 16 donor samples from a pediatric cohort, the results support a hypothesis that the human gut microbiota contributes to ASD phenotypes." I'd agree that the Sharon results add a further layer to the idea that the new triad - intestinal permeability, mucosal immunology and intestinal microbiota - could be important to at least some autism. The results offer a road map for further investigation in this area and perhaps eventually, yet another avenue for screening and intervention to complement other recent initiatives (see here); all set with the view of the (plural) 'autisms'.

Finally, I note that another study [2] mentioning the words 'mouse' and 'autism' has been published recently. With some media attention mentioning how: "Exercise reversed autistic behaviors in an animal model of the condition" there didn't seem to be the same 'keenness' to point out the flaws of the Andoh study, despite once again a reliance on 'mouse autism' and all which that entails. It makes me wonder whether the focus on the second brain (gut) and autism detailed in the Sharon study might still have the ability to raise hackles in some quarters?

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[1] Sharon G. et al. Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice. Cell. 2019 May 30;177(6):1600-1618.e17.

[2] Andoh M. et al. Exercise Reverses Behavioral and Synaptic Abnormalities after Maternal Inflammation. Cell Reports. 2019; 27: 10. June 4.

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Wednesday, 5 June 2019

"specific clinical and neuropsychological dimensions might be related to suicidal behaviors in ASD"

The quote titling this post - "specific clinical and neuropsychological dimensions might be related to suicidal behaviors in ASD [autism spectrum disorder]" - comes from the findings reported by Luisa Weiner and colleagues [1] (open-access). It adds to other recent research talking about how elements of autism *might* associate with suicidality (see here). I should warn you that some of the Weiner findings make for difficult reading.

Authors described a case report of "a 21-year-old male [Mr A] with ASD who attempted suicide twice, in the absence of other psychiatric diagnoses." They detail how, following some quite comprehensive observations, a possible *connection* was noted between his suicidality and "some of the core clinical and neuropsychological features of ASD."

A few important points are highlighted in the Weiner study: "Mr. A. reported that his suicidal thoughts started when he was 18, following an unrequited infatuation with a classmate – the result of a rational decision: he had decided to “fall in love” with her." Things did not however go as he planned, as we are told that: "He started having “obsessive negative thoughts”, and attempted suicide by jumping from a window." He survived but "his suicidal thoughts lingered, characterized by a restrictive, rigid pattern."

Researchers relied on the Beck Depression Inventory (BDI) to rule out depression in this case: his score "was in the normal range (3/63)." This inventory is one of a few that have been described as being "robust in their measurement properties in the general population" [2] but with perhaps more to do in the context of its use in autism. In the absence of depression or rather elevated self-report scores indicative of depression, authors suggest this raises "the question of whether the persistence of suicidal thoughts was associated with ASD-related features."

The Weiner findings have to be placed in the context of other independent research looking at suicidality and autism. First, risk of suicidality is seemingly heightened when autism is diagnosed (see here). Second, although depression - an important variable *linked* to suicidality - is over-represented in relation to autism (see here), questions are still being asked about the impact of depression in relation to suicidality accompanying autism in the context of an often complicated clinical picture (see here). Third, the idea that the features/traits of autism might themselves be independent predictors of suicidality in autism has been discussed on several research occasions (see here and see here and see here).

The culmination of all this work is that quite a lot more research and clinical resources need to be ploughed into looking at suicidality and autism. And, importantly, translating said research into real-world actions to potentially save lives.

If you need someone to talk to, there are organisations out there...

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[1] Weiner L. et al. A case study of suicidality presenting as a restricted interest in autism Spectrum disorder. BMC Psychiatry. 2019; 19: 126.

[2] Cassidy SA. et al. Measurement properties of tools used to assess depression in adults with and without autism spectrum conditions: A systematic review. Autism Res. 2018 May;11(5):738-754.

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