Making physical activity more attractive to teens with autism

I don't want to keep you too long today, what with it being All Hallows' Eve and all the formalities that accompany this festival. I would however like to pass the paper by Heidi Stanish and colleagues [1] your way and some details on the hows and whys of "physical activity enjoyment, perceived barriers, beliefs, and self-efficacy" when it comes to teens diagnosed with an autism spectrum disorder (ASD).

Based on questionnaire responses from 35 adolescents with ASD and 60 not-ASD controls (I'm not a great fan of the words 'typically developing'), researchers reported a few potentially important group differences in terms of enjoyment of things like physical education (84% vs. 98% respectively) and preferences to engage in physical activity in their spare time (25% vs. 58%). These and other group disparities are framed within the idea that "differences identified may inform program development" when it comes to getting teens with autism more involved in physical pursuits.

As per other occasions on this blog (see here and see here), I'm particularly interested in the various research looking at physical activity and autism; specifically the ways and means sedentary behaviours can be 'modified' when it comes to parts of the autism spectrum (see here). We're all being told these days that everyone needs to perhaps move a little more to improve physical wellbeing (see here) and those on the autism spectrum are no exception to this advice.

Some of the hurdles identified by Stanish et al focused on enjoyment of sport and exercise and the idea that "physical activities were too hard to learn" are factors that I would suggest, can be fairly easily overcome with the right advice and resources. As per the findings reported by Todd and colleagues [2] based on the use of cycling for example, certain "self-regulation interventions" can help to get children and young adults on the road to physical activity participation. Small steps and finding the right physical activity are perhaps other key tenets to improving participation and exposing those who are perhaps a little exercise-adverse to the wide, wide range of possible activities.

Have I also mentioned that I'm a bit of fan of the potential benefits of the martial arts for those on the spectrum?

Music: Safety Dance by Men Without Hats. Spooky stuff...

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[1] Stanish H. et al. Enjoyment, Barriers, and Beliefs About Physical Activity in Adolescents With and Without Autism Spectrum Disorder. Adapt Phys Activ Q. 2015 Oct;32(4):302-17.

[2] Todd T. et al. Cycling for students with ASD: self-regulation promotes sustained physical activity. Adapt Phys Activ Q. 2010 Jul;27(3):226-41.

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Stanish H, Curtin C, Must A, Phillips S, Maslin M, & Bandini L (2015). Enjoyment, Barriers, and Beliefs About Physical Activity in Adolescents With and Without Autism Spectrum Disorder. Adapted physical activity quarterly : APAQ, 32 (4), 302-17 PMID: 26485735

People commit crimes not their clinical labels

"Oregon Killer’s Mother Wrote of Troubled Son and Gun Rights" and "The Myth of the ‘Autistic Shooter’".

Those were just two of the headlines that I read recently about the tragedy that rocked the town of Roseburg in the United States and the inevitable attempts to understand such a senseless act.

Accepting that our thoughts and prayers should focus on the those murdered, and the long and painful journey that now faces families and loved ones (including that of the perpetrator's family), mention of the autism spectrum as 'potentially' being part and parcel of the killer's 'profile' is something that perhaps requires some science-based discussion. I appreciate that significant emotions come into such tragic stories as per previous instances and the question of 'why', but this is a blog about science and autism. I'm gonna stick to the available peer-reviewed literature specifically on the topic of autism and offending without hopefully sounding too cold nor too dispassionate.

I think it is worth going over a few things first for any newcomers straying across this post.

First, a few sentences about autism and/or the autism spectrum. Clinically, autism describes a developmental disorder that variably affects communication and social interactions (social affect) among other things. Alongside a heightened risk for various comorbidity - psychological and somatic - a diagnosis on the autism spectrum is both "profound and pervasive" in terms of impact on a person's life. For some that means a lifetime of round-the-clock care; for others, sometimes wrongly labelled as 'high-functioning', it can mean struggling with even mundane daily activities, not made any easier by societal attitudes and stereotypes and often accompanied by a lack of appropriate social and healthcare support. Although not wishing to paint too bleak a picture, the increased rates of suicide ideation (see here) and even requests for euthanasia (see here) for example, can represent the extremes of the struggles faced by people on the autism spectrum. I might also add that the 'lack of social and healthcare support' sentence previously mentioned similarly extends to quite a few families caring for people with autism too.

Next, although a diagnosis of autism does not provide immunity against offending behaviour, people with autism are far more likely to be a victim of crime over and above a perpetrator. Indeed, some of the traits associated with autism mean that many people on the spectrum are uniquely vulnerable to issues such as bullying (see here for the most recent research review), harassment or sometimes worse. Such traits can also lead to some people on the autism spectrum being drawn into criminality or committing criminal acts without fully comprehending the intentions of their accomplices and/or understanding the gravity of their actions. I hasten to add that such 'naivety' (if I can call it that) is likely multi-factorial in terms of the hows and whys; sometimes moderated by associated learning difficulties for example, and other times not.

OK. I hope that clears up a few things. The other point I want to make is that whilst the label of autism describes some of the behaviours of a person, I personally don't subscribe to the view that autism does (or should) define a person, in the same way that the labels of depression and anxiety or even schizophrenia don't define people. In this context, the important point is that 'people commit crimes not their clinical labels'. Keep that in mind as I continue.

Accepting that at the time of writing this post, we don't have all the details (or confirmation of of all the details) about whether indeed the killer "struggled with Asperger’s syndrome, an autism spectrum disorder" or not, there is some science on this topic in relation to such extreme offending behaviour.

Although making uncomfortable reading, I want to start with the paper by Clare Allely and colleagues [1] (open-access) which garnered quite a bit of media attention when it was first published back in 2014 on the basis of a suggestion that "a significant proportion of mass or serial killers may have had neurodevelopmental disorders such as autism spectrum disorder or head injury." Retrospectively looking at several accounts of mass or serial killers, the authors concluded that there was some evidence that "in at least some cases, neurodevelopmental problems such as ASD [autism spectrum disorder] or head injury may interact in a complex interplay with psychosocial factors to produce these very adverse outcomes." I can remember various reactions to this paper when it saw the light of day; quite a few rooted in the fear that sweeping generalisations would ensue and similar to the historical situation in schizophrenia, all autism would be generalised and equated with dangerousness.

As it turns out that didn't happen. Indeed, I actually thought the Allely paper made some important points in their review. They didn't, for example, say that every serial or mass killer 'had autism', indeed not even close: "we are able to say that probably more than 10% of serial/mass killers have ASD and a similar proportion have had a head injury." With the estimated rates of autism these days (1 in 46 according to some reports), one can perhaps see how that percentage might cover at least some of what would be expected in the general population anyway.

What Allely et al did observe is: (a) that "serial and mass killings are rare" and (b) that: "The gaps in our understanding about the actual mechanisms of development toward these most negative of outcomes are enormous." Further: "the great majority of those with ASD or head injury had also experienced psychosocial risk factors such as parental divorce, physical or sexual abuse, and major surgery during childhood." That last point might tie in with some of the details coming out of the Roseburg tragedy, although with the important provisos that (i) correlation is not necessarily the same as causation and that (ii) sweeping generalisation is usually the mother of all mistakes.

Continuing the theme of other factors/variables occurring alongside autism as also being potentially important to instances of offending behaviour are the findings reported by Newman & Ghaziuddin [2]. Surveying some of the scientific literature on the topic of violent crime specifically in relation to Asperger syndrome, the authors concluded that some 30% of cases were accompanied by "a definite psychiatric disorder" and a further 50% had a "probable psychiatric disorder at the time of committing the crime."

This research reiterates the idea that autism, some autism, offers little in the way of protection when it comes to risk of other psychopathology occurring alongside. Screening for such comorbidity should be much more of a priority than it currently is. Without hopefully shifting blame between labels - remember people commit crimes not their labels - there is a body of research emerging suggesting that issues such as psychosis for example, may show a complicated relationship with some autism. I've covered this topic a few times on this blog (see here and see here) particularly where the manifestation(s) of psychosis has led to a subsequent diagnosis on the autism spectrum. Psychosis by the way, is characterised by disrupted perception and/or interpretation of the world around. Although by no means a universal relationship, there is some evidence that particularly in first-episode psychosis, homicide rates may be heightened [3]. That all being said, I will also draw your attention to the systematic review from King & Murphy [4] on offending profiles with autism in mind which reported: "poor evidence of the presence of comorbid psychiatric diagnoses (except in mental health settings) amongst offenders with ASD."

Moving on, and the paper by Helverschou and colleagues [5] provides some further potentially important details about such offending profiles in individuals diagnosed with an ASD. So; "Unlike most others who commit criminal acts, the majority of the individuals with autism spectrum disorder in this study showed no evidence of substance abuse, had a close relationship to their victims and were willing to confess to the accused crime." Further: "in most cases, autism spectrum disorder characteristics, such as idiosyncratic comprehensions and obsessions appeared to be related to the motive for the offence."

Focusing specifically on substance abuse, this is something of a common thread in many discussions about offending profiles and psychiatry. In a recent post, I talked about some quite large-scale population research that suggested there may an intricate relationship between something like attention-deficit hyperactivity disorder (ADHD) and future risk of psychosis and/or schizophrenia. Specifically, discussions turned to how substance abuse may be one or several factors 'priming' ADHD for later psychopathology and onwards where substance abuse might fit in relation to violent crime [6] in this group. It is a complicated relationship and difficult to summarise in a few words, but the idea that substance abuse may intersect with psychiatry and violent behaviour is the key tenet.

Alongside substance abuse, I would also draw your attention to some more general science literature on various prescription medicines that have been associated with violent behaviour [7]. Moore et al surveyed the US FDA Adverse Event Reporting System (AERS) with a view to "any case report indicating homicide, homicidal ideation, physical assault, physical abuse or violence related symptoms." They found a few possible 'associations' which were reported in the mainstream media (see here) overlapping with some pharmacotherapy that might also be indicated for some aspects of autism. At the time of writing, we don't know the specific medical history of the Roseburg perpetrator nor whether illicit or prescription medication was a part of his recent clinical picture. We also don't know whether specific medicines were being withheld or any associated circumstances around compliance.

Finally, I'm going to carefully introduce the paper by O'Nions and colleagues [8] into the conversation, and some potentially pertinent discussions about a label called Pathological Demand Avoidance (PDA). PDA is an interesting diagnostic concept insofar as being described as a feature of the autism spectrum but at the time of writing, not actually being formally included in any of the standardised diagnostic texts. O'Nions et al report how most of their group with PDA met criteria for ASD yet demonstrated some important differences from more classical descriptions of autism: "this high scoring group was characterised by lack of co-operation, use of apparently manipulative behaviour, socially shocking behaviour, difficulties with other people, anxiety and sudden behavioural changes from loving to aggression." Without any further shifting of blame between labels intended (people, not labels) or indeed casting aspersions, further investigations are required on any longer-term 'correlates' of a diagnosis of PDA specifically with offending in mind. That such a diagnosis may also border on other psychopathology [9] including "anti-social traits approaching those seen in the conduct problems and callous-unemotional traits group" taps into the continuing theme of comorbidity covered a few paragraphs back.

There is other peer-reviewed literature on this topic but I'd like to think that the selected studies provide the best evidence that we have so far when it comes to what is known or suspected about offending behaviour overlapping with a label on the autism spectrum. Hopefully what you can see from the collected literature is that offending behaviour is complicated in instances where autism is mentioned; indeed, as complicated as it is when autism is not mentioned.

No-one will ever know exactly why the Roseburg killer did what he did and what were the precise circumstances around this heinous crime. It is likely however that lots of variables coincided including the ideas of notoriety and possibly a sort of 'contagion' combining with seemingly easy access to weapons. The research evidence so far on this topic tells us that any role played by a label on or off the autism spectrum is likely to be a tangled one and certainly not one working in any sort of isolation [10]. Subsequent sweeping generalisations therefore about all autism and 'dangerousness' are probably inaccurate and most certainly offer little in the way of usefulness or comfort for anyone: victims, their families or the wider autism community. Indeed perhaps only serving to wrongly stigmatise an already heavily stigmatised group as per other examples where clinical labels have been mentioned alongside murder.

What such a tragic event does however highlight is that there is a continued need for science to investigate the precipitating factors around their occurrence - biological, medical, familial, social, political - and where possible, offer evidence-based ways and means of intervening and potentially averting such extreme acts. Although of little comfort to those families and communities that have lost loved ones in such a manner, forensic analysis of the perpetrators (including those who were stopped) remains a primary tool in discerning clinical profiles and circumstances in such cases; mindful however of how sweeping generalisations can often do more harm than good [11] and also being careful not to feed any publicity that sometimes accompanies such cases.

To close, I leave you with a ray of light from the tragedy, and the story of Chris Mintz: "a father to a young boy with autism" hailed as hero.

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[1] Allely CS. et al. Neurodevelopmental and psychosocial risk factors in serial killers and mass murderers. Aggression and Violent Behavior. 2014; 19: 288-301.

[2] Newman SS. & Ghaziuddin M. Violent crime in Asperger syndrome: the role of psychiatric comorbidity. J Autism Dev Disord. 2008 Nov;38(10):1848-52.

[3] Nielssen O. & Large M. Rates of homicide during the first episode of psychosis and after treatment: a systematic review and meta-analysis. Schizophr Bull. 2010 Jul;36(4):702-12.

[4] King C. & Murphy GH. A systematic review of people with autism spectrum disorder and the criminal justice system. J Autism Dev Disord. 2014 Nov;44(11):2717-33.

[5] Helverschou SB. et al. Offending profiles of individuals with autism spectrum disorder: A study of all individuals with autism spectrum disorder examined by the forensic psychiatric service in Norway between 2000 and 2010. Autism. 2015 Oct;19(7):850-8.

[6] Fazel S. et al. Schizophrenia, substance abuse, and violent crime. JAMA. 2009 May 20;301(19):2016-23.

[7] Moore TJ. et al. Prescription Drugs Associated with Reports of Violence Towards Others. PLoS ONE 2010; 5(12): e15337.

[8] O'Nions E. et al. Identifying features of 'pathological demand avoidance' using the Diagnostic Interview for Social and Communication Disorders (DISCO). Eur Child Adolesc Psychiatry. 2015 Jul 30.

[9] O'Nions E. et al. Pathological demand avoidance: exploring the behavioural profile. Autism. 2014 Jul;18(5):538-44.

[10] Søndenaa E. et al. Violence and sexual offending behavior in people with autism spectrum disorder who have undergone a psychiatric forensic examination. Psychol Rep. 2014 Aug;115(1):32-43.

[11] Metzl JM. & MacLeish KT. Mental Illness, Mass Shootings, and the Politics of American Firearms. American Journal of Public Health. 2015; 105: 240-249.

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Newman, S., & Ghaziuddin, M. (2008). Violent Crime in Asperger Syndrome: The Role of Psychiatric Comorbidity Journal of Autism and Developmental Disorders, 38 (10), 1848-1852 DOI: 10.1007/s10803-008-0580-8




King C, & Murphy GH (2014). A systematic review of people with autism spectrum disorder and the criminal justice system. Journal of autism and developmental disorders, 44 (11), 2717-33 PMID: 24577785

Is a GFCF diet for autism inherently unhealthy? (part 2)

Consider today's entry as a sort of continuation of a previous post looking at the 'horror' that is a gluten-free, casein-free (GFCF) diet for autism (see here).

This time around I'm bringing the paper by Salvador Marí-Bauset and colleagues [1] to your attention and the idea that things might not necessarily be all bad when it comes to the use of a GFCF diet in terms of nutritional quality nor anthropometric values. Indeed, subject to the correct dietetic input, that there may be some important food exchanges going on when a diet devoid of gluten and casein is instigated specifically where an autism diagnosis is mentioned.

I realise that not everyone is as enthusiastic about how food might impact on behaviour and development with at least some autism in mind as I am, but science is coming around to the idea that what we eat (or not) might have some important influences on our being (see here). Appreciating that the GFCF diet is also probably not for everyone [2] (see here also), there continues to be some 'appetite' for such an approach for at least some autism [3]. It is therefore important to understand a little more about what might be the positives and negatives to following such a restrictive dietary regime.

Marí-Bauset et al report results for some 20 children with autism following a GFCF diet compared with 85 "on a regular diet in Valencia (Spain)." This follows a scheme of work from this authorship group looking at various aspects of nutrition when applied to autism [4]. Upon analysing 3-day food diaries, researchers concluded that: "Those on the GFCF diet had a lower weight, body mass index, and total energy, pantothenic acid, calcium, phosphorus and sodium intake." Further however, the GFCF group had: "a higher intake of fiber, legumes, and vegetables" and something of a more favourable fat intake profile that non-GFCF dieters. That last point also ties into other work from the authors [5].

As per the part 1 entry on the nutritional and health related aspects to a GFCF diet for autism (here it is again) there are some details in the Marí-Bauset data that perhaps require some clinical input. I'm thinking specifically about the lower calcium intake in this case, bearing in mind calcium and autism is a very complicated issue (see here) and some continued questioning about the more general link between calcium intake and bone health. The idea that those following a GFCF diet might also present with a lower weight and body mass index (BMI) is also interesting; particularly in light of quite a lot of the chatter in this area focusing on elevated weight and the health effects that can have with autism in mind (see here). I might add that I am in no way endorsing a GFCF diet (or any other diet) for weight loss or management; that's not my job.

The slightly more positive idea that those following a GFCF diet might have a better intake of vegetables and legumes probably also tied into a higher intake of fibre is important. I've previously talked about where the extremes of a limited diet can lead when it comes to [some] autism (see here). Although supplementation has its place in terms of as and when specific deficiencies are present and identified (see here) I think most people would agree that consumption of foodstuffs like fruit and vegetables probably do a better job of supplying nutritional needs than a pill (most of the time). In that respect, one might assume that those on a GFCF diet with more favourable vegetable consumption profile, might be slightly less prone to certain deficiencies. As per other research in this area, we would need a little more biological testing to be sure (see here). The specific idea that fibre intake was higher for the GFCF group is also an important point if one considers fibre to be an essential component when it comes to gastrointestinal (GI) motility, again, as has been specifically mentioned with autism in mind (see here).

In short, and with more research required, the horror that is a GFCF diet for autism might actually with the right clinical input, not be so horrible...

Music: Lily Allen - The Fear.

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[1] Marí-Bauset S. et al. Nutritional Impact of a Gluten-Free Casein-Free Diet in Children with Autism Spectrum Disorder. J Autism Dev Disord. 2015 Oct 1.

[2] Buie T. The relationship of autism and gluten. Clin Ther. 2013 May;35(5):578-83.

[3] Whiteley P. Nutritional management of (some) autism: a case for gluten- and casein-free diets? Proc Nutr Soc. 2015 Aug;74(3):202-7.

[4] Marí-Bauset S. et al. Nutritional status of children with autism spectrum disorders (ASDs): a case-control study. J Autism Dev Disord. 2015 Jan;45(1):203-12.

[5] Marí-Bauset S. et al. Fat intake in children with autism spectrum disorder in the Mediterranean region (Valencia, Spain). Nutr Neurosci. 2015 May 28.

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Marí-Bauset S, Llopis-González A, Zazpe I, Marí-Sanchis A, & Suárez-Varela MM (2015). Nutritional Impact of a Gluten-Free Casein-Free Diet in Children with Autism Spectrum Disorder. Journal of autism and developmental disorders PMID: 26428353

Autism symptoms in children with ADHD

"Children with ADHD [attention-deficit hyperactivity disorder] had more ASD [autism spectrum disorder] symptoms than non-ADHD controls."

So said the findings from Jessica Leigh Green and colleagues [1] following their investigation of over 300 6-10 year olds looking at the prevalence of autistic symptoms "in a community-based sample of children with attention-deficit/hyperactivity disorder (ADHD) and non-ADHD controls." Conners 3 and the DISC-IV represented the analytical starting point pertinent to a diagnosis of ADHD, with autistic symptoms assessed via the Social Communication Questionnaire (SCQ).

As per the starting sentence, those diagnosed with ADHD (n=164) tended to present with quite a few more autistic traits than those without ADHD (n=198) and, importantly: "Greater ADHD symptom severity was associated with greater ASD symptom severity." Boys with ADHD also tended to fare worse than girls with ADHD when it came to the presentation of autistic symptoms. Ergo, yet again (see here) there seems to be something of an important 'connection' between autism and ADHD.

I don't think many people with some knowledge and interest in the intersection between autism and ADHD will be surprised by the Green results added to other recent findings [2]. As per the Gillberg concept of ESSENCE (see here) the fuzziness of child behaviour when it comes to identifiying psychopathology almost implies that there will be overlap in the presentation of specific labels. That specific interventions put forward for some autism might also be affecting ADHD-type symptoms more strongly than core autistic traits (see here) offers even more evidence for a connection between diagnoses/symptoms.

More research is of course implied in such findings, including that into what other symptoms might overlap the conditions [3] (yes, I'm talking about you motor issues) and the hows and whys of ASD + ADHD translating into a greater risk for future adverse outcomes as per other research in this area (see here). Whether too other factors such as poverty might also affect an autism-ADHD combination type (see here) also requires further study. Realisation that autism nor ADHD seemingly exist in a diagnostic vacuum is an important point raised from this and related work as we move further into the idea of comorbidity clusters (see here).

Music: Foxes - Holding onto Heaven.

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[1] Green JL. et al. Autism spectrum disorder symptoms in children with ADHD: A community-based study. Res Dev Disabil. 2015 Sep 30;47:175-184.

[2] Miodovnik A. et al. Timing of the Diagnosis of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder. Pediatrics. 2015 Oct;136(4):e830-7.

[3] Biscaldi M. et al. Identification of neuromotor deficits common to autism spectrum disorder and attention deficit/hyperactivity disorder, and imitation deficits specific to autism spectrum disorder. Eur Child Adolesc Psychiatry. 2015 Aug 2.

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Green JL, Rinehart N, Anderson V, Nicholson JM, Jongeling B, & Sciberras E (2015). Autism spectrum disorder symptoms in children with ADHD: A community-based study. Research in developmental disabilities, 47, 175-184 PMID: 26433184

Gut bacteria profiles in children with autism and asymptomatic siblings

The paper by Joshua Son and colleagues [1] (open-access here) made for some interesting reading recently and various findings including: "no significant difference in macronutrient intake between ASD [autism spectrum disorder] and NT [neurotypical] siblings", "no significant difference in ASD severity scores between ASD children with and without FGID [functional gastrointestinal disorders]" and "No significant difference in diversity or overall microbial composition" when it came to the the examination of stool samples for the trillions of wee beasties that call our gastrointestinal (GI) tract home.

As quite an avid follower of the idea that the gut microbiota might be a place to look when it comes to autism research (see here) I was intrigued by the lack of significant differences reported by Son et al based on the examination of 59 children diagnosed with an ASD and 44 'neurotypical' siblings recruited via the Simons Simplex Collection / Interactive Autism Network collaboration. I've highlighted neurotypical by the way, because I personally find this description to be a little problematic (see here) in terms of the assumptions made about autism and not-autism in rather too sweeping a fashion. Hands up if you think you are 'neurotypical' or not...

Anyhow, participating families were initially asked to "complete the Pediatric ROME III Version (QPGS-RIII), the GI symptoms form in the Simon Simplex Collection Medical History (v 4.0), the Child Behavior Checklist (CBCL/6-18), a one-week food diary for the ASD proband and/or the NT sibling prior to collecting a fecal sample, and provide current information on the child’s height and weight." That stool sample by the way, was collected when children were off antibiotics or probiotics for at least one month, accepting that such formulations can seemingly have much longer term effects.

Stool samples were analysed according to two protocols: (i) quantitative PCR (qPCR) for targeted bacterial subgroups - that is looking for genetic signatures of specific families of bacteria on the basis of previous reports, including Sutterella among others (see here), and (ii) a less targeted 'fecal bacterial profile' also looking at the diversity in gut bacteria between the groups.

Interestingly, and in contrast to to some other research, there didn't seem to be very much the way of group differences to see between the autism and asymptomatic sibling controls. The lack of Sutterella findings are particularly interesting given the independent data from Williams and colleagues [2] and Wang and colleagues [3] examining this species. I should however highlight the differences between the Williams method of sample collection (intestinal biopsy) and the Son method of collection (stool sample) that may be a factor in any disparity. Williams also based their information on those children specifically with autism and GI issues too; something which might be important to discussions in the next paragraph or so.

"An alternative explanation for why a study comparing ASD children with NT siblings did not replicate differences reported between ASD children with unrelated controls, is that NT siblings of ASD children have altered microbiomes compared to that of unrelated children." The lack of an asymptomatic, unrelated control group is a weakness of the Son findings as it is in other related research. Aside from all that chatter on the broader autism phenotype (BAP) potentially being a feature of at least some familial autism (see here) coinciding with the issue of shared genetics (see here) in some cases, one must realise that these were siblings sharing quite a few of the same aspects of environment too, and onwards what impact that might have had on gut bacteria.

In amongst the various 'lack of significant difference' variables reported, there were a few important differences noted among the groups and sub-groups. So: "Functional constipation was more prevalent in ASD (17 of 59) compared to NT siblings." On top of the volumes of other peer-reviewed research that has come to the same conclusions - functional bowel issues are over-represented when it comes to a diagnosis of autism - this reflects further evidence for the need for lots more investigations in this area in terms of other possible behavioural/somatic connections (see here) and any role for more pathological bowel states (see here).

Also: "The mean CBCL scores in NT siblings with FGID, ASD children with FGID and ASD without FGID were comparably higher... when compared to NT children without FGID." I draw back from suggesting that these observations solely point to a role for functional bowel issues on the "emotional, behavioral, and social problems" measured by the CBCL because further examination is required on this matter. The fact that the Son study criteria excluded children with "a past or current history of GI diseases or other serious medical problems" kinda limits what might be said in the same way that the recent Hyman results on the gluten- and casein-free (GFCF) diet for autism did so for that area of study (see here). I don't know if it might be time to start thinking more about autisms over autism and more inclusion of comorbid issues in such research areas.

This isn't the first time that 'no significant differences' have been noted when it comes to autism and the gut microbiota (see here) and I doubt that it will be the last time. Much like the other branches of autism science, there probably isn't going to be one specific factor (genetic, epigenetic or biological) that describes all autism from all 'not-autism' and that goes the same for gut bacteria too. What perhaps I do think we have to focus more on in this early years discipline are issues such as gut bacterial diversity (see here) and how that might fit say, into certain types - endophenotypes perhaps - of autism. Whether age and developmental history (including infancy antibiotic history) also might play roles are questions as yet unanswered (Son et al relied on participants aged 7-14 years); as is the idea that diet might play a role in the balance of gut bacteria that predominate (chia seeds are mentioned in the current paper as a potential variable linked to certain bacterial strains but what about a GFCF diet for example?). Also whether as part of the new biological triad : gut bacteria, intestinal barrier function and mucosal immunity potentially relevant to some autism, there may be more to see by expanding the range of variables under study including a possible role for yeasts [4]...

Music: New Radicals - You Get What You Give.

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[1] Son JS. et al. Comparison of Fecal Microbiota in Children with Autism Spectrum Disorders and Neurotypical Siblings in the Simons Simplex Collection. PLoS One. 2015 Oct 1;10(10):e0137725

[2] Williams BL. et al. Application of novel PCR-based methods for detection, quantitation, and phylogenetic characterization of Sutterella species in intestinal biopsy samples from children with autism and gastrointestinal disturbances. MBio. 2012 Jan 10;3(1). pii: e00261-11.

[3] Wang L. et al. Increased abundance of Sutterella spp. and Ruminococcus torques in feces of children with autism spectrum disorder. Mol Autism. 2013 Nov 4;4(1):42.

[4] Kantarcioglu AS. et al. Microbiota–Gut–Brain Axis: Yeast Species Isolated from Stool Samples of Children with Suspected or Diagnosed Autism Spectrum Disorders and In Vitro Susceptibility Against Nystatin and Fluconazole. Mycopathologia. 2015 Oct 6.

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Son JS, Zheng LJ, Rowehl LM, Tian X, Zhang Y, Zhu W, Litcher-Kelly L, Gadow KD, Gathungu G, Robertson CE, Ir D, Frank DN, & Li E (2015). Comparison of Fecal Microbiota in Children with Autism Spectrum Disorders and Neurotypical Siblings in the Simons Simplex Collection. PloS one, 10 (10) PMID: 26427004

Transcendental meditation for autism: some case reports

I can appreciate that some people might have looked at the title of this post and rolled their eyes. When I first came across the paper by David Black & Norman Rosenthal [1] (open-access) I too felt a slight 'woo' like tingling given my unfamiliarity with transcendental meditation (TM) either personally or professionally. A bit of background reading and a reminder of some song lyrics - "sometimes truth is stranger than fiction" - and I decided that this is peer-reviewed science that perhaps needs a little bit of discussion.

The Black/Rosenthal paper begins with some important statements about autism insofar as (a) the numbers of people being diagnosed as on the autism spectrum is increasing for whatever reasons, and (b) of the numerous comorbidities that are over-represented when it comes to a diagnosis, the various forms of anxiety must surely rank up there as some of the most disabling aspects when it comes to quality of life day-to-day. That also there is a pretty sizeable gap in the research literature about how anxiety can be managed or treated when it comes to autism is something else to mention.

Then: "Transcendental Meditation (TM) may be beneficial for treating anxiety in individuals with ASDs [autism spectrum disorders] by reducing stress." Certainly a quick scan of the peer-reviewed literature with the words 'transcendental meditation and anxiety', does indeed reveal something of a trend insofar as as TM as a potential intervention option. Take for example the meta-analysis by Orme-Johnson & Barnes [2] that concluded: "Overall, TM practice is more effective than treatment as usual and most alternative treatments, with greatest effects observed in individuals with high anxiety" with the requirement for quite a bit more investigation in this area. I might also add that 'treatment as usual' might not necessarily be the best comparator when it comes to this kind of intervention as per other examples (see here)

Onwards to the case reports highlighted. Interviews were completed with six individuals, all diagnosed as being on the autism spectrum and all have practised TM "twice per day for 15–20 min, at least 10 times per week, for at least 3 months." The interview seemed to have been quite an unstructured affair whereby questions about the use of TM and "any changes in functioning observed since following consistent practice of TM" were intermixed with focused questions on specific symptoms. Obviously the kind of evidence garnered from this type of study is pretty subjective and provides little in the way of formal comparisons between before starting TM and where participants were at the time of questioning not also including issues such as blinding. But, and it is an important point, self-report under such circumstances can provide some important insights into personal experiences and we are [scientifically] poorer without them.

As it happens: "all participants reported that the consistent practice of TM was helpful in a number of ways." Indeed, stress and anxiety featured quite consistently in the reports provided, with other effects noted in areas of sleep and concentration for example. From what I can gather, no-one reported any adverse effects from such practice, which is also an important point. The authors conclude: "The experiences of this group of individuals suggest that at least for some individuals with an ASD, (1) TM is easy to learn and consistently practice, and (2) that it may be very beneficial in reducing stress and anxiety, thereby improving overall productivity and quality of life."

Reiterating the methodological issues associated with this study and the requirement for further investigations, I'm persuaded enough by the case reports that more research time might need to be devoted to this area of interest. Allied to other investigations on the whole mind-body bit with autism in mind (see here) including the continued interest in the concept of mindfulness (see here), a sort of 'what harm could it do' philosophy has started to leak into my thoughts about this. I don't think this kind of technique will be for everyone on the autism spectrum (no 'one size fits all' and all that) and I don't necessarily buy into the TM movement as a whole. But if anxiety is a disabling feature for some on the autism spectrum, the alternatives to treating/managing such issues are currently few and far between...

Music: Robbie Williams - No Regrets.

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[1] Black DO. & Rosenthal N. Transcendental meditation for autism spectrum disorders? A perspective. Cogent Psychology. 2015; 2: 1-5.

[2] Orme-Johnson DW. & Barnes VA. Effects of the transcendental meditation technique on trait anxiety: a meta-analysis of randomized controlled trials. J Altern Complement Med. 2014 May;20(5):330-41.

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Black, D., Rosenthal, N., & Walla, P. (2015). Transcendental meditation for autism spectrum disorders? A perspective Cogent Psychology, 2 (1) DOI: 10.1080/23311908.2015.1071028

Theatre-based intervention for autism?

"All the world's a stage, And all the men and women merely players."

So said Bill (to his friends) Shakespeare in the comedy 'As You Like It'. Personally, I think William Shakespeare was spot on with that comment, and how we all spend our lives 'acting' out various roles; fine tuning our performance depending on the context and environment we find ourselves in.

With acting and the theatre specifically in mind, I'm talking today about the paper from Blythe Corbett and colleagues [1] reporting results following the use of "a peer-mediated, theatre-based intervention on social competence in participants with autism spectrum disorder (ASD)." Using a randomised - "assigned to the treatment... or a wait-list control group" - study design, researchers explored how a 10-week theatre-based intervention might affect various aspects of their cohort diagnosed with autism. It did indeed seem to have some effects in relation to social ability and in some cases, these effects were sustained, at least in the area of communicative abilities. I might add that some of this authorship group have some previous research form in this area [2] including on some previous description on the use of the SENSE theatre intervention [3].

On the face of it, drama or theatre-based intervention potentially seems like quite a good idea when applied to autism. Whilst trying to avoid sweeping generalisations about all autism or all performers, luvvies - a very melodramatic stereotype of some theatre types - are usually quite an outgoing group on the outside as part of their job in terms of the social requirements of performances and overcoming the stresses and strains of playing live to a paying audience day after day. Most theatrical performances involve public speaking and most involve the adoption of a persona or character typically different from that of the actress/actor. You can perhaps see how some of the qualities that coincide with the adoption of the theatrical profession may well 'enable' some people on the autism spectrum to navigate the complex social world a little easier; or at the very least, provide a safe training forum for practising such skills. That and providing an arena where children and adults on the autism spectrum can become a part of something and perhaps boost important aspects such as life satisfaction [4] (see here too) and I'm finding it difficult to name too many negatives for such a proposed intervention.

To close, having watched a great theatre production of The Shawshank Redemption recently, some opera for you...

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[1] Corbett BA. et al. Improvement in Social Competence Using a Randomized Trial of a Theatre Intervention for Children with Autism Spectrum Disorder. J Autism Dev Disord. 2015 Sep 29.

[2] Corbett BA. et al. Brief Report: Theatre as Therapy for Children with Autism Spectrum Disorder. Journal of Autism and Developmental Disorders. 2011;41(4):505-511.

[3] Corbett BA. et al. Peer-Mediated Theatrical Engagement for Improving Reciprocal Social Interaction in Autism Spectrum Disorder. Frontiers in Pediatrics. 2014;2:110.

[4] Schmidt L. et al. Psychosocial Functioning and Life Satisfaction in Adults With Autism Spectrum Disorder Without Intellectual Impairment. J Clin Psychol. 2015 Sep 25.

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Corbett BA, Key AP, Qualls L, Fecteau S, Newsom C, Coke C, & Yoder P (2015). Improvement in Social Competence Using a Randomized Trial of a Theatre Intervention for Children with Autism Spectrum Disorder. Journal of autism and developmental disorders PMID: 26419766

Of vaccines and monkeys

A quote to begin:

"These data indicate that administration of TCVs [thimerosal-containing vaccines] and/or the MMR [measles, mumps, rubella] vaccine to rhesus macaques does not result in neuropathological abnormalities, or aberrant behaviors, like those observed in ASD [autism spectrum disorder]."

Those were the findings reported by Bharathi Gadad and colleagues [1] (open-access available here) and their study providing "a comprehensive analysis of the influence of TCVs on the brain and behavior in a nonhuman primate model."

Giving infant rhesus macaques "the recommended pediatric vaccine schedules from the 1990s and 2008" and various combinations of vaccinations including MMR vaccine and vaccines on an "accelerated schedule" in contrast to saline (placebo) injections, authors reported no significant differences among behavioural or neuropathological parameters inspected as a function of vaccination status.

Although a little late in getting to this research, I believe this study also ties in with other recent results from some of the same authorship group [2] also suggesting that over a 5-year period of inspection, there was "no consistent evidence of neurodevelopmental deficits or aberrant behavior in vaccinated animals." Readers might also like to read an additional paper from the authors talking about the usefulness of animal models when it comes to autism research [3] among other things.

Appreciating that to mention immunisation and autism in the same sentence can stir up some significant emotions (readers may like to read Tom Insel's post on the Four Kingdoms of Autism as a background), I was drawn to blog about the Gadad paper because it is peer-reviewed science. Alongside the growing evidence base suggesting that there probably is no population-wide link between various vaccine administrations and risk of autism (see here) and the important public health message about the value of immunisation, the Gadad data represents some good longitudinal animal science.

If I had to quibble in anyway about the study, it would be that monkeys are monkeys and not humans (similarly applied to other animal models), and that the animal participant numbers were pretty small bearing in mind that said animals were eventually sacrificed for neuropathological inspection. I'd also suggest that whilst there is evidence that autism is correlated with certain brain regions (see here for example), the jury is still out on making any generalised assumptions to the very, very wide autism spectrum complete with added risk of various comorbidity. Others have also similarly mentioned that not all vaccine groups were fully studied and data presented in the current Gadad paper, so maybe there is more to come from this research project.

The use of nonhuman primates as 'subjects' in the debate about any link between vaccination and 'neurodevelopmental outcomes' has had its fair share of twists and turns down the years. Some readers might remember the peculiar case of another paper from Laura Hewitson and colleagues [4] titled: 'Delayed acquisition of neonatal reflexes in newborn primates receiving a thimerosal-containing hepatitis B vaccine: influence of gestational age and birth weight' that is listed as 'withdrawn' under another entry on PubMed [5] albeit published in another journal. On that occasion, researchers suggested that their data pointed to a possible interaction between birth weight and gestational age when it came to hepatitis B vaccination and the presentation of early reflexes in animals. Other papers from this group [6] have similarly proved controversial, insofar as the reported effects of a pediatric vaccine schedule on aspects of opioid ligand binding for example (with others challenging the results [7] and an author reply). This area seems to court controversy.

I will end however by reiterating the findings reported by Gadad et al reporting the lack of adverse effects of the pediatric vaccine schedule on some of our closest cousins in the animal world. This does not mean that continued vigilance should figure any less (even perhaps with certain groups in mind [8] as per other musings) with regards to this aspect of our pharmaceutical armoury nor that other factors around the time of vaccination are necessarily 'off the hook' [9] as potentially being important to [some] autism. But it does provide some important data pertinent to discussions on the risk/benefit ratio of immunisations and their potentially far-reaching benefits [10].

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[1] Gadad BS. et al. Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology. Proc Natl Acad Sci U S A. 2015 Sep 28. pii: 201500968.

[2] Curtis B. et al. Examination of the Safety of Pediatric Vaccine Schedules in a Non-Human Primate Model: Assessments of Neurodevelopment, Learning, and Social Behavior. Environmental Health Perspectives. 2015;123(6):579-589.

[3] Gadad BS. et al. Neuropathology and Animal Models of Autism: Genetic and Environmental Factors. Autism Research and Treatment. 2013;2013:731935.

[4] Hewitson L. et al. Delayed acquisition of neonatal reflexes in newborn primates receiving a thimerosal-containing hepatitis B vaccine: influence of gestational age and birth weight. J Toxicol Environ Health A. 2010;73(19):1298-313.

[5] Hewitson L. et al. WITHDRAWN: Delayed acquisition of neonatal reflexes in newborn primates receiving a thimerosal-containing Hepatitis B vaccine: Influence of gestational age and birth weight. Neurotoxicology. 2009 Oct 2.

[6] Hewitson L. et al. Influence of pediatric vaccines on amygdala growth and opioid ligand binding in rhesus macaque infants: A pilot study. Acta Neurobiol Exp (Wars). 2010;70(2):147-64.

[7] Novella S. & Hines T. Autism and the amygdala: commentary on Hewitson and coauthors (2010). Acta Neurobiol Exp (Wars). 2011;71(1):178-9; author reply 180-1.

[8] Poling JS. et al. Developmental Regression and Mitochondrial Dysfunction in a Child With Autism. Journal of Child Neurology. 2006;21(2):170-172.

[9] Schultz ST. et al. Acetaminophen (paracetamol) use, measles-mumps-rubella vaccination, and autistic disorder: the results of a parent survey. Autism. 2008 May;12(3):293-307.

[10] Fullerton HJ. et al. Infection, vaccination, and childhood arterial ischemic stroke. Neurology. 2015. Sept 30.

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Gadad BS, Li W, Yazdani U, Grady S, Johnson T, Hammond J, Gunn H, Curtis B, English C, Yutuc V, Ferrier C, Sackett GP, Marti CN, Young K, Hewitson L, & German DC (2015). Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology. Proceedings of the National Academy of Sciences of the United States of America PMID: 26417083

Maths problem solving ability and autism: as varied as the label itself

I'm bringing the paper by Tasha Oswald and colleagues [1] to the blogging table today and a reiteration of the important idea that within the vast heterogeneity that surrounds the presentation of autism (or even the autisms) so too there is quite a lot of variability in the presentation of strengths and weaknesses; indeed, not so dissimilar to life in general.

Mathematics problem-solving was the specific area that Oswald et al have zoomed in on, with the aim of assessing: "the relative proportions of youth with ASD who demonstrate giftedness versus disability on applied math problems."

Researchers reported that of the 27 "high-functioning adolescents with ASD [autism spectrum disorder]" (their words not mine), just over a fifth of participants (22%) "evidenced a mathematics learning disability" whilst only 4% presenting with "mathematical giftedness." These results, by the way, were based on "standardized measures of math problem solving, perceptual reasoning, verbal ability, and test anxiety." When it came to predicting which factors might be relevant to maths problem solving ability, the authors reported a sliding scale: "perceptual reasoning, followed by verbal ability and test anxiety, then diagnosis of ASD" taking into account results from age and cognitively matched controls (n=27) also.

Outside of the idea that not everyone diagnosed with an ASD is Rainman (indeed that whilst autism is over-represented in savant skills, this does not mean that autism = savant [2]), there are some interesting lessons to be potentially learned from the quite preliminary Oswald findings. Not least is the suggestion that results "highlight possible targets of intervention for students with ASD struggling with mathematics" based on those proposed predictors of maths ability and where further educational focus might be directed. Indeed, the specific idea that 'test anxiety' might for example be a factor, ties in well with other peer-reviewed evidence hinting at how the effects of different types of anxiety may be far-reaching when it comes to autism (see here).

I might also forward the idea that whilst autism was the focus on the Oswald data, one should perhaps be mindful of how other comorbidity can similarly affect academic attainment. May and colleagues [3] talked about how aspects of attention could very well affect skills such as mathematics performance with autism in mind and specifically how: "attentional switching difficulties are linked with poorer mathematics outcomes in ASD." Without hopefully confusing attentional switching with something like a diagnosis of attention-deficit hyperactivity disorder (ADHD) (although there is overlap), I will bring in the important data hinting that ADHD difficulties may indeed be over-represented when it comes to autism (see here) and what impact this might have on maths abilities in at least some cases of autism. Further, the question of whether 'tackling' said ADHD might have some interesting effects on areas like maths ability with autism in mind, bearing in mind pharmacotherapy might not be the only suggested avenue?

I'm gonna close with reference to the paper by De Marco and colleagues [4] detailing just how impressive the human mind can be...

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[1] Oswald TM. et al. Clinical and Cognitive Characteristics Associated with Mathematics Problem Solving in Adolescents with Autism Spectrum Disorder. Autism Res. 2015 Sep 29.

[2] Treffert DA. & Rebedew DL. The Savant Syndrome Registry: A Preliminary Report. WMJ. 2015 Aug;114(4):158-62.

[3] May T. et al. The role of attention in the academic attainment of children with autism spectrum disorder. J Autism Dev Disord. 2013 Sep;43(9):2147-58.

[4] De Marco M. et al. Brief Report: Two Day-Date Processing Methods in an Autistic Savant Calendar Calculator.  J Autism Dev Disord. 2015. Oct 17.

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Oswald TM, Beck JS, Iosif AM, McCauley JB, Gilhooly LJ, Matter JC, & Solomon M (2015). Clinical and Cognitive Characteristics Associated with Mathematics Problem Solving in Adolescents with Autism Spectrum Disorder. Autism research : official journal of the International Society for Autism Research PMID: 26418313

Autism, luteolin and inflammatory markers

"We further show that the children with ASDs [autism spectrum disorders] in which the elevated serum IL-6 and TNF levels decreased at the end of the treatment period with a luteolin formulation, were the ones whose behavior improved the most."

That was an excerpt from the paper by Tsilioni and colleagues [1] (open-access available here) who looked at some of the potential biological (and behavioural) effects following supplementation with the dietary formulation known as NeuroProtek® [2] containing the flavonoid luteolin. Piggybacking on a previous open trial of luteolin [3] in relation to autism, authors report on levels of various serum cytokines between baseline and post-intervention as well as versus control specimens.

Levels of IL-6 (interleukin 6) and TNF (tumor necrosis factor) were reported to decrease in the autism group (N=38) following supplementation. Further, authors report on "two clusters of ASD children with low and high serum IL-6 and TNF levels indicating two subgroups." Specifically for those children with autism with higher values (n=10), they reported some interesting changes in scores on the Vineland Behavior Scales (VABS) suggesting that: "these children gained 9.73 months in the communication domain, 6.64 months in daily living skills and 8.09 months in the social domain."

These are intriguing results. Accepting the relatively small participant group and the open-trial methodology of the original study from which biological samples were derived, it strikes me that there may be quite a bit more to see from luteolin and related compounds when it comes to at least some autism. I'm not on this occasion going to focus too much on the cytokine results discussed by Tsilioni et al because I think there is more than enough peer-reviewed evidence implicating these various chemical messengers in at least some aspects of some autism (see here). I do think it is interesting however that the authors suggest that analysis of compounds like IL-6 and TNF might be one step towards looking for potential best responders to this type of intervention. Indeed, 'response to intervention' is something I'd like to see discussed a little more when it comes to teasing apart the different types of autism (see here).

I have mentioned luteolin previously on this blog (see here) and the link back to one or two of the authors on the Tsilioni paper including Prof. Theoharis Theoharides (he of mast cells and autism fame). "Luteolin is structurally closely related to 7,8-dihydroflavone, which was shown to have brain-derived neurotrophic factor (BDNF)-like activity" is one of the ways that the authors put forward as potentially being explanatory of their results, bearing in mind how 'mixed up' BDNF is when it comes to autism (see here). That and proposals for delivery via "intranasal administration" tapping into the rise and rise of pharmaceutical technology (see here) and I think we're going to be hearing quite a bit more about luteolin-containing preparations and autism in future research times...

Music: Sons of Pitches and a rather interesting version of MMMBop (in 10 genres).

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[1] Tsilioni I. et al. Children with autism spectrum disorders, who improved with a luteolin-containing dietary formulation, show reduced serum levels of TNF and IL-6. Transl Psychiatry. 2015 Sep 29;5:e647.

[2] Theoharides TC. et al. A case series of a luteolin formulation (NeuroProtek®) in children with autism spectrum disorders. Int J Immunopathol Pharmacol. 2012 Apr-Jun;25(2):317-23.

[3] Taliou A. et al. An open-label pilot study of a formulation containing the anti-inflammatory flavonoid luteolin and its effects on behavior in children with autism spectrum disorders. Clin Ther. 2013 May;35(5):592-602.

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Tsilioni I, Taliou A, Francis K, & Theoharides TC (2015). Children with autism spectrum disorders, who improved with a luteolin-containing dietary formulation, show reduced serum levels of TNF and IL-6. Translational psychiatry, 5 PMID: 26418275