Wednesday, 7 October 2015

On glyphosate and autism (without scaremongering)

Glyphosate use and autism rates - should I blog about it?

Well, after some deliberation I decided it was a topic worthy of an entry. There is some peer-reviewed science discussions behind it and, as per other areas of controversy on the autism research landscape, the idea that 'science is about debate' (why else does everyone keep going on about open-access and transparency) should always prevail.

I'm assuming most people have heard of the organophosphonate (that's phosphonate not phosphate) herbicide glyphosate - N-phosphonomethylglycine - over the course of its discovery and use under the trade name Roundup. First patented as a chelating agent (another area of 'discussion' with autism in mind) glyphosate has been successfully killing weeds for quite a few years by interfering with some of the chemistry of the aromatic amino acids tryptophan, tyrosine and phenylalanine via its actions on the shikimate pathway. As per many other herbicides, such formulations always require a degree of care in their use given the possibility of side-effects following accidental over-exposure. Indeed, government agencies are cottoning on to this fact (see here).

The debate on glyphosate and its potential effects on human and animal health has been a hot one in recent times. Partly overlapping with the introduction of genetically modified (GM) crops that are glyphosate-tolerant (Roundup Ready) by the company who initially brought glyphosate to the market, the safety angle of glyphosate has been scrutinised and debated. Only this year (2015), an arm of the World Health Organisation (WHO) described glyphosate (and several organophosphate pesticides I might add) as "probably carcinogenic to humans". Following such an announcement, quite a few media column inches were produced as one might expect.

Set within that context, discussions have turned to whether there may be other 'effects' following the fairly widespread use of glyphosate. Perhaps inevitably, autism, and particularly the quite phenomenal increase in cases of autism, has been suggested to be 'linked' to the use of glyphosate. One might say that in this respect, glyphosate is a victim of its own success insofar as how widely it has been and is currently used.

The paper that seems to have started the ball rolling suggesting a link between glyphosate and autism is that from Anthony Samsel and Stephanie Seneff [1]. A review paper focussing specifically on the proposed inhibitory actions of glyphosate on CYP enzymes, mention of autism in the text and particularly that "glyphosate may be the most significant environmental toxin contributing to autism" was bound to stir up debate. With added soundbites about how half of children will be born with autism in the United States by 2025 and graphs correlating autism prevalence and glyphosate use, such observations were ripe for speculation and discussion.

Further papers from Samsel & Seneff [2] have continued the theme that autism may be one of many conditions/labels where glyphosate might be implicated. Drawing on animal and plant studies implicating glyphosate use with specific depletion of manganese (Mn), a whirlwind of research studies and references have been used to link such depletions to autism (and associated aspects such as anxiety) among various other conditions. To quote: "Many diseases and conditions are currently on the rise in step with glyphosate usage in agriculture, particularly on GM crops of corn and soy. These include autism, AD [Alzheimer's disease], PD [Parkinson's disease], anxiety disorder, osteoporosis, inflammatory bowel disease, renal lithiasis, osteomalacia, cholestasis, thyroid dysfunction, and infertility. All of these conditions can be substantially explained by the dysregulation of Mn utilization in the body due to glyphosate." Just in case you thought that Samsel / Seneff are the sole research team talking about glyphosate use and autism rates, I'll also refer you to the paper by Cynthia Nevison [3] that has been previously discussed on this blog (see here).

As other commentators have noted, there are a few considerations to mention about the discussions so far on any relationship between glyphosate use and autism. That 'correlation is not the same as causation' is perhaps the most important element to the data as they currently stand given that, to my knowledge, no-one has actually published any peer-reviewed results on levels of glyphosate and/or metabolites in people with autism and/or other family members compared to asymptomatic controls for example. It's not as if such a feat is too complicated given the various means and methods already published on this topic [4].

'Correlation is not the same as causation' is one of the themes also discussed in the review paper by Miguel Faria [5] who provides an important discussion to some of the points raised by Samsel & Seneff. I don't want to head too much into this quite long commentary on the Samsel / Seneff paper (complete with author replies) but it does strike me as providing something of a counter-balance to the very hypothesis-based writings of the original authors. That glyphosate is one of a multitude of herbicides and insecticides in use is an important point made in terms of the difficulties in disentangling it from the 'chemical soup' (not to demonise) that we live our lives in these days. The only other thing that I might mention is my much-used notion about the continued pluralisation of autism (see here) and its varied comorbidity as being something to bear in mind when it comes to any discussions about aetiology.

Where next, or is there even 'a next' for looking at any possible relationship between glyphosate use and autism rates? Well, I'd like to think that autism research can learn a lesson or two about not throwing out baby and bathwater when it comes to theories about [some] autism as per what seems to have happened to something like methylmalonic acid (MMA) and autism (see here) for example. It's not beyond the realms of possibility that certain chemicals or mixtures might be linked to autism risk and/or onset as per preliminary research talk about dioxin exposure being potentially linked to [some] autism or autistic traits (see here) albeit with a lot more follow-up research required.

But such research needs to be done with care and assiduity; mindful that this is a topic that will inevitably garner significant attention (as per the editorial sentence on the original Samsel / Seneff paper: "Note added by the Publisher: This paper attracts great attention.") and knowing what can happen sometimes when science and media mix (see here).

Perhaps a little less focus on soundbites and more on cold, objective science is the best way forward in this area?

Music: Fleetwood Mac- Dreams.


[1] Samsel A. & Seneff S. Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases. Entropy 2013. 15; 1416-1463.

[2] Samsel A. & Seneff S. Glyphosate, pathways to modern diseases III: Manganese, neurological diseases, and associated pathologies. Surgical Neurology International. 2015;6:45.

[3] Nevison CD. A comparison of temporal trends in United States autism prevalence to trends in suspected environmental factors. Environ Health. 2014 Sep 5;13:73.

[4] Yoshioka N. et al. Rapid determination of glyphosate, glufosinate, bialaphos, and their major metabolites in serum by liquid chromatography-tandem mass spectrometry using hydrophilic interaction chromatography. J Chromatogr A. 2011 Jun 10;1218(23):3675-80.

[5] Faria MA. Glyphosate, neurological diseases – and the scientific method. Surgical Neurology International. 2015;6:132. doi:10.4103/2152-7806.162550.

---------- Faria MA (2015). Glyphosate, neurological diseases - and the scientific method. Surgical neurology international, 6 PMID: 26322242

Tuesday, 6 October 2015

Prenatal hormone involvement in autism risk?

The findings reported by Gayle Windham and colleagues [1] caught my eye recently and their observations based on the examination of mid-pregnancy serum hormone and protein markers for some 2500 mothers of children diagnosed with an autism spectrum disorder (ASD) compared with 600,000 controls.

Detailing results based on: "Second trimester levels of unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and maternal serum alpha-fetoprotein (MSAFP)", researchers reported that their results: "further support prenatal hormone involvement in ASD risk."

I perhaps need to do a little 'defining' before progressing any further with this post. Unconjugated estriol (uE3) refers to an estrogen. It becomes the dominant oestrogen during pregnancy; produced by the baby's liver and placenta. Measured levels of uE3 during the 2nd trimester of pregnancy have been linked to various 'outcomes' including the possibility of Down's syndrome and neural tube defects.

Human chorionic gonadotropin (hCG) is another hormone; one that is normally used to confirm pregnancy. During pregnancy, levels of hCG can also be used to determine Down's syndrome. Serum alpha-fetoprotein (MSAFP) is the most abundant plasma protein found in the developing foetus. During pregnancy, extremes in levels of MSAFP can indicate issues in pregnancy. Combined together, these various hormones/proteins make up the so-called triple test, that when added to information such as maternal age and stage of pregnancy, can classify a pregnancy as being high or low risk for chromosomal abnormalities. That being said, the test is by no means perfect.

Windham et al report some rather complicated results based on adjusted odds ratios (AOR) when it came to autism vs control samples. So: "Lower uE3 (AOR for < 10th percentile vs. 25th-74th percentiles = 1.21, 95 % CI 1.06-1.37), and higher MSAFP (AOR = 1.21, 95 % CI 1.07-1.37 for > 90th percentile) were significantly associated with ASD. A U-shaped relationship was seen for hCG (AOR = 1.16, 95 % CI 1.02-1.32 for < 10th percentile; AOR = 1.19, 95 % CI 1.05-1.36 for > 90th percentile)." Lower uE3 is a trend found in relation to Down's syndrome. Higher MSAFP however runs slightly counter to what has been discussed in relation to Down's syndrome. By contrast, elevations in MSAFP tend to be more readily linked to pregnancies where neural tube defects may be present. What this all means is that yes, these results could indicate the involvement of prenatal hormones and chromosomal issues in relation to 'some' autism, but science still needs to go a little way before anyone talks about a triple test being applied to autism (and the ethical issues that this might bring).

I think it's also worthwhile briefly bringing in a few caveats to such pregnancy testing that could be pertinent to other autism research findings. As per other information, a mother's weight during pregnancy can affect what results you get - "Serum marker levels tend to be decreased in heavier women, and increased in lighter women." If you map this on to the research talking about maternal obesity linked to some autism (being careful not to generalise here), you can see how adjustments might have been / have to be made. Ethnicity is another factor that needs to be kept in mind. Also: "AFP and uE3 levels tend to be low (about 8% and 6% respectively) in women with insulin dependent diabetes mellitus." This is particularly interesting in view of the quite consistent literature detailing how gestational diabetes seems to show a connection to risk of offspring autism (see here). Various other factors (vaginal bleeding) can similarly affect results.

The Windham results are nevertheless interesting and are strengthened somewhat by the large participant numbers included for study. That other groups have similarly talked about elevations in MSAFP in relation to autism [2] increases the confidence that there may something further to see in this area, at least for some autism.

Music: Al Green - Tired of Being Alone.


[1] Windham GC. et al. Autism Spectrum Disorder Risk in Relation to Maternal Mid-Pregnancy Serum Hormone and Protein Markers from Prenatal Screening in California. J Autism Dev Disord. 2015 Sep 14.

[2] Abdallah MW. et al. Autism spectrum disorders and maternal serum α-fetoprotein levels during pregnancy. Can J Psychiatry. 2011 Dec;56(12):727-34.

---------- Windham GC, Lyall K, Anderson M, & Kharrazi M (2015). Autism Spectrum Disorder Risk in Relation to Maternal Mid-Pregnancy Serum Hormone and Protein Markers from Prenatal Screening in California. Journal of autism and developmental disorders PMID: 26370672

Monday, 5 October 2015

The ASQ-3 and autism screening: has the UK already started?

'Can Screening with the Ages and Stages Questionnaire Detect Autism?' was the research question posed and partially answered in the paper by Sarah Hardy and colleagues [1] recently.

Drawing on data from a very healthy sized cohort (~2800 toddlers) who were "screened with the ASQ-3 [Ages and Stages Questionnaire] and M-CHAT-R across 20 pediatric sites" in the United States, researchers suggested that there may be more to see when it comes to the use of ASQ-3 and the complicated topic of early autism screening.

These are interesting if preliminary results. As many parents here in Blighty might have recently realised, there have been some changes to the health visitor visits that accompany raising young children in this day and age. The introduction of the ASQ-3 to the Healthy Child Programme this year (2015) represents a bit of a departure from sole reliance on the PCHR as a means of logging developmental milestones and other information.

Assuming that the Hardy results can be replicated, particularly the idea that: "Scores below the "monitor" cutoff on the Communication domain of the ASQ-3 can indicate initial concern requiring autism-specific follow-up", one wonders whether the UK Government might have just knowingly (or unknowingly) initiated a mass autism screening program?

Music: James Morrison - Demons.


[1] Hardy S. et al. Can Screening with the Ages and Stages Questionnaire Detect Autism? J Dev Behav Pediatr. 2015 Sep;36(7):536-43. 

---------- Hardy S, Haisley L, Manning C, & Fein D (2015). Can Screening with the Ages and Stages Questionnaire Detect Autism? Journal of developmental and behavioral pediatrics : JDBP, 36 (7), 536-43 PMID: 26348972

Saturday, 3 October 2015

One more time... the interpregnancy interval and risk of offspring autism

"Children born after an IPI [interpregnancy interval] of <12 months or ≥72 months had a 2- to 3-fold increased ASD [autism spectrum disorder] risk compared with children born after an interval of 36 to 47 months."

So said the study results published by Ousseny Zerbo and colleagues [1] looking at the increasingly interesting area of the autism research landscape: the interpregnancy interval (the time from the birth of an index child to the next conception/pregnancy of a sibling).

Looking at data derived from children "born at Kaiser Permanente Northern California (KPNC) between 2000 and 2009", researchers examined the IPI to evaluate the risk of ASD in second-born children. Various hazard ratios (HRs) are reported based on the spacing between children: "<6 months, 3.0 (1.9–4.7); 6 to 8 months, 2.1 (1.4–3.3); 9 to 11 months, 1.9 (1.3–2.1); 12 to 23 months, 1.5 (1.1–2.1); and ≥72 months, 2.4 (1.5–3.7)." Following a sort of U-shaped response curve and taking into account various factors that may potentially impact on offspring autism risk, researchers concluded that: "Children born after interpregnancy intervals <2 years or >6 years may be at increased risk of ASD."

Whilst the Zerbo findings have attracted some media attention (see here and see here) it is not necessarily new news that the IPI might show some connection to offspring autism risk. I've covered the topic on at least two other occasions on this blog (see here and see here) outside of other research suggesting similar things [2]. The findings are fairly robust and importantly, seem to cross different geographies and different ethnicities, suggesting that the IPI might be something generalisable to autism across the globe.

As per my other musings on this topic, there are several possibilities as to how a short (or long) IPI might impact on offspring autism risk, mainly associated with more general research on how IPI might influence various birth outcomes (albeit with caveats [3]). Having watched the recent BBC series called 'Countdown to Life' documenting the nine months that made us, I'm particularly interested in the idea that there may be more than one mechanism at work depending on the IPI. Specifically, whether a short IPI where the greatest HR was reported by Zerbo, might be related to a depletion of maternal stores of various micronutrients (the authors have talked about folate although I'd be careful there, indeed very careful there [4]) that comes with pregnancy and David Barker style (see here) whether intrauterine health might be a factor in the elevated risk?

Music, and something a little 'cool' today: The Specials And Fun Boy Three - Our Lips Are Sealed (complete with a sample of the Go-Go's).


[1] Zerbo O. et al. Interpregnancy Interval and Risk of Autism Spectrum Disorders. Pediatrics. 2015. Sept 14.

[2] Coo H. et al. The association between the interpregnancy interval and autism spectrum disorder in a Canadian cohort. Can J Public Health. 2015 Feb 3;106(2):e36-42.

[3] Ball SJ. et al. Re-evaluation of link between interpregnancy interval and adverse birth outcomes: retrospective cohort study matching two intervals per mother. BMJ. 2014; 349: g4333.

[4] Virk J. et al. Preconceptional and prenatal supplementary folic acid and multivitamin intake and autism spectrum disorders. Autism. 2015 Sep 25. pii: 1362361315604076.

---------- Zerbo, O., Yoshida, C., Gunderson, E., Dorward, K., & Croen, L. (2015). Interpregnancy Interval and Risk of Autism Spectrum Disorders PEDIATRICS DOI: 10.1542/peds.2015-1099

Friday, 2 October 2015

ADHD primes for psychosis and/or schizophrenia?

My efforts turn once again to Taiwan today and the results reported by Yu-Chiau Shyu and colleagues [1] that: "Compared to the control group, the ADHD [attention-deficit hyperactivity disorder] group showed significantly increased risk of developing any psychotic disorder... and schizophrenia."

As per the multitude of other instances where Taiwan is mentioned as a research powerhouse, the source data for the Shyu findings was the Taiwan National Health Insurance Research Database and the analysis of data for over 73,000 people "newly diagnosed with ADHD" compared with a similar number of age- and sex-matched non-ADHD controls. "Having a diagnosis of any psychotic disorder and of schizophrenia were set as two different outcomes and were analyzed separately" we are told, as was the possible role (or not) of methylphenidate (MPH) treatment of ADHD on psychosis / schizophrenia outcomes.

In line with the opening paragraph, there was potentially something to see when it came to a previous diagnosis of ADHD priming someone for future psychotic disorder or schizophrenia. The adjusted hazard ratios (aHRs) - "5.20; 95% confidence interval [CI], 4.30-6.30 and 4.65; 95% CI, 3.59-6.04" - for psychotic disorder and schizophrenia respectively are not to be sniffed at. Shyu et al also noted that where MPH use was part of the the ADHD intervention regime, there was a suggestion that MPH use increased the risk of developing psychotic disorder but not schizophrenia. Such a finding is not unheard of in the peer-reviewed literature [2]. The authors also noted that: "Compared to ADHD patients without psychosis, patients with ADHD who developed psychosis had significantly older age at first diagnosis of ADHD (9.4±3.3years vs. 10.6±4.0years)."

This is not the first time that ADHD has been associated with psychosis and/or schizophrenia. The results reported by Dalteg and colleagues [3] are testament to the idea of a possible connection, even if moderated by variables such as substance abuse issues. Indeed, the idea that a diagnosis of ADHD might elevate the risk of substance abuse [4] is an important point given the various voices lending support to the idea that substance abuse might also be a risk factor for psychosis [5]. That being said, I don't want to stigmatise everyone with ADHD on the basis of this connection; there may be quite a few other 'shared pathways' also to consider (see here) and not just of the genetic variety as per nutritional issues for example (see here and see here).

The Shyu results do however reiterate that birds of a developmental / psychiatric feather may very well flock together as per other research findings in related areas (see here). That such a connection can so severely affect quality of life potentially provides further evidence that continued efforts to alleviate childhood psychiatric issues should represent an important goal of modern-day medicine (see here) particularly in respect to the rising numbers being discussed (see here)...

Music: Rush Hour - Jane Wiedlin.


[1] Shyu YC. et al. Attention-deficit/hyperactivity disorder, methylphenidate use and the risk of developing schizophrenia spectrum disorders: A nationwide population-based study in Taiwan. Schizophr Res. 2015 Sep 9. pii: S0920-9964(15)00462-4.

[2] Kraemer M. et al. Methylphenidate-induced psychosis in adult attention-deficit/hyperactivity disorder: report of 3 new cases and review of the literature. Clin Neuropharmacol. 2010 Jul;33(4):204-6.

[3] Dalteg A. et al. Psychosis in adulthood is associated with high rates of ADHD and CD problems during childhood. Nord J Psychiatry. 2014 Nov;68(8):560-6.

[4] Lee SS. et al. Prospective association of childhood attention-deficit/hyperactivity disorder (ADHD) and substance use and abuse/dependence: a meta-analytic review. Clin Psychol Rev. 2011 Apr;31(3):328-41.

[5] Cantwell R. et al. Prevalence of substance misuse in first-episode psychosis. Br J Psychiatry. 1999 Feb;174:150-3.

---------- Shyu YC, Yuan SS, Lee SY, Yang CJ, Yang KC, Lee TL, & Wang LJ (2015). Attention-deficit/hyperactivity disorder, methylphenidate use and the risk of developing schizophrenia spectrum disorders: A nationwide population-based study in Taiwan. Schizophrenia research PMID: 26363968

Thursday, 1 October 2015

Immune endophenotypes in paediatric autism

Today I'm serving up the paper by Milo Careaga and colleagues [1] for your blogging delight, who concluded that: "Children with ASD [autism spectrum disorder] may be phenotypically characterized based upon their immune profile." Further that there may be: "several possible immune subphenotypes within the ASD population that correlate with more severe behavioral impairments."

With many thanks to Natasa for the paper, participants - 50 boys with a median age of 3.2 years diagnosed with an ASD and enrolled "through the Autism Phenome Project (APP) study" and who were free of any "major immune modifying medications" - provided a blood sample. A similar process was employed for a smaller group of typically developing (asymptomatic) control group (n=16). Said blood sample went through various processes to harvest peripheral blood mononuclear cells (PBMC) which were then 'stimulated' to provoke an immune reaction via "either lipopolysaccharide (LPS) or phytohaemagglutinin (PHA)." Various cytokines were then assayed for in the stimulated PBMC and results analysed according to immune responses and behavioural outcomes.

Results: as per the opening paragraph, there was potentially something to see in the findings added to a more general role for cytokines in relation to autism [2]. Those children with ASD who presented with a more 'pro-inflammatory' cytokine profile in their stimulated blood results "showed more impaired developmental and behavioral scores, as well as increased problems with sleep and aggression." That pro-inflammatory cluster by the way (n=22) tended to show significantly increased production of cytokines such as IL-6 for example, than those children with autism (n=28) "who displayed a less robust response to LPS." Ergo, perhaps more to see and certainly more investigations required in these days of plural autisms.

I was taken by one particular sentence included in the conclusion of the Careaga paper: "Although immune abnormalities were first described in ASD over forty years ago, no consensus has been reached as to what constitutes clinically significant immune dysfunction in ASD." As per quite a bit of autism research, sweeping generalisations about this, that or t'other 'causing' autism or being part and parcel of autism have been a big contributor to the noticeable lack of progress on knowledge about autism and where required and wanted, what can be done to ameliorate the more disabling aspects including that related to comorbidity (see here). Realisation that 'autism' is probably better described as providing an umbrella term for various different conditions on a genetic and molecular level is making some headway these days (see here) including that linked to immune function (see here for example). This might have important implications for intervention (see here) as per other recent results that I'll be musing over soon.

As part of a broader realisation that immune function and psychiatry probably show a lot more connections than many people first realised (see here), I think we are seeing a shift in knowledge here. As per the Careaga results, the idea that there may be distinct clusters within the presentation of autism linked to immune function, opens up a whole new world of more 'targeted' inspection and intervention which, added to other similar phenotype work (see here), is probably an important direction for autism research...

Music: Duran Duran - Pressure Off feat. Janelle Monáe and Nile Rodgers.


[1] Careaga M. et al. Immune endophenotypes in children with autism spectrum disorder. Biological Psychiatry. 2015. 10 Sept.

[2] Krakowiak P. et al. Neonatal Cytokine Profiles Associated with Autism Spectrum Disorder. Biol Psychiatry. 2015 Aug 14. pii: S0006-3223(15)00655-1.

---------- Milo Careaga, Sally Rogers, Robin L. Hansen, David G. Amaral, Judy Van de Water, & Paul Ashwood (2015). Immune endophenotypes in children with autism spectrum disorder Biological Psychiatry : 10.1016/j.biopsych.2015.08.036

Wednesday, 30 September 2015

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).


[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.

---------- 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