Friday, 14 December 2018

Estimated one in 69 children aged 8 years old with autism (not one in 68) in 2012

"On June 5, 2018, the authors informed MMWR [Morbidity & Mortality Weekly Report] about a number of inadvertent errors throughout the report that resulted from reporting of autism spectrum disorder cases among persons who did not live in the geographic surveillance area."

So said a brief note [1] recently listed in the CDC Morbidity & Mortality Weekly Report (MMWR) concerning an important article published in 2016 [2] that described the estimated autism prevalence rate in the United States in 2012 for children aged 8 years old.

The original paper by Deborah Christensen and colleagues [2] was fodder for this blog at the time of publication (see here), with their estimated figures for 2012 (one in 68) showing a potential plateauing of the autism estimated prevalence rate in the US (see here for some discussion on the previous figures for 2010). The 'plateau' proved to be short-lived; as more recent figures published this year (2018) for the surveillance year 2014 once again showed the continuation of the upward trend (see here) in the childhood autism prevalence rate, now up to an estimated 1 in 59 children. Other figures have suggested even 1 in 59 is likely an understatement (see here).

Christensen and colleagues have republished their 2016 paper [3] showing 'where they went wrong'. It's not a wildly different article from their original publication and to a large extent, does not alter the underlying figures in any hugely significant way: 'one in 68' is replaced by 'one in 69'. Looking at the tables accompanying the Christensen republication, I was first drawn to Table 2 showing the: "Estimated prevalence* of autism spectrum disorder [ASD] among 1,000 children aged 8 years, by sex —Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2012." Under the column labelled "Total no. with ASD" it looks like a few participating States had corrections. Arkansas in particular stood out; their total going from 170 with ASD down to 125. Their estimated autism prevalence subsequently dropped from 12 per 1,000 children (aged 8) to 8.8 per 1,000. Other States showed a correction in the opposite direction. New Jersey (which has had an important role to play in the CDC estimates) showed a slight increase (of 3 children) in their "Total no. with ASD" similar also to Missouri.

There's little more to say about the Christensen correction aside from reiterating that: (a) the CDC statistics citing figures like 'one in 69' or more recently 'one in 59' are estimates, and (b) how and what data you include for counting is going to have an important bearing on what (estimated) prevalence rate you arrive at. By saying all that, I've not changed my view that we are witnessing something of at least a partial 'real' increase in cases of autism (see here and see here and see here) as older 'better awareness' and 'diagnostic substitution' arguments become less and less relevant as the numbers (estimated) climb ever higher. And aside from keeping on asking 'why?' the powers-that-be should be putting a lot more money and resources into the services that will inevitably be required, to ensure that children and adults on the autism spectrum aren't (societal) disadvantaged by their diagnosis.


[1] No authors listed. Correction and Republication: Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2012. MMWR Morb Mortal Wkly Rep. 2018 Nov 16;67(45):1279.

[2] Christensen DL. et al. Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years--Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2012. MMWR Surveill Summ. 2016 Apr 1;65(3):1-23.

[3] Christensen DL. et al. PPrevalence and characteristics of autism spectrum disorder among children aged 8 years — Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2012. MMWR Surveill Summ. 2018 Nov 16;65(13):1-23.


Thursday, 13 December 2018

Middle ear infection and autism (again)

"Autism was more common in children who had had an otitis media infection or who had been treated with antibiotics."

Minus any sweeping generalisations, that was the conclusion reached in the study by Theresa Wimberley and colleagues [1] continuing some important research themes (see here and see here) examining any "interplay among otitis media, antibiotics, and the subsequent risk of developing autism."

Just in case you don't already know, otitis media infection refers to an infection of the middle ear that "causes inflammation (redness and swelling) and a build-up of fluid behind the eardrum." Aside from the use of painkillers, the seriousness of certain otitis media infections can sometimes mean that antibiotics are prescribed to combat any underlying bacterial infection or even in some cases, grommets inserted as treatment.

Wimberley et al report results based on "the entire Danish population", well, over three-quarters of a million children "followed from birth (January 1, 1997 to December 31, 2008) until December 31, 2012." They calculated various 'risk of autism' statistics as a function of a previous medical diagnosis of otitis media and "antibiotic prescriptions redeemed at Danish pharmacies." Yes folks, yet again those big data Scandinavian population registries have been used to good research effect.

Results: "The absolute risk of autism before age 10 was increased among children with otitis media (1.2% for females and 3.3% for males) and in children who had redeemed an antibiotic prescription (0.6% and 2.7% for females and males) compared to children without a history of otitis media and antibiotics usage (0.4% for females and 1.9% for males)." Researchers also reported finding "little evidence of a synergistic effect between otitis media infections and treatment with antibiotics" despite them being over-represented in relation to autism. They also caution that cause-and-effect cannot be inferred from their observational results.

What more can one say about the Wimberley findings? Well, echoing the idea that correlation is not the same thing as causation, I'd say that there is quite a bit more research to do on this topic. Further investigations are required into the possible mechanisms through which autism may manifest at least partially as a result of a history of ear infection (or indeed vice-versa). Mention of antibiotics also brings in areas of additional research interest such as the gut microbiome and what antimicrobials might 'be doing' to the trillions of passengers that are carried in the deepest, darkest recesses of the human body. I'm also minded to suggest that alongside antibiotic use to potentially treat infections like otitis media, researchers might also want to focus in on other medicines that might be accessed in such case such as over-the-counter pain relief in light of other *associations* that have been made (see here).


[1] Wimberley T. et al. Otitis media, antibiotics, and risk of autism spectrum disorder. Autism Res. 2018 Oct 3.


Wednesday, 12 December 2018

Elevated zonulin levels in ADHD = more hyperactivity and "impairment of social functioning"

"Children with ADHD [attention-deficit hyperactivity disorderhad higher serum zonulin levels and were more impaired in social functioning compared to controls."

So said the findings reported by Gonca Özyurt and colleagues [1] exploring a topic quite close to my research heart, zonulin and the assumption that "the level of zonulin increases when intestinal permeability is impaired."

Before heading further into the Özyurt findings, I'll perhaps refer you to some of my previous musings on the topic of zonulin (see here) and the hows-and-whys of this potentially important compound. It's rooted in the idea that intestinal permeability is perhaps rather more than it should be in some people with some labels (see here) and this *could* have some important implications for biochemistry and beyond; particularly the notion of a 'gut-brain' relationship (see here).

Özyurt et al examined zonulin in the context of attention deficit hyperactivity disorder (ADHD) based on the idea that: "Zonulin has been shown to be associated with social impairment in children with autism spectrum disorder" but such functions (and other attention-related behaviours) have not yet been looked at with ADHD in mind. Based on the examination of serum zonulin levels in some 40 kids diagnosed with ADHD and a similar number of not-ADHD controls, analysed via "enzyme-linked immunosorbent assay", researchers reported that: "Children with ADHD had higher serum zonulin levels and were more impaired in social functioning compared to controls." Also: "The level of zonulin was independently predicted with hyperactivity symptoms and SRS [Social Responsiveness Scalescores in regression analysis."

Bearing in mind that the Özyurt study was a fairly small scale study that utilised a methodology that has its critics (see here), I'm cautiously interested in the presented findings. I don't want to say anything further about this at the present time; aside that is, from the need for quite a bit more data on this potentially interesting relationship...


[1] Özyurt G. et al. Increased zonulin is associated with hyperactivity and social dysfunctions in children with attention deficit hyperactivity disorder. Compr Psychiatry. 2018 Oct 29;87:138-142.


Tuesday, 11 December 2018

Gut symptoms are important for 'psychiatric outcomes' in autism

"Individuals with autism spectrum disorder (ASD) are at heightened risk of psychiatric comorbidities across the lifespan, including elevated rates of internalizing, externalizing, and self-injurious behaviors." And: "Gastrointestinal (GI) conditions are of particular interest, as they are prevalent among those with ASD, may share genetic or neurobiological etiologies with the core features of ASD, and are linked with psychiatric difficulties in the general population."

Putting the issue of 'psychiatric comorbidities' and 'gastrointestinal (GI) conditions' together are the results of the findings reported by Emily Neuhaus and colleagues [1] who concluded that: "the presence and quantity of GI symptoms should be considered when evaluating psychiatric and behavioral concerns among children with ASD." Importantly too, they talk about how 'alleviating' accompanying bowel issues in the context of autism *might* also have some important influences on some of those psychiatric issues.

The starting point for Neuhaus and colleagues was a recognition that autism does not exist in some sort of diagnostic vacuum. This means that various 'comorbid' conditions/labels seem to be over-represented when it comes to autism, covering the behavioural/psychiatric (see here) and also the somatic (see here). The authors specifically zoomed in on GI symptoms because they've mentioned over and over and over again as being part-and-parcel of quite a few instances of autism (see here). Marrying the psychiatric and gastrointestinal together, they had two aims: "First, we sought to document the prevalence and variety of GI concerns within a large, well-characterized sample of children and adolescents with ASD. Second, we sought to understand relationships between ASD symptoms and GI concerns over and above the effects of psychosocial factors."

So, authors "draw on data from nearly 2,800 children and adolescents with ASD within the Simons Simplex Collection" pertinent to their aims and objectives. The Simons Simplex Collection (SSC) is no stranger to autism research for various reasons (see here and see here). Importantly too, the SSC is not stranger to specifically looking at GI issues in relation to autism (see here). They reported that: "Consistent with previous literature, families in the SSC frequently reported that their child with ASD had significant GI symptoms" to the tune of over one third of their sample experiencing at least one GI symptom.

Looking at their types of psychiatric symptoms - "internalizing, externalizing, and self-injurious behaviors" - they observed "evidence of unique variance associated with GI symptoms across all three measures of psychiatric symptoms we examined." This didn't mean that GI symptoms were 'the' [singular] cause of those psychiatric/behavioural issues; merely that the presence of such physical symptoms should be considered as one possible factor alongside things like "ASD symptoms, verbal IQ, adaptive behavior, family income." Given that something like self-injurious behaviour (SIB) can be pretty hard-hitting in terms of effects on the person and the people around them (see here), the idea that GI issues might be 'in the mix' alongside "more ASD symptoms, lower adaptive behavior, lower income" should not be ignored. To quote again: "levels of GI symptoms accounted for unique variance in psychiatric outcomes over and above these other factors, linking increased GI problems with increased psychiatric symptoms in children with ASD."

There is a further scheme of work to be followed in this important area.


[1] Neuhaus E. et al. Gastrointestinal and Psychiatric Symptoms Among Children and Adolescents With Autism Spectrum Disorder. Front. Psychiatry. 2018. Oct 22.


Monday, 10 December 2018

"the incidence of ADHD, ASD, and DD significantly increased after TBI events in early childhood"

TBI mentioned in the title of this post refers to traumatic brain injury, and represents the 'target variable' examined by Hsuan-Kan Chang and colleagues [1] in the context of rates of "attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and developmental delay (DD)."

Consistent with various other research published by this authorship group, the fantastic but sadly now defunct National Health Insurance Research Database (NHIRD) in Taiwan was the resource used by Chang et al in pursuit of their research goal. And the participant numbers under study reflected the use of the NHIRD: "A total of 7,801 and 31,204 children were enrolled in the TBI and control cohorts, respectively."

As well as instances of TBI being listed in the NHIRD "from 1998-2008", researchers also had access to "the incidence of subsequent ADHD, ASD, or DD (according to ICD-9 criteria)." They observed that: "The TBI cohort exhibited a higher incidence of subsequent ADHD, ASD, or DD than the controls" and that said developmental diagnoses tended to be made "at a younger age compared with the controls" (non-TBI controls). They concluded that TBI seemed to increase the risk of each developmental diagnosis and that "severe TBI, repeated TBI events, and TBI at a younger age" were all (variably) potentially important factors for the labels.

This is interesting and thought-provoking research. It does require some 'treading carefully' sentiments; not least with the idea that within the huge heterogeneity and variability of labels such as ADHD and autism (ASD), TBI *might* be a route or part of a possible route towards a diagnosis. Whilst not discounting the idea that sub-clinical signs and symptoms of developmental disorders could actually put someone at greater risk for TBI (see here for example), the possibility that TBI 'might lead to' a developmental diagnosis should not be shied away from. Indeed, other independent findings might also be important (see here). I say that mentioning that TBI is a general term that says nothing about the reason for the injury, the type of injury or what specific part of the brain may be affected. If one however takes autism as an example, it's not beyond the realms of possibility that certain TBIs could 'mimic' effects seen in other examples of 'acquired autism' where brain injury is part-and-parcel of the clinical picture (see here and see here). Indeed, similar sentiments have been expressed in relation to ADHD too (see here).

Whatever the relationship and mechanisms involved, the Chang findings imply that further investigations are needed in this area. Also, far greater efforts need to go into first preventing and then managing TBI...


[1] Chang HK. et al. Traumatic Brain Injury in Early Childhood and Risk of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder: A Nationwide Longitudinal Study. J Clin Psychiatry. 2018 Oct 16;79(6). pii: 17m11857.


Saturday, 8 December 2018

"Anti-Candida albicans IgG antibodies in children with autism spectrum disorders"

The quote titling this post - "Anti-Candida albicans IgG antibodies in children with autism spectrum disorders" - reflects the title of the paper by Paul Ashwood & Heather Hughes [1] who set out to "determine if children with ASD [autism spectrum disorder] exhibit elevations in antibodies that target C. albicans, indicating current or previous overgrowth of this fungal species." Such work is based on the still developing idea that "individuals with ASD have significant aberrations in the composition of their gut microbiota, known as dysbiosis" and part of that dysbiosis might also stretch to fungal as well as bacterial species.

Candida albicans also known as C. albicans is described as a 'opportunistic pathogenic yeast' quite readily observed in quite a large proportion of 'healthy adults'. For most people, this yeast does not cause any issues. On occasion however, C. albicans can lead to problems, particularly among those who are described as 'immunocompromised'. This is not the first time that C. albicans has been examined in the context of autism. Granted, the studies so far have been relatively small scale [2] and in requirement of follow-up [3] but this topic is no stranger to the peer-reviewed science literature. The Ashwood & Hughes paper should also be viewed in the context of other science discussions from this authorship group [4]; indeed several [5].

So: "We measured anti-C. albicans immunoglobulin (IgG) in plasma from eighty children enrolled in the UC Davis MIND Institute CHARGE study." IgG antibodies, represent 'immune status' with regards to a history of encountering specific pathogens. So, being positive to "anti-C. albicans immunoglobulin (IgG)" means that someone has been exposed to C. albicans at some point in their lifetime and retained something of an 'immune memory' to it. This subsequently means that your immune system is 'primed' in case that specific pathogen is encountered once again.

Results: "Plasma anti-C. albicans antibody positivity was found in 36.5% (19/52) of children with ASD. Anti-C. albicans antibodies in typically developing controls was (14.3%; 4/28)." I'm sure that you can see the disparity between the groups, bearing in mind that this was not an 'all-or-nothing' finding in relation to the separation of the groups. I should also mention that researchers also reported that gastrointestinal (GI) symptoms, also examined in this cohort, did not seemingly play a role in C. albicans antibody positivity.

Where next for this area of investigation? Well, alongside perhaps taking these results into consideration with other findings from this research group (see here), the authors mention that "exploring fungal composition within the gut as well as metabolic byproducts of yeast species such as d-arabinitol and ethanol, and identifying associations these might have with behaviors in ASD" could be one direction. In light of other independent research (see here), I'd say that was a sensible next step to take.


[1] Ashwood P. & Hughes HK. Brief Report: Anti-Candida albicans IgG antibodies in children with autism spectrum disorders. Front. Psychiatry. 2018. Nov 26.

[2] Ekiel A. et al. Intestinal microflora of autistic children. Med Dosw Mikrobiol. 2010;62(3):237-43.

[3] Iovene MR. et al. Intestinal Dysbiosis and Yeast Isolation in Stool of Subjects with Autism Spectrum Disorders. Mycopathologia. 2017 Apr;182(3-4):349-363.

[4] Hughes HK. et al. The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders. Curr Neurol Neurosci Rep. 2018 Sep 24;18(11):81.

[5] Hughes HK. et al. Immune Dysfunction and Autoimmunity as Pathological Mechanisms in Autism Spectrum Disorders. Front. Cell. Neurosci. 2018.


Friday, 7 December 2018

"hold promise as cross-cultural key indicators for autism"

The quote heading this post - "hold promise as cross-cultural key indicators for autism" - comes from the paper by Sophie Carruthers and colleagues [1] which "aimed to identify the items on the Autism Spectrum Quotient (AQ)-Child that are most predictive of an autism diagnosis among children aged 4–9 years across samples from India, Japan and the UK." Attempting to fill quite an important 'hole' in the use of the go-to 'are you autistic' screener, authors set out to look at the presentation of autistic traits across three different countries, all with some quite different cultural perspectives and contexts.

The Carruthers paper is open-access so doesn't need too many grand discussions from me. The basics: "parent-reported AQ-Child data from India (73 children with an autism diagnosis and 81 neurotypical children), Japan (116 children with autism and 190 neurotypical children) and the UK (488 children with autism and 532 neurotypical children)" was the source material. Once again I'll mention how the term neurotypical is a misnomer (see here); it's use in this paper is all the more surprising given that one of the authors wrote an editorial paper [2] mentioning how "there is no single way for a brain to be normal, as there are many ways for the brain to be wired up and reach adulthood." Oh well.

Results: from the collected data, researchers were able to undertake various statistical analyses. Pertinent to the quote titling this post were some important findings "identified to be universal key indicators" across the different countries and cultures. These were: "In a social group, s/he can easily keep track of several different people’s conversations; s/he enjoys social chit-chat; s/he knows how to tell if someone listening to him/her is getting bored; s/he is good at social chit-chat and s/he finds it difficult to work out people’s intentions." Alongside, various other indicators were rated as "performed excellently or acceptably" across the three different country groups.

The conclusion: "Cross-cultural overlap in the items most predictive of an autism diagnosis supports the general notion of universality in autistic traits whilst also highlighting that there can be cultural differences associated with certain autistic traits." I'd like to see more research done in this area. Quite a few years ago I posed the question 'Is autism the same all over the world?' (see here) and well, I don't have a good answer despite the Carruthers and other results. Obviously such a question needs also to be wrapped in the idea that the plural 'autisms' also exert an effect (see here) and take into account other factors such as comorbidity (if that is the right word). It should also perhaps appreciate that whilst the AQ is undoubtedly 'picking up' something, it might not just exclusively be autism or autistic traits (see here and see here)...


[1] Carruthers S. et al. A cross-cultural study of autistic traits across India, Japan and the UK. Molecular Autism 2018; 9:52.


Thursday, 6 December 2018

On autism and exposure to fragranced consumer products

The findings reported by Anne Steinemann [1] tap into an important issue seemingly relevant to many people diagnosed with autism or an autism spectrum disorder (ASD): exposure to various fragranced products such as air fresheners, deodorants and perfumes can seemingly cause various adverse physiological reactions. I know to some people this might not seem like particularly groundbreaking research, but when you read that almost 60% of autistic adults have been reporting "lost workdays or lost a job, in the past year, due to fragranced product exposure in the workplace" it kinda turns into something a lot more important.

Steinemann reports results across various different geographical cohorts pertinent to "the effects of fragranced products on autistic individuals ages 18–65 in the United States, Australia, and United Kingdom." This was a questionnaire-based study, a "web-based" survey, "part of the SSI [Survey Sampling Internationalweb-based panel." The numbers included for study are in the thousands, with some 4% reporting "medically diagnosed autism" upon which the Steinemann study is based.

The conclusion: "83.7% report adverse health effects from fragranced products." Said effects included "migraine headaches (42.9%), neurological problems (34.3%), respiratory problems (44.7%), and asthma attacks (35.9%)." Further: "Health problems can be severe, with 74.1% of these effects considered potentially disabling under legislation in each country."

As you can perhaps see, exposure to fragranced products is potentially an important issue for many people on the autism spectrum. The Steinemann results are based on discussions with adults (18-65 years) but I daresay there may be much to see with younger cohorts too. I'd also be interested to see whether issues like comorbidity potentially over-represented alongside autism might also exert something of an important effect too.

Solutions? Well, I don't think it's too much to ask if public and workplaces could perhaps look at some of their spaces with a view to reducing their use of fragranced products. If for example, this means cutting back on things like those automated air fresheners that periodically squirt out a cloud of smelly stuff, I'm pretty sure quite a few more people - more than just autistic people - would benefit. Indeed, with all the focus on 'autism hours' these days, I wonder if this could be something to add to the list of being 'autism-friendly'? As for personal scented products and the like, well, if you know that you're going to be interacting with autistic people who might be particularly sensitive to fragrances, how about giving those scented products a miss for that day? I promise that you will still smell OK. I don't think these are unreasonable requests.

Then the next question: why? Why do such symptoms come about and what are the biological mechanism through which such 'sensitivity' occurs? Well, it appears that Steinemann has some research history when it comes to fragrances and autism [2] albeit looking at "the neuromodifications of three selected fragrances on male and female human fetal brain neurons." Oxytocin and arginine vasopressin were the molecular targets in that study. Whether there may be more to see from these compounds in relation to fragrance sensitivity in adults is a question to ask. Such issues also perhaps overlap with other research talking about olfaction and autism (see here and see here). I'm also minded to point readers in the direction of another condition/set of symptoms that could be relevant: multiple chemical sensitivity (MCS). Yes, yes, I know that MCS is disputed in some quarters, even to the point of mentioning the word 'psychosomatic' on some occasions [3], but it strikes me that such high rates of 'fragrance intolerance' in relation to autism *could* also be tied into the presentation of MCS. And such high numbers reporting such an intolerance is probably not just 'all in the mind'.


[1] Steinemann A. Fragranced consumer products: effects on autistic adults in the United States, Australia, and United Kingdom. Air Quality, Atmosphere & Health. 2018; 10: 1137-1142.

[2] Sealey LA. et al. Environmental factors may contribute to autism development and male bias: Effects of fragrances on developing neurons. Environ Res. 2015 Oct;142:731-8.

[3] Jimenez XF. et al. Polyallergy (Multiple Chemical Sensitivity) is Associated with Excessive Healthcare Utilization, Greater Psychotropic Use, and Greater Mental Health/Functional Somatic Syndrome Disorder Diagnoses: A Large Cohort Retrospective Study. Psychosomatics. 2018 Aug 2. pii: S0033-3182(18)30418-3.


Wednesday, 5 December 2018

Cannabis treatment and autism

"This preliminary study supports [the] feasibility of CBD [cannabidiol]-based cannabis trials in children with ASD [autism spectrum disorder]."

That was the research bottom-line suggested by Adi Aran and colleagues [1] following their retrospective study of some "60 children with ASD and severe behavioral problems" who were given cannabidiol (CBD)-rich cannabis. They report that nearly two-thirds of parents/caregivers of those children in receipt of CBD-rich cannabis observed "much improved or very much improved" behaviour on the Caregiver Global Impression of Change scale, "a 7-point, caregiver rated scale, designed to assess how much the child's symptoms have improved (‘No change’, ‘Slightly improved’, ‘Much improved’, or ‘Very much improved’), or worsened (‘Slightly worse’, ‘Much worse’, or ‘Very much worse’) relative to the baseline state."

Cannabidol (CBD) is a component of cannabis. Distinct from tetrahydrocannabinol (THC) in terms of chemical arrangement, CBD is still thought to have some psychoactive properties, although perhaps not as 'detrimental' as THC [2]. Cannabis and CBD have been fairly big news lately as a consequence of the legalisation of such compounds for specific medicinal uses here in Blighty (see here).

Aran et al report findings suggesting that further controlled research is required in this area. They observed that among their 60 children (50 boys and 10 girls with an average age of 12 and 10 years respectively) taking on average between 4-5 "drugs for behavioral problems", quite a high proportion were still being treated with cannabis "≥ 6 months from treatment onset." Perhaps also importantly, a third of children received less medications or lower dosage of medication following their "cannabis treatment."

I will however add in a word or two of caution following the Aran observations. First, although there is a lot of discussion and hype around the use of medicinal cannabis and various diagnoses / conditions / labels, one still has to remember that this is a drug, and a drug of abuse at that. This mirrors the chatter about another substance of abuse being potentially indicated in the context of autism (see here). Aran et al also talked about some adverse effects noted in their cohort ("sleep disturbances (14%) irritability (9%) and loss of appetite (9%)") including: "One girl who used higher tetrahydrocannabinol [THC] had a transient serious psychotic event which required treatment with an antipsychotic." Others have also independently warned about medical cannabis use [3] citing ASD as one example. What this information imply is that alongside any potential studies of cannabis or specific compounds derived from cannabis with autism in mind, one needs to also keep a focus on the potential downsides to its use as well as any positives...


[1] Aran A. et al. Brief Report: Cannabidiol-Rich Cannabis in Children with Autism Spectrum Disorder and Severe Behavioral Problems-A Retrospective Feasibility Study. J Autism Dev Disord. 2018 Oct 31.

[2] Pierre JM. et al. Cannabis-induced psychosis associated with high potency "wax dabs". Schizophr Res. 2016 Apr;172(1-3):211-2.

[3] Bou Khalil R. Why Is It Important to Protect Children with Mental Disorders from Medical Cannabis? J Dev Behav Pediatr. 2015 Nov-Dec;36(9):766.


Tuesday, 4 December 2018

One more time... (roughly) 1 in 40 children with parent-reported autism in the US

Consider this short post an extension of another recent entry on this blog talking about new data observing that the estimated autism prevalence rate (parent-reported) is around 1 in 40 children in the United States (US) (see here). That entry was based on the paper by Michael Kogan and colleagues [1] and their examination of data "using the 2016 National Survey of Children's Health (NSCH)" initiative.

Enter then another piece of research published little over a week after the Kogan study from Guifeng Xu and colleagues [2] which concluded that: "In a large, nationwide, population-based study, the estimated prevalence of ever-diagnosed ASD [autism spectrum disorder] was 2.79% among US children in 2016." In case you were wondering, 2.79% or 2.8% roughly translates as 1 in 36 children. Xu and colleagues, I might add, are no strangers to prevalence studies on childhood neurodevelopmental disorders (see here and see here).

Both these studies have attracted some media attention (see here and see here) mainly because they show a prevalence rate quite a bit higher than the recent CDC (estimated) autism prevalence figures - 1 in 59 8-year olds - published earlier this year (2018) (see here). Those media reports also seem to make quite a big deal of the 'parent-reported' nature of the figures (both derived from the NSCH initiative). As I mentioned in my last discussion of the Kogan paper, a quote from the lead author Michael Kogan is important in the context of those parent-report 'issues' that some people seem to have: "We know that in terms of having a major condition like autism, parents are usually pretty good reporters compared to medical records." Indeed they are.

Other details to add? Well, the Xu paper also reported on "state-level prevalence of ASD in the United States." They observed variations in the reported prevalence of autism (ASD) across the different states: "The state-level prevalence varied from 1.54% (95% CI, 0.60-2.48) in Texas to 4.88% (95% CI, 2.72-7.05) in Florida." Little explanation is given about such a discrepancy in their paper and so further research is implied.

Also: "Among those who had ever been diagnosed as having ASD, 92.79% (95% CI, 90.19-95.39) reported currently having ASD." This is interesting. Allowing for the fact that the diagnosis of autism or ASD is often more of an art form than a scientific endeavour, I did wonder whether the loss of about 8% of children who were previously diagnosed with autism but did not report currently having autism might overlap with the 9% figure with regards to the term 'optimal outcome' (see here). Y'know, the ever-growing body of peer-reviewed research that seems to suggest that for some people, a diagnosis of autism is not necessarily 'lifelong' (see here) (even if 'optimal outcome' is not necessarily the best phrase to use). Again, further research is implied.

For now however, we can conclude that there is : "a relatively high prevalence of ASD among US children" mirroring that in other parts of the world (see here for example). We really need to be asking questions like 'why?' and also 'are the relevant mechanisms in place to ensure that money, resources and services are directed towards this growing population?'


[1] Kogan MD. et al. The Prevalence of Parent-Reported Autism Spectrum Disorder Among US Children. Pediatrics. 2018 Nov 26. pii: e20174161.

[2] Xu G. et al. Prevalence and Treatment Patterns of Autism Spectrum Disorder in the United States, 2016. JAMA Pediatrics. 2018. Dec 3.


Pregnancy depression (with or without antidepressant use) and offspring autism risk continued

"Women with depression during pregnancy have an increased risk of having a child with ASD [autism spectrum disorder], regardless of antidepressant use."

That was the conclusion reached by Katrina Wilcox Hagberg and colleagues [1] following their analysis of the UK Clinical Practice Research Datalink (CPRD). Their study was carried out as a result of the still-rumbling-on question of whether pregnancy depression or the pharmacological treatment of depression during pregnancy *might* be a risk factor for an offspring diagnosis of autism (see here and see here). As you might appreciate, it's difficult to pin down whether depression or the treatment of depression is the more important issue given that the two typically appear together.

The CPRD held here in Blighty is a mighty fine resource and has been used to examine all-manner of potentially important issues (see here and see here for some examples). Researchers looked at mums and offspring ("singleton infants") born between 1989 and 2011 totalling nearly 200,000 mother-baby pairs. They reported that: "Mothers were required to have at least 12 months of recorded history before the baby's delivery date, and the children were required to have at least 3 years follow-up after birth." Because antidepressants require a doctor's prescription in the UK, they were also able to identify those other important elements vital to this study: depression and it's antidepressant intervention or not, as well as "the timing of antidepressant use during the exposure period." Authors also report some additional analyses based on "a sibling case-control analysis of maternal pregnancy exposures in ASD cases compared to non-ASD siblings of the same mother."

Results: based on the examination of 'read codes', authors identified some 2100 children with a diagnosis of ASD. The old 4:1 male:female ratio yet again held true (see here). Taking into account being exposed to depression or not and whether exposure was treated or untreated, researchers formed their headline conclusion on pregnancy exposure to maternal depression being linked to an increased risk of offspring autism. Further: "The risk was slightly higher among women with treated depression... compared to untreated depression." The results of the sibling case-control part of their trial - "601 same-sex siblings who did not have an ASD diagnosis matched to 531 ASD cases" - also revealed that: "the risk of ASD in offspring of mothers with untreated depression was 1.18 (95% CI 0.64-2.20) and 1.53 (95% CI 0.89-2.62) for treated depression, compared to unexposed." Some further analysis looking at the timing of antidepressant exposure during pregnancy revealed that it didn't really matter when the exposure happened (i.e. which trimester).

Perhaps contrary to some of their findings, it's clear from some of the statements included in the Hagberg paper that the authors seem to have sided with the idea that "antidepressants are not themselves associated with the increased risk" of offspring autism. It's depression that is the important factor, and the "slight increase in risk with antidepressant use reflects differences in the underlying severity of depression." The other evidence they draw on to support their assertion is the "finding that the risk of ASD was not elevated in women who were prescribed antidepressants for other indications."

I'm not however so sure that we can be so certain about such a siding. I say that on the basis that researchers "did not evaluate the effect of antidepressant dose in this study" and: "Drug information in the CPRD covers written, but not dispensed prescriptions" so therefore they "cannot be sure that women used all the prescribed antidepressants." Their 'nested sibling case-control analysis' also revealed that: "the risk of ASD in offspring of mothers with untreated depression was 1.18 (95% CI 0.64-2.20) and 1.53 (95% CI 0.89-2.62) for treated depression, compared to unexposed." Not proof positive by any means, but interesting. I'm also inclined to direct you to other studies previously discussed on this blog, where the finger of suspicion has not rested entirely with maternal depression [2]. Indeed, where meta-analysed data [3] has been more partial to the idea that prenatal exposure to certain antidepressant formulations could still be on the menu with some offspring autism risk in mind.

Obviously one has to be very careful when talking about this area of autism research. Much like when another class of important medicines used during pregnancy are talked about with 'autism risk in mind' (see here), such medicines are not typically prescribed or dispensed willy-nilly without good reason. By saying that, I feel I must repeat my oft-said caveat on this blog: no medical or clinical advice is given or intended; if in doubt, talk to your prescribing physician.

But the weight of evidence produced so far has not let antidepressant use off the research hook just yet. And drawing on data suggesting that the frequency of depression during pregnancy might be on the increase (see here), one should perhaps also suspect that this could have something - a small part at least - to do with the ever-increasing rates of autism...


[1] Hagberg KW. et al. Maternal depression and antidepressant use during pregnancy and the risk of autism spectrum disorder in offspring. Clinical Epidemiology. 2018; 10: 1599-1612.

[2] Raj D. et al. Antidepressants during pregnancy and autism in offspring: population based cohort study. BMJ. 2017; 358: j2811.

[3] Andalib S. et al. Maternal SSRI exposure increases the risk of autistic offspring: A meta-analysis and systematic review. Eur Psychiatry. 2017 Sep;45:161-166.


Monday, 3 December 2018

Disclosure of autism and juror perceptions

The paper by Katie Maras and colleagues [1] really interested me. It describes results based on examining "mock juror perceptions of credibility and culpability of a defendant who is described as displaying autistic-like characteristics and behaviours, and whether the provision of information about the defendant’s ASD [autism spectrum disorder] diagnosis alters these perceptions." Such investigations continue a theme in autism research circles and beyond on 'how autism is viewed' (see here and see here and see here) and how disclosure of an autism diagnosis might be important and influential in various circumstances.

Given the focus on the criminal justice system and autism in this post, I'm also going to pass some brief comment on the paper by Kamaldeep Bhui [2] too. That paper was more concerned with trying to "understand radicalisation, ethical and definitional issues, and how public health approaches may help." Minus any sweeping generalisations, the label of autism was also mentioned in the Bhui paper and could be relevant to the Maras findings too.

So, autism and the criminal justice system. This is not the first time that this topic has been discussed on this blog (see here and see here for examples) reflective of some ever-increasing research interest. It highlights how a diagnosis of autism is by no means protective of someone coming into contact with law enforcement services and/or the court system, and how various discussions are still needed on the hows-and-whys of such contact, as well as ensuring that those on the autism spectrum are treated justly and fairly in the eyes of the law.

In the Maras paper researchers report that: "One-hundred-and-sixty jury-eligible participants read a vignette describing a male who was brought to the attention of police for suspicious and aggressive behaviours and displayed atypical behaviours in court." The specific imaginary crime of this individual was "assault and battery of a police officer" where "the defendant was behaving aggressively at a train station and when police officers tried to restrain him with handcuffs, he became violent and struck an officer." Further details also included: "it reportedly emerged that the defendant was trainspotting and was upset because his train was cancelled."

Half of participants were randomly allocated to receive "Label+info" and the other half "no label". The 'no label' group received no further information about the defendant or any possible diagnosis. The 'label+info' group "were informed that the defendant had been assessed by a forensic psychiatrist and was diagnosed with ASD, and they were given further information defining ASD and how it impacted on his behaviours." Participants were then asked to make various judgements about the imaginary case and defendant.

Results: "The provision of a label and information led to higher ratings of the defendant's honesty and likeability, reduced blameworthiness, and resulted in fewer guilty verdicts, and more lenient sentencing." Various themes are detailed by the authors based on their findings: honest, inappropriate language, culpability and consequences.  Interestingly, on the topic of 'consequences', even some of those in the 'no label' group indicated that "they thought the defendant might have ASD" and how punishment would perhaps be less useful than "some form of rehabilitation to help the defendant." The net result is that jurors may be sympathetic to the presentation of autism in some contexts of involvement with the criminal justice system provided they are given the appropriate information about the individual concerned.

I take some comfort from the Maras findings that the law may not be blind to the circumstances around particular defendants and the crimes for which they are accused. Similar to the guidance here in Blighty when it comes to 'mentally disordered offenders' the law recognises that whilst crime is crime, sometimes things aren't always as straightforward as they seem (see here). By saying that I'm not trying to deflect away from why the law is there and the often serious effects that crime has on individuals (victims) and society; merely that 'context' is sometimes important too.

Going back to the Bhui findings and discussions pertinent to understanding radicalisation and particularly the idea that: "Common mental illnesses appear to be a risk factor at a population level for developing extremist beliefs, and psychoses and autism are reported as more common amongst some terrorist offenders" there are also implications. One has to be sensitive and avoid any sweeping generalisations when discussing this topic, but the issue of radicalisation and autism has been talked about before (see here). One of the primary themes to emerge from the growing data in this area is that a pattern of fairly unique vulnerabilities seems to follow autism that *might* make someone more susceptible to unscrupulous individuals intent on spreading their own agendas and getting someone else to do their dirty work.

Applying the Maras results to the Bhui discussions, one would hope that both mock and real jurors would apply the same logic as and when offences linked to radicalisation in the context of autism are presented to them. One would hope that a diagnosis of autism and everything that entails would be taken into account as and when such crimes are put to them. Indeed, perhaps that is the next round of study for Maras et al if they should wish to replicate their study: replace 'assault and battery' with something linked to radicalisation. I for one, would be interested in what results they observe and what we can potentially learn from them.


[1] Maras K. et al. Mock Juror Perceptions of Credibility and Culpability in an Autistic Defendant. J Autism Dev Disord. 2018 Oct 31.

[2] Bhui K. Radicalisation and mental health. Nord J Psychiatry. 2018 Nov 1:1-4.


Saturday, 1 December 2018

'Mucosal healing' in treated coeliac disease "may come at a cost of an increased risk of mood disorders"

I was really quite intrigued by the findings reported by Jonas Ludvigsson and colleagues [1] attempting to "examine the relationship between anxiety, depression and mucosal healing in coeliac disease." Intrigued because such findings tap into a couple of potentially important areas such as the whole gut-brain 'being linked' bit (see here and see here) and how gut permeability (a.k.a leaky gut) might be something quite important to quite a few different labels/diagnoses/states (see here).

I should perhaps briefly go through a few choice terms before starting. Coeliac disease (sometimes written as celiac disease) is the archetypal 'food affects physiology' condition as per it's description encompassing the words 'gluten', 'autoimmune disease' and 'gastrointestinal'. Part of the biological profile of coeliac disease (CD) is involvement of the gut mucosal membrane and the characteristic 'flattening' of the mucosal surface reducing the capability to properly absorb various nutrients. This is known as villous atrophy and is measured using the Marsh criteria. Luckily, for most people with CD, when a gluten-free diet is installed to treat/manage CD, the gastrointestinal (GI) pathology linked to villous atrophy abate and mucosal healing can take place as long as gluten remains excluded from the diet.

Ludvigsson - a name not unfamiliar to all-research-things coeliac disease - and colleagues sought to look at the presentation of certain extra-gastrointestinal symptoms as a function of mucosal healing (through use of a gluten-free diet) or persistent villous atrophy. They analysed data collected over nearly 40 years "on all small intestinal biopsies with villous atrophy from Sweden's 28 pathology departments." They also garnered data on the presence of a diagnosis of depression and/or anxiety, and married the two data sets together...

Results: "During follow-up, 123 (2.8/1000 person-years) individuals with mucosal healing had developed anxiety, compared to 94 (2.1/1000 person-years) with persistent villous atrophy." What this means is that whilst the presentation of anxiety was spread both across those who did and did not seemingly biologically benefit from the use of a gluten-free diet, those who showed gut healing were seemingly at "a higher risk of future anxiety." A similar trend was also noted when it came to a diagnosis of depression. This led researchers to highlight how "the goal of mucosal healing may come at a cost of an increased risk of mood disorders."

I was truly in head-scratching mode when it came to these findings. I don't know if it's just me, but I would have thought that persistent villous atrophy akin to not-quite-complete mucosal healing would have been more pertinent to the expression of anxiety and depression. I say that from the point of view that micro nutrients (and specifically, the lack of them) seem to have some important relationships with mood states and related conditions (see here and see here) under other circumstances. I'd also mention that a patient with CD knowing that the gluten-free diet wasn't 'doing what it's supposed to' in relation to managing CD at a biological level might also be a cause for concern for them and possibly lead to more complicated 'issues'?

So what could be the reason for the Ludvigsson findings? Well, subject to independent replication of the findings and perhaps also looking at other variables potentially pertinent to the presentation of anxiety and depression in CD (see here for example based on the 'birds of an autoimmune feather' hypothesis), one might surmise a few things. First, that the biological expression of CD 'hides' underlying issues such as anxiety and depression, and only through (successful) treatment do such mood disorders become 'unmasked'. Anecdotally and without any supporting evidence, I remember back to some of my research days looking at gluten- and casein-free diets being used in the context of [some] autism, and how some parents / autistic people reported that the diet seemed to 'reveal' anxiety issues for example, at the costs of helping to resolve certain behavioural and somatic (bowel) issues they faced. Could similar mechanisms apply to CD bearing in mind the effect that dietary gluten removal has on gut barrier function?

Next possibility: gluten peptides. It's pretty well known that the gluten peptides - the intermediate compounds that form during the digestion of the gluten - have some important biological action insofar as them possessing potential opioid activity. The gluteomorphins as they're known, share similar structural data to other well known opioid compounds such as morphine. It's probably one of the reasons that we've had such an enduring relationship with such foodstuffs. Could the rise of mood disorders be related to such biochemistry? Y'know, removal of gluten peptides and the mucosal healing affecting transport to the wider central nervous system meaning that patients aren't getting 'their fix'?

One other possibility is also worth mentioning and investigating: Eyes should also perhaps turn to what other effects a dietary change such as gluten removal might have on physiology; specifically on the trillions of wee beasties that call our GI tract home: the gut microbiota. Does a healed mucosa have implications for the gut microbiota?

Questions, questions, questions...


[1] Ludvigsson JF. et al. Anxiety after coeliac disease diagnosis predicts mucosal healing: a population-based study. Aliment Pharmacol Ther. 2018 Oct 4.


Friday, 30 November 2018

The positives of ADHD?

I tread carefully with my discussions of the paper by Jane Ann Sedgwick and colleagues [1] talking about "insights into positive human qualities, attributes or aspects of ADHD [attention-deficit hyperactivity disorderthat can support and sustain high functioning and flourishing in ADHD life." Carefully because, just like discussions over another label closely associated with this blog, there are a myriad of different views and opinions about the way neurodevelopmental disorders / conditions / labels are presented and viewed by those who have been diagnosed with them. Who am I to tell someone what they should or shouldn't be thinking?

Sedgwick et al started from the idea that although 'disorder' is a defining part of ADHD, the subsequent focus on 'deficit' does not perhaps do justice to all that is included under the diagnostic term. They reference 'positive psychology' and its moves "away from a deficit-focused view of mental health, towards approaches that were more enabling, strength-based and emphasised positive aspects of human functioning and flourishing (i.e. positive emotions, engagement, relationships, meaning and accomplishment)." They then move to the aim of their study: "to explore ability and disability in ADHD from the participants own perspective using the WHO International Classification of Functioning, Disability and Health (ICF) framework." Mention of the WHO ICF framework also brings me back to similar discussions with autism in mind (see here).

"We recruited six successful (i.e. HF[high-functioning]-ADHD and flourishing) adult males aged between 30 and 65 years from an NHS tertiary service in London." Said participants were interviewed with questions such as: "(1) What do you think are the advantages and disadvantages of having ADHD? (2) Please describe a time when you felt that your ADHD helped to achieve something? (3) What aspects of your ADHD would you miss if it went away?" Following some content analysis of results, certain themes emerged.

"The main findings of this study are characterised by six core themes (cognitive dynamism, courage, energy, humanity, resilience and transcendence)." Alongside, a number of sub-themes were also reported including "divergent thinking, hyper-focus, nonconformist, adventurousness, self-acceptance and sublimation." Researchers concluded that because these themes and sub-themes were not listed as "sanities in positive psychology" (i.e. "relevant to people in general, with or without ADHD") they *might* be specifically linked to ADHD.

OK, a few steps back. You'll no doubt recognise that this was research based on interviewing six men with ADHD (and 'flourishing' with their ADHD at that). It's not difficult to see how the issue of 'representativeness' might be a particular problem with the Sedgwick results. If for example, they had presented data from their six participants compared with another six who perhaps weren't described as 'flourishing' (see here for one possible example), I'd be a lot more confident in their findings. Better than that would have also been the views of a few other participants representing other labels where ADHD is part-and-parcel of a more complicated clinical picture (see here and see here for examples). And don't forget their focus on one gender/sex too...

I can see how something like 'cognitive dynamism' conceptualising "ceaseless mental activity" could be seen as a double-edged sword when it comes to ADHD. Yes, it can be utterly disabling for some (many) in terms of being "scattered, chaotic and a bit random." But in some scenarios and with the right environment and encouragement, such an issue could be a lot more positive a trait to have. Likewise the concept of 'energy' whilst quite synonymous with ADHD, probably also has an upside as well as a downside, particularly when harnessed to the benefit of the person concerned and their strengths.

But... I have some difficulty with the ideas that courage, humanity and resilience for example, are somehow to be viewed as 'the positive side of ADHD'. There are plenty of people out there who demonstrate such strengths without a diagnosis of ADHD or indeed, a diagnosis of anything. The fact that Freud and Nietzsche are also referenced in relation to some of those terms suggests to me that the authors have perhaps moved slightly outside of the evidence-based arena in some of their interpretations of their findings. Similarly, the use of the term 'divergent thinking' isn't exactly what I would call science-based either, as my 'neurotypical' brow starts to furrow (see here).

I appreciate what the authors have tried to do with this paper: reaching out "to people with lived experience of ADHD: service users, patients, family members, carers, partners, to say that not all symptoms of ADHD are maleficent." It's admirable that such thinking is there, particularly when a diagnosis of ADHD can seem such a daunting prospect both in the short- and long-term (see here). I'm slightly concerned however that this paper seems to be insinuating that a clinical diagnosis of something like ADHD should be used as a framework to 'psychologise' someones life. The inference being that because ADHD undoubtedly affects many aspects of a person's life, it is something that defines them and all their behaviour(s) and attitude(s) on many aspects of life. I've seen it before in other labels too as diagnosis morphs into identity.

Personally, I don't think anyone should be defined by their clinical or related label in the same way that sex/gender, skin colour, religion or politics shouldn't define a person. It's OK to say yep, I have ADHD and it affects my life in this way or that way, and this is what I need to help overcome such issues. But I'm not convinced that adopting an 'ADHD identity' and seeing all the positives and negatives of life as part of that diagnostic identity is particularly good for anyone. A person is defined by their actions not their [diagnostic] label...


[1] Sedgwick JA. et al. The positive aspects of attention deficit hyperactivity disorder: a qualitative investigation of successful adults with ADHD. ADHD Attention Deficit and Hyperactivity Disorders. 2018. Oct 29.


Thursday, 29 November 2018

"Vitamin D and omega-3 reduced irritability symptoms in children with ASD"

The title heading this post - "Vitamin D and omega-3 reduced irritability symptoms in children with ASD [autism spectrum disorder]" - comes from the findings reported by Hajar Mazahery and colleagues [1] discussing the results of their clinical trial. I have already mentioned the Mazahery trial before on this blog (see here) as a 'study to watch' based on the publication of their study protocol [2]. It looks like the wait is finally over...

So, as researchers previously reported, there were four arms to this clinical trial: supplementation with vitamin D alone ("2000 IU/day, VID"), supplementation with an omega-3 fatty acid ("722 mg/day DHA, OM"), vitamin D plus fatty acid supplementation together ("2000 IU/day vitamin D + 722 mg/day DHA, VIDOM") and a placebo group (olive oil). Results are reported for over 70 children diagnosed with an autism spectrum disorder (ASD) - "VID = 19, OM = 23, VIDOM = 15, placebo = 16" - over a 12-month period, with the primary outcome being "the Aberrant Behaviour Checklist (ABC) domains of irritability and hyperactivity."

Aside from the main finding - "vitamin D and omega-3 LCPUFA [long chain polyunsaturated fatty acid] reduced irritability symptoms in children with ASD" (compared against placebo) - a few other observations are noteworthy: "Compared to placebo, children on VID [vitamin D] also had greater reduction in hyperactivity." All this bearing in mind that the biological testing to examine for vitamin D and fatty levels reported "a good compliance rate" indicating that supplements were routinely being taken as required by the study.

Implications? Well, strike up more peer-reviewed evidence that nutrition is important not just for physiological health but also for psychological/behavioural health and wellbeing too (see here). Add this research also to other peer-reviewed science that suggests that at least 'some autism' might be particularly 'sensitive' to elements of such nutritional medicine (see here).

I could go on about how vitamin D in particular seems to be something important to autism (see here and see here for examples). I could also go on about how fatty acids have some important evidence-based history with autism in mind (see here). But do I really need to? Minus any medical or clinical advice given or intended, the Mazahery results really speak for themselves.


[1] Mazahery H. et al. A randomised controlled trial of vitamin D and omega-3 long chain polyunsaturated fatty acids in the treatment of irritability and hyperactivity among children with Autism Spectrum Disorder. The Journal of Steroid Biochemistry and Molecular Biology. 2018. Oct 26.

[2] Mazahery H. et al. Vitamin D and omega-3 fatty acid supplements in children with autism spectrum disorder: a study protocol for a factorial randomised, double-blind, placebo-controlled trial. Trials 2016; 17:295.


Wednesday, 28 November 2018

1 in 40 children with parent-reported autism in the US

Consider this post an extension of another entry published some years ago (see here) talking about the parent-reported (estimated) autism prevalence rate in the United States.

On that last blogging occasion, the paper by Stephen Blumberg and colleagues [1] was the discussion piece, and the observation that: "Based on parent reports, the prevalence of diagnosed ASD [autism spectrum disorder] in 2011–2012 was estimated to be 2.00%" or 1 in 50. That finding was based on the examination of "the 2007 and 2011–2012 National Survey of Children’s Health (NSCH), which are independent nationally representative telephone surveys of households with children."

Enter then a more recent publication from Michael Kogan and colleagues [2] who, also using data from the NSCH, this time the 2016 NSCH, extrapolated that: "Parents of an estimated 1.5 million US children aged 3 to 17 years (2.50%) reported that their child had ever received an ASD diagnosis and currently had the condition." Their calculated estimate increased from 1 in 50 children in 2011-2012 with parent-reported autism in the United States to 1 in 40 children in 2016...

Based on an Internet survey (see here), where over 50,000 responses "focused on the health and well-being of children aged 0 to 17 years" were received, researchers examined data from well over 40,000 children aged 3-17 years old. Analysing the findings from the NSCH sample with regards to affirmative answers to questions on "whether children ever received an ASD diagnosis by a care provider, current ASD status, health care use, access and challenges, and methods of treatment", they concluded that around 1 in 40 children had parent-reported autism in their cohort.

What's more to say? Well, there's always going to be the old 'they've relied on parent report' issue to contend with, despite the fact that most parents aren't 'making it up' when they talk about autism being present in their children. Indeed, the lead author of the study, Michael Kogan, when talking to the lay media about his results (see here) put it better than I ever could: "We know that in terms of having a major condition like autism, parents are usually pretty good reporters compared to medical records." Indeed.

Then, despite arguments such as "changes in the survey make it difficult to compare the findings to data from previous years" [3] and increasingly worn out soundbites like better awareness, expanded diagnostic criteria and diagnostic substitution (see here) as potentially accounting for the increase in prevalence (estimates), I do think it's about time that we started to have some real-world conversations about the figures being presented and what could be behind them. And yes, this probably means mentioning the words 'real increase' at some point (see here) and not being ashamed to say so. Bearing in mind that this is seemingly an increase that is going on around many parts of the world (see here) and seems to be driven by new diagnoses in younger cohorts and not for example, the diagnosis of 'missed adults' (see here), science and clinical practice really needs to get to the bottom of this. Not least because resources and money need to be put in place to ensure that the growing numbers of people being diagnosed are provided with the care and support they need and require over a lifetime.

I've watched a lot of 'burying heads in the sand' around the autism prevalence figures over the past few decades (see here) similar to what's been seen with various other developmental and behavioural labels (see here and see here). It's perhaps time to wake up, pull heads out of the sand and start organising more research about what is potentially driving the ever increasing autism prevalence figures...


[1] Blumberg SJ. et al. Changes in Prevalence of Parent-reported Autism Spectrum Disorder in School-aged U.S. Children: 2007 to 2011–2012. National Health Statistics Report. 2013; 65: March 20.

[2] Kogan MD. et al. The Prevalence of Parent-Reported Autism Spectrum Disorder Among US Children. Pediatrics. 2018. Nov 26.

[3] AAP News. Study: 1 in 40 children diagnosed with autism. 2018. Nov 26.


Tuesday, 27 November 2018

Project TENDR and chemical exposures part 2: organophosphate pesticides aren't great for child health

So, without striking too many chords on the old 'we've been here before' piano, consider this post an extension of some other discussions a while back suggesting that exposure to some classes of 'chemicals' might not be particularly great for child health (see here).

The findings reported by Irva Hertz-Picciotto and colleagues [1] continue the Project TENDR theme with their assertion that there is "compelling evidence" that prenatal exposure to organophosphate (OP) pesticides "is putting children at risk for cognitive and behavioral deficits and for neurodevelopmental disorders." Their observations have also been picked up by the lay media with some striking headlines like 'Ban entire pesticide class to protect children's health, experts say' complete with the required stock photo of crops being sprayed from the air.

Organophosphate (OP) compounds such as OP pesticides have a very mixed history. As well as being the insecticide of choice in many countries as a result of their excellent pest control profile, the organophosphate chemistry has also been utilised for less desirable purposes as per its classification as a component of nerve agents. Remember all the quite recent chatter about a nerve agent called Novichok? Well, the chemistry behind Novichok apparently has a very distinctive OP "structural backbone" [2]. That's not to say that every OP pesticide is Novichok. But rather that the activity of OPs specifically targeting the action of acetylcholinesterase (AChE) enzymes, important enzymes that are required for proper nerve function, is also an important biological action of various nerve agents. This in itself would suggest caution in the use of OPs.

The Hertz-Picciotto paper (policy forum) is pretty data heavy in terms of how much OP pesticides are used across the globe, the slew of mostly observational research studies that have looked at pesticide exposure and various neurodevelopmental variables and the concerns voiced at both high and low levels of OP pesticide exposure. They make a few recommendations: better training for health professionals on the potential risks attached to OP pesticide exposure, greater moves to switching to "nontoxic approaches to pest control" and perhaps most controversially: "Governments phase out chlorpyrifos and other OP pesticides."

The caveats? Well I might mention a few, minus any charges of me somehow 'standing up for OPs'. First, I don't think it's unreasonable to suggest that children in particular, do need to be more strongly protected against pesticides that are (chemically-speaking) not a million miles away from nerve agents. As the authors mention, there is quite a bit of evidence in the peer-reviewed literature to suggest a possible *association* between pesticide exposure and diagnoses such as autism (see here and see here) or beyond (see here). The thing is that like many other non-genetic environmental factors (e.g. air pollution) *linked* to a heightened risk of autism or other neurodevelopmental labels, it's more about environment + genetics when it comes to risk (see here) rather than environment just working on its own. We need for example, to know more about the ways and means that OPs are metabolised in the body and whether there could be some interesting biochemistry potentially linked to labels like autism (see here).

Second, some thought needs to go into the possible replacements if OP pesticides were to be banned outright. Thinking back to a post not-so-long-ago talking about DDT exposure and offspring autism (see here) I was struck by how short some memories are in terms of why such products were developed in the first place. I don't think anyone would seriously contemplate that the development of OP pesticides was anything more than to stop pests attacking crops and to maintain yields that can feed the population. These compounds were developed with good intentions. Obviously, as the research literature has grown, we have come to realise that such products are not side-effect free and more stringent controls have been put into place regarding safety. But to ban them outright is not something that can be done overnight. What do we replace them with? Do we just accept that crop yields will be lower and less food will be produced? Do we instead start thinking about other ways to make crops more resistant to the pests that blight them? That last question has already had its own 'issues'.


[1] Hertz-Picciotto I. et al. Organophosphate exposures during pregnancy and child neurodevelopment: Recommendations for essential policy reforms. PLoS Med 15(10): e1002671.