Friday 29 June 2018

The estimated prevalence of childhood autism in Nepal (based on the AQ-10)

I read with some interest the paper by Michelle Heys and colleagues [1] talking about an estimated prevalence rate of autism in Nepal. The figure they arrived at was: "an estimated true prevalence of 3 in 1000 (95% confidence interval 2–5 in 1000)."

Unless you are Nepalis or really, really interested in the epidemiology of autism worldwide (raises hand slowly), you're probably not going to be particularly 'excited' by such findings. I'm blogging about them however, because there are a couple of points of interest to take from the Heys paper. Not least that the (estimated) prevalence of autism seems to be really, really low in Nepal. I'm also quite interested in the assessment tool used - the Autism Spectrum Quotient (AQ) - and some comments made about autism from some of the parents of participants as potentially also affecting the results obtained.

The Heys study is actually a few studies included in one peer-reviewed write-up. First and foremost, researchers identified a potentially suitable population-based screening tool for autism, then adapted and translated said screening tool "in the Nepali language", then checked the acceptability of the translated assessment tool and finally, set about administering the translated assessment tool and arriving at an estimated prevalence rate. As I've already mentioned, the assessment tool settled on was the AQ-10. The decision to use this tool was taken because out of 12 assessment schedules looked at, the AQ-10 'fitted best' researchers criteria (including being free to use).

The estimated prevalence rate was arrived at on the basis of over 4000 children being 'screened' using the AQ-10. "Fourteen children scored > 6 out of 10 [on the AQ-10], indicative of elevated autistic symptomatology, of which 13 also screened positive for disability." That 'screened positive for disability' refers to the "report of social and communication difficulties, as well as physical, learning and behavioral disability using the Module on Child Functioning and Disability (MCFD) produced by UNICEF and the Washington Group on disability statistics... for use in children and young people aged 2–17 years." The authors go on to mention that those 14 children who scored 6 or greater on the AQ-10 probably reflected "children with complex needs and more likely more severe autism." Indeed they also note: "Of those children who screened positive for autism symptomatology, almost all also screened positive for physical, learning and behavioral disabilities." Yet again, autism rarely appears in some sort of diagnostic vacuum (see here).

I'll freely admit that I am ever-so-slightly critical of the AQ and its application to autism screening. I'm critical because autistic traits are not necessarily something exclusive to a diagnosis of autism (see here for one example) and short screening instruments for autism like the AQ are rarely able to tease out the possibility of other diagnoses being pertinent (perhaps even more pertinent than the label of autism). When it comes to the use of the AQ as a screener for possible adult autism, well, one only needs to look at the 'English experience' of adult prevalence estimate studies to see that results weren't exactly optimal (see here) (albeit based on the use of the AQ-20 [2]).

Do I therefore agree with the use of the AQ-10 in the Heys Nepal autism prevalence study? Well, sitting in a high-and-mighty 'with hindsight' position (😉) I would have perhaps gone with something a little more comprehensive or at least included another instrument alongside. I say this on the basis that 10 questions don't really provide enough detail when it comes to big claims about estimated autism prevalence (as per the title of the paper). The fact also that the majority of the 14 children picked up by the AQ-10 as showing 'elevated autistic symptomatology' also presented with a complex pattern of disability (including 'learning and behavioral disability) is also at odds with the typical guidance on the use of the AQ-10: "A quick referral guide for parents to complete about a child aged 4-11 years with suspected autism who does not have a learning disability." This bearing in mind also that the authors used the AQ-10 in a second wave of data collection (the MCFD was used in the first wave when such 'learning and behavioral disability' would have been initially picked up). I don't want to be too critical, but...

The second reason for blogging about the Heys paper concerns some of the comments made about autism in the context that typically Western views on autism - abilities and disabilities - are not necessarily shared the world over and might have affected the results obtained. I'm not going to recite the quotes included in the Heys study but let's just say that the point made by the authors: "would find a potential diagnosis of autism challenging to accept or endorse" kinda sums up the feelings portrayed by some parents. Bearing in mind, the AQ-10 was completed by parents or primary caregivers, and well, it's not beyond the realms of possibility that some parents may have put a more 'positive spin' on some of their responses...

There are other important points raised in the Heys paper - "children who screened positive for autism symptomatology were more likely to be stunted... Nutritional deficits in children with disabilities and learning difficulties are common and can not only be a cause of cognitive deficits, but also contribute to the failure to reach full developmental potential in the presence of a developmental condition" - but I've gone on enough for now. Suffice to say that the very conservative prevalence estimates produced by Heys et al are probably not a true reflection of the scale of autism in Nepal. Much more research is indicated.

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[1] Heys M. et al. The Estimated Prevalence of Autism in School-Aged Children Living in Rural Nepal Using a Population-Based Screening Tool. J Autism & Dev Disord. 2018. May 31.

[2] Brugha TS. et al. Validating two survey methods for identifying cases of autism spectrum disorder among adults in the community. Psychol Med. 2012 Mar;42(3):647-56.

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Thursday 28 June 2018

'Growing out of autism' was talked about way back in 1993

I appreciate that for some people mention of the words 'growing out of autism' in the title of this post will be met with a furrowed brow. I appreciate that the very sweeping generalisation that all autism that is, has been or ever will be, is lifelong and immutable is something that some people adhere to almost religiously, as words like 'oh, they weren't autistic in the first place' ring out in some quarters to counter such 'growing out of' sentiments. I'm certainly not going to be able to change anyone's mind, and neither do I seek to.

But the idea that autism, for some, is not lifelong is something that is very evident in the peer-reviewed science domain and beyond. I've talked about it on a few occasions on this blog (see here and see here) and how 'subsequently not fulfilling the diagnostic criteria for autism' having previously done so, may have some quite profound implications beyond just the core presentation of autism (see here).

Recently PubMed decided to list the paper by Anne-Liis von Knorring & Bruno HĂ€gglöf [1] published way back in 1993 (the year we were all asked to 'Shake the Room'). Theirs is an interesting paper insofar as providing a window on autism research decades back; even referring to a time when the term 'childhood psychosis' was still being used.

They report 'follow-up' results of a group of children and young adults residing in Northern Sweden. Previously diagnosed with childhood psychosis, all cases were re-evaluated and: "According to DSM-III-R, 38 children met the criteria of "autistic disorder"." Authors reported on various aspects of behaviour some 8-9 years later for 34 of the original 38 participants, and what happened to signs and symptoms in terms of things like stability.

For most participants, there was little change in their diagnostic status. Autism for the majority, was lifelong and indeed for some, showed "a mildly deteriorating course" but typically with some improvements in language and communication. The authors also mention how: "In one case symptoms of schizophrenia developed" which kinda taps into another area of increasing interest these days concerning the over-representation of psychiatric comorbidity in the context of autism (see here).

But then, something interesting: "Only one boy had "grown out of" autism without showing any autistic-like symptoms at all." Yes, it's only 1 out of 34 (two others from the original cohort who did not take part in the follow-up study were reported to be "well-functioning employed adult young men living by themselves") but nonetheless...

I've often pondered why 'growing out of autism' has not been received with open arms by some. I've come to the conclusion that there are likely a few reasons why.

So first, the idea of 'autistic identity' - where autism is seen as so much more than a diagnosis - might have something to do with it. Although identities change, modify and adapt throughout the lifespan, there is perhaps something 'safe' about the idea that being defined as 'autistic' is a constant, and the sense of belonging that perhaps follows, alongside terms like 'neurodiversity' gaining popularity. The evidence suggesting that such a constant might not be a universal constant for everyone is perhaps jarring for some. Indeed, from a neurodiversity point of view, those who are no longer autistic should perhaps then be viewed as transitioning to neurotypical perhaps...?

Allied to this sense of 'identity' I do wonder if some of the terminology associated with 'growing out of autism' might also play a role in how the concept has been viewed down the years. Take for example the term 'optimal outcome' made in reference to those who were were once autistic but at a later point don't hit clinical cutoff points. The insinuation is that where a diagnosis of autism or the presentation of significant autistic traits persists, there is an opposite: 'not optimal'. You can perhaps see how this paints autism, particularly in the context of that autistic identity. And it is indeed timely that there is research chatter about 'reframing optimal outcome' [2] recently...

Similarly, the idea of 'growing out of autism' also taps into the 'medicalisation' of the label. So, minus making too many direct comparisons, when individuals don't meet the clinical thresholds for the label (having previously done so), one could argue that this is evidence that some autism is akin to other medical diagnostic labels that wax and wane, whether naturally or following intervention. I daresay also that autism as seemingly being transient for some, also sits in the same domain of autism being 'acquired' for some. Y'know, those various examples in the peer-reviewed literature that suggest that infection (viral, bacterial, etc) can lead to autism (see here) or that autism appearing alongside various inborn errors of metabolism (see here) is a reality too.

I'm just opining as an outsider looking in, but these are some of the reasons that spring to mind for the seeming lack of interest (even disdain in some quarters) for such a group. Minus any sweeping generalisations from me, all of those previous points have collectively been noted in another context: sexuality...

Personally, I don't see such 'growing out of autism' cases as a threat to either identity or any other aspect of autism. You've probably heard of the term 'if you've met one autistic person, you've met one person with autism' and well, that goes as much for those who 'lose' their diagnosis as it does for anyone else. Anyone with some scientific curiosity should really be asking the question 'why?' Why do some people manifest autism (and reach all the diagnostic cutoff points for autism) at one part in their life but not another? Is it about masking or are there more complicated processes - psychological, biological, genetics - at work?  What role does intervention play (if any)? And what lessons can we learn from such a group outside of the idea that autism is a truly heterogeneous label?

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[1] von Knorring AL. & HĂ€gglöf B. Autism in northern Sweden. A population based follow-up study: Psychopathology. Eur Child Adolesc Psychiatry. 1993 Apr;2(2):91-97.

[2] Georgiades S. & Kasari C. Reframing Optimal Outcomes in Autism. JAMA Pediatrics. 2018. June 25.

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Tuesday 26 June 2018

Headline fail: "Autism traits could be 'edited' out genetic trial suggests"

The Telegraph June 25 2018
"Autism traits could be 'edited' out genetic trial suggests" was one of the headlines that accompanied the publication of the findings by Bumwhee Lee and colleagues [1].

The Lee article details some interesting science following the use of something called CRISPR-Cas9 gene editing (see here) or more precisely the use of a new-ish development to this technique - "CRISPR–Gold, a nonviral delivery vehicle for the CRISPR–Cas9 ribonucleoprotein." CRISPR is one of the hottest things in science at the moment, as the words 'find, cut and paste' move to a genetic level (see here) and promises so much. In the Lee study, the target was the metabotropic glutamate receptor 5 (mGluR5) gene as a move to "efficiently reduce local mGluR5 levels in the striatum."

Oh, did I also mention that this research was done using mice? Indeed, this was a study of mice engineered to display some of the molecular and behavioural characteristics of a condition called Fragile X syndrome (FXS). As such, authors reported that the use of CRISPR-Gold injections into the striatum of said FXS mice correlated with a reduction in certain behaviours such as obsessive digging and leaping into the air. The authors opine that such behaviours 'overlap' with those noted in autism (FXS has a 'connection' to autism) and voilĂ , a link to autism is made.

Aside from that brief overview of the findings from Lee et al just mentioned, I'm not going to go too much into the nitty-gritty of the actual results. A cobbler should stick to his last and all that, and others have done a far better job than I ever could in discussing the science (see here). I do however want to make a case that the 'autism traits could be edited out' headline represents a fail when covering the Lee findings.

I say 'headline fail' in the title of this post because well, it is. Not only does it assume that obsessive digging and sporadic leaping into the air made by mice are singularly autistic traits, it takes a few sentences before the word 'mice' is even mentioned in the coverage. I've talked before about the caution(s) needed when translating animal findings to real people (see here) and how autism in particular, seems to be a label ripe for mass sweeping generalisations from 'autistic animals' to autistic people. I'm not saying that some of the features of autism are uniquely human (see here) but rather that is it premature to even imply that the traits of autism can be 'edited out' on the basis of a single mouse or other animal genetic study.

I've already mentioned about a 'connection' between FXS and autism but it is perhaps also important to realise that there seem to be many routes that bring someone to a diagnosis of autism. FXS is one condition that manifests autistic traits but it is not the only one and certainly science does not yet know everything there is to know about the genetics of autism and FXS. And just before anyone starts talking about autism being universally 'in-born' and 'genetic' as it is [assumed] in FXS, well, the peer-reviewed research evidence might just disagree with you (see here for one example)...

Finally there's another aspect to this work that requires sensitive media handling: the ethics of 'editing out' autistic traits. I know this is a 'hot potato' area, as an increasingly vocal - certainly on social media - group of people on the autism spectrum talk about their strengths as well as their disabilities. Much of this discussion is framed around the notion that autism is not something separate from who they are but rather a fundamental part of who they are. If one takes this viewpoint, it is logical to assume that 'editing out' autistic traits might mean something rather ominous to some people...

The point I'm trying to get across is that the Lee paper is seemingly good science. It faithfully reported the results of an exciting new technology that holds promise for many different labels, conditions and diseases (see here). The issue however, is that the reporting of such research needs to be accurate and responsible. Headlines in particular, need to mention the word 'mouse' if it was a mouse study. They need to avoid sweeping generalisations that infer that digging and leaping behaviour in animals are generalisable as autistic traits (certainly the latest ICD-11 schedule says nothing about such behaviours), and they need to be sensitive to the fact that 'editing out' may very well provoke significant anxiety among some people on the autism spectrum. All for the sake of an attention-grabbing headline...

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[1] Lee B. et al. Nanoparticle delivery of CRISPR into the brain rescues a mouse model of fragile X syndrome from exaggerated repetitive behaviours. Nature Biomedical Engineering. 2018. June 25.

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Sulforaphane and autism continued: metabolomics wades in...

"We identified 77 urinary metabolites that were correlated with changes in symptoms, and they clustered into pathways of oxidative stress, amino acid/gut microbiome, neurotransmitters, hormones, and sphingomyelin metabolism."

So said the findings reported by Stephen Bent and colleagues [1] continuing a theme in autism research circles examining the use of a compound called sulforaphane - "a supplement with indirect antioxidant effects that are derived from broccoli sprouts and seeds" - in the context of [some] autism (see here). Once again, I'm sure that there may be people out there with brows furrowing when it comes to talk of a 'broccoli chemical' potentially impacting on the presentation of autism. But peer-reviewed science (placebo-controlled) is peer-reviewed science [2] and not just to be 'put to one side' because it doesn't follow the trends or [research] fashions of the day.

This latest work from Bent et al represents a not-so-methodologically strong attempt (i.e. not placebo-controlled) to bring the science of metabolomics into research proceedings to "examine changes in physiological markers that may underlie beneficial treatment effects from sulforaphane by analyzing changes in urinary metabolites." Metabolomics by the way, as well as being music to my research ears, is something that percolates through quite a lot of autism research these days (see here and see here for examples) as small molecules in urine, blood and other biofluids are separated, detected and elucidated all in the name of science.

A small group of children participated in the Bent study; all had a "formal diagnosis of autism", all were reasonably happy to swallow a tablet containing sulforaphane ("weight-based dosing of sulforaphane") and all were able to provide urine samples before the study started and at the conclusion of the 12 week research period. Parents of participants were also willing and able to complete a couple of behavioural schedules: "the Aberrant Behavior Checklist (ABC) and... the Social Responsiveness Scale (SRS)" at "baseline, 4 weeks, and 12 weeks using an online and secure platform" about their children too.

Results: alongside looking at pre- and post-intervention behavioural scores, the authors also "examined the number of participants who had a clinical response." This is a particularly important detail in the context of autism and the continuing discussions about how the spectrum is well and truly heterogeneous (the autisms?) and so one shouldn't expect every single person diagnosed to somehow have the same genetics and/or biochemistry; also affecting response to any particular intervention. With that in mind, authors also reported that (group) scores on one of their primary outcome measures - the SRS - were significant, indicative of some positive change noted to behaviour over the course of the intervention period. I say this bearing in mind that this was an open-trial, where everyone took sulforaphane and everyone knew that they were taking sulforaphane (including the parents who did the scoring). As for those potential 'best-responders' to sulforaphane use, we are told that: "Eight participants had a clinical response compared to seven who were classified as non-responders."

Then to those metabolomic results, and from a total of nearly 700 compounds identified in urine, approaching 80 of them seemed to show some correlation with the behavioural symptom changes noted. They were put into various categories depending on their biochemical form and/or action, and correlations with behavioural scores (and significance) were presented. Some of the best correlations that I could see were with regards to sphingomyelin metabolism. The authors did seem a bit surprised by results in this area, but added: "It is not clear how sulforaphane might alter sphingomyelin metabolism or availability and whether this is related to clinical benefits, but if this association is confirmed, it has important clinical and treatment implications." I daresay that examination of sphingomyelin metabolism in other contexts (see here for example) might be revealing, particularly in the context of other behavioural/psychiatric labels [3] that could (and do) overlap with autism.

There is a further scheme of work to be followed when it comes to sulforaphane and autism on the basis of these and other scientific results [4]. I'd also suggest that the continued incorporation of the science of metabolomics is a good thing, and adds a further tier of investigation when it comes to studying intervention more generally in the context of autism. It's also an important step in (eventually) coming up with a 'test' for who might be a best-responder to the use of sulforaphane and perhaps associated compounds...

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[1] Bent S. et al. Identification of urinary metabolites that correlate with clinical improvements in children with autism treated with sulforaphane from broccoli. Molecular Autism. 2018; 9: 35.

[2] Singh K. et al. Sulforaphane treatment of autism spectrum disorder (ASD). Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15550-5.

[3] Castillo RI. et al. From Molecules to the Clinic: Linking Schizophrenia and Metabolic Syndrome through Sphingolipids Metabolism. Frontiers in Neuroscience. 2016;10:488.

[4] Sedlak TW. et al. Sulforaphane Augments Glutathione and Influences Brain Metabolites in Human Subjects: A Clinical Pilot Study. Mol Neuropsychiatry. 2018 May;3(4):214-222.

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Monday 25 June 2018

Borna disease virus antibodies and autism: baseline data setting the scene

The findings reported by Tomoyuki Honda and colleagues [1] setting out a baseline prevalence rate of antibodies against bornavirus in children diagnosed with an autism spectrum disorder (ASD) provides the blogging fodder today. Whilst the Honda findings might not exactly sound like 'exciting science' I would perhaps beg to differ...

Although no expert on Borna disease or Borna disease virus (BDV), I am an interested amateur. Borna disease was named after the town of Borna in Germany, where a fatal neurological (encephalitic) disease affected certain livestock including sheep, cattle and horses. The causative agent was found to be BDV. As well as being characterised by a "meningoencephalomyelitis" state, the symptoms of Borna disease also stretch to certain behaviours. This includes stereotypical behaviours (animals travelling in circular movements or standing in peculiar positions and poses) as well as ataxia affecting coordination and balance. Presentation in some animals has led to the name 'Staggering disease' being used.

Although predominantly seen as a disease affecting animals and livestock, there has been a gradual shift towards the idea that Borna disease virus can also infect humans too. Quite a lot of scientific resources have, for example, concluded that BDV might show an important connection to human psychiatric diagnoses/conditions such as schizophrenia [2]. This, on the basis of serological evidence for recent or continued viral exposure. Following on from a previous case report from Honda and colleagues [3] describing antibodies against BDV in a child with autism and her mother, the authors seem to have developed an interest in all-things BDV and autism. There has also been discussion about a BDV rodent model of autism from other research groups [4] including from the now [sadly] non-functioning research tag-team that was Hornig and Lipkin [5].

On this latest research occasion, Honda et al observed a few things. First: "The prevalence of antibodies against bornavirus-specific speckles, N, and P proteins were 22%, 48%, and 33%, respectively, in the ASD children." For discussions on 'Bornavirus-specific speckles, N, and P proteins' I'll refer you to some other work including Honda on the authorship title [6] on the viral nitty-gritty details. Second: "According to our criteria, the prevalence of antibodies against bornaviruses was 7.4% in the ASD children." Bearing in mind a dearth of investigations on the estimated prevalence of Borna virus more generally, particularly in children, and the various ways and means that immunological contact with the virus can be assayed by, that percentage did seem quite high. Other work [6] for example, has talked about a figure of 2% 'exposure' rate in non-clinical populations. I suppose the 'baseline data' from Honda is trying to make in-roads into this prevalence issue.

Obviously, there's a way to go yet on this topic before any sweeping generalisations are made. The impact of viral infection/illness in relation to [some] autism has quite a long peer-reviewed research history; be that the effect of congenital cytomegalovirus (CMV) (see here) or the work looking at rubella and autism (see here) for examples. The more contemporary research base examining various encephalitis conditions also presenting as autism or autistic-like disorder(s) (see here and see here) is also important. With regards to any specific possible connection between Borna disease virus and autism, future work needs to establish lots of things (infection route, exposure characteristics, etc.). We also need to know whether behavioural symptoms/traits are actually 'caused' by such viral exposure or perhaps more generally linked to immune responses as per the whole 'immune system does more than just fight infection' bit. If a link is shown beyond reasonable doubt, there could be some real scientific advances possibilities on the back of what is already emerging [7]. But at the moment, it's still 'a big if'...

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[1] Honda T. et al. Prevalence of antibodies against Borna disease virus proteins in Japanese children with autism spectrum disorder. Microbiol Immunol. 2018 May 22.

[2] Azami M. et al. The association between Borna Disease Virus and schizophrenia: A systematic review and meta-analysis. Asian J Psychiatr. 2018 Apr;34:67-73.

[3] Honda T. et al. Detection of Antibodies against Borna Disease Virus Proteins in an Autistic Child and Her Mother. Jpn J Infect Dis. 2017;70(5):599.

[4] Pletnikov MV. et al. Developmental brain injury associated with abnormal play behavior in neonatally Borna disease virus-infected Lewis rats: a model of autism. Behav Brain Res. 1999 Apr;100(1-2):43-50.

[5] Hornig M. et al. An infection-based model of neurodevelopmental damage. Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):12102-7.

[6] Matsumoto Y. et al. Bornavirus Closely Associates and Segregates with Host Chromosomes to Ensure Persistent Intranuclear Infection. Cell Host & Microbe. 2012; 11: 492-503.

[7] Honda T. et al. Neuropathogenesis of persistent infection with Borna disease virus. Uirusu. 2015;65(1):145-54.

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Saturday 23 June 2018

One in five 8-year olds "received a psychiatric diagnosis"

"Question: What is the cumulative incidence of psychiatric diagnosis and use of psychotropic medications in a Medicaid-insured birth cohort by age 8 years?"

Answer: About 1 in 5 children were in receipt of a psychiatric diagnosis at age 8, and about 10% were in receipt of psychotropic medication.

So said the findings reported by Dinci Pennap and colleagues [1] who relied on "Medicaid claims data for newborns in a mid-Atlantic state in 2007... and followed up for 96 months or less through December 31, 2014." As per the focus on Medicaid - an initiative that 'helps with medical costs for some people with limited income and resources' - this was a study conducted in the United States, and included data for over 35,000 infants/children. The sorts of psychiatric diagnoses examined by Pennap et al included "ADHD [attention-deficit hyperactivity disorder], disruptive disorders, learning disorder (LD), adjustment disorder, anxiety disorders, depression, ASD [autism spectrum disorder], and other psychiatric diagnoses" all diagnosed by a clinician, but also requiring "2 or more diagnosis claims on separate days."

Venturing further into the study results, we learn some potentially important details. So, across the years of study, approaching two-thirds of the diagnoses received were defined as 'behavioural'. As probably expected (see here), a diagnosis of ADHD was the most popular label - "accounted for 43.9% (1999 of 4550)" - followed by a learning disorder (disability) diagnosis received by just over 30% of the group. White children were seemingly more likely to receive any psychiatric diagnosis than African American children or Hispanic children, and there were some important sex/gender differences noted across various diagnostic labels. If I'm also reading the results correctly with regards to the label of ASD (autism spectrum disorder) (see here), it looks like about 2-2.5% of boys had received a diagnosis, bearing in mind that this is a figure showing as a percentage of those who had received a psychiatric diagnosis. As a function of the entire cohort (N=35,244), the cumulative incidence of ASD across the years (2007-2014) and across the genders was 0.89%.

Then to the issue of pharmacotherapy or medication prescription. Bear in mind that Pennap and colleagues were looking at psychotropic medication being delivered to infants and young children; a group where even greater caution than usual should be expected. They reported that just over 10% of the entire cohort had some history of psychotropic medication use. Alongside those stats on ADHD as a diagnosis, so the medicines classed as stimulants (indicated for ADHD) made up the biggest class of medication used. The authors also zoomed in on a few particular parts of their medication findings. First: "girls were twice as likely as boys to initiate treatment with anxiolytics and hypnotics (25.2% [173 of 686] vs 13.2% [199 of 1510]; P < .001)", also noting that "there is insufficient evidence to support the use of anxiolytics and hypnotics as first-line treatment for pediatric mental health conditions." Second, they discuss evidence suggesting that: "antipsychotics are largely used for off-label behavioral management in the birth cohort, highlighting the need for a delicate benefit-risk balance." Yes, indeed there is a need for exploring that 'delicate benefit-risk balance' (see here and see here). The other rather important finding concerned the use of more than one psychotropic medicine over a prolonged period of time: "approximately 20% of medicated children (433 of 2196 [percentage adjusted for right censoring]) received 2 or more classes concomitantly for 60 days or more." Remember again, these were young children that were under study.

The picture painted by Pennap et al is an important one. It adds to other independent evidence to suggest that across different geographies, psychiatric disorders including behaviourally and emotionally-defined conditions, are prevalent, dare I even say frequent (see here and see here). I'd also add in the 'yet newer' recent US CDC 'estimates' of autism in 8-year olds in this context too (see here).

In relation to the medication side of things, well, 10% of their total population have had some exposure to psychotropic medication, which is important. Accepting that (very) careful medicines management is required given the young age of the group, I'm gonna stick to a line that I've mentioned before regarding the clinical need for such medicines [generally] outweighing the risk(s). I say this on the basis that prescribing clinicians know their clinical population and know something about the risk-benefit profile of the medicines they're administering. I'd also add that when it comes to something like stimulants as a class of medicines, the clinical profile of such medicines is typically 'safe' (benefits outweighing risks) and can, in a few cases, literally be a life-saver (see here and see here). But all that does not mean that science shouldn't be looking to other avenues for intervention for various labels (see here and see here for examples), alongside keeping a sharp eye on ways and means of making such medicines even safer for such younger populations...

And just in case you thought the figure 1 in 5 only holds for the United States, you're wrong and resources and services here in Blighty are seemingly still struggling...

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[1] Pennap D. et al. Patterns of Early Mental Health Diagnosis and Medication Treatment in a Medicaid-Insured Birth Cohort. JAMA Pediatrics. 2018. April 30.

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Friday 22 June 2018

"results support HLA involvement in ASD"

HLA mentioned in the title of this post - "results support HLA involvement in ASD [autism spectrum disorder]" - refers to the human leukocyte antigen (HLA) system. This is an important part of our biology that "helps the immune system distinguish the body's own proteins from proteins made by foreign invaders such as viruses and bacteria." Y'know, making sure that our immune system is able to correctly distinguish between 'self' and 'not-self' in terms of its decision on who to 'attack'...

The findings reported by Meriem Bennabi and colleagues [1] provide further analysis of the HLA system in the context of autism with their study designed to "more precisely explore the polymorphisms of the HLA class II loci, at allele, genotype and haplotype levels." Before further journeying through the Bennabi paper, I'll direct you to some other discussions I've had on this blog in relation to the HLA system and autism (see here). Specifically, how certain HLA links with autoimmune conditions such as coeliac disease, *might* overlap with some autism (see here). I'd also like to take this opportunity to remember one of the first people to look at the HLA in relation to autism [2]: the late Reed Warren.

The starting point for the Bennabi study was the idea that immune 'dysfunction' is no stranger to autism research. Indeed, the authors list three important 'immune-related' areas as evidence: "(i) a deleterious effect of prenatal or perinatal infectious pathogen exposure; (ii) a pro-inflammatory state often concomitant with abnormal cell-mediated immunity or inflammatory-mediated gut dysbiosis; (iii) a frequent autoimmune component observed in mothers of ASD off-spring as well as in ASD patients, with circulating anti-brain autoantibodies sometimes correlating with disease severity and/or behavior impairments." And yes, they did actually mention 'gut dysbiosis' too...

The authors move further into speculating about a possible role for the HLA system in some of those 'immune-related issues', and specifically whether subtle genetic differences to the HLA system might be involved.

"HLA genotyping data was available only for 474 ASD and 350 HC subjects on which the statistical analysis were performed." HC refers to the pretty awful term 'healthy control' which I, personally, dislike in the context of autism and other behavioural labels. Bearing in mind that I've already mentioned the classic 'diet affects physiology' autoimmune condition that is coeliac disease (CD), I note some important findings observed by Bennabi et al: "the HLA-DRB1 *11-DQB1*07 haplotype was more prevalent in ASD patients, versus HC (Pc = 0.001), partially replicating previous data and possibly linking to gastro-intestinal (GI)-related pro-inflammatory processes, given that this haplotype associates with pediatric celiac disorders." They also note that there may be a potentially 'protective' HLA haplotype too: "the HLA-DRB1 *17-DQB1*02 haplotype was higher in HC, versus ASD patients (Pc = 0.002), indicating that this is a protective haplotype." The stuff about linking autism related scores (function and severity of autism) with haplotype also documented by the authors are interesting but perhaps fodder for another blogging occasion.

So what might this all mean? Well, y'know when people talk about dietary gluten potentially showing a *relationship* with some facets of autism? They could actually be on the something. Whether that be the 'over-representation' of a formal diagnosis of coeliac disease in relation to autism (see here) or the idea that something 'not quite coeliac disease but something close' might be present (see here and see here), there is a peer-reviewed evidence base to consider. I know this kind of 'diet' research can furrow brows in some quarters, but peer-reviewed science is peer-reviewed science and well, there's already enough physical health inequality in relation to autism.

Alongside mention of the 'gut-brain axis', authors also discuss another potentially important area that may link to their results: "the involvement of the HLA system in wider physiological processes, including synaptic pruning." Yes, it is true that the HLA system probably does more than just serve as a 'pattern-recognition' system for differentiating between 'self' and invading pathogens and this could also be important to a diagnosis like autism. And there's more, as per another quote from the authors talking about... "the presence of the human endogenous retrovirus K (HERV-K) and increased expression of C4A molecules, with both related to excessive synaptic pruning during specific developmental windows." C4A is part of the complement system related to immunity. Going back to my mention of Reed Warren, he and his research group looked at another aspect of the complement system with autism in mind: C4B [3]. Talk about HERVs - human endogenous retroviruses - by Bennabi et al, is also a subject quite close to my heart (see here). HERVs have been investigated in the context of labels such as autism before (see here and see here) and whilst 'activation' of elements of such fossil viruses probably has many different effects, there has been some chatter about them being possible 'superantigens'. This in the context that whilst parts of these fossil viruses have been 'incorporated' into our genetic being and so considered 'self', there's always the possibility that they might be recognised as 'foreign' under certain circumstances and thus setting off an autoimmune cascade. That's the theory anyway...

The HLA system is not an easy system to get your head around. It's particular link to autoimmune conditions - where self is not recognised as self by the immune system - fits well with other research-based observations with [some] autism in mind. It does still require quite a bit of further investigation; and, bearing in mind the significant heterogeneity present in autism on various different levels, is probably going to be more relevant to some people diagnosed on the autism spectrum, than for others. But where one sees potential overlaps between the HLA system in autism and other autoimmune conditions like coeliac disease, one would assume a lot more research should be really be forthcoming...

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[1] Bennabi M. et al. HLA-class II haplotypes and Autism Spectrum Disorders. Scientific Reports. 2018; 8: 7639.

[2] Warren RP. et al. Immunogenetic studies in autism and related disorders. Mol Chem Neuropathol. 1996 May-Aug;28(1-3):77-81.

[3] Warren RP. et al. Increased frequency of the null allele at the complement C4b locus in autism. Clin Exp Immunol. 1991 Mar;83(3):438-40.

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Thursday 21 June 2018

Do childhood sleep issues "have a causal role" in 'chronic disabling fatigue' in adolescence?

There's those words again: 'chronic disabling fatigue' or CDF, being used as a proxy for chronic fatigue syndrome (CFS, also known as 'ME') as per the findings reported by Simon Collin and colleagues [1].

Elements of this authorship group seem to be using CDF quite a bit (see here and see here) in their various research studies, and I have to say it's starting to get a little confusing (see here). I'll come back to my thoughts on the term CDF in a moment...

On this research occasion, Collin et al set out to explore whether "sleep might be a causal risk factor for CFS/ME" (or should that just be CDF) on the basis that sleep issues have been reported in that context previously [2]. Once again, "data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort" was the research source material, and researchers were specifically looking at: "sleep patterns of children aged 6 months to 11 years, who were subsequently classified as having (or not having) 'chronic disabling fatigue'... between the ages 13 and 18 years." Sleep duration was quite a big element to this study.

So yeah, shorter night-time sleep duration from 6 months to 11 years of age did seem to show some connection to CDF. To quote: "The odds of CDF at age 13 years were 39% lower... for each additional hour of night-time sleep at age nine years, and the odds of CDF at age 16 years were 51% lower... for each additional hour of night-time sleep at age 11 years." This and a few other observations led authors to conclude that sleep abnormalities might have a role to play in relation to CFS/ME (sorry, CDF).

I have to say however, that I'm not particularly impressed with these findings. I say that on the basis that one set of variables (sleep) are being *correlated* with another later variable (CDF) and well, correlation does not necessarily equal causation. As per other work from this authorship group [2], they've also previously suggested that level of physical activity *might* also correlate with CFS/ME (sorry CDF) albeit with a reduced timescale between the variables. This dual research based on the same cohort I assume, kinda disqualifies any one variable from being related to CDF. Assuming that is, that sleep and physical activity are not somehow connected...

And then there's the issue of how sleep duration was measured in the latest Collin paper: "The sleep durations in our study were obtained from parents’ (mostly mothers’) answers to questions about the child’s usual bedtime and waking time, rather than from data collected in a sleep/wake diary or by actigraphy." So, they basically asked what time children went to bed and what time they woke up. There's nothing wrong with asking such questions but likewise there is little to confirm that children actually closed their eyes and nodded off the minute they went to bed and/or woke up the minute of parental report on waking. Anyone who has children knows that this is 'optimistic' at best (and indeed, takes no account of things like duration of night waking or quality of sleep for examples). The lack of use of actigraphy - that fabulous wearable tech that allows us to objectively chart sleep and activity cycles - is a real problem for elements of CFS/ME research (see here), and is something that is getting harder and harder to overlook. This includes the lack of use in this particular research study too.

Then, back to CDF. CDF basically comes about because we are told that "children in [the] study were not examined by a physician" when it comes to CFS/ME. Further: "CDF at ages 13 and 16 years was defined as fatigue (feeling tired or lacking in energy) of >6 months’ duration that was associated with absence from full-time school or that had prevented the child from taking part in activities ‘quite a lot’ or ‘a great deal’, excluding fatigue possibly associated with sport, snoring, and other illnesses." So fatigue is a primary symptom. But how can you exclude fatigue associated 'other illnesses'? Did the authors for example, screen for something like fatigue due to mitochondrial issues or disorders (see here)? No, they didn't appear to. Similarly there is no mention as far as I can see of another primary symptom of CFS/ME: post-exertional malaise (PEM). Important too was another quote from the authors: "Our definition of CDF did not exclude children with comorbid depressive symptoms." I'll say little more on this topic.

So, again, unfortunately I have to say that I'm left unimpressed by these latest findings from Collin and colleagues. And once again, I have to point out that CDF whilst described as "a proxy for chronic fatigue syndrome/ME" is not necessarily CFS or ME (and indeed, neither it seems, could it be both).

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[1] Collin SM. et al. Childhood sleep and adolescent chronic fatigue syndrome (CFS/ME): evidence of associations in a UK birth cohort. Sleep Med. 2018 Jun;46:26-36.

[2] Collin SM. et al. Physical activity at age 11 years and chronic disabling fatigue at ages 13 and 16 years in a UK birth cohort. Arch Dis Child. 2018 Jun;103(6):586-591.

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Wednesday 20 June 2018

The International Classification of Diseases version 11 (ICD-11) has arrived...

Although peer-reviewed science research is the typical fodder for this blog, I am inclined to post about other important papers and/or events as they emerge. Today is such an occasion, as I draw your attention to an important announcement from the World Health Organization (WHO) recently titled: "WHO releases new International Classification of Diseases (ICD 11)."

Yes, this announcement covers the release of the the much anticipated ICD-11 system "for identifying health trends and statistics worldwide" also including "around 55 000 unique codes for injuries, diseases and causes of death." The ICD-11 schedule as it currently stands can be accessed here.

I might add that the release of ICD-11 is not the same as the 'roll out' of ICD-11, which are we informed "will come into effect on 1 January 2022." This 'advance preview' is basically a way of introducing the new schedule to the world and helping to facilitate a smooth transition from the version currently in use to this new system.

The ICD-11 has not been without some controversy as for example, a new condition known as 'gaming disorder' has been picked up by some media outlets (see here). Others have opined about the inclusion of "Traditional Medicine conditions - Module I" (see here) (where "disorders and patterns which originated in ancient Chinese Medicine and are commonly used in China, Japan, Korea, and elsewhere around the world" have been added in).

Relevant also to this blog - being a blog predominantly about autism research - is the entry on autism, and how the term 'Asperger syndrome' doesn't seem to figure (same as in the DSM-5). Instead, there is the umbrella term 'Autism Spectrum Disorder', complete with various sub-categorisation of diagnosis on the basis of intellectual development 'level' and functional language 'level'. The waning of the term Asperger syndrome is seemingly coincidental to the recent revelations about Hans Asperger (see here) but perhaps reflects long-standing 'doubts' about it's inclusion in previous versions of the diagnostic manual used (see here). There are other changes noted in ICD-11 which are also pertinent to autism (see here) including those relevant to the idea that a diagnosis of autism rarely exists in some sort of diagnostic vacuum (see here).

It's still very early days for the ICD-11 and so we'll have to wait and see what else emerges as physicians and the like across the globe come to terms with the revised schedule. I don't doubt that the evolving diagnostic nature of autism will also create discussions (and arguments) aplenty...

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Tuesday 19 June 2018

"Greater ADHD symptom severity was associated with higher odds for feeling less happy"

Of course correlation does not necessarily equal causation, but the *correlative* results published by Andrew Stickley and colleagues [1] observing that: "Greater ADHD [attention-deficit hyperactivity disordersymptom severity was associated with higher odds for feeling less happy" were worthy of some blogging attention.

Drawing on data derived from the 2007 Adult Psychiatric Morbidity Survey based here in Blighty, researchers tackled quite an important question: how do ADHD signs and symptoms potentially impact on happiness?

So: "Information was collected on ADHD symptoms using the Adult ADHD Self-Report Scale (ASRS) Screener, while happiness was assessed with a single (3-point) measure." Including data for over 7000 people - adults aged 18 years and over - researchers observed that important negative relationship between ADHD symptoms and happiness. Alongside, they also noted that various other variables might also play a role in such a [correlative] relationship: "Mood instability (percentage mediated 37.1%), anxiety disorder (35.6%) and depression (29.9%) were all important mediators of the association between ADHD and happiness."

I'm a great believer that we need more of this kind of research asking relatively simple questions about whether someone is happy or not across various different labels and combinations of labels. I reiterate the whole 'correlation does not necessarily equal causation' mantra and the fact that happiness is not a 'setting' switched to the on position every moment of someones life. One also has to be slightly careful about extrapolating the Stickley results to diagnosed ADHD, and the various issues that come with such a diagnosis (including enhanced risk of comorbidity or 'symptoms' of other diagnostic labels).

But it strikes me as 'logical' that the manifestation of certain types of behaviour - hyperactivity, inattentiveness, impulsivity - might not be all that great for a person when it comes to perceived happiness at certain points in life. I say this in the context that a diagnosis of ADHD has already been *linked* to quite a few adverse life events (see here) including some enhanced risk for something like suicidality (see here). One has to wonder therefore, what role happiness might play in the context of such extremes of behaviour, and whether intervention 'for ADHD' (whatever form this might take) might have some important effects on subjective and objective markers of happiness alongside the manifestation of signs and symptoms...

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[1] Stickley A. et al. Attention-deficit/hyperactivity disorder symptoms and happiness among adults in the general population. Psychiatry Res. 2018 May 5;265:317-323.

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Monday 18 June 2018

Selective mutism and autism

The findings reported by Hanna Steffenburg and colleagues [1] make for potentially important reading reporting: "In this study of a clinical group of children who were diagnosed with SM [selective mutismand assessed at a center for neurodevelopmental disorders, 63% also met criteria for ASD [autism spectrum disorder]."

Selective mutism (SM) refers to an anxiety disorder typically manifesting during early childhood that affects the use of spoken language in certain social situations such as at school. 'Literally being unable to speak' is a phrase that follows SM in certain contexts, where speech and language skills are not typically affected when and where family or close friends are around. It's not surprising that there is 'overlap' between SM and autism given the characterisation of SM in terms of being "nervous, uneasy or socially awkward" and "stiff, tense or poorly co-ordinated" (minus any sweeping generalisations). And just before you question it, 'poorly-coordinated' is perhaps an under-rated aspect for many people diagnosed as being on the autism spectrum (see here).

Steffenburg and colleagues - including the notable ESSENCE-related name of Christopher Gillberg - sought to examine the possible 'overlap' of SM and autism on the basis that various diagnoses/labels can occur alongside SM; quite a few of them also recognised in relation to autism (see here). Approaching 100 children/young adults diagnosed with selective mutism were assessed at the premier 'autism spectrum conditions' clinic in Gothenberg, Sweden. The clinical assessment undertaken of course covered the diagnosis of autism but also various cognitive functions too.

Almost two-thirds of those with SM who were assessed also met criteria for an autism spectrum disorder (ASD). Added to that: "A further 20% (n=19) had autistic features that were “subclinical”, but, nevertheless, sufficiently marked to have an impact on everyday life." Only 17% were described as having no ASD symptoms. Those are pretty interesting percentages.

Authors also mention how: "The level of cognitive function was average in more than half of the study group but more than one-third of the study group had a borderline IQ or an ID [intellectual disability]." They use such a finding in the context of the ESSENCE term - Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations - where overlapping diagnoses/labels is the rule not the exception.

The implications? Well, screen and keep a continual eye open for autism in cases of SM seems to be an important first implication. That also includes keeping in mind those 'subclinical' signs and symptoms, which could be relevant to discussions about the broader autism phenotype (BAP) (see here) and also that curious DSM-5 diagnostic category known as social communication disorder (SCD) (see here). The focus on 'anxiety' in relation to SM might also be important given the pretty well-established connection between autism and anxiety (see here for example) following in the footsteps of some often forgotten autism research history (take a bow Mildred Creak and colleagues for including the term "acute, excessive and seemingly illogical anxiety"). I'm also minded to mention that given the pretty high rate of autism described in SM by Steffenburg and other researchers, further investigations perhaps need to be directed towards shared biology/genetics as well as shared behavioural presentation? Y'know, along the lines of whether 'comorbidity' might be something more 'core' (see here)?

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[1] Steffenburg H. et al. Children with autism spectrum disorders and selective mutism. Neuropsychiatr Dis Treat. 2018 May 7;14:1163-1169.

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Saturday 16 June 2018

ALSPAC says... "Social communication impairments had the strongest association with a depression diagnosis at age 18 years"

ALSPAC mentioned in the title of this post refers to The Avon Longitudinal Study of Parents and Children, one of the premier research initiatives here in Blighty, that has provided all-manner of interesting and important research associations. With autism in mind, ALSPAC has opined on various different research questions (see here and see here for examples) including the issue of a possible 'real' increase in the numbers of children presenting with autistic traits (see here).

On this particular research occasion, ALSPAC was the source data for the findings reported by Dheeraj Rai and colleagues [1] who set out to "compare trajectories of depressive symptoms from ages 10 to 18 years for children with or without ASD [autism spectrum disorder] and autistic traits, to assess associations between ASD and autistic traits and an International Statistical Classification of Diseases, 10th Revision (ICD-10) depression diagnosis at age 18 years, and to explore the importance of genetic confounding and bullying." I might add that some of this authorship group are making some real research waves when it comes to investigations using population registries with autism in mind (see here).

The starting point this time around was the notion that a diagnosis of autism is in no way protective when it comes to a diagnosis of depression and/or the expression of depressive signs and symptoms. Again, it's a topic that has cropped up before on this blog (see here) and is perhaps one of the longer term associations that have been made down the years. The idea that depression or depressive symptoms *might* be something much more than just 'comorbid' in the context of at least 'some' autism is something else that has been banded around the peer-reviewed research literature before (see here) but the evidence base is not particularly big or strong in this area at the moment.

There were a few different research questions asked by Rai et al, including looking at children "with or without ASD or high scores on autistic trait measures" and any relationship(s) with depression and depressive traits. They report findings for over 6000 children ("maximum sample with complete data") where questionnaire items on bullying were also included ("Relational and overt bullying was assessed as separate yes or no items at ages 8, 10, and 13 years using the modified Bullying and Friendship Interview Schedule") alongside various other potentially confounding variables.

Results: "children with ASD and those with higher scores on all autistic trait measures had more depressive symptoms at age 10 years than the general population, and these remained elevated in an upward trajectory until age 18 years." I don't think there's anything too novel in such findings, aside from the observation that depression / depressive symptoms may start quite early on in childhood. I can remember when I started out in autism research a couple of decades ago hearing about depression being typically linked to the onset of adulthood in the context of autism. This current data suggests otherwise.

Next: "Social communication impairments had the strongest association with a depression diagnosis at age 18 years. Findings were robust to adjustment for a range of confounders, including maternal depression and anxiety and the child’s polygenic risk for autism." This is important. What it suggests is that there may something 'more than just comorbid' about depression or depressive symptoms appearing alongside autism or at least in connection to certain autistic traits. I know some people have already taken exception to this possibility alongside the use of the word 'impairment' by the authors. But much like other research on an important bedfellow to depression - anxiety - one may have to entertain the possibility that there may be some enhanced 'predisposition' to something like depression alongside the presentation of autistic traits (see here and see here) perhaps mediated by factors such as rumination and perseveration for example [2]. This doesn't mean that depression is solely a product of autistic traits; merely that certain traits may potentially form an important vulnerability factor. I'm similarly minded to bring in other work from the ALSPAC initiative [3] (including Rai and colleagues as authors) where related findings were mentioned: "Social communication impairments are an important autistic trait in relation to suicidality." This on the basis that depression and suicidality show an important association.

Also: "We found evidence of a substantial role of bullying in contributing to and explaining a higher risk of depression in individuals with ASD and autistic symptoms." Bullying in the context of autism is another long-standing topic (see here). Bullying covers a lot of ground in terms of behaviour and also source (see here). The authors opine that: "Previous work has shown strong links between the experience of bullying and later depression... although confounding could have a role, the association is considered to be at least partially causal." It's also important to note that social-communication 'issues' were reported to be potentially predictive of being bullied according to the authors. The model that then appears hints that the appearance of depression *might* be linked to "reduced self-esteem or social isolation after the bullying" accepting that causality is not established and also not accounting for other variables: "other relevant characteristics, including comorbidities with neurodevelopmental conditions (eg, attention-deficit/hyperactivity disorder) and classroom placement could be important in this association within or outside the context of bullying." That last point is important in the context that autism rarely exists in some sort of diagnostic vacuum (see here).

There are a few caveats attached to the Rai findings that need to be kept in mind outside of any 'correlation does not necessarily equal causation' sentiments. So: "atypical presentations of depression are common in ASD, and our study has the potential for outcome measurement error because we used scales... that have not been adapted for autism." Indeed. I've previously talked about how bipolar disorder for example, might not follow a typical pattern when present in the context of autism (see here). I daresay that this could also hold for other types/forms of depression too. I'm also minded to reiterate that depression, as well as being a heterogeneous condition, also seemingly has many pathways to it. Some of those pathways will include psychological and social variables such as bullying and perhaps even more extremes of 'trauma'; where a diagnosis of PTSD is for example, no stranger to autism (see here). 'Happiness' and perceived quality of life (see here) are also likely to exert an important effect too.

Other pathways to depression seem to be more biologically defined as per depression in the context of physical ailments (see here) that may have a *link* to some autism (see here) or following the use of seemingly common medicines according to recent news reports (see here). I'll also mention that things like physical activity and exercise *seem* to show an important relationship with depression (see here). This could also be pertinent to the data suggesting that physical activity levels are typically not optimal where and when autism is diagnosed (see here). Other factors (fatigue, sleep, etc) also need to be mentioned in the context of depression. In short, there are lots and lots of potential variables to consider [4].

Outside of the important messages from the Rai findings on how depression is over-represented in relation to autism and how social factors like bullying seem to be linked  to it and thus are subsequently 'modifiable', there is another important point to consider: depression is typically treatable. Minus any medical or clinical advice being given or intended, the first step in managing/treating depression is identifying it. Perhaps the Rai findings might serve as a further call to action for preferential screening in the context of autism...

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[1] Rai D. et al. Association of Autistic Traits With Depression From Childhood to Age 18 Years. JAMA Psychiatry. 2018 Jun 13.

[2] Patel S. et al. Association between anger rumination and autism symptom severity, depression symptoms, aggression, and general dysregulation in adolescents with autism spectrum disorder. Autism. 2017 Feb;21(2):181-189.

[3] Culpin I. et al. Autistic Traits and Suicidal Thoughts, Plans, and Self-Harm in Late Adolescence: Population-Based Cohort Study. J Am Acad Child Adolesc Psychiatry. 2018 May;57(5):313-320.e6.

[4] Köhler CA. et al. Mapping risk factors for depression across the lifespan: An umbrella review of evidence from meta-analyses and Mendelian randomization studies. J Psychiatr Res. 2018 May 25;103:189-207.

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Friday 15 June 2018

'What really grinds my gears': a "slight uptick' in the estimated prevalence of autism

For those who watch the sometimes 'cutting' TV show called Family Guy, the first part of the title of today's post - "what really grinds my gears" - will make sense. For those who don't, it represents a TV segment offered to one of the main characters of the series, Peter Griffin, during which he aired increasingly bizarre opinions of things that 'irk' him. At the close, he revealed that just about everything 'grinds his gears'.

Whilst I'm not typically a person that is easily irked (much of my early years irking has dissipated as a result of age and my hobby), I was a little put out by the opening sentence included in the news piece published by Bridget Kuehn [1] talking about the most recent autism estimated prevalence figures published by the US CDC [2] (see here for my take). To quote: "A slight uptick in US cases of autism spectrum disorders (ASDs) was detected in 2014 compared with the years between 2010 and 2012, according to a new CDC report."

It was the use of the word 'slight' that furrowed my brow. And how a 15% increase in the estimated autism prevalence rate in the US over 2 years - translating as a move from an estimated 1 in 66 8-years olds being diagnosed to 1 in 59 8-years olds being diagnosed - is somehow inferred to be less important than it actually was. Words matter.

I know prevalence (and incidence) rates (estimated or actual) when it comes to autism can invoke some often heated discussions. Such debates perhaps tie into wider views held about autism, and whether you're of the opinion that autism has always been with us, or autism is a relatively new 'condition'; whether autism is primarily explained by genetics or whether non-genetic environmental factors play a significant role; whether you view autism as a serious public health issue or are more inclined towards the idea of an 'autistic identity'. I'm sure there are other polar opinions to add, but the end result is that [peer-reviewed] data can sometimes become a secondary consideration when it comes to such views and opinions.

Personally, I go with the data. I go with the data that suggest that autism prevalence is still increasing, and not just in the United States (see here and see here for examples). I go with the associated idea that explanations such as 'increasing awareness' and 'diagnostic substitution' probably play some role in the increase, but don't provide a wholly intellectually satisfying explanation for the increasing numbers (see here and see here). I go with the idea that alongside increasing numbers of cases of autism being diagnosed, so more needs to be done in terms of the provision of educational and social support being offered for an often complicated clinical pictures (see here). I also go with the idea that research questions need to be asked (and answered) about what factors could be driving the remarkable increase in autism over the past couple of decades without fear or favour.

I also go with the idea that there needs to be a bit more urgency in the response to such figures. I'm not talking about the use of 'inflammatory' language or soundbites which are bound to make some people nervous or angry. Merely that behind the CDC statistics there are real children and there are families and other loved ones. And they deserve a lot more and a lot better than society is currently providing (see here)...

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[1] Kuehn B. Uptick in Autism. JAMA. 2018 Jun 12;319(22):2264.

[2] Baio J. et al. Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years — Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2014. Morbidity and Mortality Weekly Report (MMWR). 2018; 67(6): 1-23.

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Thursday 14 June 2018

"Theme 3: Inadequate Provision for Post-diagnostic Support" for autism

The qualitative findings reported by Laura Crane and colleagues [1] on the topic of autism diagnosis here in Blighty provide some useful information that *could* help make the diagnostic process easier and more 'user-friendly'. The findings also highlight some important gaps in the current mechanisms being utilised...

The paper is open-access but basically set out to examine "the views and experiences of ten autistic adults, ten parents of children on the autism spectrum, and ten professionals involved in autism diagnosis, all based in the United Kingdom (UK)." You'll note that the participant numbers for each individual category weren't huge so one has to be slightly cautious about how representative the results are to the wider autism spectrum. Indeed, although not a fan of the term 'functioning' in relation to autism, I note that only two of the children were diagnosed with a learning (intellectual) disability and over half were diagnosed with Asperger syndrome. Alongside the report that of the 10 adults interviewed, nine were diagnosed with Asperger syndrome and several were educated to degree level or above (4/10), and you might reasonably conclude that this was a study weighted towards the more 'able end of the autism spectrum'. I say that again minus the use of the 'functioning' label but understanding that there are 'parts' of the autism spectrum still very much under-represented in this and other research areas (see here)...

No mind, the authors discuss the themes that emerged during telephone interviews with regards to "three important stages of the diagnostic pathway: (1) accessing a diagnostic service; (2) the diagnostic process; and (3) post-diagnostic support." The results are revealing...

I've zoomed in on one of the themes that emerged from the study: "Theme 3: Inadequate Provision for Post-diagnostic Support." I did this because this is the part of the diagnostic machinery that probably has the longest-term effects and has been covered before on this blog (see here). It's not that I don't for example, accept the importance of "vague and inconsistent routes available for accessing an autism diagnosis" or "professionals’ tendency to focus on negatives, not positives". Merely that post-diagnosis, many children and adults are seemingly left to fend for themselves and/or take up further battles in order to get the help and support they require. This, set in a time of increasing need and continuing finite resources (see here).

Within theme 3 around post-diagnostic services and support, we hear some familiar stories. So: "Getting the diagnosis is only the start of the journey and as far as the paediatrician was concerned, that was the end of the journey" and "[you need someone] to support you and direct you…this is where the system fails" are just two of the examples included in the Crane paper. In other words, tick boxes for getting assessments and diagnoses are ticked, but then 'don't let the door hit you on the way out' sentiments seemingly follow. That's not to blame assessment teams or diagnosing clinicians who do a sterling job often under pressure (see here), merely to point out how the system is current set out.

Another phrase included by the authors adds to the 'inadequate provision' sentiments expressed: "When services were made available to support autistic people and their families, these tend not to be offered until crisis point was reached." It seems that one has to be literally be at the end of ones tether before anything like the resources needed are given out, and even then, in a reactive sense. And thereafter: "when support was provided (and was felt to be useful), financial constraints sometimes meant that services were withdrawn". Such issues were seemingly spread across both child and adult experiences, as the call for "a solid, government-backed organisation that could help rather than these sort of variegated charities that are all struggling financially" went out. What a good idea: a national post-diagnosis autism agency...

I'm also going to highlight the 'lack of emotional support' picked up in the Crane paper. The adults diagnosed with autism certainly "found their involvement in the assessment process both emotional and challenging" because sometimes the very probing questions used as part of the assessment process brought up things that some people were probably trying very hard to forget. I personally think that this is an under-appreciated side of post-diagnosis in the context of autism, where the diagnosis of post-traumatic stress disorder (PTSD) is perhaps 'under-used' (see here) in light of the effects of past traumas (I use the word 'trauma' minus the psychobabble connotations).

Crane et al also provide a dose of reality in terms of what parents go through too before, during and after the diagnostic process for their children. So: "I was literally on my knees anyway…it’s so tiring having boys with Aspergers" and "I felt quite on my own. No-one in my family really understood, I didn’t have any friends that had had similar experiences." Such reports are just as important as the other reports included in their study; illustrating how having a child diagnosed with autism can be a roller coaster of emotions, and the strong requirement for "whole family support needs" including things like respite care (see here). I say all this set against a backdrop, particularly on social media, where parents are sometimes/often castigated for speaking their truth and their reality about raising children on the autism spectrum, seemingly because their narrative doesn't fit the agenda of others. Yes, the views of people with autism / autistic people count, but so do the views of those who raise them too (see here). And social media 'discussions' for example, about 'informed consent' before posting pictures and reciting specific child-rearing events, whilst important, cannot just be solely applied to parents of autistic children either...

There are seemingly lots of things that can be done to improve the diagnostic and post-diagnostic experiences related to autism on the basis of the Crane findings. One would hope that policy - (peer-reviewed) evidence-based policy - would be listening and wanting to change things for the good of all concerned: those on the autism spectrum, their parents and other loved ones and the professionals who do a remarkable job with all-too finite resources. I fear however, that the reality is yet again going to be tied into one solitary question; a question that crops up time and time again: how much is it all going to cost?

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[1] Crane L. et al. Autism Diagnosis in the United Kingdom: Perspectives of Autistic Adults, Parents and Professionals. J Autism Developmental Disorders. 2018. June 12.

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