Autism research in 2023: a bit of a game-changing year

 So, autism research in 2023. It’s been quite a year. Let me (briefly) tell you why.

The autism numbers game: the only way is (still) up. Northern Ireland, where some great work is done to plot the annual (estimated) prevalence rate of autism spectrum disorder (ASD) in school-aged children, said 1 in 20 (or 5%) in 2023. The US CDC said an estimated 1 in 36 8-year olds (2.7%) were autistic in 2020. The CDC also said 1 in 47 4-year olds were autistic (2%). Scotland also recently produced data observing “The prevalence of autism was 2.60% (10,089 children) in 2022. This represents a 31.98% increase from the 2018 prevalence of 1.97% (7883 children).” That Scottish data, by the way, only covered those at primary school (aged 4ish-12ish years). Other sources too are still showing a growth in the prevalence of autism across other parts of the globe, including a near 5% rate of behaviours consistent with autism or ASD in the Hadza of Tanzania. All data on autism prevalence is still only heading in one direction: UP. 

Importantly, the old ‘all better awareness’ arguments are slowly fizzling out as the effects of those prevalence stats are starting to show on resources and infrastructure that seemingly haven’t kept pace with the growth in numbers. Indeed, one of the head people related to the CDC autism figures, went as far as to say that the stats don’t really support ‘better awareness’ as the primary driver given that the increase is showing across various different ‘levels’ of autism that are/were unlikely to be missed or thought to be something else. Certainly here in the UK, I don’t think I’ve ever read so many reports about school place shortages (particularly specialised school place shortages) as I have this year. And unfortunately, with an estimated 140,000 people (mostly children and young people) awaiting assessment in England alone, I fear the squeeze on resources is just going to get worse and worse. Anyone care to start asking ‘why the increase’ yet?

CDC says yes to ‘profound autism’. Speaking of autism ‘levels’ (as in DSM-5 autism levels of support or the ICD-11 condition combinations), the CDC did something else rather important this year: producing the first ever report on the rate of profound autism in the US. So, for data covering the years 2000-2016, and using the descriptor “classified as having profound autism if they were nonverbal, were minimally verbal, or had an intelligence quotient <50” they determined that 26.7% of those with autism fitted into the profound autism category. An estimated quarter of autistic people are profoundly autistic. That’s quite important.

There were mixed reactions to the CDC use of the term profound autism. Many people were happy to see it, given that it now lays the foundations for more research and more understanding that despite being united by a triad/dyad of symptom combinations, not everyone experiences autism in the same way. Look no further than the awful early mortality statistics following the deadly triad that is autism, wandering/elopement and water safety to see this in action. Of course autism by virtue of just being diagnosed, means support is required for everyone with the diagnosis. But that support will arguably differ depending on whether you possess things like communicative speech and language, present with things like self-injurious or aggressive behaviours and/or need 24-7 care to ensure that your daily needs are fulfilled. Indeed, I often think that the general lack of support post autism diagnosis is a big driver in the reticence to adopt the term profound autism in some quarters. But should people be so reticent? I mean we have similar distinctions when it comes to experiences of learning (intellectual) disability and nobody seemingly bats an eyelid there. 

There is however more to do on profound autism. This ties into other changes that are needed when it comes to assessing things like cognitive functions and communication (verbal or non-verbal) ability in relation to autism. That’ll follow as the term beds in and builds up more of a research base. Asperger syndrome gone, profound autism steps in.

What else? 

Non-persistence of autism in (some) young kids. 2023 also gave a lot more credence to the idea that the saying ‘all autism is lifelong’ probably isn’t as accurate as you might think. Looking at the developmental trajectories of around 200 kids, all diagnosed early with autism, saw about a third of them not continuing to meet the diagnostic threshold for autism/ASD at ages 5-7 years according to a big study. Other independent work also illuminated this topic and argued against the ‘just misdiagnosed’ suggestions that some people might make and that also the state of ‘autism free’ might have important implications for various other issues too.

This was a particularly important finding for me given our paper from a few years back talking about inborn and lifelong not necessarily being the most accurate phrases for all autism. It also accords with various other studies in related areas observing that diagnoses like ADHD and depression for example, aren’t lifelong labels for absolutely everyone either. Although I noted some people tried to talk about ‘masking’ and ‘camouflaging’ as being the reasons why young kids in that JAMA study didn’t meet the thresholds for autism having previously done so, I do have to ask whether they’ve ever seen autistic kids at this age. Indeed, any child at this age, who generally aren’t renowned for their developed social etiquette abilities covering masking et al (this is also the reason that the gold-standard autism assessment instrument, the ADI-R, codes 4-5 years separately from ‘current behaviour’). As to why autism doesn’t persist for some, well, we don’t know exactly. There was talk of intervention potentially playing a role (behavioural intervention) but it’s probably going to be a bit more complicated than just that. For now, we await further studies on this important topic including more longitudinal ones and perhaps also looking at the biology behind this phenomenon. If I was to speculate about why there is autism non-persistence for some, I might be inclined to say ‘look to infection’ for some, and how, more and more, we’re learning that infection and immune responses to infection can manifest as behaviour and developmental issues as well as in immune biology. Just me speculating, so pay no mind (although that autism in Hadza children study did nicely reignite my interest in how infections like malaria can, through various mechanisms, also seemingly lead to autism).

The gut-brain axis is important to autism. I know a lot of people already appreciate this, but seeing it in a peer-reviewed mega paper in 2023 adds a lot more weight to it. Said paper trawled through huge amounts of data about gut bacteria and the like, and concluded that there is something to see both as observation and also as potential intervention. Authors even mentioned the words ‘faecal matter transplant’ (FMT) in the context that what goes on in the gut doesn’t necessarily stay in the gut, and something that is rising in some autism research and other circles. Allied to the gut-brain axis stuff was the reporting from other mega review papers observing that gastrointestinal (GI) symptoms are present in roughly 55% of children with autism, compared with about a quarter of non-autistic children. Constipation comes out on top. So fixed to clinical advice about treating such issues published over 10 years ago, maybe now is the time to preferentially screen and treat such issues in the context of autism? Perhaps recognise that the gut and brain are connected for quite a few labels/conditions? More on that shortly.

Various medical issues are over-represented in autism. More important data points to the various clusters of medical (somatic) issues that seem to accompany autism across the age ranges. Ranging from cardiovascular conditions to immune-mediated conditions, various studies confirmed what quite a few people already knew. With my gluten research hat on (I don’t actually have a hat made of gluten), I was glad to see that the archetypal gluten-related autoimmune condition called coeliac disease was given mention. Who knows, between coeliac disease and the slightly greyish area of non-coeliac gluten issues that seem to be over-represented alongside autism, there’s further hope for wider screening and use of a gluten-free diet in the context of autism? Oh, and just before you inquire about the research base in this area, here’s a couple of meta-analyses from the last few years - see here and see here - saying it might be worth a shot (minus any clinical or medical advice given or intended).

And there was yet more research on the psychiatric and behavioural issues that seem to be over-represented alongside autism. Importantly, and I do think needs a lot more investigation, one study out of Canada stressed the need to look at comorbid psychiatric issues as being an important driver of suicidal behaviours in the context of autism. I know such behaviours are complex and often very individual with a heavy biopsychosocial tilt, but there’s a wealth of evidence out there already suggesting that depression, bipolar disorder, personality disorder and schizophrenia spectrum disorders all convey a heightened risk for suicidal behaviours. All those conditions are well over-represented alongside a diagnosis of autism (yep, an estimated 1 in 10 autistic people will potentially ‘transition’ to schizophrenia). Screen, screen and treat (including, where appropriate, more clinical emphasis on the archetypal anti-suicidal agent that is lithium used in the right context).

Late 2023 research entry: CM-AT results are really, really, really promising. I’ve been following the CM-AT story for quite a while on this blog and beyond. Basically, it concerns a pancreatic enzyme therapy designed for autism that has already crossed quite a few methodological trial hurdles. Then, in November 2023 lo and behold, the results of a double-blind, placebo-controlled trial that say, yes, following the gold-standard trial design, CM-AT is good for treating/managing irritability and agitation in the context of autism in pre-schoolers. Said treatment is also likely safe and effective. This is a potential game-changer and opens the door to things like regulatory approval. Also, exquisite evidence for the whole ‘behaviour is biology’ tenet and the important role of the gut-brain axis in autism, yet again.

There was so much more other science published this year, across all-manner of different topics. Certainly far too much for me to put into one blogpost. I’m a great believer in your citizen scientists and so would encourage everyone to look-see and take part. I can’t help but draw your attention to another paper that basically said the ‘person with autism’ vs ‘autistic person’ arguments typically seen on social media aren’t really worth a dime. Ask the person how they want to be addressed. Oh, and remember, people aren’t ‘neurotypes’ either. They’re people. 

And finally… Saying farewell to Donald.

Finally, [I can see you’re yawning] a non-sciency thing to mention. ‘Patient 1’ from the great Leo Kanner’s seminal paper describing autism - Donald Triplett - passed away. If you’ve ever read or watched ‘In a Different Key’ you’ll have read about him or seen him. Of all the things said about Donald in the various obituaries to him, I think the overwhelming idea that comes across is how much community was important to him; both being part of a supportive community and having a great community around him. Loads of lessons to be learned there. My advice: seek out those who wish to foster community, and there are lots of good people of this ilk. Here's to 2024 and beyond.

Iceberg! Have we reached a tipping point in autism numbers and assessment referrals?

Sorry. I really am. I'm back at the autism research blogging yet again, twice in a week. I know some people will be unhappy about that (I can hear the Twitterer cries already: 'keep yer bloody mouth shut!') but hopefully some won't be so unhappy. But writing this on a nice sunny March Sunday evening with a rerun of Titanic playing on the telly, I'm gonna talk about whether or not we've just hit the iceberg when it comes to US autism (estimated) prevalence (and those from elsewhere) and the huge backlog of autism referrals that's been making news here in Blighty aka dear old England. I'll also come clean and mention that I actually do like the film Titanic. There I said it. 

I appreciate that my use of the word 'iceberg' in the context of this blog is not likely to sit well with some people. How dare I talk about icebergs in the context of autism prevalence and such like? Well, I dare because right now there's a lot of people who are genuinely concerned that more than ever we might have started to head into and indeed, already started to scrape past, an iceberg that's been on the horizon for a number of years. And in the current climate of post-pandemic financial and resource pressures, we haven't exactly got the strongest of hulls in this societal ship in which we're all passengers on. 

So, last week we had the estimated autism prevalence figures for 8-year olds in the United States from the CDC (see here). Actually we had another set of (estimated) figures relating to 4-year olds too (see here). The headline figure: well, words like 'all-time high' have been used to cover the 1 in 36 8-year olds estimated to have autism or an autism spectrum disorder (ASD). As for 4-year olds, and as per other reports (see here), 1 in 47 4-year olds was the headline figure, a leap from previous reports for this age group (1 in 59 in 2018). Both sets of figures chart the estimated numbers of cases of childhood autism and illustrate the ever upward trend that we've been seeing over the past few decades in the US and beyond.

Most press coverage of the CDC data have not sugar-coated it. Yes, there's been talk about how racial disparities in screening and assessment have been reduced in the recent figures and that's a good thing. There's also talk about the (subtly) declining male:female ratio which again, represents good progress in detection and identification. But then the conversations move to the need to provide suitable services. Y'know things like education, social and health services, and this is where the tone gets a little more serious as per the realisation that there's probably not enough suitable or appropriate services for everyone, and what services there currently are, are probably going to become even more scarce as more people need them. As an aside it's interesting too that this time around, some discussions on the new CDC figures have basically poo-pooed the whole 'it's all better awareness' arguments: "This is not just a phenomenon of becoming more sensitive to subtly impaired kids" according to one very senior person intricately involved in the CDC process of autism counting. Progress indeed given the amount of times that argument has been used, fairly unscientifically, in the past.

On this side of the Pond, I think we're starting to really see that process of 'lack of suitable services' playing out in real time. We - the UK we - are still waiting for a truly national autism prevalence initiative but we have some good counting processes in place in relation to countries of the UK like Northern Ireland and their forward-thinking in collecting and publishing school-aged autism prevalence data (see here). Northern Ireland is, I think, due to report in a few weeks time but the last time around the prevalence of autism in school-aged children came it at 1 in 21 children (see here) or 4.7% of school-aged children with autism in 2021/2022. I also happened to stumble on some other, more England-based data recently (see here) that mentioned that "2.84% of 10-14-year olds were diagnosed (1 in 35)." Obviously, one has to be a little careful with that last statistic. What this means is that the latest CDC figures for the US are not an isolated incident. They're more likely part of a global trend where the old 1% prevalence figure is completely out of sight in the rear view mirror.

As to that 'lack of suitable services'? Loads of examples to pick from. Take for example the recent BBC news report (see here) on twins, yes twins, both diagnosed with autism (and dare I say autism heading more towards 'profound'), both with EHCPs (education and healthcare plans) yet one twin offered a place at a specialised setting, the other not. The reason: the specialised setting is 'over-subscribed'. Twins. There's loads more other examples like this. Such examples complemented (if that's the right word) by multiple reports of plans to build more and more specialised schools with seemingly little realisation that said schools take a while to be built and then also need to be suitably staffed, which leads us down another potential rabbit hole. Another aside: we have some of the best teaching cupboards (yes, you heard right) in the world here in England (see here).

And if you think things are critical when it comes to resources for those lucky enough to already have a diagnosis, spare a thought for the thousands and thousands of people - predominantly school-aged children - who are waiting just to get on a waiting list for autism assessment (see here). In England alone there's about 140,000 people waiting at the time of writing (see here), again predominantly school-aged children. And now another reality: one particular part of England has recently decided that the huge numbers of people, again predominately children, wanting an autism assessment will be 'triaged' to filter out 'the most needy' (see here). That's triage as in what's normally seen on the battlefield when care is rationed according to those most in need. So children now have to be 'in crisis' before they're put on a list for a referral for autism assessment. We've hit the iceberg, haven't we? 

I don't really know what else to say about all this. Yes, it's great that everyone is getting better at recognising autism. Yes, it's great that more people are being detected and referred for an assessment. We can pat ourselves on the back for that. Unfortunately, as a society we've had our collective heads buried in the sand about what rising numbers of need actually means. And now, it's having real-world implications for many people and their loved ones. 

How many lifeboats did you say we have?

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Maenner MJ, Warren Z, Williams AR, Amoakohene E, Bakian AV, Bilder DA, Durkin MS, Fitzgerald RT, Furnier SM, Hughes MM, Ladd-Acosta CM, McArthur D, Pas ET, Salinas A, Vehorn A, Williams S, Esler A, Grzybowski A, Hall-Lande J, Nguyen RHN, Pierce K, Zahorodny W, Hudson A, Hallas L, Mancilla KC, Patrick M, Shenouda J, Sidwell K, DiRienzo M, Gutierrez J, Spivey MH, Lopez M, Pettygrove S, Schwenk YD, Washington A, Shaw KA. Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2020. MMWR Surveill Summ. 2023 Mar 24;72(2):1-14. doi: 10.15585/mmwr.ss7202a1. PMID: 36952288.

Shaw KA, Bilder DA, McArthur D, Williams AR, Amoakohene E, Bakian AV, Durkin MS, Fitzgerald RT, Furnier SM, Hughes MM, Pas ET, Salinas A, Warren Z, Williams S, Esler A, Grzybowski A, Ladd-Acosta CM, Patrick M, Zahorodny W, Green KK, Hall-Lande J, Lopez M, Mancilla KC, Nguyen RHN, Pierce K, Schwenk YD, Shenouda J, Sidwell K, Vehorn A, DiRienzo M, Gutierrez J, Hallas L, Hudson A, Spivey MH, Pettygrove S, Washington A, Maenner MJ. Early Identification of Autism Spectrum Disorder Among Children Aged 4 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2020. MMWR Surveill Summ. 2023 Mar 24;72(1):1-15. doi: 10.15585/mmwr.ss7201a1. PMID: 36952289.

The ICD-11 diagnostic criteria for autism: criteria that actually gets it right?

I'd love to say that this post represents me getting back into autism research blogging but alas, I'm not sure I'd be able to stick to any sort of routine or plan. Work, family, karate, so many Star Wars spin-offs to watch, you know what it's like. Suffice to say that something important brought me back to making this entry: the ICD-11 criteria for autism (see here). 

So why blog about it? Well simply because I reckon that this latest version of one of the major ways that autism or autism spectrum disorder (ASD) is diagnosed is basically as good as we've ever got at defining autism and the various nuances around an autism diagnosis. 

Why? Lots of reasons, and I would invite as many people as possible to survey the criteria which is free for all to read. For me, it's as follows:

1. Autism, the catch-all diagnosis, is now not just singular autism, it's more. Much more. The criteria still consists of the timeless social communication issues (social affect as it was once called) and "persistent restricted, repetitive, and inflexible patterns of behaviour, interests, or activities." It's still talks about early onset (although the 'before 3 years of age' bit is long gone as in previous versions). Importantly it still talks about symptoms resulting in "significant impairment in personal, family, social, educational, occupational or other important areas of functioning." This last point is often not as well remembered as it should be, particularly in certain social media circles. But more than all that we now have separate diagnostic sub-codings for things like the presence of intellectual (learning) disability and functional language impairment in a sort of pick-and-mix matrices combination. The DSM-5 also tried this with their 'levels of support' or, dare I say it 'severity levels' (see here). Allied to all that is another sub-coding: loss of previously acquired skills. Y'know, all those reports of regression or plateau in skills that parents and caregivers talked about? They've been taken seriously and at last, now feature as part of the diagnostic work-up. Minus any 'I told you so' sentiments, we've already published on this a few years back (see here). The road has been long. Wow.

2. Alongside the core clinical features are quite a few other headings covering other types of behaviour that one may see accompanying autism. Anxiety, seizures and here's one: self-injurious behaviours (SIB). No it doesn't make for great reading (SIB can be absolutely devastating to the person concerned and their family) but at last, acknowledgement that it's an issue for some. There's also talk about other comorbidities / multi-morbidities (that's comorbidity not co-occurrence) to look out for. Some psychiatric, some behavioural and some somatic. Get ready for another 'I told you so' moment (see here). 

3. Standby for something really important included in the ICD-11 criteria: a list of some 18 other conditions where autistic signs and symptoms can significantly present is also provided. This is new. The list ranges from things like ADHD (attention-deficit hyperactivity disorder) to schizophrenia to personality disorder(s). Developmental coordination disorder (DCD) aka dyspraxia is also in there and acknowledges something that even the great Leo Kanner talked about. This will help clinicians (yes, the people who conduct formal autism assessments) no end. It means that they should also be on the look out for various other conditions when they make their assessments (indeed, if any of those listed overlapping conditions are also present in clinic, it might mean looking for autism too). I'll also, at this point, add in the almost forgotten issue of social (pragmatic) communication disorder (SCD) from the DSM-5 too. I'm also interested in that list of overlapping conditions because they seem to becoming more and more important to autism. Take schizophrenia for example. Did you know that an estimated 1 in 10 people with autism might be at risk of transitioning over to schizophrenia over a 10 year period according to this study from 'big data Taiwan'? And more recently we've seen research all about ADHD 'transitioning' into ASD as a primary diagnosis (see here); prodromal period anyone? Oh, and I should also mention that the word 'encephalitis' figures in those boundary conditions. I'd like to think this would trigger a lot more discussion and study on how immune system / inflammatory conditions *might* play a role in at least some autism. I say this on the back of our recent-ish review of autoimmune encephalitis and autism (see here) and my continuing interest in such things.

So there you have it citizens (hat-tip to the late great Christopher Plummer!), the ICD-11 diagnostic criteria for autism. Obviously we'll have to see where it all goes, but certainly, as the criteria beds in, diagnostic reports will get more and more detailed which has to be a boon for things like EHCPs (Education, Health and Care Plans) and getting things right for people (particularly children) when diagnosed. As for research, well, that will benefit too, given the more detailed diagnostic starting point other than just 'autism vs. non-autistic controls'. I reckon we're going to be seeing more and more objective biological markers in the coming years. One more thing: you've no doubt heard about the term 'profound autism'? Well, it looks like ICD-11, like DSM-5, is going to forward this concept a lot more in times to come. 

Peace be with you.

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Hsu TW, Chu CS, Tsai SJ, Hsu JW, Huang KL, Cheng CM, Su TP, Chen TJ, Bai YM, Liang CS, Chen MH. Diagnostic progression to schizophrenia: A nationwide cohort study of 11 170 adolescents and young adults with autism spectrum disorder. Psychiatry Clin Neurosci. 2022 Dec;76(12):644-651. doi: 10.1111/pcn.13468. Epub 2022 Sep 27. PMID: 36057134.

Kopp S, Asztély KS, Landberg S, Waern M, Bergman S, Gillberg C. Girls With Social and/or Attention Deficit Re-Examined in Young Adulthood: Prospective Study of Diagnostic Stability, Daily Life Functioning and Social Situation. J Atten Disord. 2023 Mar 13:10870547231158751. doi: 10.1177/10870547231158751. Epub ahead of print. PMID: 36915033.

Sala R, Amet L, Blagojevic-Stokic N, Shattock P, Whiteley P. Bridging the Gap Between Physical Health and Autism Spectrum Disorder. Neuropsychiatr Dis Treat. 2020 Jun 30;16:1605-1618. doi: 10.2147/NDT.S251394. PMID: 32636630; PMCID: PMC7335278.

Whiteley P, Carr K, Shattock P. Is Autism Inborn And Lifelong For Everyone? Neuropsychiatr Dis Treat. 2019 Oct 7;15:2885-2891. doi: 10.2147/NDT.S221901. PMID: 31632036; PMCID: PMC6789180.

Whiteley P, Marlow B, Kapoor RR, Blagojevic-Stokic N, Sala R. Autoimmune Encephalitis and Autism Spectrum Disorder. Front Psychiatry. 2021 Dec 17;12:775017. doi: 10.3389/fpsyt.2021.775017. PMID: 34975576; PMCID: PMC8718789.

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Neurodiversity 2.0: Judy Singer setting the record straight

I know I've kinda let this blog slip a little in recent months but work is work and blogging is blogging. Anyhow, I'm back with a short post to bring to your attention a rather important 'revision' presented by Judy Singer on her blog titled: NeuroDiversity 2.0 (see here).
I'm not going to rehash everything that Judy talks about in her post because it's all done exceptionally well in her blogpost. Neurodiversity is the term that has kinda turned into a movement (even a political movement) which has found something of a voice particularly on social media. As a critical voice to neurodiversity (see here) I would say that the concept of neurodiversity has been pushed way beyond it's original meaning and intention and well outside the scientific remit of the description (no, no-one is 'neurotypical' or NT). In her blogpost, Judy aims to clarify some important points about her description of neurodiversity and, as with all good ideas, adapts and modifies them as knowledge has increased. 

Some important things are mentioned by Judy which are worthy of note:

• "Neurodiversity is NOT a Psycho-Medical diagnosis for individuals." She goes on to say that "if Worker A has identified themselves with a specific syndrome, e.g. Autism, in which case call them "autistic". But they are no more neurodiverse than anyone else on the planet." In other words, neurodiverse or neurodivergent are not replacements for autism or autism spectrum disorder (ASD) and they don't magically bestow some differing neurological feature(s) or advantage(s). And just before you ask, "undiagnosed neurodiversity issues" (see here) is basically psychobabble BS and a good example of how neurodiversity has gone well beyond it's remit.
• "Neurodiversity is a term that refers to an obvious and indisputable feature of Earth's biosphere." Basically, everyone is neurodiverse. With all the millions of differing biological processes that everyone encounters and undergoes, every second of every day, neurodiversity is the property of populations not individuals.
• "It is not a synonym for "Neurological Disorder"." I might be repeating myself here but whether diagnosed or 'self-diagnosed' (another inherently problematic issue) with anything remotely related to behaviour and/or the brain, identifying as 'neurodiverse' says nothing about a person and their presentation. 
• "Neurodiversity is a positive principle, but it is NOT a moral principle." As the property of a population, neurodiversity says just that: everyone is different, and we should be proud of our individual differences. I know sometimes people don't like to be seen as different (group membership is a powerful thing), but everyone has strengths and everyone has weaknesses at an individual level. Yes, there are things that society can do to ensure that more strengths are seen as strengths, but that's a different topic altogether.

I'm not expecting Judy's revisions to be immediately and universally accepted by everyone. There are some really ingrained views and opinions about neurodiversity out there, and to some degree, people have already adapted the term to fit their experience and/or agenda. I am hopeful however that we can move on from identity politics (of which neurodiversity has certainly been a focal point) and start to move forward on this. Moving forward means reclaiming labels like autism and ADHD and various other labels that have often got missed from the whole neurodiversity thing (e.g. schizophrenia and psychosis) and moving away from the idea that there is something universally and inherently 'different' about the minds of those with such labels. Science has yet to pinpoint anything that universally distinguishes those diagnosed with autism from those not diagnosed with autism outside of the diagnostic features (similar to every other diagnostic label with a behavioural element to it). If and when it does, then we can start talking about possible neurodivergence, but until then it's all hot air and bluster. 

Bravo Judy for the revision and clarification.

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Autism diagnosis, numbers and politics

It's been a while since I lasted posted on this blog. Apologies to those who've enjoyed my musings but time has been in short supply these past few weeks. But I'm here now...

Today I want to bring to your attention a couple of papers and news items that have caught my eye in the past few weeks. The first is the paper by Eya-Mist Rødgaard and colleagues [1] which garnered quite a bit of media attention (see here). The crux of the Rødgaard findings were that "differences between individuals with autism and those without autism have decreased over time, which may be associated with changes in diagnostic practices." It was a meta-analysis paper and so kinda reiterated what had already been discussed in the peer-reviewed science literature before, in that the autism of today might not necessarily the same as the autism of yesteryear (see here).

Second up is another recent paper from Benjamin Zablotsky and colleagues [2] (a name mentioned a few times on this blog) indicating that the only way is up when it comes to diagnoses of developmental disabilities such as autism. I noted that some interpretations of the Zablotsky results headed down the old 'better awareness' and 'not a true rise' routes (see here) despite the quite astounding increase in cases from "1 in 91 children in 2009 to 1 in 40 in 2017." In any other label / condition / disorder, such a rise would probably provoke some important questioning about why the increase and what factors could be associated with it (including the Rødgaard explanation). Needless to say that children become adults, and quite a lot of those 1 in 40 children are going to require more Government planning and money to ensure that they live good, healthy and productive lives as both children and adults. And just in case you think such a rise is a United States issue only, take a look at the stats for Northern Ireland in recent years (see here and see here) and tell me that there isn't a true rise there either.

Finally a few interesting lay articles have been published in recent weeks which deserve highlighting and debating. The first from neuroscientist and science writer Mo Costandi ruffled some feathers in his critique of the concept of neurodiversity. The by-line to the article said it all: "The movement has good intentions, but it favours the high-functioning and overlooks those who struggle with severe autism." The second article from Steve Silberman tackles a slightly different, but nonetheless related issue, on how "Greta Thunberg became a climate activist not in spite of her autism, but because of it." Both articles, whilst sharing some differences, stress how the label of autism covers a wide, wide variety of presentations and outcome. They also serve to highlight how there is seemingly no way that one can possibly advocate for the entire autism spectrum as some sort of singular label / condition / disability based on the different wants, needs and desires of such a diverse population. The sooner we start to take the plural 'autisms' more seriously, the better for everyone...

To close, no two brains are the same as seen in this 'cool' graphic. In the coming weeks, I'll be talking about a few papers that should be appearing in the peer-reviewed domain that I've been involved in authoring that stress such an important point.

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[1] Rødgaard EM. et al. Temporal Changes in Effect Sizes of Studies Comparing Individuals With and Without Autism: A Meta-analysis [published online ahead of print, 2019 Aug 21]. JAMA Psychiatry. 2019;e191956.

[2] Zablotsky B. et al. Prevalence and Trends of Developmental Disabilities among Children in the United States: 2009–2017. Pediatrics. 2019. September.

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The things people say about neurodiversity...

"Being neurodiverse means that your brain is wired differently and thinks differently about things."

That was one of the memorable quotes that was included in a piece on the BBC Newsround website recently highlighting an arts project designed "to raise awareness and celebrate a range of conditions under the umbrella term of Neurodiversity, including autism and dyslexia." More information about neurodiversity by the way, can be seen here. The page has seemingly since been altered for whatever reason...

Whilst noble in intent, the inclusion of evidence-free phrases about 'being wired differently' were included in the original text. Even more worryingly was the suggestion that: "The idea behind Neurodiversity is that conditions - such as autism - should be seen not as disabilities, but as perfectly normal differences between people." Autism shouldn't be seen as a disability eh? I'm sure that lots and lots of autistic people and their families and loved ones may disagree with such a contravention to how autism is actually diagnosed (on the basis that: "symptoms cause clinically significant impairment in social, occupational, or other important areas of current functioning").

Such a piece did not go unnoticed, with even the person credited with coming up with the term neurodiversity calling it out and posting a reminder to everyone about what was intended by her original description of the term. She's of course right to point out that everyone is neurodiverse, and how associated terms like neurotypical (NT), that still keep cropping up in the peer-reviewed science literature, are about as evidence-free as one could possibly get (see here).

The inclusion of other phrases citing 'famous people' who should also be considered neurodiverse adds to the fluffiness of the original news piece. That being said, at least there wasn't an attempt to rewrite history as has kinda been suggested on other occasions (see here) nor were the words 'everyone hovers somewhere along the autistic spectrum' used (see here) so one should be thankful for that.

I get that such news pieces want to encourage people to think differently about those with autism, ADHD and various other labels. I get that role models are important to young people whether diagnosed or not with this, that and t'other. But I do expect more from valued news channels such as the BBC. I expect them to be evidence-based. Even Newsround (which served me well in my younger years) should be evidence-based given the audience that it's aimed at. And to perpetuate a myth that autism is not a disability is, in my view, only going to further contribute to the wide-ranging inequalities that many people on the autism spectrum face day in, day out whether their disability is 'hidden' or not.

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Asking about "growing up with a sibling with autism"

The findings reported by Philippa Moss and colleagues [1] provide the blogging fodder today, and another important research venture into asking siblings about their experiences of growing up with a brother / sister diagnosed with autism. Such work continues an important theme whereby a diagnosis of autism doesn't just impact on the person concerned, but also on significant others around them too (see here). It also reiterates that the 'nothing about us without us' phrase should really be extended to include siblings as well as parents/primary caregivers and of course, those diagnosed with autism (see here)...

Researchers talked to over 50 adult siblings with a brother and/or sister with autism. They asked them questions about growing up with their sibling and importantly "about their worries for the future." The results provided an important snapshot into the experiences of siblings. It was a mixed bag in terms of positive and negative experiences; where themes like tolerance and caring were discussed in relation to how their autistic sibling had positively impacted on their lives. The not-so-positive themes included things like "coping with behavioural difficulties (39%) and disruption to family relationships (32%) or social life (23%)."

There was another important observation to come from the Moss study too: "The main concerns for the future, expressed by the majority of participants, focussed on problems of finding appropriate care (77%) and the potential emotional impact on the autism siblings of loss of parents." Such sentiments take us into some difficulty territory as the issue of long-term care comes into the discussion, alongside other issues voiced by parents such as 'why I can never die' (see here).

Given that siblings will probably emerge as the primary caregiver or at least responsible person when it comes to their brother(s) / sister(s) with autism as parents age, one can see the logic in the suggestion from Moss to "involve siblings in care planning and decision-making." Support for siblings is also required to prepare them for the future and ensure that the sentiments of 'caring for the carers' extends to them too.

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[1] Moss P. et al. Growing older with autism – The experiences of adult siblings of individuals with autism. Research in Autism Spectrum Disorders. 2019; 63: 42-51.

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"being autistic does not always make someone bad at seeing the world from another's viewpoint"

The quote titling today's post - "being autistic does not always make someone bad at seeing the world from another's viewpoint" - comes from the findings reported by Shisei Tei and colleagues [1].

Their research paper observing that "more careful attention should be paid to the idea of egocentricity in individuals with ASCs [autism spectrum conditions]" is part of a research mash-up post today that also includes the findings reported by Hidetsugu Komeda and colleagues [2]. Both papers help to put a 'real-life perspective' on to sweeping generalisations that everyone on the autism spectrum is completely egocentric and lack the capacity to help others.

The Tei study was initially based on the idea that: "Individuals with autism spectrum conditions (ASCs) often experience difficulty and confusion in acknowledging others' perspectives and arguably exhibit egocentricity." Egocentrism can mean a few things, but all have in common that self is the be-all-and-end-all, and the interests, beliefs and attitudes of others are of secondary regard. It's a concept that we all engage in to some degree at certain times of development and maturation, and from an evolutionary perspective, probably served (and continues to serve) as an important survival mechanism. But: "whether this egocentricity necessarily results in selfish behavior during social situations remains a matter of debate." Tei et al examined the possibility of a link between egocentricity and selfish behaviour in the context of autism...

I'm not totally au fait with all the ins-and-outs of the Tei study techniques - "derived from cognitive psychology and behavioral economics" - but it looks like it was quite a bit to do with response times to a "computerized visuospatial perspective-taking task (VPT)" and the use of a task to measure altruism ("disinterested and selfless concern for the well-being of others"). Compared with a non-autistic control group, they observed some differences among their tested groups but, and it is an important 'but', "having ASCs does not always exhibit selfish behavior during interpersonal communication."

Then we have the findings reported by Komeda et al. The starting point was a sweeping one: "Individuals with Autism Spectrum Disorder (ASD) often lack cognitive empathy, so they experience difficulty in empathizing with others." Their study was perhaps less complicated than the Tei study as a group of adults with autism and control non-autistic adults were asked to read a number of stories - "(12 stories featured protagonists with characteristics of ASD and the other 12 featured TD protagonists)" - and answer questions about said stories. Questioning included "How did the protagonist feel?" and "Would you help if the protagonist were in trouble?"

Results again were interesting. So: "individuals with ASD empathize with other people who have ASD and are motivated to help other people with ASD." Based also on examination of autism spectrum quotient (AQ) scores and when "controlling for alexithymia" (marked dysfunction in emotional awareness, social attachment, and interpersonal relating), authors concluded that: "the reason why individuals with ASD are considered to have limited cognitive empathy and helping behaviors could be related to alexithymia and the lack of social skills and attention to detail, which are related to atypical perception."

OK, both the Tei and Komeda findings have to be put into some perspective. They don't for example, completely exonerate the social cognition or perspective-taking issues that are seen in autism. They can't do so either, because issues with social interaction for example, are a core facet of a diagnosis of autism. In effect, they define autism. I should also add that the reliance on participants who were very much cognitively able in both the Tei and Komeda studies means that one has to be quite careful of generalising such findings to all quarters of the autism spectrum, particularly the under-studied and under-represented (see here) parts.

But as I mentioned earlier in this post, the combined findings do help to put a 'real-life perspective' on things; specifically that such core issues that have defined autism for many, many years - empathy and perspective-taking - don't always manifest in a uniform fashion across people or situations. They also suggest that various other variables also might serve to promote issues with empathy and perspective-taking in relation to autism, as per mention of alexithymia; something that has been noted before by other independent study (see here).

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[1] Tei S. et al. Egocentric biases and atypical generosity in autistic individuals. Autism Res. 2019 May 17.

[2] Komeda H. et al. Do individuals with autism spectrum disorders help other people with autism spectrum disorders?: An investigation of empathy and helping behaviors in adults with ASD. Front. Psychiatry. 2019. May 13.

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Maternal polycystic ovary syndrome (PCOS) and autism yet again

Another mash-up post for you today as I bring two papers to the blogging table discussing a topic which has already had quite a bit of airtime on this blog: maternal diagnosis of polycystic ovary syndrome (PCOS) and risk of offspring diagnosis of autism (see here and see here). The papers in question are from Maria Katsigianni and colleagues [1] and Carolyn Cesta and colleagues [2] and, via different experimental means, both papers suggest that women with PCOS have a significantly greater risk of having a child diagnosed with autism or autism spectrum disorder (ASD).

PCOS, in case you didn't know, is a fairly common condition according to the NHS entry. It's characterised by three main features: irregular periods, the presence of high levels of androgens (male hormones) and polycystic ovaries ("ovaries become enlarged and contain many fluid-filled sacs (follicles) that surround the eggs"). Mention of (male) sex hormones in relation to PCOS have led quite a few researchers to suspect a connection between PCOS and autism but another important angle to the diagnosis is a link between PCOS and insulin (the hormone involved in blood sugar control)...

Anyhow, the Katsigianni paper first. This was a systematic review and meta-analysis of the existing peer-reviewed science on the topic of "whether women with PCOS have increased odds of having a child with ASD, while, secondarily, if these women themselves are at high risk of having the disease." Now just before anyone gets shirty with the use of the word 'disease', those are the authors words not mine. I fully go with the idea that autism is not a disease. Their 'boiling down the research literature' efforts yielded 10 studies which included over 30,000 children with autism and some 320,000 "non-ASD children." The results: "Diagnosed PCOS was associated with a 1.66 times increase in the odds of ASD in the offspring" and: "Women with PCOS were 1.78 times more likely to be diagnosed with ASD." Most data on which those findings were based were deemed to be of 'good quality'.

Then to the Cesta study. The primary aim was to "measure, in the general population, the association between maternal PCOS and offspring neuropsychiatric disorders where prenatal androgen levels and/or altered androgen function have been implicated in their etiology." That population was the Sweden, and yet another example of those fantastic Scandinavian population registries being put to good research use. Autism, by the way, wasn't the only label looked at by Cesta et al: "offspring attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and Tourette's disorder and chronic tic disorders (TD/CTD)."

Results: based on detecting some 20,000 PCOS-exposed offspring and 200,000 "unrelated PCOS-unexposed offspring" authors concluded that: "PCOS-exposed offspring had increased risk of being diagnosed with ADHD, ASD, and TD/CTD compared with unrelated PCOS-unexposed offspring." Interestingly Cesta observed that the association between maternal PCOS and autism and ADHD was stronger in girl offspring than boy offspring. They then go on to talk about prenatal androgen exposure "leading to ‘hyper-masculine’ behavioral and cognitive traits" in offspring as being one potential biological mechanism.

What's more to say? Well, despite the whole 'male sex hormone' *link* to autism I'd like to see a lot more investigation looking at biological mechanisms. Going back to the insulin link with PCOS, there is a requirement for further study in light of other findings (see here and see here). Insofar as implications for policy, well, preferential screening for autism in offspring when mum has a diagnosis of PCOS could be indicated. This adds to the growing number of other circumstances where such preferential screening seems to be indicated.

Oh, and there could be other areas of potential investigation to consider too (see here)...

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[1] Katsigianni M. et al. Maternal polycystic ovarian syndrome in autism spectrum disorder: a systematic review and meta-analysis. Molecular Psychiatry. 2019. March 13.

[2] Cesta CE. et al. Maternal polycystic ovary syndrome and risk of neuropsychiatric disorders in offspring: prenatal androgen exposure or genetic confounding? Psychol Med. 2019 Mar 12:1-9.

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The rise and rise of CM-AT for autism

Today's post surrounds a poster presentation delivered at INSAR 2019, the (still) premier international autism conference, albeit not without its battles. The poster was delivered by Heil and colleagues [1] and talks about a compound / preparation that has been discussed a few years back on this blog: CM-AT (see here).

CM-AT is described as a "pancreatic enzyme preparation" with chymotrypsin - a digestive enzyme - seemingly placed quite prominently in its list of ingredients. CM-AT is, from what I understand, something that is still going through the research processes with regards to its use in the context of autism. Heil and colleagues presented data on part of that research agenda, specifically pertinent to ascertaining "whether or not behavior (e.g., symptoms of irritability, hyperactivity) in preschoolers with autism could be improved with CM-AT."

Bearing in mind a conference poster presentation is not necessarily the same as a published peer-reviewed research article, the Heil data was based on the use of a "randomized, placebo-controlled, 12-week clinical trial" methodology where 92 children, aged between 3-5 years, diagnosed with an autism spectrum disorder (ASD) received CM-AT "as granules sprinkled on food" and almost a hundred boys with ASD received a placebo "which consisted of visually identical inert sprinkles." The 'Irritability' scale of the Aberrant Behavior Checklist (ABC) was the primary outcome measure.

Results: "children receiving CM-AT (relative to those receiving placebo) demonstrated significant reductions in Irritability... Hyperactivity... Inappropriate Speech... over the 12 weeks of the trial." Researchers further reported that those children with higher levels of irritability at baseline tended to show a greater positive response than when the participant sample as a whole was analysed.

I think you can perhaps see why these results - preliminary as they are - are worthy blogging material. Irritability, perhaps listed as a 'challenging behaviour' in the context of autism is something that many, many people would love to be able to effectively tackle; if not just because of the impact it can have on those with autism and those around them who have to 'cope' with such behaviours. Indeed, given the other options for managing such behaviour such as the antipsychotic risperidone (see here) and the issues which that drug and its similars can bring (see here), the idea that there may be other, less side-effect heavy options (see here) is definitely something to consider.

I'm hopeful that soon, very soon, I can talk more about CM-AT in the context of irritability and beyond in relation to autism...

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[1] Heil MF. et al. Pancreatic Replacement Therapy with CM-at Is Associated with Reduction in Maladaptive Behaviors in Preschoolers with Autism. INSAR 2019.

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Nighttime body movements and autism

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

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

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

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

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

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SHANK3, gut issues and (mouse) autism continued

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

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

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

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

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

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

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

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Constipation and autism is not an uncommon combination

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

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

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

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

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

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

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Preventing, yes preventing, elopement in kids with autism

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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