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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NMDAR encephalitis presenting with "behavioral changes and some autistic features"

Anti N-methyl-D-aspartate (anti-NMDA) receptor encephalitis is yet again (see here) the blogging topic today, as I bring the case report published by Yasmin Khundakji and colleagues [1] to your attention. It's an important case report because, in keeping with the primary focus of this blog, the words 'autistic features' also appear in the Khundakji account. This follows quite a bit of other independent research where autism or autistic features has been mentioned in the context of NMDA receptor encephalitis (see here and see here).

The details? "The patient was a healthy girl" ('was' being the operative word). Some time before she was 2 years of age, she experienced some really quite sudden and stark behavioural changes "manifesting as bouts of irritability, aggression, inconsolable crying, and self-mutilatory behavior (self-biting)." A fever brought about various other somatic symptoms, as eye contact was lost and insomnia set in. "In addition, she developed a progressive regression in gross and fine motor skills and an inability to swallow" with seizures following. Things were getting really serious.

Various tests were carried out which in the most part came up within typical reference ranges (including a "brain MRI"). Someone had their suspicions that NMDA receptor encephalitis *might* fit with the presented profile. Lo and behold, following testing a positive result was received albeit "one month later" (samples had to be sent out of country for analysis). Interventions were put in place ("intravenous immunoglobulin (IVIg) and intravenous methylprednisolone... plasma exchange... rituximab") with some being more successful than others. Of particular note: "A dramatic improvement in her social skills and irritability appeared within hours following plasma exchange." Interesting. Things did eventually improve for the young girl at the centre of the Khundakji paper as we are told that: "Apart from mild speech delay, her neurological exam and developmental milestones are normal."

What lessons can be learned from such case reports? How about starting with the idea that rapid onset childhood regression that includes 'autistic features' should always be investigated as a sign of unmet medical need such as a response to infection (see here)? Perhaps also acknowledge that the presentation of autism or autistic features is not a life-long, immutable, set-in-stone scenario for some people (see here and see here and see here)? And as for the effects of plasmapheresis (plasma exchange) on this particular young child linked to a "dramatic improvement in her social skills and irritability", I'm wondering whether there is a research study or two to be designed and conducted on this topic (with due care)?

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[1] Khundakji Y. et al. Anti-NMDA receptor encephalitis in a toddler: A diagnostic challenge. International Journal of Pediatrics and Adolescent Medicine. 2018; 5: 75-77.

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Autism: a spectrum, dimensions or clusters? How about a multi-dimensional cluster of spectrums?

A write-up (see here) of the paper by Hyunsik Kim and colleagues [1] was the initial impetus for formulating this blog post, but it quickly escalated into something a little larger when the findings from Frank Duffy & Heidelise Als [2] also popped up.

The question at hand: how should one conceptualise autism? Is it truly a spectrum as per the Lorna Wing proposition, or is it something a trifle more complicated? As per the title of this post, should we perhaps be thinking about autism as some sort of "multi-dimensional cluster of spectrums?" I'll come back to that idea shortly.

Well, it's not for me to make definitive conclusions on this blog. Science rarely, if at all, provides an absolute 'truth' but rather the probability that something is approaching truth. Such a notion goes double when you consider the singular label of autism and the huge heterogeneity that it encompasses. There are no easy answers and probably little or no truths.

Starting with the Kim paper (including some notable names such as the surname 'Gadow') and the name of the research game was modelling, modelling in a computational sense. So: "The sample comprised 3,825 youth, who were consecutive referrals to a university developmental disabilities or child psychiatric outpatient clinic." The CASI-4R - formulated by Prof. Gadow - was the schedule administered, which includes "an ASD [autism spectrum disorder] symptom rating scale" among other things. Some nifty statistics were applied to the data and the initial findings were 'tested' on a further group of over 2500 children.

Results: "Based on comparison of 44 different models, results indicated that the ASD symptom phenotype is best conceptualized as multi-dimensional versus a categorical or categorical-dimensional hybrid construct." And the dimensions mentioned in that 'multi-dimensional' statement? Well, lucky for us they were something familiar: "social interaction, communication, and repetitive behaving."

Then to the Duffy/Als paper (again, these authors are no stranger to autism research) and a similar starting point: "The authors postulate that the broad definition of an omnibus 'spectrum disorder' may inhibit delineation of meaningful clinical correlations." Indeed, very familiar (see here). The conclusion: "evidence that an objectively defined, EEG [electroencephalogram] based brain measure may be helpful in illuminating the autism spectrum versus subgroups (clusters) question." The tool used by Duffy/Als in their study was something called NbClust "specifically designed to provide an objective means, i.e. independent of investigator choice, to identify the ‘optimal’ cluster number within a population." Said tool was applied to EEG data derived from 400 participants diagnosed with an ASD. Statistics and more statistics applied to the data revealed that: "430 subjects diagnosed as being on the autism “spectrum” and represented by 40 EEG coherence factors..., fell into two distinct clusters." These autism spectrum clusters differed from each other and importantly, from "554 subject neuro-typical control group subjects, not involved in the clustering process." Interesting results but an unfortunate use of the term 'neurotypical' (see here). Duffy & Als conclude that their data support a view whereby "autism disorder should not be seen as a continuous spectrum." So Kim & Duffy/Als arrive at similar conclusions: a singular 'spectrum' idea of autism is probably not the best way of conceptualising the essence of the label.

I would perhaps add in a little more evidence for the idea that 'multi-dimensional clusters of spectrums' is a potentially better fit. I used the words 'spectrums' (plural) because there is a growing body of evidence to support the idea of more than one 'type' of autism. I say that from the perspective of evidence for autism being 'acquired' under several different circumstances (e.g. accompanying inborn errors of metabolism, linked to exposure to certain infections or diseases, etc). There's also evidence that clinical profiles under the umbrella term autism are not uniform (e.g. regressive autism, the so-called 'optimal outcomers', differing developmental trajectories, etc). And when one looks at something like the success (or not) of intervention, it's plain to see that there is no universally shared genetics and/or biology of autism in the singular either (see here and see here for examples). Add in the idea that autism rarely appears in a diagnostic vacuum (see here) and that said comorbidity might 'cluster' in some subgroups of autism (see here), and I hope you can see why 'plural' might be a good addition to any attempt to re-conceptualise autism: spectrum, dimension, tapestry, cluster or however you think it should be defined...

Oh, and since we're on the topic of trying to conceptualise autism, a new book out recently has been reviewed in Nature (see here). It talks about how "conclusive findings about sex-linked brain differences have failed to materialize" which is particularly apt in relation to previous talk about 'extreme male brains' as a way of conceptualising [some] autism (see here). One quote I particularly liked from the review is this one: "The brain is no more gendered than the liver or kidneys or heart."

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[1] Kim H. et al. Quantifying the Optimal Structure of the Autism Phenotype: A Comprehensive Comparison of Dimensional, Categorical, and Hybrid Models. J Am Acad Child Adolesc Psychiatry. 2018 Oct 29. pii: S0890-8567(18)31894-X.

[2] Duffy FH. & Als H. Autism, spectrum or clusters? An EEG coherence study. BMC Neurol. 2019 Feb 14;19(1):27.

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"Our findings beg the question, what is going on with these children who no longer have an ASD diagnosis?"

The quote heading this post - "Our findings beg the question, what is going on with these children who no longer have an ASD [autism spectrum disorder] diagnosis?" - comes from some media coverage of the findings reported by Lisa Shulman and colleagues [1]. Shulman et al (bravely) set about examining an important phenomenon in autism research and practice circles: those who were previously diagnosed as being autistic / having autism but at a later date 'no longer met the diagnostic criteria for autism'.

I've talked about these so-called 'optimal outcomers' quite a bit on this blog (see here and see here and see here for examples). I know such discussions aren't everyone's cup of tea, particularly those who see autism as so much more than a diagnostic label, perhaps akin to an identity. The fact of the matter is however that there is what I would call 'substantial evidence' in the peer-reviewed science domain and beyond that the idea that 'autism is a lifelong condition/disorder' does not necessarily cover the huge heterogeneity encompassed under the label autism. Some people, for whatever reasons, do not reach critical diagnostic cut-off points for autism on a lifelong basis.

So, what did Shulman and colleagues do and find? They reviewed the clinical records of over 500 children who were diagnosed with autism or autism spectrum disorder (ASD) at a specific clinic. Most were aged around 3 years old when first diagnosed and were followed up about 3-4 years later. Importantly most of the children participated in one or more intervention programs aimed at improving skills and the like and (hopefully) quality of life. Again, although not everyone's cup of tea, the words 'applied behavioural analysis' (ABA) are also mentioned as an intervention; something that has been discussed in the context of optimal outcome before (see here).

Shulman et al noted that 38 children, equating to around 7% of their group (38/569), "subsequently experienced resolution of ASD symptomatology and no longer met diagnostic criteria for ASD at follow-up." This figure (7%) is not a million miles away from other figures noted in other independent studies (see here and see here).

Further examination of records however revealed that not meeting diagnostic cut-off points for autism did not necessarily mean 'symptom-free' as various other symptoms/conditions were noted in about two-thirds of their 'optimal outcomers'. This included language disorders, attention-deficit hyperactivity disorder (ADHD) and even the signs and symptoms of psychosis in a few. Three of the 38 optimal outcome children were noted to be completely symptom-free (described as 'recovered from autism' with no other issues); something that has again been noted in other studies too (see here).

Then back to that quote titling this post: what is going on with these children who no longer have an ASD diagnosis? I'm sure some people will put it wholly down to initial misdiagnosis. Y'know, something along the lines of 'they weren't autistic in the first place' despite the fact that they previously met clinical cut-off points for a diagnosis. Minus sweeping generalisations, misdiagnosing autism is not something that can be completely taken off the table as per other examples in the peer-reviewed literature and beyond (see here and see here). Indeed, if one ventures down the pathway of misdiagnosis as accounting for results such as those by Shulman and colleagues, one must logically then assume that such misdiagnosis is pretty widespread (at least in 7-12% of cases of autism). Such a situation also plays into other ideas too; particularly how self-diagnosis of autism is even more dangerous than has been hitherto suggested (see here and see here) with regards to the risk of misdiagnosis.

Other people might talk about things like 'masking' as accounting for such optimal outcome, where symptoms are merely being consciously hidden by those with autism (see here). It's an important area of study by all means but seriously ask yourself the question: how likely is it that a 6 or 7-year old child would be able to mask some fundamental signs and symptoms of autism so as to mislead a professional clinician that they didn't have autism having previously met cut-off points? Adults, yes perhaps some (see here). But young children? Be honest now...

Personally, I'm inclined to believe that at least some of those optimal outcome cases are genuine. That is, children (and adults) did meet the diagnostic criteria and clinical cut-off points for autism (including the criteria about symptoms significantly affecting day-to-day life) and then for whatever reason(s) symptoms abated. Intervention certainly could have played a role, but I'm also inclined to believe that behavioural intervention in particular, does not have the power to render someone who was autistic to be not-autistic. I know some big claims have been made about certain interventions down the years, but I've seen little [longitudinal] convincing evidence in the peer-reviewed literature yet.

There must be other factors at work. There must, for example, be a biological element to this. And as one example, just head back to all those discussions about certain types of infection potentially *leading* to the presentation of autism or autistic traits (see here and see here) as a possible template, and the outcomes mentioned for some. One possibility at least.

Much like discussions on another sometimes contentious topic - regression and autism (see here and see here) - there's enough peer-reviewed science literature to suggest that optimal outcome (or however you want to describe such 'growing out of' issues) is a very real scenario for some. Not all, but for some. And so once again the call goes out to start studying the genetics and biology of these so-called optimal outcomers, and then ascertaining whether any findings might have some important implications more widely for the [plural] label of autism...

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[1] Shulman L. et al. When an Early Diagnosis of Autism Spectrum Disorder Resolves, What Remains? J Child Neurol. 2019 Mar 12:883073819834428.

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"The MMR Vaccine Is Not Associated With Risk for Autism"

The quote heading this rather long post - "The MMR [measles, mumps and rubella] Vaccine Is Not Associated With Risk for Autism" - comes from a patient summary covering the the findings reported by Anders Hviid and colleagues [1].

Hviid et al utilised some of those oh-so-useful Scandinavian population registries to provide support for the hypothesis that "MMR vaccination does not increase the risk for autism, does not trigger autism in susceptible children, and is not associated with clustering of autism cases after vaccination." As per some media reporting of the study (see here), such a finding comes at a time when cases of measles in particular, are on the rise (see here) in various parts of the developing and developed world (see here) as a possible/probable consequence of specific viewpoints around vaccination (see here).

The Hviid data, as important as it is, is nothing new in terms of research that has been done on the topic of childhood vaccination and autism risk (see here). Indeed, the author is no stranger to this area of the autism research 'scene' as per other population-based cohort studies looking at "whether vaccination with a thimerosal-containing vaccine is associated with development of autism" [2]. The answer on that peer-reviewed research occasion was probably not: "results do not support a causal relationship between childhood vaccination with thimerosal-containing vaccines and development of autistic-spectrum disorders." The authors have also previously looked specifically at the MMR vaccine and autism risk too [3] albeit with caveats, some of which they addressed in this more recent investigation...

The basics this time around: look through the registry data of some 650,000 children "born in Denmark from 1999 through 31 December 2010, with follow-up from 1 year of age and through 31 August 2013." Collect and collate various information - use of "MMR and other childhood vaccinations, autism diagnoses, sibling history of autism" - and undertake some statistical analysis pertinent to the question of "whether autism developed in children who got the MMR vaccine compared with those who did not during the follow-up period." Researchers also included various potential confounders in their statistical analyses: "maternal age, paternal age, smoking during pregnancy, method of delivery, preterm birth, 5-minute Apgar score, low birthweight, and head circumference."

As per the opening paragraph, the results did not detect any link: "Comparing MMR-vaccinated with MMR-unvaccinated children yielded a fully adjusted autism hazard ratio of 0.93 (95% CI, 0.85 to 1.02)." This based on data where around 95% of the population received the vaccine (around 31,000 were classed as 'MMR-unvaccinated') and 1% (n=6,517) of the total population were diagnosed with autism. A few other observations were also noted by Hviid and colleagues: "The highest risk for autism was conferred by being a boy..., being born in a late birth cohort (2008-2010...), having no early childhood vaccinations..., and having siblings with autism at study entry." Such observations have some important links to other independent findings; for example, children with a sibling already diagnosed with autism are more likely to be diagnosed with autism (see here) and children who did not receive the MMR vaccine were actually slightly more likely to be diagnosed with autism than those who were vaccinated (a trend particularly noted in girls I believe). That last result might tie into other independent findings too (see here).

As with any research study, there were limitations attached to the Hviid investigation. So: "No individual medical chart review was performed" meaning that registry data, as strong as it is, is not the same as "medical records or direct examination of the children by research staff." The use of such population registries across a wide variety of different research topics (see here and see here for examples) carries the same limitation. I'm also minded to mention that population registry data is good for ascertaining population trends, but tends to say little about rare events. Individual issues can sometimes get lost in the statistical noise [4]. The focus of the Hviid study was also specifically on the MMR vaccine. Although not completely au-fait with the vaccination schedule in Denmark (see here) the data say little about the use of other vaccinations, their timing, and any connection (or not) to autism. And finally, I might quibble with the idea that Hviid et al looked at 'susceptible groups' on the basis of the variables they included in their 'autism risk score'. 'Smoking during pregnancy' for example has shown little to no association with autism (see here and see here) (something we can't say when it comes to offspring risk of ADHD for example). Other variables such a maternal metabolic syndrome signs and symptoms during pregnancy (see here) or maternal vitamin supplementation during pregnancy (see here) might have provided some stronger indications of autism risk/susceptibility. And then there's the recent results from Xie and colleagues [5] to also consider...

Still, the Hviid data provide further pretty powerful evidence disproving any population-wide link between MMR vaccine receipt and autism risk. The big question is whether such results, added to quite a lot of other science on this topic, are actually going to make any difference to something like vaccination rates against diseases like measles?

As per an editorial [6] accompanying the Hviid paper we live in an age where scientific data seems to have 'limited persuasive value' for some people and where the concept of 'risk' is often not well understood. The editorial authors also opine that "an alternative explanation of the perceived phenomenon should be provided" which is something else rather important. Not least because some parents, right or wrong, are still adamant that their child had a reaction to one or more of their childhood vaccinations (see here and see here). Autism research has tended to shy away from looking at this specific scenario (see here) thus leaving it unchallenged. Perhaps therefore the time is right for some brave researcher to study those children who were reported to have allegedly undergone a reaction to vaccination and see if anything is significantly 'different' about them on a behavioural and/or biological level? Whether indeed an alternative explanation could be provided for their clinical regression including the influence of variables immediately after the vaccination event [7]?

And as for the message about ensuring children (and adults, particularly vulnerable adults) are vaccinated and protected against diseases, I once again turn to the writings of Roald Dahl, and how measles devastated his family (see here) and what vaccination would have meant to his daughter. A powerful personal message that perhaps needs to be used a little more often alongside the dissemination (and translation) of scientific data to promote the benefits of vaccination to individuals and populations alike...

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[1] Hviid A. et al. Measles, Mumps, Rubella Vaccination and Autism: A Nationwide Cohort Study. Ann Intern Med. 2019 Mar 5.

[2] Hviid A. et al. Association between thimerosal-containing vaccine and autism. JAMA. 2003 Oct 1;290(13):1763-6.

[3] Madsen KM. et al. A population-based study of measles, mumps, and rubella vaccination and autism. N Engl J Med. 2002 Nov 7;347(19):1477-82.

[4] Poling JS. et al. Developmental regression and mitochondrial dysfunction in a child with autism. J Child Neurol. 2006 Feb;21(2):170-2.

[5] Xie S. et al. Family History of Mental and Neurological Disorders and Risk of Autism. JAMA Network Open. 2019; 2: e190154.

[6] Omer SB. & Yildirim I. Further Evidence of MMR Vaccine Safety: Scientific and Communications Considerations. Ann Intern Med. 2019 Mar 5.

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

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Regression and autism: "The regression group was significantly more functionally impaired..."

The quote forming part of the title of today's post - "The regression group was significantly more functionally impaired..." - comes from the findings reported by Lucy Thompson and colleagues [1] (open-access available here). It continues something of an important theme in autism research circles whereby regression, as in a regression of previously acquired skills, is being seen as important not just for a few but for many (see here).

There were a few aims to the Thompson study such as establishing "the relative prevalence of regression in autism" and "possible predictors, mediators and moderators of regression in autism, including pre- and perinatal factors." The data for the study were derived from "two community-based cohorts" in Sweden totalling just over 300 participants (children) diagnosed with an autism spectrum disorder (ASD) who were observed over two different time points (T1 and T2 2 years later). Another important detail is mentioned by Thompson et al: "Given the lack of previous systematic representative studies in the field, our study sets out to be descriptive rather than hypothesis-driven." Figures and details on regression in the cohort(s) were obtained via specific questioning on this topic "defined as loss of expressive language skills (loss of 5 or more words that had been used communicatively) in connection with the onset of autism." This data was also combined with other medical records information to determine 'consistency'.

Results: "Just over 20% (62/303) of the combined sample of children had regressive autism." That's 1 in 5 children with autism experiencing some kind of regression in relation to language skills. When looking at those who regressed (n=62) compared with those with no regression (n=241), a few details emerged: "Those with regressive autism had a younger age when they first walked... had a more severe language impairment at T1... and more often intellectual disability... [and] lower mean VAB [Vineland Adaptive Behaviour Scales-II] scores." Also: "Severity of autism was higher in the regressive group, with a higher proportion of children with autism... (as opposed to autistic-like condition)."

This is important data. It kinda tallies with other studies of regression accompanying autism suggesting that those who regress tend to have a more 'severe' form of autism with accompanying learning (intellectual) disability. The diagnostic issues - as in more likely to be diagnosed with Kanner's autism rather than other diagnoses - similarly ties in with other findings.

Caveats? Well, a few: "We have chosen to focus on language regression specifically (rather than social, play or motor regression) as communication is by far the most common skill to be lost or diminished in regressive autism." That being said, regression accompanying autism seems to take many, many forms and does not always just mean a loss or partial loss of vocal communication (see here).

Also: "There was also a similar level of maternal disease in pregnancy in the regressive and non-regressive groups, suggesting that prenatal exposure via maternal disease does not seem to be a key feature in the development of regressive autism." I have to question why the authors stuck to looking at just pre- and perinatal factors as possibly being *linked* to regression when regression is likely to occur quite some time after such a developmental window. Surely it would have made more sense to ask a few further questions about the timing of regression - "The average age at regression was 20.13 months... with 54 children (88.5%) showing regression by the age of 24 months" - and whether one or more event might have proceeded such regression in a similar time frame. Y'know whether infection might be a feature (see here and see here for examples) or whether other events might require further investigation (see here). I know this might take such research down some uncomfortable paths, but temporality is surely an important factor for some regression in some cases of autism? Or am I being too unreasonable?

I might also advance the idea that the time to start asking questions about the biology of regression accompanying autism is fast approaching. We've already had some clues in the recent (at the time of writing) peer-reviewed research literature (see here) but lots more needs to be done in this area. Are there important genetic and/or epigenetic variables to consider? Do mitochondrial issues play a role in some regressive autism (see here)? We just don't know enough yet. And yes, this does mean also asking about whether regression in behaviour or cognitive skills was also accompanied by any changes to somatic variables too (see here).

And then there is another question to ask/answer: does regression mean that certain 'therapeutic' options might be particularly useful? I'm thinking back to some research a few years back talking about corticosterioid therapy *potentially* being indicated for some cases of regressive autism (see here). No, I'm not making any medical or clinical claims or giving any advice on such an issue. Merely mentioning that regressive autism needs to be more of a research priority than it currently is. To quote Thompson and colleagues again: "Children with a regressive developmental trajectory, with or without autism, always need a careful neuropediatric work-up to investigate possible neurological disorders that may lead to developmental regression, taking into account possible treatable conditions." Who would argue with that?

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[1] Thompson L. et al. Autism With and Without Regression: A Two-Year Prospective Longitudinal Study in Two Population-Derived Swedish Cohorts. J Autism Dev Disord. 2019 Feb 4.

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Psychiatric and seizure medicines for autism: what 'works' best

The paper by Devon Coleman and colleagues [1] represents pretty good scientific value for money by my reckoning. Describing the results of a 'survey' called the "National Survey on Treatment Effectiveness for Autism" created by the researchers, the aim was to provide "separated... scales for overall benefits and overall AEs [adverse effects]" for a wide range of interventions used in the context of autism.

The focus this time around was on "Psychiatric and Seizure medications data" but it looks like there may be quite a bit more to see from this group in future with regards to data on "supplements, diets, therapies, and educational interventions" also collected during this initiative. Before continuing on with this paper I have to hat-tip the authors for mentioning a great and much under-valued resource in autism circles: "the Parent Ratings of Behavioral Effects of Biomedical Interventions Survey,... conducted by the Autism Research Institute (ARI) and published in 2008." Indeed, in other posts talking about the medicines cabinet and autism (see here) I've expressed my positive views of the ARI resource albeit with caveats.

Anyhow: "we report ratings of 26 psychiatric and seizure medications by 505 participants." Researchers actually noted that nearly 900 people completed their survey; most of whom were described as the "Primary caregiver of an individual with autism." Some people might um-and-ah about the lack of 'authentic autistic representation' in this study, but one needs to bear in mind that most participants - about three-quarters - were under 18 years of age, most diagnosed with autism and not autism spectrum disorder (described as "less severe than a diagnosis of autism") and most were currently described as having mild, moderate or severe autism. I know this won't be enough for some people, but there you have it.

Then to the medicines that were 'graded', which fell into "five general categories: stimulants (four medications), SSRIs [selective serotonin reuptake inhibitors] (five medications), antipsychotics (four medications), seizure (nine medications), and other (four medications)." There's a lot of data included in the Coleman paper which really is too much for a blog post. I'll direct you to Figure 8 of the Coleman paper which provides a handy 'net benefit score' taking into account an 'overall benefit score' and an 'overall adverse score' for each medicine. When it came to SSRI medicines - typically indicated for treating depression - sertraline came top. When it came to antiepileptic medicines - primarily used to manage epilepsy and/or seizures - lamotrigine came top. When it came to antipsychotic medicines, aripiprazole came top. I was also interested to see that buspirone, a medicine typically indicated for anxiety, also did pretty well according to the Coleman results, which kinda ties in with some continuing research interest in this medicine with autism in mind (see here). Researchers also provide a handy 'medications for symptoms' overview as a consequence of their results (see Table 7) covering various symptoms from aggression/agitation to tics/abnormal movements. I can see this being particularly useful when it comes to physicians having to make big medication decisions (which should never be entered into lightly).

There's a couple of other details that are also mentioned in the Coleman paper outside of those 'how was medicine rated?' sentiments. Some details are not likely to make many friends in some quarters. So, around 2% of participants were described as follows: "No current diagnosis, but he/she was on the autism spectrum previously." Yes folks, such data once again harks back to the idea that for some people at least, autism is not a lifelong diagnosis (see here and see here). And also: "Thirty-four percent of participants had early onset of symptoms, but 56% had normal development followed by a plateau or regression." Regression accompanying autism is not the 'dirty' concept that it used to be (see here). Indeed, in the few years that I've been blogging about autism research, I've seen it become a lot more commonplace to talk about regression and autism (see here) even to the point that some now talk about it being 'the rule rather than the exception' (see here). Interesting.

And then there's something even more controversial in the Coleman paper: "The perceptions of possible causes of the regression are listed in Table 2." So we have things like high fever, illness, seizure and then... vaccination. I know this takes us into some uncomfortable territory, but the authors report that 51% of respondents to their survey who cited regression as part of the clinical picture mentioned vaccination as the 'perceived cause' whether singly or in conjunction with other factors. Of course I'm going to provide a link to what the population-based science says on this matter (see here) with the caveat that such 'perceived cause' data perhaps needs objective and dispassionate follow-up (see here and see here).

The Coleman results are not without their limitations as per author comments such as: "The survey is retrospective and based on respondent memory which reduces the accuracy" and "The results are subject to “placebo effect” since it represents clinical data without a placebo control, so the real benefit is likely less than the perceived benefit." But let's not take too much away from the findings and how they may, as well as informing clinical practice, also hopefully lead to further inquiry to make medicines safer and more reliable for those on the autism spectrum who access them.

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[1] Coleman DM. et al. Rating of the Effectiveness of 26 Psychiatric and Seizure Medications for Autism Spectrum Disorder: Results of a National Survey. J Child Adolesc Psychopharmacol. 2019 Feb 6.

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"Has Daniel always been autistic?"

"Has Daniel always been autistic?"

That was the question that led to Twitter uproar and newspaper headlines calling a TV presenter an 'idiot' and "embarrassing" and "ignorant" these past few days. Some have even called for veteran daytime TV presenter Richard Madeley to be sacked, as one of the premier national autism charities here in Blighty authoritatively announced "autism is a lifelong condition, people are born autistic, it’s not something a child grows out of" following the reporting of an interview between Madeley and Daniel Wakeford, one of the stars of the not particularly well titled TV series called The Undateables. Personally, I would have liked to have seen said charity comment on how the term 'undateable' really shouldn't be used in this day and age with any diagnosis/label in mind...

Emotions ran high following the interview, as many parents of children with autism and autistic people voiced their opinions about their own personal experiences of autism. These are all valid opinions. The problem however, is that within the wide - very wide - heterogeneity that is autism, some of the peer-reviewed science on the topic of autism actually supports the line of questioning from Madeley. Some of the peer-reviewed science highlights the sweeping error in saying that autism is (a) lifelong for everyone and (b) that everyone, past, present and future is 'born autistic'.

OK, first things first, autism is a label ripe for sweeping generalisations. We've seen it numerous times as psychological theories for example, have swept through proclaiming that everyone with autism is lacking a theory of mind or empathy or some other related construct. Likewise, I've seen people quite vehemently opine that autism is the product of this or that 'environmental factor' insinuating that simple changes to drink, food or medicines use for example, will 'stop autism'. The reality however is that autism is a label used to describe vast heterogeneity. It's also a label that says nothing about how a person came to be autistic and nothing about the prognosis of their presentation or their life in general.

So what is the cold, objective peer-reviewed scientific evidence to say that autism is not present from birth for everyone? Well, it's multi-fold. It comes from a number of studies that have followed children from early infancy into later childhood to see whether autism *always* manifest from the very earliest days. Take the recent findings from Sally Ozonoff and colleagues [1] (see here for my take) that concluded among late diagnosed children in their cohort: "Seven showed very little evidence of ASD [autism spectrum disorder] in preschool, whereas 7 demonstrated subtle, subthreshold symptomatology." Add it to other independent data [2] that "validate parents' reports that ASD may appear after a period of nonautistic development" (also that "such reports should not be attributed to recall bias") and then throw in the idea that 'regression', as in a regression of previously acquired skills, is perhaps no stranger to many instances of autism (see here). Then to top it all add in other data highlighting specific cases of 'acquired autism' following exposure to particular post-natal infections for example (see here), and the old 'autistic from birth' mantra does not universally hold for everyone diagnosed as being on the autism spectrum. The evidence against the sweeping 'autism is a lifelong condition' statement made following the interview? I'll direct you to some of the numerous occasions that I've talked about such an idea on this blog (see here and see here and see here) based again on the available peer-reviewed science. Cold. Objective. Science.

Minus making any sweeping generalisations of my own, there is scientific evidence out there that 'born autistic' is not something that can be universally applied to everyone on the autism spectrum no matter how many people would like it to be so. In that respect, the question from Richard Madeley was not ignorant nor disrespectful but rather quite sensible and easily discernible from the available science. The fact also that Daniel's mother Carol talked about a 'loss of his language abilities' in her reply to the question (something I'm sure must have been mentioned before the interview took place and was aired) kinda adds to the sound reasoning for Madeley to ask. It also implies that science should keep studying such an important phenomenon.

It seems that when Carol Wakeford responded with the words 'yes, well there's controversy about that' as the first part of her answer to Madeley's question about Daniel, she certainly wasn't wrong...

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[1] Ozonoff S. et al. Diagnosis of Autism Spectrum Disorder After Age 5 in Children Evaluated Longitudinally Since Infancy. J Am Acad Child Adolesc Psychiatry. 2018 Nov;57(11):849-857.e2.

[2] Landa RJ. et al. Social and communication development in toddlers with early and later diagnosis of autism spectrum disorders. Arch Gen Psychiatry. 2007 Jul;64(7):853-64.

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Regressive vs. non-regressive autism: limited chemical differences noted

The paper published by Antonio Gomez-Fernandez and colleagues [1] examining whether or not there may be some potentially important biological differences as a function of reported regression vs. no regression in autism provides the blogging fodder today. Not for the first time has the immune system and 'regressive autism' been mentioned in the peer-reviewed science literature (see here and see here), but the current work focuses on the examination of various immune system and other related compounds: in a seemingly well-defined cohort: "Analyses of plasma molecules, such as cathepsin, IL1β, IL6, IL8, MPO, RANTES, MCP, BDNF, PAI NCAM, sICAM, sVCAM and NGF."

"Fifty-four children (45 males and nine females) aged 2-6, who were diagnosed with ASD [autism spectrum disorder], and a control group of 54 typically-developing children of similar ages were selected." Authors relied on quite an extensive battery of assessments looking at behaviour, alongside their use of the DSM-5 diagnostic criteria for autism (see here). Also accompanying physical examination "with a special emphasis on neurological and nutritional status", authors garnered blood samples from participants (overnight fasting) for their immune system and related functioning evaluations.

"The group of ASD children was further divided into two subgroups based on the presence or absence of neurodevelopmental regression during the first two years of life, which was assessed using a five-item questionnaire following the guidelines used by the Autism Diagnostic Interview-Revised (ADI-R) for the evaluation of this process." The ADI-R has been previously discussed on this blog in relation to regression in autism (see here). And just in case you might not be totally convinced that regression can be part of a pathway to autism, here's some more evidence for you (see here)...

Results: "there were 20 children included in the AMR [neurodevelopmental regression] subgroup and 32 in the ANMR [without neurodevelopmental regression] subgroup; two children could not be classified in these subgroups because they were adoptees, allocated by a national adoption agency." Bearing in mind that we cannot rule out any recruitment bias that might have leaned towards including those with regressive autism on the Gomez-Fernandez study, the figure of approaching 40% of their cohort showing such a regressive profile is notable. I'd also draw your attention to the finding that the behavioural profile for the regressive group (AMR) was also significantly different from the non-regressive group (ANMR) insofar as perhaps painting a picture of greater [group] autism severity...

Interestingly, the study did not show too many immune system and other compound differences between those diagnosed with autism and the asymptomatic (for autism) control group. So: "No differences were found between the two groups in terms of the cytokine and adhesion molecule levels studied, except for NGF [nerve growth factor], in which the group of ASD children was found to have twice the plasma levels compared to the control group." NGF is no stranger to autism research, and other studies have come to a similar conclusion [2].

When it came to examining results based on comparing the regressive (AMR) and non-regressive (ANMR) groupings, things got slightly more interesting but again no complicated pattern of difference was noted. So, for the ANMR (non regression) grouping: "lower plasma levels of the NCAM adhesion molecule were detected compared to the levels in the AMR subgroup and the control group. This ANMR group also exhibited higher NGF levels than the typically-developing children, which could indicate an alteration in neuronal development." Again, adhesion molecules have been mentioned in other autism research (see here).

"In conclusion, the results of this study show that there is not a typical profile for the expression of relevant plasma cytokines, adhesion molecules or growth factors in children with ASD compared with that in typically-developing children." OK, there are caveats to the phrasing used by the authors; not least that the participant numbers were quite small in the Gomez-Fernandez study and the idea that within the very heterogeneous autism spectrum, there may be smaller groupings (phenotypes) that perhaps show a tendency to greater immune system and related 'issues' (see here). But there are also some strengths attached to the Gomez-Fernandez study; not least the study "benefits from a careful selection of children of similar ages, as well as the complete diagnosis of ASD with multiple tests, clinical follow-up and associated complementary tests."

Questions still remain. Perhaps an important one is the question around why some children show a regressive pattern of behaviour as part of their path to a diagnosis of autism? Yes, issues such as infection do seem to be part-and-parcel of the clinical profile for some (see here and see here for examples) and perhaps more detailed focus is required in such areas. But much like a group showing the opposite of regressive autism - those who seemed to 'grow out' of autism - currently thought to include as many as one in ten (see here), a wider range of biological as well as psychometric measures are required to help pick out potentially important mechanisms pertinent to the idea that autism is not necessarily 'hard-wired' for all...

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[1] Gomez-Fernandez A. et al. Children With Autism Spectrum Disorder With Regression Exhibit a Different Profile in Plasma Cytokines and Adhesion Molecules Compared to Children Without Such Regression. Front. Pediatr. 2018. September 26.

[2] Dinçel N. et al. Serum nerve growth factor levels in autistic children in Turkish population: a preliminary study. Indian J Med Res. 2013 Dec;138(6):900-3.

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PET scanning as a biomarker for ketogenic diet response in autism? Not quite...

The case report findings reported by Iwona Żarnowska and colleagues [1] provide the blogging fodder today and an interesting idea: could PET imaging - "non-invasive positron emission tomography (PET) with 18 fluoro-deoxyglucose (18FDG PET) of the resting brain" - serve as "a biomarker in identifying individuals with autism who might benefit from the KD [ketogenic diet] due to underlying abnormalities related to glucose hypometabolism"?

'We need more research' is the conclusion reached by authors, who describe a case report of a 6-year old boy who seemed to regress into autism (yes, he regressed - "At the age of 2, he was developmentally on target in motor and cognitive skills, used language for communication, and displayed normal interests, social activities, and behaviours that were appropriate for his age") and was subsequently introduced to a ketogenic diet. The ketogenic diet (KD) has been discussed before on this blog in relation to autism (see here and see here for examples), and how "a very strict, high-fat, low-carbohydrate, adequate-protein and vitamin-supplemented diet with meals distributed evenly throughout the day" seems to have some important effects on behaviour for some.

Indeed, we are told that use of the KD diet for this young man diagnosed with autism and ADHD (attention-deficit hyperactivity disorder) seemed to *correlate* with some important changes to his behavioural presentation. So: "improvements in clinical outcomes were observed as early as 1 month after the classic KD initiation." The sorts of things reported included less hyperactive and aggressive behaviours and some important differences in his scores on schedules such as the CARS (Childhood Autism Rating Scale) focusing on autistic behaviours. Cognitively, there were also some positive changes reported too: "The intellectual development of the patient, as measured by the WISC-R at the age of 7 years and 5 months, also improved his Full Scale IQ increased from 82 to 99..., Verbal Scale IQ increased from 102 to 113..., and Performance Scale IQ increased from 62 to 83." All of this bearing in mind the 'case report' status of this study.

Then to the mention of that word 'biomarker' as PET scanning was conducted "before treatment (baseline study) and 11 months later on the KD (follow-up study)" and results compared. Although no expert on PET (see here for an overview) the aim was to look at glucose and where the glucose-like tracer 'stuck' in terms of parts of the brain. Researchers observed that at baseline, before the KD was put in place, there was evidence of "regional glucose hypometabolism... observed bilaterally in the mesial temporal lobes, basal ganglia, and cerebellum." At follow-up, when the various manifestations of the ketogenic diet had been in place for a year, they reported different findings based on PET scanning: "18F-FDG uptake decreased markedly and diffusely in the whole cerebral cortex with a relatively low reduction in basal ganglia." The authors add that such observations are not a million miles away from similar metabolic changes seen in others when a KD is put in place in relation to the management of epilepsy (a set of conditions where the KD has found a particular usefulness). The shift away from glucose metabolism in those brain areas is thought to represent "a metabolic shift from the utilization of glucose to utilization of ketone bodies as a primary source of energy" a key aim of the ketogenic diet.

Do the Żarnowska live up to their possible 'biomarker' discussions? Erm, I'm afraid not yet they don't. They do make some interesting observations about the use of a ketogenic diet in the context of a single case report including the label autism. They also present some interesting 'brain imaging' data gathered before and after the use of a KD. But as a biomarker? Not on this occasion. Not yet. But don't however discount the potential usefulness of the ketogenic diet in the context of [some] autism however...

To close, of course you know that it's Star Wars Day today. Don't you? 'Penny for your thoughts.'

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[1] Żarnowska I. et al.Therapeutic use of carbohydrate-restricted diets in an autistic child; a case report of clinical and 18FDG PET findings. Metabolic Brain Disease. 2018. April 11.

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On mitochondrial DNA (mtDNA) changes and autism

Mitochondrial issues accompanying some diagnoses of autism have quite a bit of peer-reviewed research backing (see here for example). Not for everyone, but for some people diagnosed with an autism spectrum disorder (ASD), there seems to be something afoot with regards to these 'powerhouses of the cell' that could well impact on various aspects of their lives [1]. Indeed, keep that paper from Poling et al [1] in mind...

Although by no means an expert on mitochondrial issues in any context, I believe that there are a few ways in which mitochondrial dysfunction can manifest. It can present as a secondary disorder for example (see here), where some acquired biochemistry (non-genetic) provides some of the 'answers'. Or it can present as a primary mitochondrial disorder, a genetic condition "confirmed by a known or indisputably pathogenic mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) mutation" [2], where issues in the genetic code of mitochondria are present.

The recent findings reported by Noémi Ágnes Varga and colleagues [3] focused on that latter route looking at issues with mtDNA in the context of autism. They turned up some rather interesting results...

So: "The aim of the present study was to investigate the presence of the most common pathogenic mtDNA alterations in patients with ASD." Researchers screened 60 children with autism and 60 not-autism controls. One detail stuck out when it came to those controls: "Our control group for mtDNA screening consisted of 60 European adults (26 females and 34 males, median age = 28 years, IQR = 13.75) selected from our biobank." Compared with those participants diagnosed with autism, they were quite a bit older (median age = 7 years vs. median age  = 28 years) and indeed, the gender ratios were a little bit more balanced.

Anyhow: "Mitochondrial deletions were identified in 16.6% (10/60) of our patients with ASD." OK, 'patients' is not exactly the word I would use for participation in such a research project but that shouldn't distract from the findings. Varga et al also provide some further insights into those 10 'participants' with a diagnosis of autism and mtDNA deletion(s) which turned up some other interesting details, such as the finding that various other symptoms presented alongside autism. Quite a few of them were connected to muscle and movement functions (limb and truncal ataxia, hypotonia, dyspraxia) which ties into other independent findings [4]. I also noted the words 'gluten sensitivity' were mentioned in one case, which is guaranteed to perk my professional interest (see here) although I'm still a little unsure of whether this connected to mtDNA issues or not.

Another set of potentially important details were also observed by researchers when comparing those with autism with and without mtDNA deletion(s). Keeping in mind the small numbers falling into that autism with mtDNA deletion(s) category, developmental regression seemed to be an important facet of the clinical profile of this group. Regression of previously acquired skills is something else I've talked about quite a bit on this blog with regards to autism (see here and see here for examples). Going back to that paper by Jon Poling and colleagues [1] that I told you to keep in mind, it's interesting to note the overlap of regression reported by them and also reported by Varga in the context of mitochondrial disorder. And this isn't the only occasion that regression and mitochondrial issues have been talked about in the same breath as autism [5] and even with other potentially important clinical indicators [6]. Correlation is not necessarily causation but...

There are quite a few other details listed in the Varga paper that I'd encourage readers to pursue but I think I've gone on enough about this topic for now. It, yet again, appears that a diagnosis of autism is protective of nothing when it comes to other conditions/diseases/symptoms/labels appearing and perhaps implies that preferential screening for mitochondrial disorder should be more commonplace than it is as and when autism is diagnosed. I'm also inclined to draw your attention to other clinical labels where mitochondrial issues might be relevant for some (see here) albeit not always with genetics in mind (see here). How perhaps investigations need to be carried out looking at any possible intersection between *some* autism and something like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) (see here) for example, also in light of other important data (see here). Indeed, I'll be coming to the findings reported by Bilevicute-Ljunger and colleagues [7] on this topic quite soon in a separate post...

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

[2] Niyazov DM. et al. Primary Mitochondrial Disease and Secondary Mitochondrial Dysfunction: Importance of Distinction for Diagnosis and Treatment. Mol Syndromol. 2016 Jul;7(3):122-37.

[3] Varga NA. et al. Mitochondrial dysfunction and autism: comprehensive genetic analyses of children with autism and mtDNA deletion. Behavioral and Brain Functions. 2018. 14: 4.

[4] Ghaoui R. & Sue CM. Movement disorders in mitochondrial disease. J Neurology. 2018. Jan 6.

[5] Rossignol DA. & Frye RE. Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry. 2012 Mar;17(3):290-314.

[6] Shoffner J. et al. Fever plus mitochondrial disease could be risk factors for autistic regression. J Child Neurol. 2010 Apr;25(4):429-34.

[7] Bilevicute-Ljunger. I. et al. Patients with chronic fatigue syndrome do not score higher on the Autism-apectrum quotient than healthy controls: comparison with autism spectrum disorder. Scandinavian Journal of Psychology. 2018.

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Regression in autism: the rule rather than the exception?

"Declining trajectories of development, consistent with a regressive onset pattern, are common in children with ASD [autism spectrum disorder] and may be more the rule than the exception."

So said the findings reported by Sally Ozonoff and colleagues [1] who reported results based on a study of developmental / behavioural regression in autism, and specifically: "how rates of regression differed by measurement method."

Regression in relation to autism is a topic I've covered a few times on this blog (see here and see here for examples). I've followed the [peer-reviewed] story from where behavioural and/or developmental regression was initially thought to be a figment of the [parental] imagination, right up to these days where regression is pretty much accepted as being part and parcel of quite a few cases of autism. The road has not been a smooth one; but the question of whether autism is universally something inborn and hereditary for everyone is slowly starting to be answered: no, it is probably not. The reason(s) for regression still remain fertile grounds for discussion / debate / argument, but there are some important clues in the science literature (see here and see here for examples) with the caveats that autism is a very heterogeneous condition and onset patterns are likely to be influenced by all-manner of different variables. Think different phenotypes in the context of autism (see here) for example; and that's outside of the label previously known as Heller's syndrome.

Anyhow, Ozonoff et al report results for infants "with (n = 147) and without a family history of ASD (n = 83)" who were "seen prospectively for up to 7 visits in the first three years of life." Various different ways and means of assessing reports of symptom onset were collected, "that systematically varied the informant (examiner vs. parent), the decision type (categorical [regression absent or present] vs. dimensional [frequency of social behaviors]), and the timing of the assessment (retrospective vs. prospective)."

Depending on who said what and how they said it, patterns of regression in skills were noted in quite a large proportion of the Ozonoff cohort. So: "A majority of the sample was classified as having a regressive onset using either examiner (88%) or parent (69%) prospective dimensional ratings." The authors suggest that their observations highlight how quite a few more resources (and cautions) need to go into looking at symptom onset patterns in relation to autism.

For quite a few people, the findings reported by Ozonoff et al are 'catch-up' rather than something novel. I can think of quite a few instances where parents / guardians have had their important observations - very important observations - described as being 'talked down' when it came to reporting a regression in previously acquired skills in the context of autism. This should no longer be the case; particularly when also set in the context of the increasing pluralisation of the label of autism (see here) and perhaps even, the changing face of autism (see here) compared with yesteryear.

Then to the next important questions: how and why? I've already alluded to a role for infection in relation to the onset of regressive autism for some, but much more data is required on the specific details and mechanisms. There is also the issue of what *might* potentially be done to minimise factors linked to regression in autism too. Minus any sweeping generalisations, I'd also direct your attention to other mentions of regressive autism in the peer-reviewed science literature [2] and where, minus any hype, there could be some important clues for some. The important point once again, is that the diagnosis of autism should be the start of further investigations, not the finishing line.

To close, don't ask me how or why but one of my brood has started watching and enjoying an old staple part of the weekend TV quiz scene in 1980s Blighty... BFH by the way, is most classically referred to as your 'bus fare home'.

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[1] Ozonoff S. et al. Onset patterns in autism: Variation across informants, methods, and timing. Autism Res. 2018 Mar 10.

[2] Poling JS. et al. Developmental regression and mitochondrial dysfunction in a child with autism. J Child Neurol. 2006 Feb;21(2):170-2.

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