On autism symptom trajectories and diagnosing autism late...

It's another one of my mash-up posts today, as two paper are brought to the blogging table. The first paper is from So Hyun Kim and colleagues [1] and looked at the rather interesting topic of differing symptom trajectories in the context of diagnosing autism. The second paper by Sally Ozonoff and colleagues [2] follows in a similar vein in terms of their analysis of children "who had undergone multiple comprehensive assessments in preschool and were determined to be ASD [autism spectrum disorder]-negative, only to meet criteria for ASD when tested in middle childhood."

Both these paper originate from well-respected autism research groups and appear in the same respected journal (Journal of the American Academy of Child & Adolescent Psychiatry). The common theme between them is that within the significant heterogeneity seen under the label of 'autism', there are various different developmental and presented symptoms trajectories, some of which (a) are not as stable as one might imagine, and (b) do not seemingly follow the oft-used assertion that 'autism is present and manifests from birth'. Indeed, on that last point, the implications are that autism is sometimes very much associated with regression (see here) and onward, that genetic and/or non-genetic post-natal factors may very well influence some children reaching clinical cut-off thresholds for a diagnosis of autism (see here for example).

So, to the Kim paper first: authors looked at over 900 "observations of the Autism Diagnostic Observation Schedule (ADOS)" from nearly 150 young children. They were specifically looking at symptoms trajectories based on those ADOS scores and whether or not 'clusters' of similar symptom trajectories were evident. The answer: yes, yes there were some different clusters of symptom trajectories noted. Not six developmental trajectories as per other research (see here) but four clusters: "Nonspectrum ∼25%; Worsening ∼27%; Moderately-Improving ∼25%; Severe-Persistent ∼23%)." Authors also report how: "Trajectory clusters varied significantly in the proportions of confirmatory ASD diagnosis, the level of baseline and final verbal/nonverbal abilities, and symptom severity."

Then to the Ozonoff paper: "Fourteen children met inclusion criteria for the Late Diagnosed group and were compared to a large sample of high- and low-risk siblings from the same sites who had ASD or typical development (TD) outcomes at age 3." Authors focused in on these 14 children and concluded that: "Seven showed very little evidence of ASD in preschool, while seven demonstrated subtle, subthreshold symptomatology." They also suggest that their results identifying a small but important group of children who seemingly first present with 'typical' behaviour but then 'grow into' the presentation of autism "shed light on reasons why the mean age of ASD diagnosis remains over 4 years." Indeed (see here).

I don't really need to say much more than I have already on these studies. Aside that is, from reiterating that the autism spectrum is truly wide and heterogeneous in both symptom presentation and also it seems, with regards to symptom onset and stability too. Alongside other research (see here) talking about how the presentation of autistic signs and symptoms wax and wane for some, I'm wondering when autism research is going to start looking beyond just presented behaviour, at whether for example, genetic and biological 'changes' might accompany such fluidity in behaviour and 'cluster' differences. Y'know, the same way that another group seemingly heading in the opposite direction - those who 'lose their diagnosis' (see here and see here) - also need to be closely investigated from a biological point of view too. It's only when we have such biological data that we can then start meaningfully probing the possible hows-and-whys...

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[1] Kim SH. et al. Variability in Autism Symptom Trajectories Using Repeated Observations from 14 to 36 Months of Age. Journal of the American Academy of Child & Adolescent Psychiatry. 2018. Sept 5.

[2] Ozonoff S. et al. Diagnosis of Autism Spectrum Disorder After Age 5 in Children Evaluated Longitudinally Since Infancy. Journal of the American Academy of Child & Adolescent Psychiatry. 2018. Sept 3.

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Trends in the diagnosis of autism in Australia

"The frequency of ASD [autism spectrum disorder] diagnoses in Australia has increased substantially from previously published estimates."

That was one of the conclusions reached in the study by Catherine Bent and colleagues [1] (open-access here) who aimed to "investigate the frequency and age at diagnosis of autism spectrum disorder (ASD) in children aged under 7 years living in Australia."

Drawing on "de-identified data" extracted from Helping Children with Autism Package (HCWAP) - an Australian Government initiative - covering the period 1 July 2010 and 30 June 2012, researchers examined various variables including: age at diagnosis, frequency of an ASD diagnosis and how particular child characteristics might have influenced both age and frequency of diagnosis.

Some 15,000 children under 7 years of age were reported to be in receipt of an ASD diagnosis over the study period. The blanket ASD description included the labels of classical autism (autistic disorder), Asperger syndrome and Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS). Autistic disorder took the lion's share of diagnoses, with over two-thirds of the cohort in receipt of this label.

"The average age at diagnosis of ASD in children registered with the HCWAP is currently 49 months, with the most frequently reported age being 71 months." There were however some interesting differences noted in terms of age at diagnosis as a function of label under the ASD umbrella. Those diagnosed with autistic disorder showing a pretty clear advantage in mean age at diagnosis (46.5 months) compared with those with Asperger syndrome (mean age: 59.5 months) and PDD-NOS (mean age: 51.1 months). Taken as a whole, the cohort tended to be diagnosed between 25-72 months of age with the peak age for diagnosis falling between 37-48 months of age. Compared with previous prevalence/incidence estimates for ASD in Australia, the data from Bent et al also "suggests that the incidence of ASD in Australia has increased substantially from previous estimates" with 0.74% of under-7 year olds diagnosed with ASD between 2010 and 2012.

These are interesting findings. I've briefly touched upon some of the research behind the epidemiology of autism (autism spectrum disorder) in Australia before on this blog (see here) and how parts of Oz seemed to be lagging behind other estimated population rates of autism [2]. Accepting that there may be various factors affecting the estimates of autism prevalence across different countries and even different regions of countries, the figures from Bent (0.74%) start to become more comparable with the Danish estimates reported some 4 years ago.

The idea that individual diagnoses covered under the umbrella term ASD might also translate into differences in age at diagnosis is also interesting if not new news. I recently covered some of the issues around the diagnosis of autism (see here) and in particular, some of the factors that seem to have some bearing on age at diagnosis (see here). Thinking back to some of my own research in this area [3] I remember detecting some differences in age of symptom onset/diagnosis according to diagnostic grouping albeit not significant in that particular cohort. The larger numbers from Bent and colleagues add to that sentiment and how, outside of sex differences in presentation, the differences between the various labels might affect the diagnostic journey.

"Given that research suggests a reliable and accurate diagnosis is possible for many children with ASD at 24 months... finding[s] represents a possible average delay of 2 years (and common delays of up to 4 years)." Accepting that in amongst the various 'autisms' there may be cases where onset is not normally present before 2 years of age, even potentially confounded by other behaviours/comorbidity, the onus seems to be very much on improved screening and detection of autism and quite a few more resources put into investigating "barriers that delay the diagnosis of ASD." Said barriers might also focus on healthcare providers as well as other factors [4] (see here for my take on this paper).

Music: Portishead - Sour Times.

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[1] Bent CA. et al. Mapping the diagnosis of autism spectrum disorders in children aged under 7 years in Australia, 2010-2012. Med J Aust. 2015 Apr 6;202(6):317-20.

[2] Parner ET. et al. A comparison of autism prevalence trends in Denmark and Western Australia. J Autism Dev Disord. 2011 Dec;41(12):1601-8.

[3] Whiteley P. Developmental, behavioural and somatic factors in pervasive developmental disorders: preliminary analysis. Child Care Health Dev. 2004 Jan;30(1):5-11.

[4] Zuckerman KE. et al. Parental Concerns, Provider Response, and Timeliness of Autism Spectrum Disorder Diagnosis. Journal of Pediatrics. 2015. 14 April.

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Bent CA, Dissanayake C, & Barbaro J (2015). Mapping the diagnosis of autism spectrum disorders in children aged under 7 years in Australia, 2010-2012. The Medical journal of Australia, 202 (6), 317-20 PMID: 25832158

Late, delayed and mis-diagnosis of autism

It's inevitable that with all the mountains of autism research published on a daily basis, certain themes will occur at certain times. My post today is reflective of one of those themes and how, on occasion, the autism diagnostic process does not run as smoothly as we would all like to think.

I start this post with a link to an article discussing some forthcoming research to be published titled: 'The autistic pupils ‘traumatised’ by delayed diagnosis'. Describing the results of a survey of parents included as part of a scheme of work (see here) where experiences of the diagnostic process were gauged, researchers reported that over half of parents were "unhappy with the diagnostic process" for their children. The observation that children were waiting an average of 3.5 years from initial contact with healthcare professionals to final receipt of a diagnosis is a pretty eye-watering statistic too, albeit a step up from previous research in this area [1].

Next up is the paper from Davidovitch and colleagues [2] reporting that: "Subsequent late diagnosis of ASD [autism spectrum disorder] after an initial ASD-negative comprehensive assessment is a common clinical experience." Based on an: "Extensive chart review of patients' electronic medical records" from "a representative population-based registry of patients seen during 2004 to 2011" researchers reported that over 200 children were diagnosed with an ASD after their 6th birthday "although their initial comprehensive developmental evaluations before the age of 6 were negative for ASD." The authors discuss possible reasons for the reversal of diagnosis including "evolving diagnosis as well as missed and overdiagnosed cases of ASD."

Finally, is the paper from Aggarwal & Angus [3] with the conclusion: "ASDs can go undetected during childhood and these clients can sometimes present during adolescence to mental health services for a psychiatric comorbidity." This followed their experiences of a diagnosis of autism being potentially missed or masked during childhood, only to be picked up during adolescence when a referral was made "for a psychiatric comorbidity."

Taken as a collection, these articles/features reiterate that the diagnosis and diagnostic process of autism is often a very complicated thing even before one starts to talk about politics, the availability of resources to undertake such a task and on occasion, actually getting someone to take notice of the need for a referral (see here). I've talked before on this blog about the various factors than can influence the age of autism diagnosis (see here) stressing for example, the fluidity in behavioural expression particularly during the early years (see here) and even into adulthood (see here). Outside of the idea that there may be a number of diverse developmental trajectories when it comes to autism (see here) impacting on presentation, including the idea of regression potentially being present for some (see here), even the most seasoned autism professionals are not error-free when it comes to something like autism screening and diagnosis (see here).

Insofar as the Aggarwal/Angus results, and the idea that the label of autism may only come to diagnostic attention when other psychiatric comorbidity lead, this is something discussed previously on this blog (see here and see here). The overlap between the autism and for example, the schizophrenia spectrums (see here) is an area crying out for further research attention and how intersecting with the idea of ESSENCE in autism (lots of different labels/symptoms potentially following a diagnosis of autism), symptom masking can be a real issues (see here). That also goes for the potential appearance of autism in other conditions such as Down's syndrome for example (see here).

With the growing tide of research suggesting that early (sometimes very early) intervention may be able to make a real impact on the course of autism for some (see here and see here), late, delayed or even mis-diagnosis should be viewed not only as a source of significant stress for those on the autism spectrum and their loved ones, but also as an area of vital importance to autism research on the ways and means of minimising such issues.

[Update: 25 March 2015: The paper from Crane and colleagues [4] has been published. The full-text is available here.]

Music then. I've probably linked to this before but here is Blondie and One Way Or Another.

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[1] Howlin P. & Asgharian A. The diagnosis of autism and Asperger syndrome: findings from a survey of 770 families. Dev Med Child Neurol. 1999 Dec;41(12):834-9.

[2] Davidovitch M. et al. Late Diagnosis of Autism Spectrum Disorder After Initial Negative Assessment by a Multidisciplinary Team. J Dev Behav Pediatr. 2015 Feb 2.

[3] Aggarwal S. & Angus B. Misdiagnosis versus missed diagnosis: diagnosing autism spectrum disorder in adolescents. Australas Psychiatry. 2015 Feb 4. pii: 1039856214568214.

[4] Crane L. et al. Experiences of autism diagnosis: A survey of over 1000 parents in the United Kingdom. Autism. 2015. March 25.

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Davidovitch M, Levit-Binnun N, Golan D, & Manning-Courtney P (2015). Late Diagnosis of Autism Spectrum Disorder After Initial Negative Assessment by a Multidisciplinary Team. Journal of developmental and behavioral pediatrics : JDBP PMID: 25651066



Aggarwal S, & Angus B (2015). Misdiagnosis versus missed diagnosis: diagnosing autism spectrum disorder in adolescents. Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists PMID: 25653302