Following ADHD long-term: "a persistence rate of 27.8%"

Studies such as the one published by Michel Lecendreux and colleagues [1] always catch my attention. Research that follows a group of people over a period of years makes for interesting reading; not least because one gets a flavour for what *could* happen when such findings are applied to a larger population.

The Lecendreux findings focused on a few important issues pertinent to a diagnosis of attention-deficit hyperactivity disorder (ADHD) specifically related to (a) the persistence of ADHD, and (b) the idea that signs and symptoms of ADHD not meeting the thresholds for a diagnosis of ADHD might be rather important. Indeed, that they may merit "a subthreshold diagnostic category" of their own.

So, based on a starting participant sample of just over a thousand families including a child in the "6-12 years age range", interviews were conducted covering various aspects of ADHD and beyond: "symptoms of ADHD, conduct disorder, and oppositional defiant disorder as well as family living situation, school performance, sleep disturbance, eating habits, use of supplemental iron, and history of ADHD treatment." Approaching half of the original sample (492 / 1012) were followed up some 9 years later where "the persistence of ADHD and its impairments and the emergence of new conditions were assessed."

Results: "At follow-up, 16.7% of the children diagnosed with ADHD at baseline met full criteria for ADHD and 11.1% met criteria for subthreshold ADHD, yielding a persistence rate of 27.8%." Diagnosis of ADHD was, by the way, based on DSM-5 criteria (see here). That figure of 27.8% in terms of ADHD persistence from childhood to early adulthood is potentially an important one. It tells us that for a majority of children diagnosed with ADHD in childhood, their symptoms of inattention, hyperactivity and impulsivity will reduce to such a degree that they are no longer considered clinically significant or at least not reaching thresholds for a diagnosis of ADHD. Whether such a reduction in symptoms is through processes such as maturation or the timely implementation of intervention/management strategies needs quite a bit more work. Whether also ADHD potentially 'morphs' into something else as people age also needs further exploration (see here).

Another important detail was also mentioned by Lecendreux et al: "Among children not diagnosed with ADHD at baseline, 1.1% met criteria for ADHD at follow-up." Such a figure is important in relation to the concept of adult-onset ADHD [2] and the question of whether ADHD is a diagnosis with foundations always rooted in infancy. The Lecendreux findings suggest that for some people, this might not be the case and opens the door to possible talk about acquired ADHD for examples. This also sounds very familiar (see here).

Insofar as the issue of a possible 'subthreshold diagnostic category' for ADHD, I find myself agreeing with the "dimensional conceptualization" mentioned by the authors. Several other conditions / states / diagnoses have recognised 'lite versions' of the label. In autism for example, one might see this as social communication disorder (SCD) or mention of the broader autism phenotype (BAP). I'm even minded to place the label known as pathological demand avoidance (PDA) in a similar bracket given recent opinions (see here). Such chatter about 'lite' does not and should not downplay the effects of such sub-threshold labels. It merely acknowledges that there may be a wider spectrum of issues / difficulties experienced outside of the receipt of a core diagnosis.

So it should perhaps be the same with ADHD too, given what is beginning to emerge on the long-term 'effects' that a diagnosis of ADHD and subthreshold ADHD might bring (see here and see here).

----------

[1] Lecendreux M. et al. A 9-Year Follow-Up of Attention-Deficit/Hyperactivity Disorder in a Population Sample. J Clin Psychiatry. 2019 May 7;80(3). pii: 18m12642.

[2] Cooper M. et al. Investigating late-onset ADHD: a population cohort investigation. J Child Psychol Psychiatry. 2018 Oct;59(10):1105-1113.

----------

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."

----------

[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.

----------