Psychiatric symptoms in minimally verbal kids with autism: filling a gap

The findings reported by Daniela Plesa Skwerer and colleagues [1] (open-access available here) provide the blogging fodder today. They include some important information on an under-studied group on the autism spectrum (see here) with regards to the "overall burden of psychiatric comorbidities and emotion dysregulation" in those diagnosed with an autism spectrum disorder (ASD) "who had limited verbal abilities (i.e., few to no words used spontaneously)." Such work follows the recent publication of a paper by Ginny Russell and colleagues [2] who observed that those diagnosed with autism + intellectual (learning) disability were not exactly well-represented in the peer-reviewed autism research arena.

The Plesa Skwerer paper started with the observation that various psychiatric symptoms and conditions seem to be over-represented when it comes to a diagnosis of autism (see here for example). They noted that much of the research on this topic tended look at those who could be considered to be at the 'more able end' of the autism spectrum based on skills like self-report ability. They noted that "the population most severely affected, the ~30% of individuals with ASD who remain non- or minimally verbal beyond school-age" are not particularly well-represented in such comorbidity studies. The specific words they use are the "neglected “severe end of the spectrum”."

So: "Sixty-five participants diagnosed with ASD who had limited verbal abilities" were invited to participate in their study. They were already part of a larger research initiative. When I say 'invited' what I really meant is that: "Informed consent was obtained from the parents." All were diagnosed with an autism spectrum disorder (ASD) and the group was fairly equally split between children (5-11 years old) and young adults (12-18 years old). Parents/caregivers had a big role to play in the Plesa Skwerer study as we told that they were asked to complete various questionnaires about their children, including the Child and Adolescent Symptom Inventory (CASI-5) to "examine the frequency and severity of comorbid psychiatric symptoms." Completing the CASI-5 is no mean feat as per it having "173 items, which rate behaviors as occurring never, sometimes, often and very often."

Results: "All participants met cutoff criteria for at least one CASI-5 classification, and the number of categorical classifications parents endorsed ranged from 1 to 15, with a mode and a median of 6 classifications." This is an important detail. It tells us that, based on proxy reporting, every participant, child or young adult, presented with potentially clinically significant symptoms for one or more psychiatric/behavioural disorder. Some of the most popular labels that featured were things like vocal tics, phobia and the various types of attention-deficit hyperactivity disorder (ADHD). Further: "except oppositional defiant disorder and conduct disorder, more participants showed clinically concerning severity scores than expected based on general population norms." Authors concluded that: "The overall picture to emerge from this study is that minimally verbal children and adolescents present with extremely heterogeneous profiles of co-morbid psychopathology that are not easily predicted by autism symptom severity, intellectual disability, or limitations in communication."

There are some important caveats to the Plesa Skwerer findings, not least that proxy-reporting was the method used to ascertain the presence of not of such psychiatric comorbidity. This point tells us that a lot more needs to be done to help those who are minimally-verbal to be able to communicate much more readily. Yes, it's a tall order but where there's a will, there's a way. Also, researchers admit that they "excluded those with the most severe behavior problems including aggression, self-injury or non-compliance, and therefore our findings must be viewed in the context of whom our participants represent." Personally I see this is being a pretty issue across quite a lot of research on autism. Indeed, in light of legal rulings here in the UK (see here) talking about aggression 'not being a choice for children with autism' I daresay that by excluding those who present with such issues means that many, many children and adults on the autism spectrum are under-represented in autism research as it stands.

Still, the important message from Plesa Skwerer et al stands: those with autism who are described (defined?) as minimally-verbal seem to show a similar profile of psychiatric comorbidity and a "high degree of maladaptive behavior" as that identified in other parts/regions of the autism spectrum. Screening is implied and, so as to ensure that health inequalities are minimised, access to intervention is also indicated.

Bravo to the researchers who look at the under-studied parts of the autism spectrum.

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[1] Plesa Skwerer D. et al. Prevalence and Correlates of Psychiatric Symptoms in Minimally Verbal Children and Adolescents With ASD. Front Psychiatry. 2019 Feb 18;10:43.

[2] Russell G. et al. Selection bias on intellectual ability in autism research: a cross-sectional review and meta-analysis. Molecular Autism. 2019; 10: 9.

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Carnitine supplementation and autism: "side-effects and behavioral outcomes"

'Favourable outcomes' is a term mentioned in amongst the various findings reported by Robin Goin-Kochel and colleagues [1] following their examination of "dose compliance, attrition, and potential side effects of short-term, high-dose carnitine supplementation" in a small group of boys diagnosed with an autism spectrum disorder (ASD). Understanding that the Goin-Kochel study was primarily directed at looking at safety, on the basis of 'high-dose' carnitine supplementation, it appears that an elevation of plasma carnitine and related metabolites was not the only effect noted in their small cohort (N=10).

Tracking back slightly, carnitine is an important compound. Not quite an amino acid, carnitine plays an important role in energy production; as per use of the word 'mitochondria' and it's transporting duties of long-chain fatty acids to the cell powerhouse for energy conversion. You probably won't be surprised to hear that carnitine has a *connection* to some autism (see here and see here). Indeed, Goin-Kochel et al mention the findings reported by Patrician Celestino-Soper and colleagues [2] and their identification of a genetic issue that impacts on 'carnitine biosynthesis' in some people diagnosed with ASD. At least one of the authors on the Goin-Kochel paper has some pretty important knowledge about that finding of trimethyllysine hydroxylase epsilon (TMLHE) gene issues in the context of autism...

Alongside looking for reports of any side-effects from the use of carnitine - "oral suspension or tablets of levocarnitine in 3 divided doses, starting at 200 mg/kg/day and increasing to 400 mg/kg/day, with a maximum daily dose of 6 g" - various behavioural schedules were included in the study protocol. Some were objective measures of autism symptomatology; others were parent-report measures. The use of the Clinical Global Impression Scale (CGIS) also provided a helpful 'clinicians' overview' of before and after supplementation in this open-trial.

Results: a few side-effects coinciding with carnitine use were reported. These included: "heavy odor (4 parents), diarrhea (4 parents), and sporadic vomiting (1 parent)." Such reported side-effects meant that three children remained at the lower dose of carnitine over the experimental period (8 weeks).

Alongside, a few other 'favourable outcomes' were also reported: "calmer behavior (2 parents), more energy (2 parents), increased prosocial behaviors (4 parents), greater awareness (2 parents), better eye contact (2 parents), and improved language skills (2 parents)." These parental reports were accompanied by some 'changes' noted on the various schedules included in the study protocol, including those CGIS ratings. The authors used the study results produced by Geier and colleagues [3] as their comparator; highlighting how both studies had picked up "improvements in overall ASD symptoms... and some language ratings." Importantly too, Goin-Kochel et al talk about how none of their cohort were rated as "worse at post treatment."

Where next? More research please. Bigger participant numbers, more methodologically sound study designs and perhaps also, investigation of the potential pros-and-cons of carnitine supplementation over a longer period of time. By all means keep an eye on those side-effects and perhaps look to the biochemistry as to why such side-effects might appear; indeed look to the biochemistry for potential best-responders to this type of intervention too ("One child had documented TMLHE deficiency and 3 had low carnitine levels" in the Goin-Kochel cohort). But more study is definitely indicated...

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[1] Goin-Kochel RP. et al. Side Effects and Behavioral Outcomes Following High-Dose Carnitine Supplementation Among Young Males With Autism Spectrum Disorder: A Pilot Study. Global Pediatric Health. 2019; 6: 1-8.

[2] Celestino-Soper PB. et al. A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism. Proc Natl Acad Sci U S A. 2012 May 22;109(21):7974-81.

[3] Geier DA. et al. A prospective double-blind, randomized clinical trial of levocarnitine to treat autism spectrum disorders. Med Sci Monit. 2011 Jun;17(6):PI15-23.

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"An estimated 7.7 million children in the United States (16.5 percent) have at least one mental health disorder"

The press release carrying the quote titling this post - "An estimated 7.7 million children in the United States (16.5 percent) have at least one mental health disorder" - concerns the findings reported by Daniel Whitney & Mark Peterson [1]. Their research letter discussed findings (from the United States) "providing recent national and state-level estimates of the prevalence of treatable mental health disorders and mental health care use in children."

Based on data derived from the 2016 National Survey of Children’s Health (NCSH), a "nationally representative, parent-proxy survey of US children younger than 18 years" that has been mentioned more than once on this blog (see here and see here), researchers present some important data. Including information from over 46 million children (now that's what I call a decent sample size) various trends were observed, notably that almost one in seven children and young adults were reported to have a mental health condition. Such conditions covered "depression, anxiety problems, or attention-deficit/hyperactivity disorder" and by present, I mean that parents responded in the positive to the question: "Has a doctor or other health care provider EVER told you that this child has” a mental health disorder?"

Another detail was also mentioned in the Whitney & Peterson paper: "half of the estimated 7.7 million US children with a treatable mental health disorder did not receive needed treatment from a mental health professional." This was based on responses to the question: "DURING THE PAST 12 MONTHS, has this child received any treatment or counseling from a mental health professional? Mental health professionals include psychiatrists, psychologists, psychiatric nurses, and clinical social workers." Other media on the Whitney / Peterson paper have picked up on this trend (see here) and the possible whys-and-wherefores.

The primary weakness of the NCSH - "parent-proxy survey" - is more than compensated for by the huge participant numbers included for study. The figures arrived at also follow a trend seemingly present across many nations (see here and see here and see here) suggesting that significant numbers of young people are experiencing mental health disorder. We can quibble about the reasons for the increase but there is no mistaking the fact that something is going on. And it's seemingly affecting millions of children and young people around the world...

And as if to prove the point further [2] the startling findings from Gräf et al: "School performance was available for 1462 children (51% boys, mean age 7.3 years). Of these, 41% had signs of at least one MHP [mental health problem]."

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[1] Whitney DG. & Peterson MD. US National and State-Level Prevalence of Mental Health Disorders and Disparities of Mental Health Care Use in Children. JAMA Pediatrics. 2019. Feb 11.

[2] Gräf C. et al. Mental health problems and school performance in first graders: results of the prospective cohort study ikidS. European Child & Adolescent Psychiatry. 2019. Feb 26.

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"Fatigue, fluctuation and payback were described by all adolescents with CFS/ME in this study"

The quote titling this post - "Fatigue, fluctuation and payback were described by all adolescents with CFS/ME in this study" - comes from the findings reported by Roxanne Parslow and colleagues [1] during their study designed "to explore outcomes important in paediatric chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) and what improvements in fatigue and disability are key."

Indeed, this latest study seems to follow a theme of looking at the personal experiences of CFS/ME [2] by members of this authorship team, potentially onward to the development of a PROM (Patient Reported Outcome Measure) [3] specifically with children and adolescents in mind. If this was a goal, I wondered if perhaps this *could* also be linked to some other work from some of the Parslow paper authors that has also been previously discussed on this blog too (see here)?

I specifically wanted to talk about this paper because of the word 'payback' and it's particular use to mean an "increase in fatigue and symptoms following activity." Mentioning it only twice in their article (one of those occasions being the use of a reference), I think the authors mean post-exertional malaise (PEM) (see here and see here for more discussion of this concept). They however, seemed a little reluctant to use that term. In answering one of the reviewers of their paper prior to acceptance for publication, the authors did say: "Payback is defined as a core symptom in NHS guidance, and is used in the clinical setting." They also clarified how "the term ‘payback’ was used instead of exhaustion."

No mind, based on interviews with "21 adolescents and their parents (20 mothers and 2 fathers)", most adolescents being female with a mean age of around 14 years, several key themes emerged. To reiterate: "All adolescents with CFS/ME report fatigue, a natural fluctuation of the condition, as well as an increase in fatigue and symptoms after activity (payback)." Several sub-themes also emerged from such reporting including how: "Adolescents and parents reflected on how CFS/ME naturally fluctuates" and "Adolescents and parents recognised patterns of good and bad days" and "Adolescents were limited in the amount of time they could spend on activities, which ranged from minutes, ‘5 min’ to hours, ‘an hour at the most’." These aren't exactly novel findings by any means but it's always useful to see them described in the peer-reviewed research domain.

Heading back to that 'payback' issue, researchers mention how their results are "consistent with previous research where children described the intensity of symptoms fluctuating as well as ‘overextension’ making it worse, resulting in ‘paying the price’." Accepting that such payback or PEM or 'payback exhaustion resulting in fatigue and other symptoms following activity' if you prefer, is widely present in CFS/ME (albeit individual and 'variable' in nature), one might see the Parslow results perhaps as further justification for being slightly critical of the use of something like graded exercise therapy (GET) in relation to CFS/ME (see here). GET relies on the assumption that increasing or grading in physical activity will eventually 'help' facets of CFS/ME. Unfortunately, whilst still expounded in some circles, there is accumulating (peer-reviewed) evidence that many patients with CFS/ME experience GET as more of a hindrance rather than a help for their symptoms (see here). Indeed, allied to terms like 'deconditioning' as part of suite of 'psychobabble' that seems to have enveloped CFS/ME down the years, the idea that CFS/ME is something that can be just 'exercised out of' seems to have been a truly damaging policy that has not seemingly served many patients particularly well.

The Parslow findings are revealing and add something further to the idea that an overhaul of current thinking on CFS/ME in children and adults is perhaps required (see here). Obviously the results are small-scale and require some follow-up, but listening to patients and their parents/caregivers and their collected experiences is a good idea in my book; particularly when it comes to a group of conditions like CFS/ME that have seen more than their fair share of 'assumptions' down the years.

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[1] Parslow RM. et al. Adolescent’s descriptions of fatigue, fluctuation and payback in chronic fatigue syndrome/myalgic encephalopathy (CFS/ME): interviews with adolescents and parents. BMJ Paediatr Open. 2018;2(1):e000281.

[2] Parslow RM. et al. Children's experiences of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a systematic review and meta-ethnography of qualitative studies. BMJ Open. 2017 Jan 13;7(1):e012633.

[3] Parslow RM. et al. Important factors to consider when treating children with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): perspectives of health professionals from specialist services. BMC Pediatr. 2017 Feb 1;17(1):43.

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"hold promise as cross-cultural key indicators for autism"

The quote heading this post - "hold promise as cross-cultural key indicators for autism" - comes from the paper by Sophie Carruthers and colleagues [1] which "aimed to identify the items on the Autism Spectrum Quotient (AQ)-Child that are most predictive of an autism diagnosis among children aged 4–9 years across samples from India, Japan and the UK." Attempting to fill quite an important 'hole' in the use of the go-to 'are you autistic' screener, authors set out to look at the presentation of autistic traits across three different countries, all with some quite different cultural perspectives and contexts.

The Carruthers paper is open-access so doesn't need too many grand discussions from me. The basics: "parent-reported AQ-Child data from India (73 children with an autism diagnosis and 81 neurotypical children), Japan (116 children with autism and 190 neurotypical children) and the UK (488 children with autism and 532 neurotypical children)" was the source material. Once again I'll mention how the term neurotypical is a misnomer (see here); it's use in this paper is all the more surprising given that one of the authors wrote an editorial paper [2] mentioning how "there is no single way for a brain to be normal, as there are many ways for the brain to be wired up and reach adulthood." Oh well.

Results: from the collected data, researchers were able to undertake various statistical analyses. Pertinent to the quote titling this post were some important findings "identified to be universal key indicators" across the different countries and cultures. These were: "In a social group, s/he can easily keep track of several different people’s conversations; s/he enjoys social chit-chat; s/he knows how to tell if someone listening to him/her is getting bored; s/he is good at social chit-chat and s/he finds it difficult to work out people’s intentions." Alongside, various other indicators were rated as "performed excellently or acceptably" across the three different country groups.

The conclusion: "Cross-cultural overlap in the items most predictive of an autism diagnosis supports the general notion of universality in autistic traits whilst also highlighting that there can be cultural differences associated with certain autistic traits." I'd like to see more research done in this area. Quite a few years ago I posed the question 'Is autism the same all over the world?' (see here) and well, I don't have a good answer despite the Carruthers and other results. Obviously such a question needs also to be wrapped in the idea that the plural 'autisms' also exert an effect (see here) and take into account other factors such as comorbidity (if that is the right word). It should also perhaps appreciate that whilst the AQ is undoubtedly 'picking up' something, it might not just exclusively be autism or autistic traits (see here and see here)...

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[1] Carruthers S. et al. A cross-cultural study of autistic traits across India, Japan and the UK. Molecular Autism 2018; 9:52.

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The positives of ADHD?

I tread carefully with my discussions of the paper by Jane Ann Sedgwick and colleagues [1] talking about "insights into positive human qualities, attributes or aspects of ADHD [attention-deficit hyperactivity disorder] that can support and sustain high functioning and flourishing in ADHD life." Carefully because, just like discussions over another label closely associated with this blog, there are a myriad of different views and opinions about the way neurodevelopmental disorders / conditions / labels are presented and viewed by those who have been diagnosed with them. Who am I to tell someone what they should or shouldn't be thinking?

Sedgwick et al started from the idea that although 'disorder' is a defining part of ADHD, the subsequent focus on 'deficit' does not perhaps do justice to all that is included under the diagnostic term. They reference 'positive psychology' and its moves "away from a deficit-focused view of mental health, towards approaches that were more enabling, strength-based and emphasised positive aspects of human functioning and flourishing (i.e. positive emotions, engagement, relationships, meaning and accomplishment)." They then move to the aim of their study: "to explore ability and disability in ADHD from the participants own perspective using the WHO International Classification of Functioning, Disability and Health (ICF) framework." Mention of the WHO ICF framework also brings me back to similar discussions with autism in mind (see here).

"We recruited six successful (i.e. HF[high-functioning]-ADHD and flourishing) adult males aged between 30 and 65 years from an NHS tertiary service in London." Said participants were interviewed with questions such as: "(1) What do you think are the advantages and disadvantages of having ADHD? (2) Please describe a time when you felt that your ADHD helped to achieve something? (3) What aspects of your ADHD would you miss if it went away?" Following some content analysis of results, certain themes emerged.

"The main findings of this study are characterised by six core themes (cognitive dynamism, courage, energy, humanity, resilience and transcendence)." Alongside, a number of sub-themes were also reported including "divergent thinking, hyper-focus, nonconformist, adventurousness, self-acceptance and sublimation." Researchers concluded that because these themes and sub-themes were not listed as "sanities in positive psychology" (i.e. "relevant to people in general, with or without ADHD") they *might* be specifically linked to ADHD.

OK, a few steps back. You'll no doubt recognise that this was research based on interviewing six men with ADHD (and 'flourishing' with their ADHD at that). It's not difficult to see how the issue of 'representativeness' might be a particular problem with the Sedgwick results. If for example, they had presented data from their six participants compared with another six who perhaps weren't described as 'flourishing' (see here for one possible example), I'd be a lot more confident in their findings. Better than that would have also been the views of a few other participants representing other labels where ADHD is part-and-parcel of a more complicated clinical picture (see here and see here for examples). And don't forget their focus on one gender/sex too...

I can see how something like 'cognitive dynamism' conceptualising "ceaseless mental activity" could be seen as a double-edged sword when it comes to ADHD. Yes, it can be utterly disabling for some (many) in terms of being "scattered, chaotic and a bit random." But in some scenarios and with the right environment and encouragement, such an issue could be a lot more positive a trait to have. Likewise the concept of 'energy' whilst quite synonymous with ADHD, probably also has an upside as well as a downside, particularly when harnessed to the benefit of the person concerned and their strengths.

But... I have some difficulty with the ideas that courage, humanity and resilience for example, are somehow to be viewed as 'the positive side of ADHD'. There are plenty of people out there who demonstrate such strengths without a diagnosis of ADHD or indeed, a diagnosis of anything. The fact that Freud and Nietzsche are also referenced in relation to some of those terms suggests to me that the authors have perhaps moved slightly outside of the evidence-based arena in some of their interpretations of their findings. Similarly, the use of the term 'divergent thinking' isn't exactly what I would call science-based either, as my 'neurotypical' brow starts to furrow (see here).

I appreciate what the authors have tried to do with this paper: reaching out "to people with lived experience of ADHD: service users, patients, family members, carers, partners, to say that not all symptoms of ADHD are maleficent." It's admirable that such thinking is there, particularly when a diagnosis of ADHD can seem such a daunting prospect both in the short- and long-term (see here). I'm slightly concerned however that this paper seems to be insinuating that a clinical diagnosis of something like ADHD should be used as a framework to 'psychologise' someones life. The inference being that because ADHD undoubtedly affects many aspects of a person's life, it is something that defines them and all their behaviour(s) and attitude(s) on many aspects of life. I've seen it before in other labels too as diagnosis morphs into identity.

Personally, I don't think anyone should be defined by their clinical or related label in the same way that sex/gender, skin colour, religion or politics shouldn't define a person. It's OK to say yep, I have ADHD and it affects my life in this way or that way, and this is what I need to help overcome such issues. But I'm not convinced that adopting an 'ADHD identity' and seeing all the positives and negatives of life as part of that diagnostic identity is particularly good for anyone. A person is defined by their actions not their [diagnostic] label...

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[1] Sedgwick JA. et al. The positive aspects of attention deficit hyperactivity disorder: a qualitative investigation of successful adults with ADHD. ADHD Attention Deficit and Hyperactivity Disorders. 2018. Oct 29.

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1 in 40 children with parent-reported autism in the US

Consider this post an extension of another entry published some years ago (see here) talking about the parent-reported (estimated) autism prevalence rate in the United States.

On that last blogging occasion, the paper by Stephen Blumberg and colleagues [1] was the discussion piece, and the observation that: "Based on parent reports, the prevalence of diagnosed ASD [autism spectrum disorder] in 2011–2012 was estimated to be 2.00%" or 1 in 50. That finding was based on the examination of "the 2007 and 2011–2012 National Survey of Children’s Health (NSCH), which are independent nationally representative telephone surveys of households with children."

Enter then a more recent publication from Michael Kogan and colleagues [2] who, also using data from the NSCH, this time the 2016 NSCH, extrapolated that: "Parents of an estimated 1.5 million US children aged 3 to 17 years (2.50%) reported that their child had ever received an ASD diagnosis and currently had the condition." Their calculated estimate increased from 1 in 50 children in 2011-2012 with parent-reported autism in the United States to 1 in 40 children in 2016...

Based on an Internet survey (see here), where over 50,000 responses "focused on the health and well-being of children aged 0 to 17 years" were received, researchers examined data from well over 40,000 children aged 3-17 years old. Analysing the findings from the NSCH sample with regards to affirmative answers to questions on "whether children ever received an ASD diagnosis by a care provider, current ASD status, health care use, access and challenges, and methods of treatment", they concluded that around 1 in 40 children had parent-reported autism in their cohort.

What's more to say? Well, there's always going to be the old 'they've relied on parent report' issue to contend with, despite the fact that most parents aren't 'making it up' when they talk about autism being present in their children. Indeed, the lead author of the study, Michael Kogan, when talking to the lay media about his results (see here) put it better than I ever could: "We know that in terms of having a major condition like autism, parents are usually pretty good reporters compared to medical records." Indeed.

Then, despite arguments such as "changes in the survey make it difficult to compare the findings to data from previous years" [3] and increasingly worn out soundbites like better awareness, expanded diagnostic criteria and diagnostic substitution (see here) as potentially accounting for the increase in prevalence (estimates), I do think it's about time that we started to have some real-world conversations about the figures being presented and what could be behind them. And yes, this probably means mentioning the words 'real increase' at some point (see here) and not being ashamed to say so. Bearing in mind that this is seemingly an increase that is going on around many parts of the world (see here) and seems to be driven by new diagnoses in younger cohorts and not for example, the diagnosis of 'missed adults' (see here), science and clinical practice really needs to get to the bottom of this. Not least because resources and money need to be put in place to ensure that the growing numbers of people being diagnosed are provided with the care and support they need and require over a lifetime.

I've watched a lot of 'burying heads in the sand' around the autism prevalence figures over the past few decades (see here) similar to what's been seen with various other developmental and behavioural labels (see here and see here). It's perhaps time to wake up, pull heads out of the sand and start organising more research about what is potentially driving the ever increasing autism prevalence figures...

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[1] Blumberg SJ. et al. Changes in Prevalence of Parent-reported Autism Spectrum Disorder in School-aged U.S. Children: 2007 to 2011–2012. National Health Statistics Report. 2013; 65: March 20.

[2] Kogan MD. et al. The Prevalence of Parent-Reported Autism Spectrum Disorder Among US Children. Pediatrics. 2018. Nov 26.

[3] AAP News. Study: 1 in 40 children diagnosed with autism. 2018. Nov 26.

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"a Brief Parent-Report Screen for Common Gastrointestinal Disorders in Autism"

I wanted to bring the findings reported by Kara Margolis and colleagues [1] to your attention today. Their observations pertinent to the "development of a brief, parent-report screen that relies minimally upon the child’s ability to report or localize pain for identifying children with ASD [autism spectrum disorder] at risk for one of three common gastrointestinal disorders (functional constipation, functional diarrhea, and gastroesophageal reflux disease)" represent something that 'fills a gap' in autism research and practice. Their authorship group including some of the great and the good looking gastrointestinal (GI) issues being over-represented in autism (see here and see here) was also an attraction to blogging about these results.

So, GI or gut problems are no stranger to autism. I don't think anyone (anymore) would seriously question such a finding given the multitude of times it has been recorded in the peer-reviewed science domain and beyond. Indeed, it's now even becoming more readily accepted that outside of functional bowel issues such as constipation and diarrhoea being over-represented in autism (see here), so other more pathological bowel states are also present for some too (see here and see here). And be in no doubt that such issues can be truly life-altering in their effects (see here and see here)...

It should also be acknowledged that when it came to starting the conversation about bowel issues and autism, it was parents and caregivers that led the way with their very astute observations of their nearest and dearest. Yes, there have always been 'professionals' who've shown an interest (and concern) in such observations, but parents and caregivers were there first. And despite many parents not (initially) being 'gastrointestinal experts', their observations, in the most part, were/are typically considered pretty accurate ones (see here).

So, Margolis et al talk about how the development of a screening instrument is the next logical step to ensure that parent reports of their children with autism potentially presenting with bowel issues are accurately recorded, onward to eventually leading to more specialised screening, evaluation and hopefully, appropriate intervention. Over 130 parents of children diagnosed with autism registered with the Autism Treatment Network (ATN) initiative agreed to take part in the study. Initially, parents were given a 35-item questionnaire looking at 3 particular functional bowel issues: "functional constipation, functional diarrhea, and gastroesophageal reflux disease" and asked to respond on behalf of their children. Gastroenterologists were also asked to evaluate the children; said professional were blinded to the parental responses to the questionnaire. When looking at these combined data sources, researchers were able to whittle down the 35-item questionnaire to 17 questions that seemed most important to the lay identification of potential bowel issues. Some further nifty statistics led authors to conclude that: "this 17-item screen identified children having one or more of these disorders with a sensitivity of 84%, specificity of 43%, and a positive predictive value of 67%." Ergo, the authors have 'the makings of' a potentially important parent/caregiver-based questionnaire to assess for the possible presence of bowel issues in autism. The makings of...

Obviously more work is required in this area. This instrument is labelled a 'screen' for such bowel issues so there is still the requirement for professional involvement when it comes to diagnosis and intervention. But one should never forget the very important perspective that parents/caregivers can have with regards to the presence of bowel issues in their children...

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[1] Margolis KG. et al. Development of a Brief Parent-Report Screen for Common Gastrointestinal Disorders in Autism Spectrum Disorder. J Autism Dev Disord. 2018. Oct 22.

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Relative age and ADHD: more data and a meta-analysis

So, relative age and ADHD. The observation that in amongst the various pathways that might lead someone to a diagnosis of attention-deficit hyperactivity disorder (ADHD), "the youngest children within a school class are at a disadvantage in many aspects compared with their older classmates" including increasing "the probability of having ADHD-related symptoms... or other psychopathology..., of receiving a diagnosis of ADHD... or being treated with stimulant medications."

I've talked about this issue a few times on this blog (see here and see here) and am blogging today about a couple of other studies that add to the literature in this area. The first investigation was undertaken by Janine Wendt and colleagues [1] and concluded that: "Using a prospective study design and comprehensive adjustment for confounding and baseline symptoms, we confirmed prior evidence of the association between young ASE [age at school entry] and teacher-reported ADHD symptoms in primary school." The second study was published by Josephine Holland & Kapil Sayal [2] who, following a systematic review of the peer-reviewed science literature on this topic, concluded that "the majority of studies show evidence of a relative age effect influencing both the diagnosis of and receipt of medication for ADHD."

Both studies are open-access so really don't require too much explanation from me. The Wendt study relied on data collected from over 120 "Rudolf Steiner Schools (Waldorf Schools) located within Germany" (Waldorf schools are based on the philosophy of producing "free, morally responsible, and integrated individuals equipped with a high degree of social competence") covering over 3000 children. We are told that this prospective study gathered data via parent- and teacher- reports: "ADHD-related symptoms were assessed at school entry and second and fourth grades by parent-reported and teacher-reported versions of the Strengths and Difficulties Questionnaire (Hyperactivity-Inattention Subscale)." Their results found a possible *association* between age and school entry (ASE) and teacher-reported ADHD symptoms using the SDQ: "ASE was negatively associated with ADHD-related symptoms in the second grade... and fourth grade. Associations remained after adjusting for potential confounders and pre-existing symptoms at baseline." Those 'potential confounders' included "gender, time of observation and source of information." I'm also inclined to point out that the prevalence of possible ADHD overall in the Wendt study was pretty high in some scenarios: "The frequency of ADHD indications ranged from 3.7% (girls, second grade, parent reports) to 25.0% (boys, second grade, teacher reports)."

Then to the Holland-Sayal study. This was a systematic review of the existing research literature pertinent to the questions: "Is there an association between younger relative age, defined as being in the second half of the academic year, and: (1) the presence of high levels of ADHD symptoms, (2) receiving a clinical diagnosis of ADHD and (3) receiving medication for ADHD?" Based on an examination of the literature "published from the 1st of January 2000 to the search date of the 7th September 2017" and including 20 papers for review, the answer: yes, generally-speaking, there is more evidence for a relative age effect in relation to ADHD symptoms, diagnosis or receipt of medication for ADHD than against it.

Holland & Sayal do caution that their findings were not totally unambiguous. They discuss how differences across the various studies included for analysis might be important to the final outcome determined. So: "studies differed by sample size, years studied, ages studied and methods of reporting and recording ADHD diagnosis and medication." They also noted that: "The culture of diagnostic practice within a country’s health system may have an influence on the relative age effects found" implying that the willingness to diagnose ADHD in a particular country or region could very well have had an effect on the main findings.

Overall however, these studies add to the existing research-based message observing that age and maturation may be important 'influencers' of reported ADHD symptoms, diagnosis and/or receipt of ADHD medicines.

The big question now is 'what is science and clinical practice going to do about it? bearing in mind that there may be 'redshirting' models to follow [3]...

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[1] Wendt J. et al. Young age at school entry and attention-deficit hyperactivity disorder-related symptoms during primary school: results of a prospective cohort study conducted at German Rudolf Steiner Schools. BMJ Open. 2018;8:e020820.

[2] Holland J. & Sayal K. Relative age and ADHD symptoms, diagnosis and medication: a systematic review. European Child & Adolescent Psychiatry. 2018. Oct 6.

[3] Whitely M. et al. Attention deficit hyperactivity disorder late birthdate effect common in both high and low prescribing international jurisdictions: systematic review. J Child Psychol Psychiatry. 2018 Oct 14.

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The Scotland Census 2011 and autism again: focus on children and young adults

Consider this post an extension of some previous chatter on this blog (see here). That previous chatter was based on the work published by Ewelina Rydzewska and colleagues [1] talking about how (a) Scotland seems to be pretty unique insofar as 'asking about autism' in their population Census, and (b) how examination of such a query, alongside asking a few other questions, represents an important research resource particularly pertinent to the idea that autism rarely appears in some sort of diagnostic vacuum (see here).

Now there's more from Rydzewska and colleagues [2] and their analysis of the Scotland 2011 Census. This time the specific focus was on under 25 year olds (their previous research was dedicated to looking at "the prevalence of comorbid mental health conditions and physical disabilities in a whole country population of adults aged 25+ with and without reported autism").

Researchers report that 1.6% of their population (25,063/1,548,819) were reported to have (or someone on their behalf) ticked the box to the question 'have any of the following conditions' that was labelled 'Developmental disorder (for example, Autistic Spectrum Disorder or Asperger's Syndrome)'. This was quite a bit higher than the 0.2% of adults (over 25 years old) that was previously reported on. They also reported that the traditional 4:1 male:female ratio regarding autism was intact as other recent population (estimated) prevalence studies have also indicated (see here and see here).

Then to the main event: "Autism had an odds ratio of 5.4 (5.1–5.6) for predicting deafness/partial hearing loss, odds ratio of 8.9 (8.1–9.7) for blindness/partial sight loss, odds ratio of 49.7 (38.1–64.9) for intellectual disabilities, odds ratio of 15.7 (13.4–18.5) for mental health conditions, odds ratio of 15.8 (14.1–17.8) for physical disability and odds ratio of 3.9 (3.8–4.0) for other conditions."

It's worthwhile reiterating some of those observations made by Rydzewska et al: the chances (odds ratio) of intellectual or learning disability appearing alongside autism in under 25 year olds was about 50 times more likely than in those not ticking that 'Developmental disorder' option. In terms of specific percentage frequencies, the figures for learning disability in the age groups 0-15 years (children) and 16-24 years (young adults) where autism was mentioned were 13-14% and 18% respectively. This was contrasted against percentages of 0.3% and 0.4% in similar non-autistic age groupings. I'm also minded to include the observation that girls with autism across both age groups seemed to be at some elevated risk of learning disability when compared to boys. The next highest risk values came in for the presence of a mental health condition where again girls with autism seemed to shoulder the highest risk (a divide that seemingly grew as children aged into young adults). The conclusion yet again is that for quite a few people, autism is not a stand-alone condition/label and that such "conditions are disabling and have a significant impact on long-term quality of life; their coexistence with autism adds extra complexity."

On the last blogging occasion when the first research paper from Rydzewska using the Scotland Census 2011 data was discussed, I held back from commenting too much on the adult prevalence figure picked up by authors. This time I'm not going to, because the difference between children/young adults with autism (or a developmental disorder) (1.6%) and autistic adults (0.2%) is too stark not to mention. I appreciate that there may be many variables/factors contributory to such figures, and that such figures are perhaps prone to some degree of error (bearing in mind the legal requirements behind completing a Census), but the disparity between them cannot be just brushed under the scientific carpet. They show that for the year 2011 in Scotland, autism - all forms of autism - was quite significantly over-represented in children and young adults compared with autism in over 25 year old adults. They show that arguments about the prevalence of adult autism potentially being on a par with childhood autism were/are wrong. They show that autism is disproportionately affecting children/young adults and by inference, the trend in autism being diagnosed is an upward one primarily stemming from childhood/young adulthood diagnoses and not from the late diagnosis of adults.

By saying that I'm not ruling out the idea that there may be adults in Scotland in 2011 who had slipped through the diagnostic net with autism in mind. I'm not saying that some 7 years later, things haven't moved on with regards to autism awareness and the like. But I do find it extremely unlikely that there were literally thousands and thousands of 'hidden' people 'undiagnosed' in Scotland in 2011 however much some people have inferred, and continue to infer, that this is true. The peer-reviewed evidence for this phenomenon is just not there, and certainly nowhere near there when it comes to those with 'very visible' autism who for example, require significant day-to-day social and health care support (see here and see here for examples).

I am hoping that when the next Scottish Census (2021) results eventually come in we might see more from this fabulous research opportunity with autism in mind. Even better would be for other countries to follow the Scottish lead in their questioning of their nation and perhaps provide a more accurate picture of the rates of autism across the age groupings.

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[1] Rydzewska E. et al. Prevalence of long-term health conditions in adults with autism: observational study of a whole country population. BMJ Open. 2018 Sep 1;8(8):e023945.

[2] Rydzewska E. et al. Prevalence of sensory impairments, physical and intellectual disabilities, and mental health in children and young people with self/proxy-reported autism: Observational study of a whole country population. Autism. 2018 Oct 17:1362361318791279.

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