Baclofen is back: "Baclofen as an adjuvant therapy for autism"

"Our data support [the] safety and efficacy of baclofen as an adjuvant to risperidone for improvement of hyperactivity symptoms in children with ASD [autism spectrum disorder]."

So said the findings reported by Seyedeh-Mahsa Mahdavinasab and colleagues [1] talking about the use of baclofen as an add-on medicine in the context of risperidone use in relation to autism. Baclofen by the way, is typically known as "a gamma-aminobutyric acid (GABA) agonist" (binds to the GABA receptors and activates them) which accounts for its use as "a skeletal muscle relaxant" given the inhibitory function of GABA and GABA receptors.

Why the 'baclofen is back' sentiment expressed in the title of this post? Well, a few years back there was some excitement about a compound called STX209 otherwise known as arbaclofen in the context of a genetic condition manifesting autistic signs and symptoms (see here) and autism itself. Arbaclofen is an enantiomer (mirror image in a chemical sense) of baclofen, but unfortunately fell by the wayside after some less than impressive results emerged from clinical trials (see here). Arbaclofen might have been kicked into the long grass for now but baclofen it seems, is still on the autism research agenda...

Researchers report results based on a "10-week randomized-controlled study aimed at evaluating the potential of baclofen as an adjuvant therapy to enhance the effect of risperidone in children with ASD." Risperidone is an antipsychotic which is indicated for selective use with children with autism (see here) specifically to treat/manage aggressive and challenging behaviours. They reported that several outcome measures saw a change - a positive change - specifically in relation to hyperactivity behaviours which can often accompany aggression. Importantly, they also noted that during and after 10 weeks of add-on baclofen use, adverse events were reported to be at a minimum.

There is more to do in this area before any sweeping generalisations are made. I personally would like to see more data on potential best- and non-responders in the context that GABA is still a topic of interest to autism research (see here). I know also that some people might be a little put-out by the idea that more medication is added to the lives of young children with autism and worries about how this might impact them in later years. We need a lot more data.

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[1] Mahdavinasab SM. et al. Baclofen as an adjuvant therapy for autism: a randomized, double-blind, placebo-controlled trial. Eur Child Adolesc Psychiatry. 2019 Apr 12.

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Managing ADHD: pharmacotherapy use and quality of life

"The QoL [quality of life] of the children with ADHD [attention-deficit hyperactivity disorder] and the subjective well-being of the parents improved significantly after introducing pharmacotherapy."

That was the research 'bottom line' described by Hanife Temizsoy and colleagues [1] following the publication of their study results designed to "investigate the changes of QoL of children with ADHD and their parents' subjective well-being before and after starting pharmacotherapy." Pharmacotherapy is the fancy word for medication; and the Temizsoy findings add to quite a large bank of peer-reviewed research suggesting that some medicines 'for ADHD' have a pretty good benefit-risk profile (see here). Indeed, the use of indicated medicines for ADHD seems to have some good potential for decreasing various future risks that seem to follow a diagnosis of ADHD (see here and see here).

"We assessed the QoL and the parental well-being in 60 children and adolescents with ADHD between the ages of 6 and 12 years." Various questionnaires were utilised, including the KINDL designed to assess "Health-Related Quality of Life in children and adolescents aged 3 years and older" and "the World Health Organization (WHO) Big Five Questionnaire", a short questionnaire on (current) well being. The results obtained were encouraging.

Bearing in mind that the Temizsoy was a straightforward 'before and after' study lacking important methodological features such as blinding and objective measures from physicians or other objective viewers for example, the results are important. I'm also minded to add that whilst certain medicines indicated for ADHD do seem to have quite a good track record for improving features of the condition, they are not without potential side-effects as per just about every other medicine in existence.

But... if children with ADHD and their parents/carers are reporting that their quality of life is getting better with medication compared to times without medication, surely this counts for something. With regular monitoring, good medicines management and possibly alongside the use of other potential intervention options (see here and see here for examples), ADHD for many people, is a condition that can be managed and managed well.

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[1] Temizsoy H. et al. Influence of Psychopharmacotherapy on the Quality of Life of Children with Attention-Deficit/Hyperactivity Disorder. J Child Adolesc Psychopharmacol. 2019 Mar 29.

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(Subclinical) mania symptoms in kids with autism

Although published a few years ago, PubMed recently brought the paper by Yu Okada and colleagues [1] to my attention and the finding that: "school-aged ASD [autism spectrum disorder] children frequently present subclinical BP [bipolar disorder] symptoms."

As per the authors' idea that "there has been increasing interest in bipolar disorder (BP) in children" and specifically that bipolar disorder might be important to at least some autism (see here and see here), a study idea emerged. That idea merged into a hypothesis: "to identify [the] reliable prevalence of BP and to evaluate a variety of subclinical BP symptoms in children with ASD."

Okada report case-control study results based on "110 referred children aged 6-15 years: 46 with ASD (the case group), 64 without ASD (the control group)" who were first time outpatients at a clinic in Osaka in Japan. As well as the use of a quite comprehensive "diagnostic approach for ASD", researchers also measured various types of cognitive functioning, also looking for the possible presence of the signs and symptoms of a diagnosis of bipolar disorder (via something called the K-SADS-PL-J). Results were collated.

"None of the children were diagnosed with BP in the case [autism] group, although two children were diagnosed with BP in the control group." Various other diagnoses were also recorded in the control (not-autism) group including anxiety disorder (n=28) and depressive disorder (n=16). When however researchers looked at subclinical mania symptoms - "elation/expansive mood, increased goal-directed activity, racing thoughts" - there was something to see for the autism group: "Based on the subclinical BP symptoms, the prevalence of elation/expansive mood and racing thoughts was significantly higher in the case group than in the control group: 26.1% versus 3.1% (p<.001) and 32.6% versus 9.4% (p=0.002), respectively."

There are a couple of ways to take the Okada findings. You could say that bipolar disorder in children with autism, with an average age of about 12 years, is low to non-existent. That's a good thing. But you could also argue that the increased frequency of subclinical mania symptoms noted in those with autism compared to not-autism controls might not be such a good thing. Indeed it could foretell a future greater risk of bipolar disorder in that group or even more pronounced mania in times to come (see here). With specific regard to the possible future diagnosis of bipolar disorder, I'm thinking specifically of the word 'prodrome' to mean early signs and symptoms indicating the onset of future 'disease' (psychopathology). I'll leave you to make the decision as to which option is more important but perhaps further investigation [2] may be indicated...

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[1] Okada Y. et al. Subclinical Manic Symptoms in Children with Autism Spectrum Disorder. Osaka City Med J. 2016 Dec;62(2):103-110.

[2] Van Meter A. et al. Bipolar Prodrome Symptom Scale - Abbreviated Screen for Patients: Description and validation. J Affect Disord. 2019 Feb 12;249:357-365.

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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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"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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Childhood lead (Pb) exposure and "greater psychopathology across the life course"

I've talked about the effects of lead (Pb) on cognition, behaviour and psychology before on this blog (see here and see here for examples). A (heavy) metal with no confirmed biological function, lead represents something that pretty much everyone should be avoiding exposure to, despite it still being used in everything from roofing materials to batteries. The findings reported by Aaron Reuben and colleagues [1] add further to the 'avoid lead' sentiments, and specifically how: "Childhood lead exposure may have long-term consequences for adult mental health and personality."

The aim of the Reuben paper was to conduct "the longest and largest psychiatric follow-up to date in a cohort of adults who were lead exposed and lead tested as children." Participants and their data came from "the Dunedin Multidisciplinary Health and Development Study, a longitudinal investigation of health and behavior in a birth cohort." This study specifically drew on data from over 500 Dunedin study members who were tested for lead exposure around age 11 years and were followed up until their late 30s. A range of psychometric measures were employed in adulthood to complement participants' blood lead test results during childhood, including "(1) repeated clinical interviews assessing psychopathology symptoms across adulthood up to 38 years of age; (2) comprehensive, dimensional measures of psychopathology that account for severity, comorbidity, and reoccurrence; and (3) a broad measure of adult personality (Big Five Personality Inventory)... that did not rely on self-report." Importantly, researchers relied on a sample where "the extent of children's exposure to lead was unrelated to their socioeconomic origins."

Results: most of the cohort (over 90%) had tested blood lead levels above the 5 μg/dL level that the US CDC currently describes as a "reference value for clinical attention." This threshold value replaced the 10 μg/dL level that used to be thought to be important. Indeed within the Reuben cohort: "The mean (SD) blood lead level was 11.08 (4.96) μg/dL."

Researchers also observed that: "After adjusting for covariates, each 5-μg/dL increase in childhood BLL was associated with a 1.34-point increase... in general psychopathology." Covariates included "family socioeconomic status, maternal IQ, and family history of mental illness." This seemingly dose-dependent relationship looked to be quite important.

Onward: "study members with higher BLLs [blood lead levels] at 11 years of age were viewed in adulthood by their informants as more neurotic..., less agreeable..., and less conscientious" than those with lower levels. Personality it seems *might* also be affected by childhood lead exposure (at least partially). These and other factors lead Reuben et al to conclude that: "the association between lead exposure and psychopathology may begin to manifest broadly well before adulthood" and "early-life lead exposure in the era of leaded gasoline experienced by individuals who are currently adults may have contributed to subtle, lifelong differences in emotion and behavior that are detectable at least up to 38 years of age."

I know there are caveats to this type of observational work - "there was only one time point of lead testing" - and even controlling for some potential covariates does not mean that the total spread of covariates has been covered in this study. Personally, I'm not overly enthused by the whole personality types bit either; particularly in light of further revelations about some of the historical proponents of such an idea (see here). But taken as part of a wider series of research on lead exposure and psychopathology, the Reuben work is in line with other results on how an environmental factor can seemingly affect both development and psychopathology. And minus any sweeping generalisations about psychopathology and crime, the so-called 'lead-crime hypothesis' under the guise of biosocial criminology for example, doesn't exactly suffer as a result of the Reuben findings...

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[1] Reuben A. et al. Association of Childhood Lead Exposure With Adult Personality Traits and Lifelong Mental Health. JAMA Psychiatry. 2019. Jan 23.

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"Having accessed treatment was associated with reporting lower levels of work/school attendance"

I have to admit that I did a bit of a double-take when I came across the quote titling this post - "Having accessed treatment was associated with reporting lower levels of work/school attendance" - in the paper published by Sheila Ali and colleagues [1] (open-access available here).

The findings came from a study that set out to investigate the "factors associated with fatigue, disability and school attendance in young people with severe CFS/ME [chronic fatigue syndrome/myalgic encephalomyelitis]." Part of the study also looked (in a preliminary manner) at whether some of the therapeutic options offered 'for ME/CFS' were up to scratch based on participants' responses and views.

"Questionnaire data were collected in two waves: at baseline (T1), and at follow-up (T2), which was 3–9 months later" as such data were collected from 51 young people "required to have a self-reported diagnosis of CFS/ME." Researchers mention how they focused on participants with "severe CFS" as measured by a self-report 'functional ability scale'. That being said, recruitment phases for the Ali study were not uniform, as two different thresholds for severity were eventually used in different recruitment phases.

No mind, Ali et al asked participants to complete various questionnaires around things like mobility, meaningful education and/or work (including attendance), and level of fatigue. Bearing in mind the use of words like 'fear avoidance' in the Ali paper (possibly denoting the biopsychosocial (BPS) 'sway' of some of the authors), various 'psychological' concepts were also included for study. The data were collated and analysed.

Results: although data for 51 participants were eventually analysed, nearly 400 young people were sent a letter inviting them to participate in the Ali study. Only 56 responses (consent forms and questionnaires) were eventually received which, even taking into account the 'severe CFS' inclusion criteria, represents a pretty low study turnout. This seems to follow a trend among certain types of study of ME/CFS (see here) which is starting to become quite noticeable.

"Thirty-seven (72.5%) participants reported using assistive equipment such as crutches, walking frames, ramps, stair-lifts and shower chairs. Thirty-three participants (64.7%) reported that they used a wheelchair. Nine participants (17.6%) reported that they were bed-bound." Contained within those sentences is the real cost of ME/CFS to something like mobility. On top of all that, researchers also observed that approaching 90% of their cohort were also taking some form of medication (I assume pertinent to things like mobility issues and beyond). In terms of how things like mobility issues impacted on participation in 'meaningful' education and/or work, we are told that only a quarter of participants "had been able to attend school, college or work in the past year." That's 'in the past year'.

Then back to those 'treatments' and their effects. So: "Although this was a naturalistic study and not an evaluation of treatment, it is notable that the majority of participants reported that they had accessed some form of treatment, and yet the mean scores for fatigue and social functioning had not changed considerably by T2." What sorts of treatments had they tried I hear you ask? Well, table 1 (see here) provides some details. The most popular treatment 'accessed' was "CBT, GET or both with at least one other treatment" closely followed by "CBT, GET or both." Allied to other independent data suggesting that cognitive behavioural therapy (CBT) and graded exercise therapy (GET) are failing many patients with ME/CFS (see here and see here and see here), and the case grows ever stronger for new treatment directions to be pursued. Such research directions should perhaps also be minus words like 'fear avoidance' or other psychobabble inclinations that have pervaded ME/CFS thought down the years. Indeed, one has to ask who would advocate for treatments that are seemingly at best ineffective and at worst downright detrimental to the patient group who are 'accessing' them?

There are some other points noted in the Ali paper including things like how "low mood is a consequence of having CFS/ME" and how "symptoms of CFS/ME and levels of functioning can fluctuate over time." These follow similar sentiments expressed in other research (see here and see here) along the lines of CFS/ME being very much a real physical illness with both physical and psychological effects.

There are some obvious caveats to mention about the Ali study, specifically around the sole use of questionnaires without any other 'actigraphic' form of inquiry (to measure something like activity levels), the representativeness of results, and the reliance on self-report when it came to diagnoses. Although I've also been pretty harsh on the effectiveness of the treatment options accessed, I will direct you to some author comments on this issue and how "the effects of treatment would not be seen within such a short period of time." I'm not too sure about such sentiments but, in the interests of balance, give them airtime in this study write-up.

Despite all that, the Ali findings add further to our knowledge about ME/CFS in young adults. They demonstrate how 'life-destroying' the illness is (are) and can be, and what that means to those who suffer with it (them). They also add to the multiple voices - research and patient voices - demanding a greater clinical focus on ME/CFS, and how objective, biological science in particular, needs to be front-and-centre of any new direction. But I'll also reiterate that any new focus and new direction needs to be minus the psychobabble; indeed it may be unethical not to [2]...

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[1] Ali S. et al. Psychological and demographic factors associated with fatigue and social adjustment in young people with severe chronic fatigue syndrome/myalgic encephalomyelitis: a preliminary mixed-methods study. J Behav Med. 2019 Jan 25.

[2] O'Leary D. et al. Ethical classification of ME/CFS in the United Kingdom. Bioethics. 2019 Feb 8.

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"Anxiety and sleep problems may be an early indicator of autism in young children"

The quote titling this post - "Anxiety and sleep problems may be an early indicator of autism in young children" - comes from the findings reported by Jacqueline Uren and colleagues [1]. Researchers dipped into data derived from the Raine study initiative to investigate any "longitudinal associations between sleep and anxiety at 2 years and sleep and anxiety at 8 years controlling for demographic variables" and also "the additional influence of autistic traits at 2 years on sleep problems and anxiety at 8 years."

The Raine study has produced fodder for this blog before (see here and see here for examples). Described as "one of the largest successful prospective cohorts of pregnancy, childhood, adolescence and now early adulthood to be carried out anywhere in the world", the sample size is not to be sniffed at (~2900 pregnant women). It has provided a number of important longitudinal *associations* of interest.  Mention of the name Andrew Whitehouse on the paper authorship is also kinda expected given his interest in autism-related data derived from the Raine study in particular.

So: "Children's sleep and anxiety at 2 and 8 years and autistic traits at 2 years were measured using the Child Behavior Checklist." The data was crunched to assess for any possible associations. And associations there were, as we are told that: "Sleep problems at 2 years and 8 years, anxiety at 2 years, and autistic traits at 2 years were significantly associated with anxiety at 8 years." Further: "Sleep problems at 2 years and anxiety at 8 years were significantly related to sleep problems at 8 years." Such statements also led to that headline observing that anxiety and sleep issues *may* be an early indicator of childhood autism (with a stress on the *may*).

Of particular interest to me was the suggestion that "early autistic traits may also contribute to anxiety problems later in childhood." I say this because I am becoming more and more interested in how anxiety may be something much more 'core' to autism than many have hitherto believed (see here). Yes, there are those that might disagree (see here); perhaps using the 'social model' pathway and the notion that society shoulders a lot of responsibility for things like anxiety and depression in the context of autism (see here) as evidence for some 'acquired anxiety' effect. But the data is becoming compelling to suggest that for some 'types' of autism at least, anxiety may represent something of a core feature (in line with some previous thoughts on this matter [2]) and is present pretty early on for many. And in this respect, the way that one manages something like anxiety in the context of autism, may very much depend on looking at 'managing' certain other core autistic features...

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[1] Uren J. et al. Sleep problems and anxiety from 2 to 8 years and the influence of autistic traits: a longitudinal study. Eur Child Adolesc Psychiatry. 2019 Jan 19.

[2] Evans B. How autism became autism. Hist Human Sci. 2013 Jul; 26(3): 3–31.

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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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"Children are getting weaker, study finds"

The title of this post - "Children are getting weaker, study finds" - comes from one of the media headlines covering the study findings presented by Gavin Sandercock & Daniel Cohen [1]. In their study, the authors detail results derived from the Chelmsford Children's Fitness and Activity Survey, an initiative that has been monitoring the fitness of local children (local to Chelmsford) for about 20 years. Their results for the most recent cohort (2014) compared with previous study cohorts (2008, 1998) make for worrying reading: children are getting weaker alongside "a decrease in self-reported physical activity concurrent with the accelerated declines in fitness from 2008 to 2014."

So: "We measured; height, weight, standing broad-jump, handgrip, sit-ups and bent-arm hang in 10-year-old boys and girls from Chelmsford, England in: 2014 (n = 306), 2008 (n = 304) and 1998 (n = 310)." Researchers also asked about recent physical activity among their cohort using the Physical Activity Questionnaire for Children/Adolescents (PAQ-C), a self-report questionnaire. The collected results were analysed and among other analyses, authors "compared percentage change per year 1998–2008 with 2008–2014" across the variables being studied.

As per the headline, the results were worrying: "Pairwise comparisons showed muscular fitness of both sexes was significantly lower in 2014 than in 1998." They also observed that self-reported physical activity was lower in the later cohort. Obviously, I need to stress that this was self-reported physical activity information, so not exactly objective actigraphic data for example. Out of the several results reported relating to specific aspects of fitness across the cohorts, the issue of handgrip strength stuck out for me in light of some still emerging research suggesting that handgrip strength might have "prognostic value for mortality" according to some studies. Without wishing to make connection when none might exist, I do wonder whether such data might one day eventually tally with some other quite worrying statistics on longevity recently published?

Another detail discussed by Sandercock & Cohen is their finding that "Ten-year-olds in 2014 were taller and heavier than in 2008 and 1998 but there were no differences in BMI [body mass index]." They authors talk about this more in their media interviews: "As today's ten-year-olds are taller and heavier than the children measured six and 16 years ago we expect them to be stronger and more powerful, but this was not the case." Worrying. And it also appears that the declines in strength were increasing more rapidly in the later cohort than compared with the earlier ones, as the authors mention that from 1998 to 2008, strength (group strength) fell by just over half a percent per year, whereas from 2008 to 2014 this decline increased to 1.6% per year.

So what does this all mean for the health and well being of the next generation, and what can be done to reverse such trends? Well, health in childhood is often a good indicator of what health will look like in adulthood. I say this not only from a physiological point of view but also bearing in mind that habits bred in childhood tend to persist into adulthood. Low levels of physical activity probably also follow that pattern.

The possible reasons to account for the cohort disparities? Minus any sweeping generalisations I don't think it would be out of place to mention that things have changed quite a bit when it comes to hobbies and pastimes for at least some parts of the paediatric population. More time spent playing video games or on the Internet have perhaps replaced previous scenarios when kids would meet (in person), play out, run around, climb trees, play football and the like. I don't say that to demonise such digital pastimes (see here) but rather to point out a shifting pattern in activities that also have been noted in other relevant studies [2]. It's perhaps also worthwhile pointing out that opportunities for physical activity have also perhaps changed as a function of the environment we now live in. Why else would schools have had to implement strategies such as the daily mile for example?

Possible solutions? When I first tweeted about the publication of the Sandercock & Cohen article I added in the idea that physical activity specifically along the lines of strength and conditioning could perhaps be added to the learning curriculum. So, alongside maths and English (here in Blighty), there is also a focus on physical education too. Yes, I know physical ed(ucation) is part of the school agenda, but I actually meant something like getting kids into a gym and doing something akin to circuit training at least a few times a week. I know this is ambitious and I know that not every kid is going to be able to do this. But surely in these days of adaption and flexibility in teaching and learning, there are also ways to make such exercise open to all. And you never know, start children young with the mindset that exercise is fun and good for physical (and mental) health, and it might just serve them for a lifetime...

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[1] Sandercock GRH. & Cohen DD. Temporal trends in muscular fitness of English 10-year-olds 1998–2014: An allometric approach. Journal of Science and Medicine in Sport. 2018. Aug 1.

[2] Walsh JJ. et al. Associations between 24 hour movement behaviours and global cognition in US children: a cross-sectional observational study. The Lancet Child & Adolescent Health. 2018. Set 26.

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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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Autistic traits assessed between 5 and 8 years old are 'primarily stable'

The findings reported by Hideyuki Haraguchi and colleagues [1] (open-access available here) provide the [brief] blogging fodder today and their conclusion that: "total and two subdomain-related autistic trait scores remained primarily stable in males and females" in the general population. Further that "assessing autistic traits before school entrance may aid in predicting later autistic traits as well as other co-occurring social and emotional problems."

Autistic traits were measured "by a mother-reported quantitative measure, the Social Responsiveness Scale, at age 5 and 8 years." The Social Responsiveness Scale or SRS has some good history with autism in mind both from a research and clinical perspective. In this case the Japanese version of the SRS was used, and data from total scores and "Social Communication and Interaction (SCI)" and "restricted and repetitive behaviors (RRBs)" domains also reported on in approaching 170 "Japanese community-based children."

Results: "We found that although autistic traits assessed by the SRS decreased slightly from age 5 to 8, the extent of this change did not reach statistical significance in this sample, indicating that autistic traits are primarily stable during this transition period at the group level."

This is an important finding. Whilst one has to be careful of any sweeping generalisations that for example, the expression of autistic traits by individual children or smaller subgroups might not be as stable as you think (see here and see here), the results do have implications for various areas. Not least those areas connected to the idea that autistic traits might have some subsequent important 'influence' on later psychopathology (or indeed, a subsequent diagnosis of autism). I say this in several important contexts covering the presence of depression and anxiety (see here) and also in relation to other 'overlapping' spectrums (see here and see here) and what this *could* mean for some potentially life-threatening risks (see here and see here).

The next stage of such research? Look beyond the late childhood years and into adulthood with autistic traits in mind.


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[1] Haraguchi H. et al. Stability of Autistic Traits from 5 to 8 Years of Age Among Children in the General Population. J Autism Dev Disord. 2018 Oct 5.

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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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"anxiety occurring as a consequence of ASD symptoms"

Although not necessarily a popular idea, I have for a while been coming around to the possibility that various 'comorbidities' associated with a diagnosis of autism or autism spectrum disorder (ASD) represent more than just 'comorbidity'. I'm not specifically talking about medical comorbidity such as epilepsy or seizure disorder being intricately related to autism (although there is evidence for such a relationship) but rather that co-occurring clinical and sub-clinical psychiatric issues such as depression and anxiety potentially 'come about' partially as a result of the presence of autistic traits and characteristics (see here and see here).

As I said, this is not a universally popular idea. In the age of the emergence of an 'autistic identity' and an increasingly vocal group of people wanting to discuss what role societal factors play with regards to quality of life in the context of autism (see here), the idea that autistic traits themselves might in some way predispose for various other, often very disabling conditions, is not easy to reconcile. Even more so if the implication for managing things like anxiety and/or depression might mean 'targeting' core autistic features for intervention...

The findings such as those reported by Elizabeth Shephard and colleagues [1] "testing the specificity of early-life (infant and toddler) predictors of mid-childhood ADHD [attention-deficit hyperactivity disorder] and anxiety symptoms compared to ASD symptoms" provide however, another tier of evidence that (a) autism rarely exists in some sort of diagnostic vacuum (see here), and (b) something like the symptoms of anxiety appearing alongside autism could "reflect the presence of common developmental pathways or convergence in early behavioural manifestations."

Shephard et al discuss results obtained from the British Autism Study of Infant Siblings (BASIS) initiative, a collaboration based here in Blighty aiming to "provide a platform for the study of infants at-risk for autism in the UK and to facilitate collaborative links between scientists working in the area." High-risk (i.e. having a sibling diagnosed with ASD) and low-risk infants were followed and tested for various symptoms and traits covering autism and also ADHD and anxiety at various points during their childhood development: "7, 14, 24 and 38 months, and 7 years of age." Importantly, because measuring things like anxiety in young children is still quite a challenge, researchers used other soft signs and symptoms - fearfulness and shyness - as "early-life predictors of anxiety symptoms." Some nifty statistical methods were applied to the collected data.

Results: "Increased activity levels and poor inhibitory control were correlated with ADHD symptoms and not ASD or anxiety; these associations were unchanged in path models controlling for risk-group and ASD symptoms." The authors interpreted these findings as evidence that "these disorders may have distinct developmental origins and are therefore unlikely to reflect a common condition" with a specific focus on autism and ADHD. Ergo, when one sees the data pointing to a rather large over-representation of ADHD in the context of autism (see here), this does not necessarily translate into autism being ADHD or vice-verse or them sharing a common developmental pathway.

Additionally: "early‐life markers of anxiety (without ASD) were associated with later anxiety..., but were also associated with later ASD symptoms." When looking at those early-life markers of [possible] anxiety, and how they *linked* to the symptoms of autism, authors highlighted how "these disorders are difficult to differentiate early in life, which could reflect the presence of common developmental pathways or convergence in early behavioural manifestations of these disorders." In other words, there may be some intricate links between them.

Of course, lots more research is needed in this area, as authors mention about the use of "parent‐rated measures of early‐life predictors and mid‐childhood symptoms of ADHD, anxiety and ASD" and what that could mean for the quality of the information obtained. Personally, I'd be inclined to suggest that parents are often 'under-rated' in their contributions to autism research (see here for example) including on the specific issue of anxiety and autism (see here). But I guess every study can be improved in some respect.

What's more to say on this topic? Well, I'm minded to bring in some other, rather 'left-field' evidence for how autism and anxiety might be more intricately linked than hitherto suggested, in the form of some work looking at selective mutism and autism (see here). How, a condition centrally identifying with anxiety (selective mutism), also seemingly heightens the risk of autism being subsequently diagnosed well beyond what would be expected. I don't doubt that there other examples of anxiety-related conditions also potentially increasing the likelihood of autism presenting clinically further strengthening the 'beyond just comorbidity' sentiments.

And set within this emerging research/clinical picture [2], we then go back to the idea that some autistic traits might be 'promoters' of something like anxiety in the context of autism, and back to the important question of what to do about them...

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[1] Shephard E. et al. Early developmental pathways to childhood symptoms of attention-deficit hyperactivity disorder, anxiety and autism spectrum disorder. J Child Psychol Psychiatry. 2018 Jul 2.

[2] Spain D. et al. Social anxiety in autism spectrum disorder: A systematic review. Research in Autism Spectrum Disorders. 2018; 52: 51-68.

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"Cognitive behavioral therapy for children with autism spectrum disorder"

I'll admit that I was the one with the furrowed brow when the paper by René Kurz and colleagues [1] cropped up on my research radar. Detailing results from a "prospective observational study", authors set out to examine "the effectiveness of cognitive behavioral therapy (CBT) in children with autism spectrum disorder (ASD)." They concluded that: "CBT is an effective therapy for children with ASD." You'll note that I've underlined the word 'children' in those past sentences...

OK, CBT represents one of the talking therapies that seem so popular these days. The NHS Choices website describes it as being based on "the concept that your thoughts, feelings, physical sensations and actions are interconnected, and that negative thoughts and feelings can trap you in a vicious cycle." Kurz et al applied such principles to autism, and specifically what effect CBT had based on pre- and post-scores on the Aberrant Behavior Checklist (ABC) over 12 months. They observed significant changes to things like irritability, lethargy and hyperactivity, and called for further investigations.

Why my furrowed brow on this topic? Well, several reasons. Methodologically, the Kurz study was pretty weak. A participant group of 9 boys, including pre- and post observations over 12 months, no control group, no blinding, no comparison intervention... not exactly a stand-out study. It's not inconceivable that changes to behavioural presentation might have been due to lots of other reasons aside from the use of CBT (and that's before one considers how N=9 might impact on the statistical methods used by the authors).

Then there's the use of CBT. I know that CBT is finding some favour when it comes to 'managing' certain conditions/symptoms over-represented in relation to autism such as anxiety (see here for example). The purpose however of the Kurz study was slightly more specific: "To evaluate prospectively the effectiveness of cognitive behavioral therapy (CBT) in children with autism spectrum disorder (ASD)." It strikes me that in much the same way that CBT is being utilised in relation to another set of conditions (see here), the focus on the 'biopsychosocial' angle in the context of autism harks back to a shady past. And yet again, I'm going to emphasise the word 'children' in the Kurz study group.

I don't want to totally poo-poo things like talking therapy in the context of 'some' autism. I don't doubt that for some on the autism spectrum, there could be some merit in 'breaking down' thoughts and feelings in order to try and help resolve some more problematic features. I don't doubt that just being able to talk to someone about things like feelings and the like is probably going to be useful for some people including young children aged 6 or 7 years old.

But the idea that children (with a mean age of about 6 years old) are somehow going to be responsive to CBT in the context of their autism seems to be based on something a little more 'old-fashioned' in the authors' thinking. Y'know, going back to those days when sweeping (and illogical) psychological theories had a stranglehold on the way that autism was viewed. I'm also minded to mention that CBT and related therapies are not somehow 'side-effect' free, even if science needs to do more to report on possible adverse effects (see here).

The evidence for using something like CBT in the general context of autism is not great (see here). Part of this is because methodologically vigorous trials are still few and far between [2] and with regards to using children as participants, even more few and far between. I know psychology and psychological theory upon which CBT is based, still wants to play a part when it comes to autism - one need only look at the continuing fixation on Theory of Mind (ToM) to see that. But there must come a time when one steps back and asks whether a talking therapy will significantly impact on the core features of a developmentally-defined condition with strong evidence for an organic basis? Would we for example, ever entertain the use of CBT 'for' a condition like phenylketonuria (PKU) for example, where autism can and does occur alongside? No, we wouldn't.

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[1] Kurz R. et al. Cognitive behavioral therapy for children with autism spectrum disorder: A prospective observational study. Eur J Paediatr Neurol. 2018 May 30. pii: S1090-3798(17)31856-1.

[2] Weston L. et al. Effectiveness of cognitive behavioural therapy with people who have autistic spectrum disorders: A systematic review and meta-analysis. Clin Psychol Rev. 2016 Nov;49:41-54.

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One in five 8-year olds "received a psychiatric diagnosis"

"Question: What is the cumulative incidence of psychiatric diagnosis and use of psychotropic medications in a Medicaid-insured birth cohort by age 8 years?"

Answer: About 1 in 5 children were in receipt of a psychiatric diagnosis at age 8, and about 10% were in receipt of psychotropic medication.

So said the findings reported by Dinci Pennap and colleagues [1] who relied on "Medicaid claims data for newborns in a mid-Atlantic state in 2007... and followed up for 96 months or less through December 31, 2014." As per the focus on Medicaid - an initiative that 'helps with medical costs for some people with limited income and resources' - this was a study conducted in the United States, and included data for over 35,000 infants/children. The sorts of psychiatric diagnoses examined by Pennap et al included "ADHD [attention-deficit hyperactivity disorder], disruptive disorders, learning disorder (LD), adjustment disorder, anxiety disorders, depression, ASD [autism spectrum disorder], and other psychiatric diagnoses" all diagnosed by a clinician, but also requiring "2 or more diagnosis claims on separate days."

Venturing further into the study results, we learn some potentially important details. So, across the years of study, approaching two-thirds of the diagnoses received were defined as 'behavioural'. As probably expected (see here), a diagnosis of ADHD was the most popular label - "accounted for 43.9% (1999 of 4550)" - followed by a learning disorder (disability) diagnosis received by just over 30% of the group. White children were seemingly more likely to receive any psychiatric diagnosis than African American children or Hispanic children, and there were some important sex/gender differences noted across various diagnostic labels. If I'm also reading the results correctly with regards to the label of ASD (autism spectrum disorder) (see here), it looks like about 2-2.5% of boys had received a diagnosis, bearing in mind that this is a figure showing as a percentage of those who had received a psychiatric diagnosis. As a function of the entire cohort (N=35,244), the cumulative incidence of ASD across the years (2007-2014) and across the genders was 0.89%.

Then to the issue of pharmacotherapy or medication prescription. Bear in mind that Pennap and colleagues were looking at psychotropic medication being delivered to infants and young children; a group where even greater caution than usual should be expected. They reported that just over 10% of the entire cohort had some history of psychotropic medication use. Alongside those stats on ADHD as a diagnosis, so the medicines classed as stimulants (indicated for ADHD) made up the biggest class of medication used. The authors also zoomed in on a few particular parts of their medication findings. First: "girls were twice as likely as boys to initiate treatment with anxiolytics and hypnotics (25.2% [173 of 686] vs 13.2% [199 of 1510]; P < .001)", also noting that "there is insufficient evidence to support the use of anxiolytics and hypnotics as first-line treatment for pediatric mental health conditions." Second, they discuss evidence suggesting that: "antipsychotics are largely used for off-label behavioral management in the birth cohort, highlighting the need for a delicate benefit-risk balance." Yes, indeed there is a need for exploring that 'delicate benefit-risk balance' (see here and see here). The other rather important finding concerned the use of more than one psychotropic medicine over a prolonged period of time: "approximately 20% of medicated children (433 of 2196 [percentage adjusted for right censoring]) received 2 or more classes concomitantly for 60 days or more." Remember again, these were young children that were under study.

The picture painted by Pennap et al is an important one. It adds to other independent evidence to suggest that across different geographies, psychiatric disorders including behaviourally and emotionally-defined conditions, are prevalent, dare I even say frequent (see here and see here). I'd also add in the 'yet newer' recent US CDC 'estimates' of autism in 8-year olds in this context too (see here).

In relation to the medication side of things, well, 10% of their total population have had some exposure to psychotropic medication, which is important. Accepting that (very) careful medicines management is required given the young age of the group, I'm gonna stick to a line that I've mentioned before regarding the clinical need for such medicines [generally] outweighing the risk(s). I say this on the basis that prescribing clinicians know their clinical population and know something about the risk-benefit profile of the medicines they're administering. I'd also add that when it comes to something like stimulants as a class of medicines, the clinical profile of such medicines is typically 'safe' (benefits outweighing risks) and can, in a few cases, literally be a life-saver (see here and see here). But all that does not mean that science shouldn't be looking to other avenues for intervention for various labels (see here and see here for examples), alongside keeping a sharp eye on ways and means of making such medicines even safer for such younger populations...

And just in case you thought the figure 1 in 5 only holds for the United States, you're wrong and resources and services here in Blighty are seemingly still struggling...

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[1] Pennap D. et al. Patterns of Early Mental Health Diagnosis and Medication Treatment in a Medicaid-Insured Birth Cohort. JAMA Pediatrics. 2018. April 30.

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