"There is broad parent interest in a genetic/epigenetic test for ASD"

The quote heading this post - "There is broad parent interest in a genetic/epigenetic test for ASD [autism spectrum disorder]" - comes from the findings reported by Kayla Wagner and colleagues [1]. As per the observation that most parents of those diagnosed with an ASD, or developmental delay (DD) or asymptomatic controls "had positive perceptions toward genetic/epigenetic research in ASD", far from being the 'danger' that it is sometimes portrayed as, the science of genetics seems to have an important standing among many parents.

The Wagner results came about as a result of this research group publishing studies "that demonstrate the utility of RNA sequencing technology (non-coding RNA) to identify children with ASD." They did what few genetic studies have done: asked parents participating in their studies whether what they were doing/finding was of interest to them. This was achieved via the use of a questionnaire which included six themes: "(1) reasons for participating in the epigenetic study; (2) prior knowledge of genetics/epigenetics, and the source of this information; (3) overall interest in genetic/epigenetic testing for ASD; (4) concerns about genetic/epigenetic testing for ASD; (5) preferences about the approach for genetic/epigenetic testing (including age of administration and biofluid of choice); and (6) extent of results to be returned." You'll probably have noted that alongside their use of the term 'genetics' they also talk about a still up-and-coming branch of genetics called epigenetics. I've talked about epigenetics and autism before on this blog (see here and see here) but the description Wager et al use just about says it all: "changes in gene expression, where the changes are not due to modification of the actual DNA sequence, but instead result from modifications that regulate DNA structure and expression." Gene expression seems to be particularly important to the science of epigenetics as per the notion that we don't all walk around with all our genes permanently switched to the 'on' or 'off' position.

Results: quite a few important points emerged from the obtained data. Most parents understood at least a little bit about genetics and some of the processes involved. Epigenetics wasn't as well known about or understood (something which is probably not so surprising). Other points also emerged: "There were no parents (0%, 0/244) concerned about a lack of scientific evidence supporting genetic and epigenetics." But that's not to say that some parents weren't concerned about the implications of genetics and epigenetics, as mention about issues like privacy and insurance status were raised during the Wagner study.

Also: "Nearly all parents (96%, 235/244) indicated that if there were genetic testing for ASD, they were interested in learning results about their child’s risk for ASD." And when it came to results, over three-quarters of all parents expressed a preference for "all epigenetic/genetic results, regardless of whether they were implicated in health and disease" and not just an overview or interpretation of any results. People want data not overviews.

And then to some important but potentially controversial findings: "The majority of parents (71%, 164/231) desired results of a genetic/epigenetic test for ASD when their child was 12 months of age or younger. Over half of parents were interested in receiving results at conception (34%, 78/231) or at birth (37%, 86/231), while fewer requested results at 12 months (17%, 40/231) or at 2 years of age (12%, 27/231)." You can perhaps see where this might be going - particularly 'receiving results at conception' - even if the authors seem to have chosen not to pursue it any further in their discussions.

I'm no bioethicist and so am nowhere near qualified to talk about the ins-and-outs of genetic testing in the context of autism and what implications this could have. I note other commentators have approached this subject previously based on some of the peer-reviewed science in this area (see here) and various points have been raised. One of the important things to bear in mind is that, as it currently stands, there is no single genetic test for all autism. Indeed, allied to the idea that the concept of 'a universal autism gene' is fast becoming a distant memory, genetic studies are serving to further highlight how complex autism actually is.

But there is always the possibility that some day someone will potentially deliver a genetic/epigenetic 'test for some autism'. The question then is how will it be used? What checks and balances will be in place to ensure that it is not misused?

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[1] Wagner KE. et al. Parent Perspectives Towards Genetic and Epigenetic Testing for Autism Spectrum Disorder. Journal of Autism & Developmental Disorders. 2019. March 22.

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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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a "family history of mental and neurological disorders is associated with autism risk"

There's a couple of ways that one could interpret the findings reported by Sherlly Xie and colleagues [1] who concluded that: "family history of mental and neurological disorders is associated with autism risk, and the familial component of autism etiology may differ by presence or absence of co-occurring intellectual disability."

You could 'use' such findings to imply that autism is much more likely expected as and when one or other parent presents with something like "ADHD [attention-deficit hyperactivity disorder], ID [intellectual disability], other childhood disorders, alcohol misuse, drug misuse, NAPD [non-affective psychotic disorder], bipolar disorder, depression, anxiety disorders, OCD [obsessive-compulsive disorder], stress-related disorders, other neurotic disorders, eating disorder, or personality disorder." Indeed, when I tweeted the Xie paper out, I got one (joking) reply saying something along the lines of 'my kids didn't stand a chance' in light of the familial connection being made.

The other way that one could approach the Xie findings is to look at them as part of a bigger picture, where familial genetic, epigenetic and perhaps even non-genetic influences might overlap across an array of different labels. Further, the possibility that if one was able to get to the source(s) of such shared 'risk', one might potentially be able to positively affect a whole range of labels and diagnoses and perhaps mitigate some of their more quality-of-life sapping characteristics associated with them.

I'm an optimist and take the Xie findings with option number 2 in mind. I say that on the basis that whilst some people talk about the 'positives' of something like ADHD or bipolar disorder (perhaps in the context of the movement known as 'neurodiversity') I'm very much more influenced by the peer-reviewed research talking about the heightened risks that come with such diagnoses. Risks that can very much influence important facets of quality of life and sometimes in some pretty extreme ways (see here and see here for examples).

Anyhow, back to the Xie findings and yet another population-based cohort study with participant numbers totalling about half a million. With those sorts of numbers, you probably won't be surprised to hear that this was a study yet again (see here) utilising some of those marvellous Scandinavian registries; this time in Sweden. 'Index people' comprised births where among other things, their medical and other records could be "linked to both biological parents" and beyond (i.e. "Through the eligible index persons, we ascertained their first- to fourth-degree relatives who had resided in Sweden for at least 2 years"). Researchers trawled the records looking for one or more of those psychiatric and/or neurological diagnoses and looked to see if there was an connection to the index cases where autism was diagnosed.

Results: "Having a first-degree relative with ASD [autism spectrum disorder] without ID was associated with a 9-fold increase in odds of ASD without ID in index persons compared with those with unaffected first-degree relatives." Nothing particularly novel about those findings in light of other independent studies reaching similar conclusions (see here and see here).

Then: "Having a first-degree relative with ADHD, ID, other childhood disorders, alcohol misuse, drug misuse, NAPD, bipolar disorder, depression, anxiety disorders, OCD, stress-related disorders, other neurotic disorders, eating disorder, or personality disorder was associated with 1.5- to 4.7-fold increases in odds of the index person having ASD without ID compared with those with first-degree relatives without each of these conditions." Again, alongside other independent results, we are told that: "These associations diminished for more distant family relations."

When it came to autism with intellectual (learning) disability, authors reported some equally important connections: "Having a first-degree relative with ASD with ID was associated with a 14.2-fold increase in odds of the same outcome in index persons compared with those with unaffected first-degree relatives." They also observed some similar connections with regards to first degree relatives (defined as fathers, mothers, and full siblings) with one or more of those psychiatric disorder and the risk of autism and ID as that seen in the risk of autism without ID. In short, the familial presence of various psychiatric and/or neurological diagnoses seemed to up the risk of autism (with or without learning disability).

Oh, and lest I forget, another important detail was mentioned in the Xie paper: "The prevalence of ASD with and without ID was 0.4% and 1.5%, respectively."

I don't think anyone should be particularly surprised by the Xie findings, but that doesn't mean that they aren't important. They're important for the implementation of screening programmes for potentially 'at-risk' populations when it comes to the early diagnosis of autism, bearing in mind that autism can seemingly come about for lots and lots of different reasons (see here and see here) and early diagnosis might not necessarily be relevant to everyone (see here). The findings are also important for future research looking at what 'common mechanisms' might be at work. And, as I've said, they're important because of what it might eventually mean when it comes to intervening in various diagnoses with some potentially shared biology.

Just before I go, there is another angle to mention as a consequence of the Xie results. An angle that I've talked about quite a bit on this blog in two parts: (i) 'autism genes are probably not just genes for autism' (see here) and (ii) 'autistic traits are not just confined to a diagnosis of autism' (see here and see here). It strikes me that the Xie findings provide some quite strong support for both these points...

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[1] Xie S. et al. Family History of Mental and Neurological Disorders and Risk of Autism. JAMA Netw Open. 2019;2(3):e190154.

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"The burden of care of mothers as caregivers of ASD children leads to suicidal ideation among them"

I appreciate that the title heading this post - "The burden of care of mothers as caregivers of ASD [autism spectrum disorder] children leads to suicidal ideation among them" - derived from the findings reported by Bushra Akram and colleagues [1] is (a) a rather sweeping generalisation, and (b) not likely to be met with great enthusiasm by some/many people. I say that on the basis that words like 'burden of care' carry significant emotional meaning, even if only trying to describe "the psychological, emotional, social and economic challenges that are experienced by a caregiver of mentally or physically ill person."

Language aside, I did want to blog about the Akram findings because they represent another uncomfortable topic that needs to be talked about and further researched in relation to autism. They bring to our attention how parenting is not always about smiles, fluffy clouds and rainbows but sometimes can be bloody difficult. More so when something like autism is part and parcel of the family unit (see here and see here). Such recognition of reality is not meant to stigmatise anyone or devalue them as a person. It merely implies that burying heads in the sand for the sake of good PR or other reasons helps no-one in the long run. Least of all children. And in that respect, there seems a change recently (see here)...

I think you've kinda got the gist of what Akram et al were looking at in their study. They managed to recruit over 300 mums of children diagnosed with an autism spectrum disorder (ASD) from various cities in Pakistan. Diagnosis was apparently 'assessed' via DSM-5 criteria (see here). We're also told that: "Single mothers or those with more than 1 child with disability were excluded." Various questionnaires were delivered to participants - "the 19-item Burden Assessment [Scale]... (BAS), 12-item Multi-Dimensional Scale of Perceived Social Support...(MSPPS) and 5-item Suicidal Ideation Attributes Scale... (SIDAS)" - pertinent to the study aims. The quality of the translation of some of the instruments into Urdu was tested on a favourite cohort, psychology students.

Results: "The relationship between burden of care and suicidal ideation was positive, but perceived social support had a negative association with burden and with suicidal ideation." What this translates into is that if mums reported that a high score when it came to 'burden of care' so their scores regarding suicide ideation also seemed to be high. Also, if mums perceived themselves to have little or less social support, so they more more likely to experience a burden of care and/or suicidal ideation. This is important if not entirely unexpected.

Of course there are other potential explanations for the findings. Depression, something that seems to have some important links to something like suicidal ideation, was not looked at in the Akram study. Given some previous independent research on depression in parents/guardians of children with autism (see here), depression can't be discounted as playing an important role in suicidal ideation in this case. Likewise, factors such as money and employment would probably play some sort of role too. There are probably a myriad of other intrinsic and external variables to consider.

But let's not over-analyse this over-and-above the actual results obtained by Akram. They really do make a case of more 'caring for the carers' investigation and action (see here). Minus any psychobabble [2] it's the small things that can make a difference. Y'know, things like offering respite to parents/guardians (see here) and ensuring that in these days of a connected world, parents/guardians of children with autism are also connected too (see here). I know it's not politically correct in some quarters to mention it, but such data also make a good case for looking at what can be done to alleviate/reduce some of the more challenging behaviours that can make parenting a child with autism more difficult. Oh, and whilst on the topic of parenting, yes, there is a place for helping parents who are struggling to manage and cope via the teaching of various strategies, but please, leave off the 'super-parenting' stuff for now (see here). Many parents are already super-parents.

And whilst on the topic of caring for the carers, it's worthwhile mentioning that where an autistic child has siblings they also require 'parenting' attention too (see here)...

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[1] Akram B. et al. Burden of care and Suicidal Ideation among Mothers of Children with Autism Spectrum Disorder: Perceived Social Support as a Moderator. J Pak Med Assoc. 2019; 69: 504.

[2] Lee GK. et al. Needs, strain, coping, and mental health among caregivers of individuals with autism spectrum disorder: A moderated mediation analysis. Autism. 2019 Mar 20:1362361319833678.

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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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"parental asthma was associated with slightly elevated risk of ASD in offspring"

The paper by Tong Gong and colleagues [1] provides the blogging fodder today and the finding that "parental asthma was associated with slightly elevated risk of ASD [autism spectrum disorder] in offspring."

As unusual as it might sound to some people that a condition primarily affecting the lungs *might* show a connection to a developmental diagnosis in offspring, this is not the first time that asthma and autism has been talked about on this blog (see here and see here). Granted, much of that previous peer-reviewed research has been looking at the possible *connection* between asthma and autism diagnosed in the same person (albeit not necessarily always describing a link). But there is some research history connecting the two labels. Indeed, one of the primary comorbidities that can follow a diagnosis of autism - attention-deficit hyperactivity disorder (ADHD) - seems to have an even stronger *association* with asthma (see here).

Gong et al set out to investigate a few important issues: "the association between (a) maternal/paternal asthma and offspring ASD, and (b) prenatal exposures to β2-agonists, other asthma medications and offspring ASD." It would be difficult to describe the Gong study as 'underpowered' given that their use of those fabulous Scandinavian population registries - this time in Sweden - covering "all children (N=1,579,263) born in Sweden 1992-2007." From the total population, researchers identified some 22,000 children diagnosed with an ASD. They looked at their exposure to "parental asthma or prenatal asthma medications" and compared the data with other populations (not diagnosed with autism) including various degrees of siblings and extended family members.

As per the title of this post, a possible *association* was revealed between parental medical history of asthma and offspring risk of a diagnosis of ASD. Asthma in either parent seemed to show a connection, but maternal asthma showed the stronger connection. Also: "The risk of offspring ASD in mothers with asthma showed similar estimates when adjusting for shared familial factors among paternal half-siblings... full-cousins... and half-cousins." This suggests that familial factors were not 'confounding' factors. Another detail is important to mention: "Prenatal exposure to asthma medications among subjects whose mothers had asthma was not associated with subsequent ASD." This is an important detail. It mirrors the findings reported in the paper by Su and colleagues [2] looking at another Scandinavian cohort, and their conclusion: "children born to women who used β2AA [β2-adrenoreceptor agonist] during pregnancy have an increased risk of ASDs in later life" with the caveat that risk of offspring autism was "more likely due to underlying maternal diseases rather than the exposure to β2AA itself."

Implications? Well, several. Not least that more study is required looking at the biological and genetic links between autism and asthma. Y'know, something along the lines of the fact that 'autism genes are probably not just genes for autism' (see here) and how autism has been previously studied in the context of lung architecture too (see here).

What else? How about examining the possibility of some shared biological mechanisms also at work? Perhaps start with inflammation for example [3] and work through other potential immune-related issues as well (see here). And how about also thinking about the possibility of shared 'exposure' events being potentially important? Asthma is a condition affecting the lungs. Something like air pollution is therefore a prime suspect when it comes to the development and continuation of the condition. Likewise, air pollution is no stranger to the autism peer-reviewed research landscape (see here for example). Is it possible that air pollution might be implicated in asthma and autism?

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[1] Gong T. et al. Parental asthma and risk of autism spectrum disorder in offspring: a population and family based case-control study. Clin Exp Allergy. 2019 Feb 11.

[2] Su X. et al. Prenatal exposure to β2-adrenoreceptor agonists and the risk of autism spectrum disorders in offspring. Pharmacoepidemiol Drug Saf. 2017 Jul;26(7):812-818.

[3] Murdoch JR. & Lloyd CM. Chronic inflammation and asthma. Mutat Res. 2010;690(1-2):24-39.

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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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Cannabis treatment and autism continued

Consider this post talking about the findings reported by Lihi Bar-Lev Schleider and colleagues [1] on the topic of "the epidemiology of ASD [autism spectrum disorder] patients receiving medical cannabis treatment and to describe its safety and efficacy" an extension of other discussions on this blog (see here). Indeed, similar to the paper from Adi Aran et al [2] the name of research game was to look at 'real life experiences' of medicinal cannabis use 'for autism' in Israel (where medicinal cannabis use has been approved for some groups). I foresee this research area growing in months to come...

The focus of the Bar-Lev Schleider paper was CBD - cannabidiol - once again, a component of cannabis distinct from another compound, tetrahydrocannabinol (THC), which is described as being "the principal psychoactive constituent of cannabis." I say the focus was on CBD, but authors mention how: "The treatment in majority of the patients was based on cannabis oil containing 30% CBD and 1.5% THC."

Researchers relied on data "prospectively collected as part of the treatment program of 188 ASD patients treated with medical cannabis between 2015 and 2017." Said participants were an average age of around 13 years old, mostly male and all diagnosed with autism or ASD "in accordance with the accepted practice in Israel." Epilepsy was also mentioned in about 15% of cases, which is interesting in light of the increasing (media) focus on the use of medical cannabis 'for' certain types of epilepsy.

Results: I'm not entirely sure how outcomes with regards to safety and efficacy were actually collected. What I mean by this is that authors describe the use of "the global assessment approach" which meant asking questions like "How would you rate the general effect of cannabis on your child condition?" to participants' parents, but don't seemingly provide details on any specific validated questionnaires used. You might well ask if any such questionnaires exist at the moment with reference to the use of medicinal cannabis, but this doesn't really help matters. Bearing such an issue in mind, researchers reported that: "After six months of treatment 82.4% of patients (155) were in active treatment and 60.0% (93) have been assessed; 28 patients (30.1%) reported a significant improvement, 50 (53.7%) moderate, 6 (6.4%) slight and 8 (8.6%) had no change in their condition." 'Improvement in what?' you might ask. Well, various classes of behaviour are described including those implicated in daily activity - sleep, concentration on daily tasks - among other things. The authors also commented on how medicinal cannabis also seemed to have positively impacted on the occurrence of seizures too: "The improved symptoms at 6 months included seizures, of the 13 patients on an active treatment at six months 11 patients (84.6%) reported disappearances of the symptoms and two patients reported improvement."

And then to another important issue to consider when examining any kind of medicinal product: the presence of (adverse) side-effects. In this respect, we are told: "The most common side effects, reported at six months by 23 patients (25.2%, with at least one side effect) were: restlessness (6 patients, 6.6%), sleepiness (3, 3.2%), psychoactive effect (3, 3.2%), increased appetite (3, 3.2%), digestion problems (3, 3.2%), dry mouth (2, 2.2%) and lack of appetite (2, 2.2%)." Although most of these seem quite minor side-effects, it's still important to recognise them and the distress that they might bring particularly when 'digestion problems' *might* very well compound some already over-represented gastrointestinal (GI) issues already talked about with autism in mind (see here).

"Cannabis as a treatment for autism spectrum disorders patients appears to be well-tolerated, safe and seemingly effective option to relieve symptoms." That's the conclusion reached by Bar-Lev Schleider and colleagues on the basis of their findings. They do note how their results are based on "an observational study with no control group and therefore no causality between cannabis therapy and improvement in patients’ wellbeing can be established" which is important. Important too is the need for further discussions about the ethics of using something like medicinal cannabis in the context of autism [3] and then, if further hurdles are overcome, discussions about the hows-and-whys of a clinical trial or two. Indeed, speaking of clinical trials (see here)...

And as I write this [4] there's more, lots more [5]...

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[1] Bar-Lev Schleider  L. et al. Real life Experience of Medical Cannabis Treatment in Autism: Analysis of Safety and Efficacy. Scientific Reports. 2019: 9.

[2] Aran A. et al. Brief Report: Cannabidiol-Rich Cannabis in Children with Autism Spectrum Disorder and Severe Behavioral Problems-A Retrospective Feasibility Study. J Autism Dev Disord. 2018 Oct 31.

[3] Duvall SW. et al. Ethical Implications for Providers Regarding Cannabis Use in Children With Autism Spectrum Disorders. Pediatrics. 2019 Jan 4. pii: e20180558.

[4] Barchel D. et al. Oral Cannabidiol Use in Children With Autism Spectrum Disorder to Treat Related Symptoms and Co-morbidities. Front Pharmacol. 2019 Jan 9;9:1521.

[5] Aran A. et al. Lower circulating endocannabinoid levels in children with autism spectrum disorder. Molecular Autism. 2019; 10:2.

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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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Gut symptoms are important for 'psychiatric outcomes' in autism

"Individuals with autism spectrum disorder (ASD) are at heightened risk of psychiatric comorbidities across the lifespan, including elevated rates of internalizing, externalizing, and self-injurious behaviors." And: "Gastrointestinal (GI) conditions are of particular interest, as they are prevalent among those with ASD, may share genetic or neurobiological etiologies with the core features of ASD, and are linked with psychiatric difficulties in the general population."

Putting the issue of 'psychiatric comorbidities' and 'gastrointestinal (GI) conditions' together are the results of the findings reported by Emily Neuhaus and colleagues [1] who concluded that: "the presence and quantity of GI symptoms should be considered when evaluating psychiatric and behavioral concerns among children with ASD." Importantly too, they talk about how 'alleviating' accompanying bowel issues in the context of autism *might* also have some important influences on some of those psychiatric issues.

The starting point for Neuhaus and colleagues was a recognition that autism does not exist in some sort of diagnostic vacuum. This means that various 'comorbid' conditions/labels seem to be over-represented when it comes to autism, covering the behavioural/psychiatric (see here) and also the somatic (see here). The authors specifically zoomed in on GI symptoms because they've mentioned over and over and over again as being part-and-parcel of quite a few instances of autism (see here). Marrying the psychiatric and gastrointestinal together, they had two aims: "First, we sought to document the prevalence and variety of GI concerns within a large, well-characterized sample of children and adolescents with ASD. Second, we sought to understand relationships between ASD symptoms and GI concerns over and above the effects of psychosocial factors."

So, authors "draw on data from nearly 2,800 children and adolescents with ASD within the Simons Simplex Collection" pertinent to their aims and objectives. The Simons Simplex Collection (SSC) is no stranger to autism research for various reasons (see here and see here). Importantly too, the SSC is not stranger to specifically looking at GI issues in relation to autism (see here). They reported that: "Consistent with previous literature, families in the SSC frequently reported that their child with ASD had significant GI symptoms" to the tune of over one third of their sample experiencing at least one GI symptom.

Looking at their types of psychiatric symptoms - "internalizing, externalizing, and self-injurious behaviors" - they observed "evidence of unique variance associated with GI symptoms across all three measures of psychiatric symptoms we examined." This didn't mean that GI symptoms were 'the' [singular] cause of those psychiatric/behavioural issues; merely that the presence of such physical symptoms should be considered as one possible factor alongside things like "ASD symptoms, verbal IQ, adaptive behavior, family income." Given that something like self-injurious behaviour (SIB) can be pretty hard-hitting in terms of effects on the person and the people around them (see here), the idea that GI issues might be 'in the mix' alongside "more ASD symptoms, lower adaptive behavior, lower income" should not be ignored. To quote again: "levels of GI symptoms accounted for unique variance in psychiatric outcomes over and above these other factors, linking increased GI problems with increased psychiatric symptoms in children with ASD."

There is a further scheme of work to be followed in this important area.

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[1] Neuhaus E. et al. Gastrointestinal and Psychiatric Symptoms Among Children and Adolescents With Autism Spectrum Disorder. Front. Psychiatry. 2018. Oct 22.

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One more time... (roughly) 1 in 40 children with parent-reported autism in the US

Consider this short post an extension of another recent entry on this blog talking about new data observing that the estimated autism prevalence rate (parent-reported) is around 1 in 40 children in the United States (US) (see here). That entry was based on the paper by Michael Kogan and colleagues [1] and their examination of data "using the 2016 National Survey of Children's Health (NSCH)" initiative.

Enter then another piece of research published little over a week after the Kogan study from Guifeng Xu and colleagues [2] which concluded that: "In a large, nationwide, population-based study, the estimated prevalence of ever-diagnosed ASD [autism spectrum disorder] was 2.79% among US children in 2016." In case you were wondering, 2.79% or 2.8% roughly translates as 1 in 36 children. Xu and colleagues, I might add, are no strangers to prevalence studies on childhood neurodevelopmental disorders (see here and see here).

Both these studies have attracted some media attention (see here and see here) mainly because they show a prevalence rate quite a bit higher than the recent CDC (estimated) autism prevalence figures - 1 in 59 8-year olds - published earlier this year (2018) (see here). Those media reports also seem to make quite a big deal of the 'parent-reported' nature of the figures (both derived from the NSCH initiative). As I mentioned in my last discussion of the Kogan paper, a quote from the lead author Michael Kogan is important in the context of those parent-report 'issues' that some people seem to have: "We know that in terms of having a major condition like autism, parents are usually pretty good reporters compared to medical records." Indeed they are.

Other details to add? Well, the Xu paper also reported on "state-level prevalence of ASD in the United States." They observed variations in the reported prevalence of autism (ASD) across the different states: "The state-level prevalence varied from 1.54% (95% CI, 0.60-2.48) in Texas to 4.88% (95% CI, 2.72-7.05) in Florida." Little explanation is given about such a discrepancy in their paper and so further research is implied.

Also: "Among those who had ever been diagnosed as having ASD, 92.79% (95% CI, 90.19-95.39) reported currently having ASD." This is interesting. Allowing for the fact that the diagnosis of autism or ASD is often more of an art form than a scientific endeavour, I did wonder whether the loss of about 8% of children who were previously diagnosed with autism but did not report currently having autism might overlap with the 9% figure with regards to the term 'optimal outcome' (see here). Y'know, the ever-growing body of peer-reviewed research that seems to suggest that for some people, a diagnosis of autism is not necessarily 'lifelong' (see here) (even if 'optimal outcome' is not necessarily the best phrase to use). Again, further research is implied.

For now however, we can conclude that there is : "a relatively high prevalence of ASD among US children" mirroring that in other parts of the world (see here for example). We really need to be asking questions like 'why?' and also 'are the relevant mechanisms in place to ensure that money, resources and services are directed towards this growing population?'

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[1] Kogan MD. et al. The Prevalence of Parent-Reported Autism Spectrum Disorder Among US Children. Pediatrics. 2018 Nov 26. pii: e20174161.

[2] Xu G. et al. Prevalence and Treatment Patterns of Autism Spectrum Disorder in the United States, 2016. JAMA Pediatrics. 2018. Dec 3.

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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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Quality of life and autism continued

"In this study it was found that psychiatric comorbidity, sleeping difficulty, intellectual disability, maladaptive behavior, adaptive functioning, autism symptomatology, main daytime activity and residence were associated with QoL [quality of life], independent of respondent type."

So concluded the findings reported by Ane Knüppel and colleagues [1] continuing an important research theme looking at quality of life with autism in mind (see here and see here and see here). There's nothing specifically novel about the factors reported on as affecting quality of life (QoL) where a diagnosis of autism is mentioned (mental health issues, autism severity, comorbidity, activities, social inclusion) but the fact that authors drew on data from both self-reports and proxy-reports is important and perhaps provides an important dual perspective. Indeed as the authors noted: "Proxy-reported QoL is different from self-reported QoL and should be considered as an alternative source of information." Similar sentiments have been expressed recently (see here).

Having previously talked [2] about the properties of the specific instrument used to gauge QoL with autism in mind, the authors relied on responses on the INICO-FEAPS scale in their investigation. More than 1700 participants with autism completed the scale where: "For 165 individuals with ASD [autism spectrum disorder], self-reports only were available, and for 863 individuals with ASD, only parental proxy-reports were available." The scale itself is pretty comprehensive, consisting of "72 items divided into the following eight subdomains: self-determination, rights, emotional wellbeing, social inclusion, personal development, interpersonal relationships, material wellbeing, and physical wellbeing." A higher score on the INICO-FEAPS scale denotes a higher QoL 'level'. Various other measures were also included for study; some of them based on the setting of the study in Denmark and the fact that Scandinavian countries are particularly 'geared up' for collecting all-manner of details on the basis of various national registries held on the population.

Alongside the results suggesting that various factors seemed to be important to QoL, there were some details to consider. So: "Across all respondent groups, the lowest rated QoL domains were emotional wellbeing (range of means = 71.10–74.05) and interpersonal relationships (range of means = 65.07–71.88), and the highest rated QoL domains were rights (range of means = 83.79–86.21) and material wellbeing." Further, researchers also observed that being employed or in education also correlated with a higher QoL score "compared to individuals without any regular daytime activity" and "significant associations were found for all respondent groups, with lower levels of QoL among individuals living with their parents... and among individuals with ASD living outside the family home with support... compared to individuals living independently without support."

I was also interested in the idea discussed by the authors that: "treating psychiatric comorbidity, reducing maladaptive behavior, raising the level of independence, and offering individuals with ASD an opportunity to be involved in any job-related occupation or to receive education may raise the level of QoL." 'Treating psychiatric comorbidity' is already a research and clinical priority when it comes to autism (see here and see here). Yes, science needs to do a lot better in terms of establishing the 'hows-and-whys' of such comorbidity being over-represented alongside autism but there are some important themes starting to emerge (see here) including that looking at core autism symptoms as being potential risk factors for the appearance of such issues. And once again we can look to an important group of people for further clues as to how such psychiatric issues are indeed perhaps more 'core' than comorbidity (see here).

Although 'reducing maladaptive behaviour' potentially covers a lot of 'challenging' ground - "Behavior classified as self-destructive, breaking belongings, defiant, disruptive, hurtful to others and/or socially offensive" - I don't think anyone would seriously argue against the idea that such behaviours are neither good for the individual nor good for those around them. I'm minded to suggest that the reason(s) for such behaviour are likely to be complex (see here and see here), but one thing that could be useful would be to look at some of the research on particular 'profiles' being present and connected to autism and beyond (see here) as a starting point.

And then there is also the suggestion of a possible effect for society more generally, as in ensuring that education and employment opportunities are available to all and making 'an inclusive society' a priority...

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[1] Knüppel A. et al. Quality of life in adolescents and adults with autism spectrum disorder: Results from a nationwide Danish survey using self-reports and parental proxy-reports. Research in Developmental Disabilities. 2018; 83: 247-259.

[2] Knüppel A. et al. Psychometric properties of the INICO-FEAPS scale in a Danish sample with autism spectrum disorders. Research in Developmental Disabilities. 2018; 75: 11-21.

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Depressive symptoms in ADHD: "comparing child and parent reports"

I was drawn to blogging about the results published by Annie Fraser and colleagues [1] for a few reasons. Their observation that: "Young people with ADHD [attention-deficit hyperactivity disorder] are at high risk of experiencing symptoms of depression but may under‐report the severity of their symptoms" was interesting. It potentially ties into some other important observations about 'happiness' in the context of ADHD (see here) and also how there is an elevated risk of suicidality when ADHD is part of the clinical picture (see here). Similarly, it fits the narrative that various developmental and/or behavioural labels/conditions/disorders are typically never really stand-alone diagnoses...

So: "This study used a subsample of children originally recruited as part of the Cardiff University Study of ADHD Genes and Environment (SAGE)." As per the 'comparing child and parent reports' part of the Fraser paper, both parents and children completed the Mood and Feelings Questionnaire (MFQ) to measures depressive signs and symptoms in participating children/young adults ("mean age was 14.6 years (range 8–20 years)"). The MFQ "is a widely used depression screening instrument" according to the authors, and has some pretty good backing. Results from the MFQ were compared with a non-ADHD (I assume?) general population sample from a similar part of the United Kingdom (UK) and statistics were applied.

Having already alluded to the observation that depression scores on the MFQ were higher (indicative of more depressive symptoms) in the ADHD group than the population control group (N=1460), there are some further details to mention. Both parent- and child-rated MFQs showed the trend of more depressive symptoms in participants with ADHD. And when it came to clinical cut-off points for suspected depression, quite a few more of those diagnosed with ADHD reached them compared with controls (parent‐report 54.5% vs. 10.6%... child‐report 32.4% vs. 10.5%).

"Amongst the most common depression symptoms found in our ADHD sample were difficulty concentrating, restlessness and feeling grumpy with parents. These symptoms overlap with those of ADHD, so it is unsurprising that they were common in our sample." Think of those last sentences in one particular context: the rise and rise of the term 'ESSENCE' (Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations) and all the chatter about how behavioural symptoms across various different labels seem to 'overlap' with one and another. How also, developmental and behavioural labels rarely exist alone or in some sort of diagnostic vacuum (see here for example). And add them to another sentence from the authors: "This could suggest that depression scores in this sample are artificially elevated by symptoms which overlap with ADHD symptoms." Indeed.

"Suicidal thoughts and symptoms of psychomotor and cognitive retardation (i.e. talking more slowly than usual, moving and walking more slowly than usual, and sleeping more than usual) were the lowest scoring symptoms on both parent‐ and child‐report." Having already mentioned those quite worrying statistics on how a diagnosis of ADHD seems to elevate the risk of suicidality, this might initially seem like better news from the Fraser paper. Items such as "S/he thought about death or dying.... S/he thought his/her family would be better off without him/her... S/he thought about killing him/herself" were not, in the majority, reported on with great fervour. But one needs to be cautious. I say that because the authors also added: "symptoms of suicidality (‘I thought about killing myself’) were present in 20%–25% of the ADHD sample, according to both parent‐report and child‐report, compared to 2%–7% of the population sample." This is a more worrying way of looking at the findings.

So to conclude: depression or depressive symptoms are no stranger to ADHD, the symptoms of ADHD probably overlap with some of the symptoms of depression (at least according to the MFQ), and an enhanced risk of suicidality seems to be confirmed as and when ADHD is diagnosed. There's more than enough further investigations to be done on those topics; perhaps also drawing on a few other important observations too (see here and see here and see here).

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[1] Fraser A. et al. The presentation of depression symptoms in attention‐deficit/hyperactivity disorder: comparing child and parent reports. Child and Adolescent Mental Health. 2018;23(3):243-250.

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