Saturday, 24 March 2018

ATEC (Autism Treatment Evaluation Checklist) still rising

The paper by Shreyas Mahapatra and colleagues [1] (open-access available here) provides the blogging fodder today and some important data relating to an important instrument in autism research circles: the Autism Treatment Evaluation Checklist (ATEC).

I'm a fan of the ATEC. Not only because it was one of the first instruments specifically devised to look at measuring changes to autistic symptom severity but also because it's freely available to use. No royalty payments required; free and open for anyone and everyone to use.

Devised by the late Bernard Rimland and Stephen Edelson of the Autism Research Institute (ARI), the ATEC was born out of the need for researchers and non-researchers alike to measure how autism / autistic features can, on some occasions, fluctuate, specifically in response to intervention. It's perhaps no coincidence that the ARI also holds some important data on parent ratings of how useful certain interventions were reported to be when it comes to autism (see here). Although probably not loved by all, such ratings - derived from those who probably know their children best - provide an important rough-and-ready measure of what intervention options perhaps need a little more investigation and which should probably be avoided. The fact that they're based on the reports of over 27,000 parents also helps matters too...

Anyhow, one thing that did seem to be missing from the increasing interest (see here and see here) in the ATEC is data on "the norms on the longitudinal changes in ATEC in the “treatment as usual population." The Mahapatra paper sought to partially remedy that situation based on an "observational cohort who voluntarily completed ATEC evaluations over the period of four years from 2013 to 2017."

Based on observations for some 2600-odd children (mostly males) all of whom scored 20 or above on the ATEC total score, researchers provided some important baseline data. They for example, show how total ATEC scores, a measure of autism severity, seem to change / fluctuate as children age (see Table 1). They also show how subscale scores - Speech / Language / Communication, Sociability, Sensory / Cognitive awareness, Health / Physical / Behavior - move around as a function of 'starting position' and age too. In short, it provides researchers and non-researchers alike some data on what might be expected to happen to the presentation of autism based on ATEC scoring.

But it's not by any means a perfect start. As the authors point out: "In the selection of participants for inclusion in this study, a baseline of ASD [autism spectrum disorder] diagnosis could not be established as child’s diagnosis is not part of ATEC questionnaire" indicating that not every child who participated might have had a diagnosis of autism or ASD. There were other methodological 'issues' too that need to be kept in mind.

I'm still however happy to talk about the ATEC and its potential usefulness to lots more autism studies aside from that already discussed in the peer-reviewed literature. Assuming also that ATEC has some overlap with other more standardised measures used in autism research [2] I think the future continues to look rather rosy for this rather important instrument.


[1] Mahapatra S. et al. Autism Treatment Evaluation Checklist (ATEC) Norms: A "Growth Chart" for ATEC Score Changes as a Function of Age. Children (Basel). 2018 Feb 16;5(2). pii: E25.

[2] Geier DA. et al. A Comparison of the Autism Treatment Evaluation Checklist (ATEC) and the Childhood Autism Rating Scale (CARS) for the Quantitative Evaluation of Autism. J Ment Health Res Intellect Disabil. 2013 Oct;6(4):255-267.


Friday, 23 March 2018

What do parents/caregivers want from medication for ADHD among offspring?

I know the title of this post - "What do parents/caregivers want from medication for ADHD among offspring?" - might seem a little obvious but I don't see such research as meaningless. Indeed, I was drawn to blogging about the paper from Melissa Ross and colleagues [1] precisely because it is obvious that parents/caregivers have a vested interest in the management of offspring issues with attention-deficit hyperactivity disorder (ADHD) and as such, their views should and do count.

Medicines indicated for treating/managing ADHD have cropped up on this blog before (see here for example). Allowing for the fact that such medicines are like all medicines insofar as having a cost-benefit ratio to consider, the medicines typically indicated for ADHD can literally be life-changing (see here) and indeed on occasion, life-saving (see here). The key I always think is good medicines management and regular clinical input in terms of monitoring for efficacy and any unwanted side-effects.

Ross et al talked to approaching 200 parents/caregivers of children and young adults diagnosed with ADHD, asking them to consider various issues including "desired improvements in their child's ADHD" in light of quite a bit of ADHD medication use. We are told that: "A validated Best-Worst Scaling instrument assessed priorities among 16 concerns when considering ADHD medication."

Results: white mothers of children with ADHD formed the majority voice among participants, and they listed some important priorities for their children. "Overall, the most important ADHD medication concerns were the child becoming a successful adult..., school behavior improvements..., and better grades." I also cast a 'good for you' smile over another observation: "Others thinking badly of the child was a significantly less important concern" as I hark back to other work on another label where 'negative judgements' have been mentioned (see here).

'Nuff said.


[1] Ross M. et al. Caregivers' Priorities and Observed Outcomes of Attention-Deficit Hyperactivity Disorder Medication for Their Children. J Dev Behav Pediatr. 2018 Feb/Mar;39(2):93-100.


Thursday, 22 March 2018

PACE trial for chronic fatigue syndrome (still) being put through its paces

'Chronic fatigue trial results 'not robust', new study says' went the BBC headline reporting on the findings published by Carolyn Wilshire and colleagues [1].

Authors reports peer-reviewed results following their re-examining various aspects of the PACE trial - "pacing, graded activity, and cognitive behaviour therapy: a randomised evaluation" - with regards to chronic fatigue syndrome (CFS) also known as myalgic encephalomyelitis (ME).

This latest research and accompanying media attention continues a quite long-running saga (see here) known in some quarters as 'PACE-gate' (see here) where questions have been raised about a premier study that was "designed to examine the effectiveness of graded exercise therapy (GET) and cognitive behavioural therapy (CBT)" in relation to CFS/ME. Quite a few of those interventions are set within the still unfortunately believed idea that CFS/ME represents a 'biopsychosocial' illness (see here) and that 'changing mindsets and/or behaviour' will magically transform peoples lives. I say 'still unfortunately believed' because patient experiences do not seemingly match some of the peer-reviewed science in this area (see here).

The various twists-and-turns (see here and see here) around the PACE trial have involved bigger discussions about trial design, outcome threshold 'issues' and even the accessibility of research study data. Indeed, the Information Commissioner here in Blighty has even played a hand in the PACE saga (see here) leading to some rather messy and very public arguments.

The paper by Wilshire et al continues a theme from this research group re-examining the PACE trial protocols and findings. It encompasses various elements in terms of definitions of 'overall improvement' and even 'recovery' (see here) between 'specified in trial protocol' and 'used in published reports'. Wilshire and colleagues report: "Our findings suggest that, had the investigators stuck to their original primary outcome measure, the outcomes would have appeared much less impressive."

Insofar as recovery rates - other work [2] related to the original PACE trial paper had indicated some impressive recovery rates following CBT and/or GET - Wilshire has more things to say here too. So: "when recovery rates were calculated using the definition specified in the published protocol, these were extremely low across the board, and not significantly greater in the CBT or GET groups than in the Control group." It might seem like common-sense to know what recovery should look like when it comes to CFS/ME, but again, the waters have been continually muddied (see here).

"Some notable strengths of the PACE study included the large sample size..., the random allocation of patients to treatment arms, the use of a well-formulated protocol to minimise drop-outs, and the reporting of the full CONSORT trial profile (including detailed information about missing data)." Wilshire et al illustrate how the PACE trial was, initially, a good piece of science from a methodological point of view, but: "the design, analysis and reporting of the results introduced some significant biases."

And now it may be time to move on: "The time has come to look elsewhere for effective treatments." CBT and/or GET are still the topics of study when it comes to ME/CFS (see here and see here) but are seemingly finding it more and more difficult to find acceptance. The recent news that NICE are looking to update their guidance on CFS/ME in light of 'changes' made by other official bodies (see here) and some significant patient (and political) power, reflect an increasingly changing mood. An increasing realisation that talking and exercise therapies might not be the best treatment options for a somatic condition that has the propensity to *significantly* drain both health and other aspects of quality of life (see here).


[1] Wilshire CE. et al. Rethinking the treatment of chronic fatigue syndrome—a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT. BMC Psychology. 2018; 6: 6.

[2] White PD. et al. Recovery from chronic fatigue syndrome after treatments given in the PACE trial. Psychol Med. 2013 Oct;43(10):2227-35.


On mitochondrial DNA (mtDNA) changes and autism

Mitochondrial issues accompanying some diagnoses of autism have quite a bit of peer-reviewed research backing (see here for example). Not for everyone, but for some people diagnosed with an autism spectrum disorder (ASD), there seems to be something afoot with regards to these 'powerhouses of the cell' that could well impact on various aspects of their lives [1]. Indeed, keep that paper from Poling et al [1] in mind...

Although by no means an expert on mitochondrial issues in any context, I believe that there are a few ways in which mitochondrial dysfunction can manifest. It can present as a secondary disorder for example (see here), where some acquired biochemistry (non-genetic) provides some of the 'answers'. Or it can present as a primary mitochondrial disorder, a genetic condition "confirmed by a known or indisputably pathogenic mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) mutation" [2], where issues in the genetic code of mitochondria are present.

The recent findings reported by Noémi Ágnes Varga and colleagues [3] focused on that latter route looking at issues with mtDNA in the context of autism. They turned up some rather interesting results...

So: "The aim of the present study was to investigate the presence of the most common pathogenic mtDNA alterations in patients with ASD." Researchers screened 60 children with autism and 60 not-autism controls. One detail stuck out when it came to those controls: "Our control group for mtDNA screening consisted of 60 European adults (26 females and 34 males, median age = 28 years, IQR = 13.75) selected from our biobank." Compared with those participants diagnosed with autism, they were quite a bit older (median age = 7 years vs. median age  = 28 years) and indeed, the gender ratios were a little bit more balanced.

Anyhow: "Mitochondrial deletions were identified in 16.6% (10/60) of our patients with ASD." OK, 'patients' is not exactly the word I would use for participation in such a research project but that shouldn't distract from the findings. Varga et al also provide some further insights into those 10 'participants' with a diagnosis of autism and mtDNA deletion(s) which turned up some other interesting details, such as the finding that various other symptoms presented alongside autism. Quite a few of them were connected to muscle and movement functions (limb and truncal ataxia, hypotonia, dyspraxia) which ties into other independent findings [4]. I also noted the words 'gluten sensitivity' were mentioned in one case, which is guaranteed to perk my professional interest (see here) although I'm still a little unsure of whether this connected to mtDNA issues or not.

Another set of potentially important details were also observed by researchers when comparing those with autism with and without mtDNA deletion(s). Keeping in mind the small numbers falling into that autism with mtDNA deletion(s) category, developmental regression seemed to be an important facet of the clinical profile of this group. Regression of previously acquired skills is something else I've talked about quite a bit on this blog with regards to autism (see here and see here for examples). Going back to that paper by Jon Poling and colleagues [1] that I told you to keep in mind, it's interesting to note the overlap of regression reported by them and also reported by Varga in the context of mitochondrial disorder. And this isn't the only occasion that regression and mitochondrial issues have been talked about in the same breath as autism [5] and even with other potentially important clinical indicators [6]. Correlation is not necessarily causation but...

There are quite a few other details listed in the Varga paper that I'd encourage readers to pursue but I think I've gone on enough about this topic for now. It, yet again, appears that a diagnosis of autism is protective of nothing when it comes to other conditions/diseases/symptoms/labels appearing and perhaps implies that preferential screening for mitochondrial disorder should be more commonplace than it is as and when autism is diagnosed. I'm also inclined to draw your attention to other clinical labels where mitochondrial issues might be relevant for some (see here) albeit not always with genetics in mind (see here). How perhaps investigations need to be carried out looking at any possible intersection between *some* autism and something like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) (see here) for example, also in light of other important data (see here). Indeed, I'll be coming to the findings reported by Bilevicute-Ljunger and colleagues [7] on this topic quite soon in a separate post...


[1] Poling JS. et al. Developmental Regression and Mitochondrial Dysfunction in a Child With Autism. J Child Neurology. 2006;21(2):170-172.

[2] Niyazov DM. et al. Primary Mitochondrial Disease and Secondary Mitochondrial Dysfunction: Importance of Distinction for Diagnosis and Treatment. Mol Syndromol. 2016 Jul;7(3):122-37.

[3] Varga NA. et al. Mitochondrial dysfunction and autism: comprehensive genetic analyses of children with autism and mtDNA deletion. Behavioral and Brain Functions. 2018. 14: 4.

[4] Ghaoui R. & Sue CM. Movement disorders in mitochondrial disease. J Neurology. 2018. Jan 6.

[5] Rossignol DA. & Frye RE. Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry. 2012 Mar;17(3):290-314.

[6] Shoffner J. et al. Fever plus mitochondrial disease could be risk factors for autistic regression. J Child Neurol. 2010 Apr;25(4):429-34.

[7] Bilevicute-Ljunger. I. et al. Patients with chronic fatigue syndrome do not score higher on the Autism-apectrum quotient than healthy controls: comparison with autism spectrum disorder. Scandinavian Journal of Psychology. 2018.


Wednesday, 21 March 2018

Autistic traits + borderline personality disorder traits = enhanced risk of suicide ideation?

Following some quite recent discussions on this blog about how autism-related dimensions are not necessarily always autism-specific dimensions (see here) in the context of Borderline Personality Disorder (BPD), I'm talking today about the findings reported by Henri Chabrol & Patrick Raynal [1].

They detail some still emerging evidence that, alongside "significant comorbidity between ASD [autism spectrum disorder] and BPD", there could be some rather important outcomes arising from possessing both significant autistic traits and borderline personality disorder traits in the more general population when it comes to risk of suicide ideation. Further, that such data could also cast some light on that important issue for both clinical conditions and contribute to the pressing need to reduce any excess risk(s).

I've covered the issue of suicide - ideation, attempted and completion - on this blog a few times (see here). It's a topic that requires careful handling (see here) and something that, in respect of the core blogging material here, requires important continued attention (see here and see here).

Chabrol & Raynal detail results following the self-report of several parameters: autistic and BPD traits, thoughts of suicide and "depressive symptomatology" in a cohort of college students (N=474). They reported that, whilst BPD traits and autistic traits were only "weakly correlated", those participants who presented with both high BPD and high autistic traits (approaching 20% of their total sample) were the ones who expressed "the highest level of suicidal ideation."

Bearing in mind that this was research carried out with a 'non-clinical' population and a population that might not be necessarily completely representative of everyone else, additional investigations are warranted. Whether for example, the clinical combination of autism and BPD might elevate the risk of suicide ideation or beyond is one issue to be explored, particularly given research observing that suicide risk is not unknown to the diagnosis of BPD. I might also add that given the possibility of even greater complexity in behavioural/psychiatric presentation [2] coinciding with other observations in relation to some autism (see here), quite a wide research view might need to be taken. This coinciding with more and more evidence to suggest that autism is not typically a stand-alone diagnosis (see here).

And if anyone needs to talk to someone, organisations like the Samaritans are only an email or phone call away...


[1] Chabrol H. & Raynal P. The co-occurrence of autistic traits and borderline personality disorder traits is associated to increased suicidal ideation in nonclinical young adults. Comprehensive Psychiatry. 2018. Feb 15.

[2] Fan AH. & Hassell J. Bipolar disorder and comorbid personality psychopathology: a review of the literature. J Clin Psychiatry. 2008 Nov;69(11):1794-803.


Tuesday, 20 March 2018

"given that 81.6% of the children diagnosed with ASD had IQs below 40"

The quote titling this post - "given that 81.6% of the children diagnosed with ASD [autism spectrum disorder] had IQs below 40" - was part and parcel of the findings published by Zhijuan Jin and colleagues [1] who set about estimating the prevalence of autism or ASD among children resident in Shanghai, China.

This is not the first time that research groups have set out to determine the estimated prevalence of autism at a city / region / countrywide level in China [2], but does, I think, mark the first time that said prevalence estimates have been based on the DSM-5 description of autism (well, almost the first time [3]).

Looking at a population of some 75,000 children resident in Shanghai and aged between 3-12 years old, details of a two-stage project are described this time around. Parents and teachers completed the Social Communication Questionnaire to identify those children who might be 'at-risk' for autism/ASD. Those who were picked up as being 'at risk', were then subject to some rather more comprehensive assessment based on the use of DSM-5, of which just over 200 children were "identified as ASD cases." The estimated prevalence figure arrived at was 8.3 per 10,000 although the authors suspect that this is an underestimate...

But then back to that opening quote, and a quite a notable percentage of children diagnosed with autism who also presented with a low IQ classification. Bearing in mind the fact that there are differences in IQ ranges across different instruments, an IQ rating of 40 or below (age-adjusted) typically indicates quite a significant cognitive impairment or delay and is one facet of the diagnosis of learning (intellectual) disability. The observation from Jin et al that over 80% of their cohort could potentially be defined as such provides some important data on the combination of autism and learning disability (LD).

On previous blogging occasions when the topic of autism and LD has been discussed, the question of how prevalent is LD in autism has been a difficult one. On some occasions, the data has suggested that around 35% of children with autism have LD on the basis of IQ scores (see here). On other occasions, a figure nearer 70% has been implied (see here). The Jin data suggest that in their cohort, 70% may actually be quite a conservative estimate.

I would like to see more study on this topic. I'd like to know whether, seemingly like other ethnic groups, learning disability + autism is the more typical presentation when it comes to autism in Chinese children and how this plays out as children age into adulthood. I'd like to know whether the distinction between autism and social (pragmatic) communication disorder (SCD) noted in the DSM-5 exerted any effect on the Jin data. I'd like to know quite a bit more on this rather interesting area of investigation...


[1] Jin Z. et al. Prevalence of DSM-5 Autism Spectrum Disorder Among School-Based Children Aged 3-12 Years in Shanghai, China. J Autism Dev Disord. 2018 Feb 16.

[2] Sun X. et al. Prevalence of autism in mainland China, Hong Kong and Taiwan: a systematic review and meta-analysis. Mol Autism. 2013 Apr 9;4(1):7.

[3] Jiang L. et al. Epidemiological investigation on autism spectrum disorders among preschool children in Shanghai. Zhonghua Liu Xing Bing Xue Za Zhi. 2015 Dec;36(12):1365-8.


Monday, 19 March 2018

One more time... ADHD is over-represented in cases of epilepsy

"Among the 73 children with epilepsy, 23% (n = 17) had comorbid ADHD [attention-deficit hyperactivity disorder], of whom 59% (n = 10) had predominantly inattentive type, 35% (n = 6) combined type, and 6% (n = 1) predominantly hyperactive-impulsive type."

So said the findings reported by Anita Choudhary and colleagues [1] adding to an ever growing body of peer-reviewed research literature suggesting that a diagnosis of epilepsy may, for whatever reason(s), elevate the risk of ADHD being diagnosed or, at the very least, the symptoms of ADHD occurring (see here).

This time around, Choudhary et al focused on data derived from a children's neurology service where epilepsy was "defined as two or more unprovoked seizures occurring 24 hours apart after four weeks of age, with at least one epileptic seizure in the previous five years, regardless of AED [anti epileptic drugtreatment, based on International League Against Epilepsy definitions."

As per the opening sentence, some 73 children aged 6-12 years old met their study eligibility criteria; being part of a larger trial where data on behavioural comorbidity in the context of epilepsy had already been published [2]. Importantly for this latest study, the authors excluded those who "had an intellectual disability or comorbid chronic systemic disease" which seems to be rather relevant to the clinical picture emerging with regards to epilepsy in the context of a condition 'over-represented' in ADHD, autism (see here). Alongside a behavioural/psychiatric evaluation based first on parent/caregiver ratings and if required, followed up with a more professional consultation, researchers also carried out assessments related to cognitive functions and reviewed health records.

Aside from noting that ADHD seemed to be over-represented among their cohort with epilepsy, authors also talked about a couple of variables that also seemed to be important to the presentation of ADHD in those with epilepsy. So: "Children with both epilepsy and ADHD had lower IQ scores and were significantly less likely to be attending school, with epilepsy being the primary reason." That point about the presence of epilepsy *correlating* with lower IQ scores is not necessarily something prevalent across the research in this area, but some authors have talked about a "subgroup of about 10–25% of children that shows a clinically significant intellectual decline" [3] which could potentially be relevant.

Pertinent biological mechanisms crossing both epilepsy and ADHD? Well similar to the last blogging occasion, one has to mention that epilepsy does affect various brain functions (see here) so that is something to consider as also impacting the likelihood of ADHD. Whether this means affecting something structural or something like connectivity, we just don't know at present. I'm also minded to highlight the possibility of genetic overlaps too; drawing on work in autism where autism genes are not just genes for autism (see here) so one might consider a similar scenario pertained for at least some with the epilepsy-ADHD diagnostic combination...


[1] Choudhary A. et al. Childhood epilepsy and ADHD comorbidity in an Indian tertiary medical center outpatient population. Sci Rep. 2018 Feb 8;8(1):2670.

[2] Choudhary A. et al. Behavioral comorbidity in children and adolescents with epilepsy. J Clin Neurosci. 2014 Aug;21(8):1337-40.

[3] Vingerhoets G. Cognitive effects of seizures. Seizure. 2006; 15: 221-226.


Saturday, 17 March 2018

"specificity for diagnosis was relatively low": the psychometric properties of autism diagnostic measures

The quote accompanying this fairly brief post - "specificity for diagnosis was relatively low" - comes from the findings reported by Sarah Wigham and colleagues [1] who undertook a systematic review of various "structured questionnaires and diagnostic measures" used in the assessment of autism in adults.

Their conclusions, based on some 20 studies identified in the current peer-reviewed literature, suggest that 'could do better' is a phrase best suited to various measures currently used to identify adults with autism, particularly in the context of an often complicated clinical picture (see here).

Similar things have already been discussed on this blog (see here for one example). In particular, how individual self-report 'are you autistic?' screening instruments whilst making good 'pop psychology' (see here) are absolutely no match for a thorough professional clinical assessment, save other important diagnoses/conditions being overlooked and going unmanaged (see here and see here). I know this puts the concept of 'self-diagnosis' as a result of the use of such instruments in some hot water, but as in many other branches of medicine and psychiatry, professionals and the assessments they conduct are there for a very good reason. Whether you can access such assessments in a timely fashion is an entirely different issue...

When I first tweeted about this paper being published, I emphasised one author on the Wigham paper in particular: Dr Tom Berney. The reasoning behind this was because of his involvement/link to research that has looked at how we identify adults with autism here in Blighty on the back of some headlines a few years back on estimating how many adults have autism here (see here). He, alongside some other notable authors who highlighted that '1% of adults with autism' figure, also talked about how some of the screening/assessment instruments used in that study weren't really cutting the epidemiological mustard [2]. It appears they might have been right.

So what lessons can be learned from this recent review? Well first, that whilst autism-related behavioural dimensions are vitally important to a diagnosis of autism, they are not universally specific to a diagnosis of autism, is important. Second is the need to perhaps move away from often very brief autism screening instruments that seem to provide a 'quick snapshot' to something rather more far-reaching and comprehensive. I know we all want a 'quick answer' that uses as few finite resources as possible, but sometimes, to get something right, you need to spend time and resources looking at it carefully. And diagnosing professionals also need to be mindful of notions of 'frank autism' too (see here). Finally, I'd like to re-emphasise that autism plus [3] does seem to be more typical these days, over autism appearing in some sort of diagnostic vacuum. As Wigham et al opine: "Robust autism spectrum disorder assessment tools specifically for use in adult diagnostic health services in the presence of co-occurring mental health and neurodevelopmental disorders are a research priority." Indeed they are.


[1] Wigham S. et al. Psychometric properties of questionnaires and diagnostic measures for autism spectrum disorders in adults: A systematic review. Autism. 2018 Feb 1:1362361317748245.

[2] Brugha TS. et al. Validating two survey methods for identifying cases of autism spectrum disorder among adults in the community. Psychol Med. 2012 Mar;42(3):647-56.


Friday, 16 March 2018

Carefully: effect of SSRI use on "rating-scale-assessed suicidality in adults with depression"

I stress the word 'carefully' in the title of this post discussing the findings reported by Jakob Näslund and colleagues [1] because it covers the very sensitive idea that "selective serotonin reuptake inhibitors (SSRIs) have been claimed to elicit or aggravate suicidal ideation."

I think it's sensible to begin this post by stressing that (a) NO medical or clinical advice is given or intended on this blog, and (b) anyone with concerns about their taking this class of medicines really needs to speak to their physician BEFORE making any changes to their prescribed medication routine. I know that point (b) sounds like me giving medical / clinical advice but it's common sense to talk to your medical professional first who's spent years studying and probably years practising medicine, rather than tinker around yourself...

There is always a balancing act to consider when discussing research such as this. A medicine indicated for various clinical conditions, that is taken by many, many people, and quite successfully treating / treated (nay, very successfully [2]) a condition that can, without treatment, have life-limiting consequences. No-one wants to rock the boat and scare or deter people from accessing such a treatment. At the same time however, one needs to know everything about that medicine; not least whether for some, there may be side-effects to possibly consider...

It's been a quite a long running saga talking about the possible additional effects of SSRI use for some (see here). It's drawn heavily on often harrowing individual stories and perspectives and not also been helped by the seeming (in)actions of some of the manufacturers of such medicines (see here). Näslund et al decided to approach this delicate topic from the point of view of analysing "the effect of [SSRI] treatment on rating-scale-assessed suicidal ideation in individual patients." This is distinct from other work that has focused on actual suicides or "suicide-related adverse events" that have been carried out before. The authors suggested that their approach might have the advantages of measuring the "net influence of treatment on suicidality at a group level" as well as the ability to "detect individual cases of emergence or aggravation of suicidal ideation." To this end, scores on the Hamilton Rating Scale for Depression (HRSD) particularly focused on "item 3 of the HRSD" covering suicidal ideation/attempts, was a core feature of their study covering "young adults (18–24) (n = 537) and adults (≥25) (n = 7725)." Said participants were derived from "all industry-sponsored, HRSD-based, FDA-registered placebo-controlled studies undertaken to explore the effects of citalopram, paroxetine or sertraline in major depression in adults."

Results: "In patients above the age of 24, SSRIs were found to reduce the mean rating of the HRSD suicidality item from week 1 until study end-point and also to reduce the risk for aggravation of suicidal ideation and emergent suicidal behaviour." This is very good news. It provides "strong support for the view that the net effect of SSRI treatment is beneficial rather than harmful" when it comes to suicide ideation/contemplation bearing in mind the specific focus on on item on the HRSD. I will again link to the recent findings by Cipriani and colleagues [2] reporting that: "All antidepressants were more efficacious than placebo in adults with major depressive disorder." It doesn't, as Näslund et al suggest, rule out rare cases of 'adverse effects', but does suggest that any such extreme side-effects are not likely to be encountered by most people who take such medicines.

When however it came to those younger adults (aged 18-24 years), the results were a little less straight-forward. So: "In young adults, those given an SSRI were at enhanced risk for worsening of suicidal ideation (in the unadjusted analysis) or emergent suicidality (loose but not strict definition) during the late (weeks 3–6) but not the early phase (weeks 1–2) of treatment." You'll see from the number of brackets used in that last quote that the authors provide some caveats to such findings; but this shouldn't take away from the trends observed. Indeed, bearing in mind such findings and also that "both SSRIs and placebo resulted in an end-point rating of suicidality equal to that observed in adults given an SSRI and lower than that observed in adults given placebo" you kinda get the impression that further investigations are needed to ascertain for example, whether depression and/or suicidality in the 25 and overs is somehow 'different' from depression in the younger age group. At least, different insofar as what treatment choices might be primarily made available. No, I'm not saying that this is evidence enough that SSRIs should have some sort of age restriction, just that cost/benefit ratios might perhaps have to be a little more 'age-sensitive' as well as individual-sensitive.

And, if anyone needs someone to talk to, there are resources available.


[1] Näslund J. et al. Effects of selective serotonin reuptake inhibitors on rating-scale-assessed suicidality in adults with depression. Br J Psychiatry. 2018 Feb 5:1-7.

[2] Cipriani A. et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018. Feb 21.


Thursday, 15 March 2018

Childhood ADHD and vitamin D meta-analysed

The results of the systematic review and meta-analysis published by Yadollah Khoshbakht and colleagues [1] (open-access available here) make for interesting, if not totally unexpected, reading.

Covering the existing peer-reviewed research literature (up to June 2017) on the topic of vitamin D status and attention-deficit hyperactivity disorder (ADHD), researchers concluded that: "The present review provides evidence supporting the relation between vitamin D deficiency and ADHD."

Vitamin D and ADHD is a topic already covered on this blog (see here). The general direction of findings so far have kinda mirrored that seen in other developmental diagnoses such as autism, insofar as vitamin D deficiency / insufficiency as measured by concentrations of 25-hydroxyvitamin D, tending to be pretty over-represented alongside the label (see here). It's perhaps also pertinent to mention that the diagnostic combination of autism and ADHD seems to be quite widespread (see here); particularly in these days of ESSENCE or autism plus (see here). This could very well have a bearing on any observations obtained as per other examples in other areas (see here).


Khoshbakht et al looked at various studies and aspects of studies as part of their analyses. They also pre-registered their intention to undertake some research on vitamin D and ADHD as per a PROSPERO entry (see here) containing some details on hows-and-whys.

From various 'retrieved articles' numbering in the thousands, authors eventually settled on 13 studies ("9 case-control or cross-sectional studies and 4 prospective studies") that examined "the association between vitamin D concentration and the risk of ADHD." The final cumulative study participant number was not bad at all: "3484 patients with ADHD (2183 from the case-control and cross-sectional studies, 1301 from the prospective studies) and 11,837 healthy children (8151 from the case-control and cross-sectional studies, 3686 from the prospective studies) aged between 5 and 18 y were included." Authors also noted that various methods were used to measure 25-hydroxyvitamin D - 25(OH)D - ranging from the gold-standard that is liquid chromatography tandem mass spectrometry (LC-MS/MS) to something perhaps a little less accurate e.g. high-performance liquid chromatography (HPLC) minus the mass spec bit. All-in-all however, most studies were judged to be of moderate or high quality.

Results: "we found modest but significant lower serum vitamin D concentrations in children and adolescents with ADHD compared with healthy control subjects." Based on 9 studies where "the mean ± SD vitamin D concentrations in subjects with and without ADHD" was reported, authors concluded that "children with ADHD had 6.93 ng/mL lower serum vitamin D concentrations compared with healthy controls." And that wasn't all, as authors also looked at prospective studies where for example, vitamin D was measured in maternal serum or umbilical cord blood and then mapped onto risk of ADHD in offspring. With this type of study in mind, they observed that: "lower maternal or cord serum vitamin D concentrations increase the risk of developing ADHD in childhood or adolescence by 40%" albeit with some statistical caveats.

Khoshbakht and colleagues provide some possible pointers about how vitamin D *might* influence the pathophysiology of ADHD. They for example, mention an enzyme that I've been pretty interested in down the years - tryptophan hydroxylase 2 (TPH2) - and how the starting gene for this enzyme has been both linked to ADHD [2] in some studies (but not others). Further: "The TPH2 gene is activated by vitamin D hormone through its vitamin D response element." Personally, I find this interesting but not intellectually satisfying enough to provide an authoritative explanation for any effects of vitamin D deficiency on ADHD. Going also back to the vitamin D story with autism in mind, I'd like to think lessons could be learned about more particular vitamin D genetics (see here) and what role they might also play with regards to ADHD too. There are no doubt other pertinent mechanisms too.

There is still more research to do when it comes to vitamin D and ADHD of that there is no doubt. Again, going back to the relationship between ADHD and autism, I'm wondering whether more focus needs to be on this diagnostic combination (and perhaps other overlaps too) to ascertain whether one condition / label over another shows any stronger relationship with vitamin D levels. In light also of other meta-analysis work talking about lower vitamin D levels being linked to 'poorer cognition' (see here) for example, one might also reasonably suggest that an even broader research agenda might need to be followed.

And then there's the question of supplementation (see here) to consider and whether it may / may not do more than just raise vitamin D levels [3]? Oh wait, and there's more [4]...


[1] Khoshbakht Y. et al. Vitamin D Status and Attention Deficit Hyperactivity Disorder: A Systematic Review and Meta-Analysis of Observational Studies. Adv Nutr. 2018 Jan 1;9(1):9-20.

[2] Park TW. et al. Association between TPH2 gene polymorphisms and attention deficit hyperactivity disorder in Korean children. Genet Test Mol Biomarkers. 2013 Apr;17(4):301-6.

[3] Elshorbagy HH. et al. The Impact of Vitamin D Supplementation on Attention-Deficit Hyperactivity Disorder in Children. Ann Pharmacother. 2018 Feb 1:1060028018759471.

[4] Sahin N. et al. Vitamin D and vitamin D receptor levels in children with attention-deficit/hyperactivity disorder. Neuropsychiatr Dis Treat. 2018 Feb 19;14:581-585.


Wednesday, 14 March 2018

Bullying and autism: not always originating from where you might expect...

There is something rather uncomfortable about the findings reported by Imar Toseeb and colleagues [1] but, at the same time, they do raise an important issue that needs to be openly discussed. Specifically their findings on: "sibling bullying, and the associated psychopathological adversities, in children with and without ASD [autism spectrum disorder]" deserve some airtime.

Bullying and autism is quite a regular talking point in the peer-reviewed research literature (see here) and beyond. Although a diagnosis of autism is by no means protective of someone becoming a bully or being involved in what could be considered bullying behaviour, it is far more typical that those with autism are going to be a victim of bullying rather than perpetrator (see here). Indeed, I reluctantly use the word 'vulnerable' yet again on this occasion but...

When one thinks about bullying in any context including that with autism in mind I would imagine that the school bully who name calls or becomes physical aggressive towards someone - usually smaller and quieter than them - probably first springs to mind. Siblings by contrast, conjure up an image of being caring, supportive and again, with autism in mind, often very protective of their brother(s) and/or sister(s) given their important role, present and probably future. And indeed, many, many siblings are just that (see here).

But real life is rarely so clear-cut or 'homogeneous' as many parents, whether with children diagnosed with autism or not, will attest. Siblings argue, fight and probably because of how well they 'know each other', often know all the right buttons to press to get their required reaction. And yes, behaviour sometimes can spill over to what would be considered bullying under any other circumstance...

Toseeb et al started with the hypothesis that: "children with ASD (child has ASD but their sibling does not) would experience higher levels of sibling bullying compared to those without ASD (child and sibling do not have ASD)." They arrived at this hypothesis on the basis of various factors such as a role for the social-communicative issues that follow autism, the possible effect of the 'broader autism phenotype' (BAP) on siblings, and issues such as a greater frequency of aggression - "reactive aggression" - accompanying particularly boys with autism.

They relied on data from the Millennium Cohort Study (MCS) (a resource that has been mentioned before on this blog) and eventually included data from nearly 500 children with autism alongside over 13,000 not-autism controls. The question(s) on sibling bullying were asked at 11 years of age and went: "he/she was asked to respond to two questions on a six-point scale (never, less often, every few months, approximately once a month, approximately once a week, most days): “how often do your brothers or sisters hurt you or pick on you on purpose?” (victimization) and “how often do you hurt or pick on your brothers or sisters on purpose?” (perpetration)." Responses were coded according to who did what and how often. Various other measures were also examined as part of the MCS and used in the Toseeb paper: socio-demographic data (single parent status, birth order, number of siblings, household incomes), parenting style, psychopathology and cognition.

Results: children diagnosed with autism or ASD were more likely to be bullied by their non-autistic sibling compared with those who did not have autism. This finding held "even after controlling for socio-demographic and family level variables" and "was associated with adverse psychopathologies." Further: "having ASD, being a girl, of White ethnicity, having more siblings, and experiencing harsher parenting were all associated with increased odds of being bullied by a sibling." Whilst we're on the topic of 'adverse psychopathologies, it's perhaps pertinent to mention the findings reported by Dantchev and colleagues [2] observing a possible connection between sibling bullying receipt and psychotic disorder. Yes, it is quite an extreme example, but nonetheless demonstrates the effects bullying can have long-term. I might also refer you back to some discussion arising from the ICF core sets development with autism in mind too (see here).

I digress. I note also that authors discuss sibling bullying as a two-way street: "Our findings indicate that children with ASD are specifically at increased risk of sibling victimization as a bully-victim."

As I said at the beginning of this post, this all makes for uncomfortable reading. If it's not bad enough that a child may be being bullied at school to also then potentially learn that there is little respite from such behaviour at home, makes for an uncomfortable (intolerable?) situation all-round. The question then arises minus any sweeping generalisations: what can be done about sibling bullying for the good of all concerned? And please, don't just solely suggest 'coping strategies' for the bullying victim either.


[1] Toseeb U. et al. The Prevalence and Psychopathological Correlates of Sibling Bullying in Children with and without Autism Spectrum Disorder. J Autism Dev Disord. 2018 Feb 8.

[2] Dantchev S. et al. Sibling bullying in middle childhood and psychotic disorder at 18 years: a prospective cohort study. Psychological Medicine. 2018. Feb 12.


Tuesday, 13 March 2018

Regression in autism: the rule rather than the exception?

"Declining trajectories of development, consistent with a regressive onset pattern, are common in children with ASD [autism spectrum disorder] and may be more the rule than the exception."

So said the findings reported by Sally Ozonoff and colleagues [1] who reported results based on a study of developmental / behavioural regression in autism, and specifically: "how rates of regression differed by measurement method."

Regression in relation to autism is a topic I've covered a few times on this blog (see here and see here for examples). I've followed the [peer-reviewed] story from where behavioural and/or developmental regression was initially thought to be a figment of the [parental] imagination, right up to these days where regression is pretty much accepted as being part and parcel of quite a few cases of autism. The road has not been a smooth one; but the question of whether autism is universally something inborn and hereditary for everyone is slowly starting to be answered: no, it is probably not. The reason(s) for regression still remain fertile grounds for discussion / debate / argument, but there are some important clues in the science literature (see here and see here for examples) with the caveats that autism is a very heterogeneous condition and onset patterns are likely to be influenced by all-manner of different variables. Think different phenotypes in the context of autism (see here) for example; and that's outside of the label previously known as Heller's syndrome.

Anyhow, Ozonoff et al report results for infants "with (n = 147) and without a family history of ASD (n = 83)" who were "seen prospectively for up to 7 visits in the first three years of life." Various different ways and means of assessing reports of symptom onset were collected, "that systematically varied the informant (examiner vs. parent), the decision type (categorical [regression absent or present] vs. dimensional [frequency of social behaviors]), and the timing of the assessment (retrospective vs. prospective)."

Depending on who said what and how they said it, patterns of regression in skills were noted in quite a large proportion of the Ozonoff cohort. So: "A majority of the sample was classified as having a regressive onset using either examiner (88%) or parent (69%) prospective dimensional ratings." The authors suggest that their observations highlight how quite a few more resources (and cautions) need to go into looking at symptom onset patterns in relation to autism.

For quite a few people, the findings reported by Ozonoff et al are 'catch-up' rather than something novel. I can think of quite a few instances where parents / guardians have had their important observations - very important observations - described as being 'talked down' when it came to reporting a regression in previously acquired skills in the context of autism. This should no longer be the case; particularly when also set in the context of the increasing pluralisation of the label of autism (see here) and perhaps even, the changing face of autism (see here) compared with yesteryear.

Then to the next important questions: how and why? I've already alluded to a role for infection in relation to the onset of regressive autism for some, but much more data is required on the specific details and mechanisms. There is also the issue of what *might* potentially be done to minimise factors linked to regression in autism too. Minus any sweeping generalisations, I'd also direct your attention to other mentions of regressive autism in the peer-reviewed science literature [2] and where, minus any hype, there could be some important clues for some. The important point once again, is that the diagnosis of autism should be the start of further investigations, not the finishing line.

To close, don't ask me how or why but one of my brood has started watching and enjoying an old staple part of the weekend TV quiz scene in 1980s Blighty... BFH by the way, is most classically referred to as your 'bus fare home'.


[1] Ozonoff S. et al. Onset patterns in autism: Variation across informants, methods, and timing. Autism Res. 2018 Mar 10.

[2] Poling JS. et al. Developmental regression and mitochondrial dysfunction in a child with autism. J Child Neurol. 2006 Feb;21(2):170-2.


Monday, 12 March 2018

"A pilot study of high-dose intravenous immunoglobulin 5% for autism"

Intravenous immunoglobulin (IVIG), the treatment of choice for "patients with antibody deficiencies" [1] has some research history when it comes to autism (see here).

Quite a few years back, I remember some chatter about the use of IVIG for at least a subset of children/adults diagnosed with autism [2]. Interest in IVIG subsequently waxed and waned, partly as a result of some politics 'accompanying' research but also because of things like the cost of such an intervention.

Judging by the recent results published by Isaac Melamed and colleagues [3] however, it looks however, like IVIG *might* be coming back into research fashion...

So: "we investigated the efficacy and tolerability of intravenous immunoglobulin (IVIG) infusion in children with ASD [autism spectrum disorder]." The words "immune dysregulation" and "neuroinflammation" are mentioned a few times in the Melamed paper so you can probably work out the reason(s) why IVIG was examined. I might add that this study appears to have been registered with too (see here).

This was a pilot study so, of course, one always needs to be a little bit cautious when it comes to the study and any findings. But, from what I can see, the authors put in place quite a few 'primary' and 'secondary' endpoints covering various aspects of behaviour - "Children's Communication Checklist [CCC-2], Social Responsiveness Scale [SRS], Aberrant Behavior Checklist [ABC], Clinical Global Impressions-Severity [CGI-S] and -Improvement [CGI-I], Autism Diagnostic Observation Schedule [ADOS], and Peabody Picture Vocabulary Test [PPVT]" - and also some 'experimental' biomarkers of immune function in this study. That's quite a comprehensive battery all-in-all.

Based on the use of a "high-dose intravenous immunoglobulin" (1g/kg dose of Gammaplex 5%) for ten 21-day treatment cycles with some 14 research participants diagnosed with autism, researchers reported some signs of 'effect'. Behaviourally speaking, they talk about significant improvements in core areas such as reciprocal social interaction, communication and repetitive and/or stereotyped behaviours being observed. This, alongside significant reductions in "numerous secondary outcomes of immunological biomarkers indicative of neuroinflammation." In short, IVIG seemed to show effects and, importantly: "no subjects withdrew due to an adverse event" providing some well needed 'first, do no harm' data.

One study - an open label study at that - does not an evidence base make. Not even close, and that's despite other open label studies also being published [3] in this area. One also needs to bear in mind that IVIG is a blood product typically derived from more than one donor which, although screened for various infectious diseases, might still leave some people a little nervous about its use.

But... results such as the ones from Melamed cannot be easily ignored. Not least set within the context of a growing interest in immune function being *related* to some autism (see here for example) and specifically where 'regression' seems to be part and parcel of symptom onset (see here and see here), further [controlled] investigations are required. And that includes what happens to any behavioural / immunological gains / changes as and when IVIG intervention is stopped too...


[1] Jolles S. et al. Clinical uses of intravenous immunoglobulin. Clinical and Experimental Immunology. 2005;142(1):1-11.

[2] Gupta S. Treatment of children with autism with intravenous immunoglobulin. J Child Neurol. 1999 Mar;14(3):203-5.

[3] Melamed IR. et al. A pilot study of high-dose intravenous immunoglobulin 5% for autism: Impact on autism spectrum and markers of neuroinflammation. Autism Res. 2018 Feb 10.

[4] Boris M. et al. Improvement in children with autism treated with intravenous gamma globulin. Journal of Nutritional & Environmental Medicine. 2005; 15.


Saturday, 10 March 2018

The ICF core sets for autism in action

The findings reported by Soheil Mahdi and colleagues [1] (open-access available here) reiterate that 2018 looks like being the year of the ICF core sets for autism.

Having covered this topic yet again only recently (see here), I'm back to talking about the core sets and, once again, get to use the beautiful word 'melange' with reference to the "complex melange of functioning experiences beyond the diagnosis" of autism.

This time around it was about trying to "capture aspects of functioning and contextual factors pertaining to individuals with ASD [autism spectrum disorder] as assessed by the ICF-CY [International Classification of Functioning, Disability and Health (ICF, and Children and Youth version, ICF-CY)] in a clinical practice setting." I must admit to making a cold shudder when seeing the words: "The ICF-CY is grounded on an interactive bio-psycho-social model of functioning" in light of what the biopsychosocial model has 'done' to other conditions (see here). But in this case, I'm willing to give it the benefit of the doubt... at least for now.

So, from a starting participant group of 126 children, adolescents and adults with ASD (even though researchers used the children and youth version of the ICF), this number was slightly whittled down to some 122 who completed the study. It was a worldwide effort, as participants were drawn from 10 countries and, perhaps notably, the United States and United Kingdom were not among the countries taking part on this occasion. I was pleased to read that inclusion criteria for the study was a diagnosis of autism of course, but also did not exclude participants who also presented with "any given common co-morbidity." This, in light of 'autism plus' perhaps being more 'realistic' than autism appearing in some sort of diagnostic vacuum (see here).

Results: "In total, 139 of 161 ICF-CY categories assessed met the cut-off in at least 10% of the participants." The authors observed that this included "64 categories in the activities and participation component, 40 body functions and 35 environmental factors." Although you can look for yourself what issues/factors are included under those headings, I might point out a few of interest including the handling stress and other psychological demands, sensory functions and pain, functions of the digestive, metabolic and endocrine systems and the role of immediate family.

Continuing: "Examples of supportive personal factors included high IQ, acceptance towards own diagnosis and specific interests (e.g., art, sports)." These are also interesting. The role of 'acceptance towards own diagnosis' is something that has cropped up before in the peer-reviewed literature (see here). On that research occasion, the authors leaned towards a role for 'others' (external sources) accepting a person with a diagnosis of autism as being potentially 'positive' when it came to good mental health in the context of autism. I was perhaps more sceptical of the primacy of this 'other' influence - based as it was on rating statements such as "over the past week, I have felt accepted by society as an autistic person/person with autism" on a 5-point scale - insofar as 'personal acceptance' potentially being the more important variable. The Mahdi data seems to agree. The other 'supportive' variable, talking about having specific interests such as art or a sport, also tallies with a lot of other independent research findings (see here for an example, also using a certain WHO tool relevant to the ICF core sets for autism).

Onwards: "Past traumatic life events (e.g., getting bullied at school) were mentioned as a hampering personal factor, as it affected the individual’s self-esteem and self-worth." This, alongside various other routes to stress that "exacerbate ASD symptoms", provides some useful information about what could be done to mitigate such negative influences. I'm not sure that it is possible to completely eradicate issues such as perfectionism, but I daresay that it could be minimised through certain talking interventions for example, thus potentially improving quality of life. Insofar as the role bullying might play, well, probably quite a bit (see here) and any efforts to reduce things like bullying at school should be welcomed.

I do want to pass one final comment on the Mahdi data going back to the issue of comorbidity appearing alongside autism. As I've mentioned, this was a study that did not shy away from comorbidity being central to quite a few people diagnosed on the autism spectrum. The types of comorbidity reported included old friends such as attention-deficit hyperactivity disorder (ADHD), present in about a quarter of participants, and intellectual (learning) disability, present in about 15%. Whilst part of the clinical picture for quite a few, there is always the possibility that some of factors discussed in relation to the ICF core sets for autism *may* be more directly influenced by such comorbidity than by the 'core features' of autism themselves. I guess it doesn't matter if said comorbidity is part of the clinical picture, but if it's not, there may be some assumptions being incorrectly generalised...

And it appears that autism is not alone in its receipt of the ICF core sets treatment [2]...


[1] Mahdi S. et al. An International Clinical Study of Ability and Disability in Autism Spectrum Disorder Using the WHO-ICF Framework. J Autism Dev Disord. 2018 Feb 8.

[2] Mahdi S. et al. An international clinical study of ability and disability in ADHD using the WHO-ICF framework. Eur Child Adolesc Psychiatry. 2018 Feb 17.


Friday, 9 March 2018

Physical conditions accompanying intellectual disabilities

By linking to some media discussing the inquest findings for Richard Handley (see here) I don't want to trivialise his death or use it as some kind of 'I told you so' example. Here was a man who died as a result of "gross failures" in his care as someone with Down's syndrome who also had a history of bowel issues. His death, linked to chronic constipation and "as a result of choking on his own vomit having inhaled gastric contents following complications with surgery", represents failures on many different levels. Not least is a seeming lack of appreciation of how bowel issues can very much be part of the clinical profile of many conditions / labels / diagnoses considered within the spectrum of intellectual or learning disabilities. Said issues require both regular monitoring and appropriate and timely intervention.

It is perhaps notable then that the paper by Deborah Kinnear and colleagues [1] is published these days, highlighting how various physical conditions are over-represented alongside diagnoses characterised by intellectual (learning) disability. The authors reported that: "The five most prevalent were visual impairment, obesity, epilepsy, constipation and ataxic/gait disorders."

Based on the examination of data for "people with intellectual disabilities living within the geographical area of Greater Glasgow Health Board, Scotland" between 2002 and 2004, researchers reviewed case records and "completed a comprehensive semi-structured health interview and targeted physical examination and followed a phlebotomy protocol, with the person with intellectual disabilities and their carer." This was time consuming affair - the "complete assessment process took about 4 hours per participant" - covering over 1000 people.

Alongside the reporting of those 'top five most prevalent conditions', researchers also observed several other important details. Namely that nearly all of their cohort had a least one co-existing health condition. The average number of comorbid conditions was 11. Yes, that's 11. And some people had over 25 comorbid physical conditions. When also taking into account the presence or not of Down's syndrome, not much changed in relation to the detected physical comorbidity. Similarly, when age and sex/gender were examined, the authors concluded that there only minor differences noted in terms of comorbidity profiles for example.

Relevant to the case of Richard Handley are some discussions in the Kinnear paper about constipation and learning disability. So: "Constipation was the fourth most prevalent physical health condition." Further, they note in another study [2]: "Eight people with chronic constipation had serious side effects (rectal prolapse, diverticula of colon, intestinal obstruction, megacolon and haemorrhoids) and four eventually died of intestinal obstruction... Thus, as well as being painful, constipation may remain undetected for a long time and can cause death due to missed clinical symptoms." Constipation can cause death. It shouldn't in this day and age, but it still does...

In relation to the implications of their findings, the authors make some additional comments. So: "Medical education is also focused on assessment and management of single conditions, yet management of multimorbidity is far more complex." This is important. It implies that outside of the view of one [primary] diagnosis being present per patient, clinicians and others need to have a more plural view, particularly when it comes to something like learning disability. The focus also on 'physical' comorbidities is also important insofar as how various developmental / behavioural / psychiatric conditions can very much manifest other non-developmental / behavioural / psychiatric conditions. This kinda mirrors what has been discussed with autism in mind (see here and see here for examples) and, alongside, the barriers that need to be overcome when it comes to appropriate diagnoses being made in such contexts (see here).

Set within other data indicating that premature mortality is very much over-represented when it comes to learning disability (see here), and that much of that early mortality is due to the presence of physical health conditions, the Kinnear findings should serve as a wake-up call to many sectors of the professional and other communities. Screening, diagnosing and implementing timely and appropriate intervention(s) are key recommendations; with a specific focus on the person as a whole rather than just being the sum of individual somethings like the diagnosis of learning disability. Bear in mind also that guidance on the management of something like constipation in the context of learning disability does exist in the peer-reviewed domain [3].

And finally, just in case you think that today's discussions aren't directly relevant to autism, constipation has also been mentioned in the death of another young person (see here)...


[1] Kinnear D. et al. Prevalence of physical conditions and multimorbidity in a cohort of adults with intellectual disabilities with and without Down syndrome: cross-sectional study. BMJ Open. 2018; 8: e018292.

[2] Evenhuis HM. Medical aspects of ageing in a population with intellectual disability: III. Mobility, internal conditions and cancer. J Intellect Disabil Res. 1997 Feb;41 ( Pt 1):8-18.

[3] Robertson J. et al. Constipation management in people with intellectual disability: A systematic review. J Appl Res Intellect Disabil. 2017 Nov 23.