Participatory research in autism continued

Consider this post discussing the findings reported by Gregory Hollin & Warren Pearce [1] a continuation of some previous chatter on the topic of participatory research and autism (see here). Participatory research means just that: meaningful engagement of "users, publics, and stakeholders with scientific research." It's something that has come further and further to the forefront in recent years, as the term 'Nihil de nobis, sine nobis' ('Nothing About Us Without Us') has steadily moved from the textbook to real life.

The tone of the Hollin & Pearce article is somewhat different from that of the Fletcher-Watson article [2] which was covered in my last post on this topic. That previous article was heavy on themes derived from some seminars on how participatory research with autism in mind should look including: "Respect, Authenticity, Assumptions, Infrastructure and Empathy." The latest article deals more with the practicalities of such participation, warts and all, from the sole perspective of [assumed] non-autistic autism researchers.

Before heading into the Hollin & Pearce article, I should warn viewers that this is not going to be one of those 'everything's rosy' kinda discussions. There are some uncomfortable results reported as part of the Hollin/Pearce qualitative analysis as per their talking to various research persons about their experiences of participatory research. Their cohort: "The sample consisted of seven Professors, two Readers, one Senior Lecturer, one Associate Professor, two Lecturers, and seven Postdoctoral Researchers." All held academic posts at a British university and all "had self-declared interests in psychology, neuroscience, and autism."

Warts and all is a good description of the findings discussed by the authors. They mention two key themes relating to the experience of participatory research and autism in their cohort. First: "disagreements within the autistic community are caused, in part, by the heterogeneity of the autistic condition." An example: "During the debate one individual stands up and says ‘I am a neurodiverse person and you must respect me’. At this point another autistic individual invariably rises and says ‘if I could throw a switch tomorrow and get rid of it I would’." I've previously talked about the idea that a singular 'autism community' is wishful thinking at best, despite such a term being thrown about willy-nilly in all-manner of different circumstances. There is no 'autism community' in the same way that there is no 'schizophrenia community' or 'depression community'. The label(s) just cover too much ground to describe anything other than an overarching diagnostic code. Such a label says nothing about the life, views, opinions and politics of an individual in receipt of the diagnosis.

Second: "the socio-communicative impairments typical of autism... make any form of rapprochement or compromise particularly difficult." Some people will take offence to that last sentence. They'll take offence by the use of the word 'impairments'. They'll take offence at the idea that some of the features of autism *might* not be 'all positive' and on occasion, might make ideas like 'compromise' particularly difficult for someone. And to prove a point, the authors cited one viewpoint: "I mean I got in trouble with a lot of autism advocates for suggesting that having specialist interests wasn’t always a great thing. You know, they came down on me like a ton of bricks but, you know, then this is it, they can’t sometimes see that it’s not." I'm not a great fan of concepts like 'theory of mind' and how it's been almost universally applied to autism down the years (see here). But when reading such viewpoints, it is kinda hard to say that 'perspective' and specifically 'taking another's perspective' might not be an issue for some people. And just before anyone gets a bee in their bonnet about the focus being just on those with autism, I do have a great deal of time for the idea of a double-empathy issue in relation to autism and not-autism too.

Onward: "scientists consistently said that they valued the input of autistic individuals and advocates." Hollin & Pearce mention how, despite the inherent difficulties in ensuring that participatory research in autism is truly participatory across the spectrum, researchers do value the input from those on the autism spectrum. Terms like 'inner experience' and 'shaping research priorities' are mentioned in their paper, and how autism research is all the better for engaging with the autism communities (plural). I agree.

They also go on to suggest a few ways in which participatory research could be improved: "it is important that dissensus is recognized and embraced." What this means is that autism researchers shouldn't set out to 'please all of the people all of the time' when it comes to their professional interests and study of autism. Acknowledge that their research will pretty much always have a mixed reception but at least serve one part of the heterogeneous autism spectrum, hopefully in terms of improving quality of life. I'd also highlight the idea that social media is not necessarily representative of real life or any particular diagnostic group, so don't also go looking for Twitter appreciation either. Next: "far greater effort needs to be invested in developing mechanisms and venues which allow fruitful dialogue." Employ strategies such as focus groups and round table discussions by all means; talk to people, listen to people and learn from people. But bear in mind that for some on the autism spectrum, such discussion are in reality going to be a very distant prospect as things currently stand, as their 'disabilities' will undoubtedly affect their participation (see here). Indeed, as I mentioned in my last post on participatory research and autism, one of the big research priorities coming from the joint research and autistic communities should perhaps be moves to providing a voice to all of those on the autism spectrum, particularly those who seemingly don't have a voice (see here). Oh, and bear in mind that parents are often the biggest advocates for their autistic children so be a little careful before disregarding their important input too.

What else? Well, I'm inclined to add that participation from those on the autism spectrum shouldn't just be taken as being voluntary. Pay people. Pay people for their time and effort. And pay them as you would anyone else who involves themselves in research.

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[1] Hollin G. & Pearce W. Autism Scientists’ Reflections on the Opportunities and Challenges of Public Engagement: A Qualitative Analysis. J Autism Dev Disord. 2018. Oct 24.

[2] Fletcher-Watson S. et al. Making the future together: Shaping autism research through meaningful participation. Autism. 2018 Aug 10:1362361318786721.

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New name: Systemic Exertion Intolerance Disease?

The name is: Systemic Exertion Intolerance Disease (SEID) (which as one of my very observant Facebook friends pointed out is DIES backwards).

A very quick post to direct you to the public release of the findings from the US Institute of Medicine (IoM) looking at the name and current criteria used to diagnose Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS/ME) (see here). The proposed diagnostic criteria for CFS/ME, sorry SEID can be viewed here.

Some of the background to these findings can be seen here and some of the media about the new IoM recommendations can be seen here and here.

Many with either personal or professional experience of CFS/ME will know all about the issue of diagnosis and CFS/ME, and outside of the struggle to recognise that this is a very real condition which can severely impact on a person's life, how confusing the diagnostic criteria can be. This has also had various implications on both research and practice [1].

The IoM was charged with looking at the existing ways and means that CFS/ME was defined and "recommend clinical diagnostic criteria for the disorder to address the needs of health providers, patients, and their caregivers" (see here). To that end, their guidance now reflects these efforts although at the current time I'm having some difficulty in locating how they tackled the idea of "distinguish[ing] between disease subgroups" which I think should have represented quite a big leap forward in these days of plural labels and heterogeneity in symptoms and comorbidity (see here). At this point I might refer you to a paper I wrote that touched upon this a few years back [2]. I am however happy to see that pediatric ME/CFS or SEID has been mentioned in their various guidance in light of the growing realisation that the condition can manifest in children and young people too (see here).

Obviously it's going to take time for these findings to find their way from guidance to practice and beyond so I don't think massive changes will be immediately forthcoming. One would hope that alongside the growing interest in the biology/genetics of CFS/ME (acknowledging how the condition can also impact on psychology too) that moves towards the development and testing of biological therapeutics in particular, might be accelerated (see here).

To close: Breaking Bad and Say My Name... 'sorta Greg'.

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[1] Morris G. & Maes M. Case definitions and diagnostic criteria for Myalgic Encephalomyelitis and Chronic fatigue Syndrome: from clinical-consensus to evidence-based case definitions. Neuro Endocrinol Lett. 2013;34(3):185-99.

[2] Whiteley P. et al. Correlates of Overlapping Fatigue Syndromes. Journal of Nutritional and Environmental Medicine. 2004; 14: 247-259.

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Morris G, & Maes M (2013). Case definitions and diagnostic criteria for Myalgic Encephalomyelitis and Chronic fatigue Syndrome: from clinical-consensus to evidence-based case definitions. Neuro endocrinology letters, 34 (3), 185-99 PMID: 23685416

Six developmental trajectories, autism and bloomers

"If you've met one person with autism, you've met one person with autism" is how the saying goes. Heterogeneity is a keyword accompanying most descriptions of autism spectrum conditions; that and the fact that comorbidity is a mighty complex thing when it comes to presentation and interaction with core autism features.

Enter then a study by Christine Fountain and colleagues* (full-text) and the suggestion that from diagnosis in early infancy to aged 14 years old, children with autism spectrum conditions are likely to fall into one of six developmental trajectories related to their symptom presentation and progression. Perhaps even more surprising is the suggestion that within one of these trajectory groups, about 10% of children experience "rapid gains", blooming and outgrowing their severe disabilities by adolescence according to some of the media reports. Interesting isn't it?

The paper is open-access but here is a short summary of the findings:

• Group based trajectory modelling was carried out based on the core triad of symptoms for 6975 children with autism identified through the California Department of Developmental Services (DDS) records.
• Core symptoms of autism were assessed based on a Client Development Evaluation Report (CDER) which whilst not diagnostic for autism, has items covering the domains of communication, social interaction and repetitive behaviours. Several CDERs for each participant provided a longitudinal measure of how symptoms developed over time.
• Six groups were modelled from the cumulative data and grouped high to low based on functioning within the triad of domains.
• The results: based on the CDER scores for the communication domain, all groups showed an improvement in communicative function at 14 years compared with 2-3 year old baseline scores. Where you started in terms of 'functioning' seemed to determine where you ended up: more able children finished with better scores at study end. This was true aside from one group, termed 'bloomers', who showed some quite astonishing improvements in communicative function crossing over other group profiles and peaking at the time puberty would be expected before plateauing slightly. Same scenario for the social area trajectory. Group scores for repetitive behaviours were less uniform, with several groups actually showing a greater frequency of such behaviours over time and maturation as per other studies (here and here).
• There was some noticeable heterogeneity between participants and groups and intellectual / learning disability also seemed to play a hand in outcome.
• What were the characteristics of 'bloomers'? Well, generally-speaking, aside from presenting with quite severe problems in communicative and social areas at an early age, they were more likely not to have intellectual disability comorbid and perhaps have mothers who were white and quite well-educated. I'm not totally impressed by these last socio-economic factors and their involvement, but can perhaps see why they might be included in the analysis.

As the authors note, this study is a bit of a first in that it collected lots of consistently-derived data over quite a long period of time charting childhood for quite a lot of children diagnosed with autism. Following on from another quite recent paper asking about whether it is possible to grow out of autism, the answer from this study is that at least for a proportion of children who start with quite severe autism, the prospects for improvement are potentially really quite good over the period of childhood. Puberty however seems to offer its own little challenges as many parents of children with autism can testify.

There are however a few gaps not covered in this latest paper. So for example, how many children used some kind of intervention, be it educational, behavioural or biomedical and what effect this might have had on core symptom presentation; whether other important comorbidity such as epilepsy or seizure-type disorders had any bearing on symptom progression; and more practically whether behavioural scores relating to the triad of autism symptoms reflected real-world progression in terms of educational attainment and use or loss of the diagnostic label of autism.

I have to say that I am really interested in this paper. Interested because of the close developmental trajectory across both language and social domains noted in this paper as conceivably offering support for the proposed dyadisation (is that a real word?) of the diagnosis of autism. But mainly interested in the 'bloomer' category of children across the different domains.

All participants were diagnosed with autism, but I wonder about this bloomer group and whether their 'autism' was somehow different in terms of something mimicking a more classical presentation of the condition. Without trying to sound too contentious, the first thing that passed my mind was infection as being potentially related. Encephalitis, meningitis and other related conditions affecting children early and leading to the kind of symptoms noted in the current paper. As time goes on, the infection passes, the brain taps into its fantastic plasticity properties and hey presto, symptoms start to abate - at least to some degree.

Post-encephalitis cases of autism have been reported down the years (here and here) and whilst correlation does not imply causation, autism cases overlapping with the seasonality of viral meningitis have also been recorded. Of course there are lots and lots of other potential infections which could also show some involvement as per the suggestion 40 years ago now linking autism and rubella. I made a suggestion a post back about looking at T.gondii antibodies in relation to autism given the quite startling links being made with other conditions. Who's to say that they might also show some involvement? (Dare I even mention PANDAS or is it called PANS now?)

Those that read this blog will know that I am a fan of looking at endophenotypes in relation to autism and other conditions. The way I see it is that the categories reported in this study are ripe for this 'phenotype' kind of approach and in particular a detailed inspection of those bloomers in relation to the immune system, mitochondrial function, overlapping autoimmune conditions, even bowel symptoms, alongside lots and lots of other parameters just to see if there are any potentially important differences.

I don't want to lose sight of the 'individuality' that accompanies autism and its presentation despite the evidence presented by Fountain and colleagues. The move however to recognising that a group of children on the autism spectrum may possess a slightly different developmental trajectory to others is something that really should start to make people sit up and ask 'who' and 'why'?

* Fountain C. et al. Six developmental trajectories characterize children with autism. Pediatrics. April 2012.
DOI: 10.1542/peds.2011-1601

Genes, SNPs, CNVs and autism

I open this post with a quote from a relatively new article:

"We show that as many as 2193 genes, 2806 SNPs/VNTRs, 4544 copy number variations (CNVs) and 158 linkage regions have been associated with ASD by GWAS, genome-wide CNV studies, linkage analyses, low-scale genetic association studies, expression profiling and other low-scale experimental studies".

The paper in question is this one (open-access) from Li-Ming Xu and colleagues*.

The first thing that struck me when I read this abstract is wow... autism is complicated. OK, nothing new in that statement and for those regular readers who quite often see me gently tugging at the loose threads of various genetic findings, I suppose summaries like this go to show that the concept of an 'autism gene' is pretty well past distant memory seemingly heading the same direction as Voyager 1. In fact reading through this quite complicated paper, perhaps too complicated for me, several things popped into my mind. Stop me if you heard these before:

• If there was a prize for really knuckling down, collecting and collating data, Li-Ming Xu and colleagues might very well be in the running for it. I say this not only for their paper but also the database they developed on the genetic findings related to autism which is quite brilliant (here). If you have a few hours free (don't we all!), I would definitely recommend browsing the dataset which covers everything including population differences, gender differences and even how the diagnosis of autism was arrived at.
• Yep, lots of genetic findings related to lots of different autisms. When you see the the various studies all laid out and summarised like this, I tend to wonder what similar analyses might look like for other developmental conditions like ADHD, dyslexia, learning disability, etc. How about if researchers conducted genome wide analyses of a group of children randomly selected from your average town or city, how would they compare with these results? How much overlap would there be and how many genes might be associated with this random group? I would wager that there would be quite a bit of overlap in terms of the number of genes, SNPs, CNVs et al related to our random group simply because we are all the product of mutation.
• Heterogeneity is something most people with a connection to autism will know about. If you've met one person with autism, you've met one person with autism is a common saying. Further complicating that heterogeneity is the issue of comorbidity; so like everyone else, people with autism carry varying risks for other conditions. Whether these conditions are more or less likely to be related to some of the collected genetic findings... [fill in the blank].
• Given the wide range of genetic findings in "autism", is this perhaps a sign that the field of genetics needs to start (continue) diversifying; looking at sub-groups or phenotypes for example, a little more closely if it wishes to more ably describe autism or at least certain types of autism. There are already some signs of this happening as exemplified by the paper a few years back looking at paraoxonase gene SNPs in Italian vs. US cohorts.
• As per previous posts, there is a new sheriff coming to town with regards to genetics; epigenetics: changes to gene function not due to changes to DNA. "Hey Pilgrim, you forgot your pop-gun".

Still today some people talk about an autism gene as if right on chromosome X [fill in the blank], findings are going to emerge to say that 100% of people with autism will show issues with gene X compared with 0% of the non-autism population (however you define this as) and that genetic tests for autism are only years away. The problem is that there is no evidence of this either happening now or going to happen any time soon. Indeed as with everything, the more you look at it, the more complicated technology you apply to it, the less you seem to know about it and the more questions start to be asked. Yes, our genes are a big part of us and control lots and lots and lots of different things. But they don't do it in isolation. Crikey, even our gut bacteria might be involved in some processes!

To end a song for Mrs Robinson.

* Li-Ming Xu. et al. AutismKB: an evidence-based knowledge base of autism genetics. Nucleic Acids Research. December 2011.

Biomarkers for autism

Perhaps one of the primary stumbling blocks for the various strands of autism research is the lack of objective 'markers' to denote cases of autism from not-autism. Sure, we have the various diagnostic descriptions of autism based on observable behaviour and analysis of developmental history, and these do a pretty good job of providing diagnostic information. The problem however is that the 'label' of autism, whilst good for assessing strengths and weaknesses, accessing the relevant services and opportunities and in some cases providing an 'explanation' for the presentation of specific behaviours, is not actually a very objective and definitive concept when it comes to studying autism. Don't believe me? How about the relative stability / instability of autism presentation?

I must add that not for one minute I am suggesting that autism is not autism or there is anything wrong with the 'observe and checklist' method currently used; there is not - its the only thing we have at the moment and the clinicians who carry out such assessments are indeed skilled. My point is that the lack of markers outside of just presented behaviour is a significant hindrance to autism research and in particular the various searches for genetic and environmental factors potentially linked to the condition.

A new paper published in Nature Reviews by Walsh and colleagues* discusses some of the issues around biomarker research in autism. The paper is open-access and can be viewed here.

It is quite a good read and provides a good overview of the various challenges facing biomarker research in autism (or should that be autisms).  Issues such as heterogeneity, co-morbidity and the changing ideas of what autism is both diagnostically and culturally, are all covered in the paper. Gone perhaps are the days when autism was going to be diagnosed on the basis of one or perhaps two genes, compounds or anatomical structures to be replaced by something altogether more complex and multi-disciplinary. I am taken back to my post a few days ago on the presentation by Prof David Amaral and the sterling work at the MIND Institute on more than on 'type' of autism.

It strikes me that one of the ways forward in trying to determine biomarkers for autism is to concentrate less on a 'universal' biomarker for autism and instead similar to the MIND Institute model, looking at subgroups. Move away from the autism diagnostic label as your starting point and focus on other things, such as response to a particular intervention or strategy and compare your 'responders' and 'non-responders' to ascertain any biological/genetic/anatomical differences. Not only would this inform about which people on the autism spectrum might benefit from which interventions, but eventually one might assume that such markers would delineate those all important subgroups which might lead into some interesting areas.

Just a thought.

* Walsh P. et al. In search of biomarkers for autism: scientific, social and ethical challenges. Nature Reviews: Neuroscience. Vol 12. October 2011.