Are early "movement and sensory differences" prodromal signs of autism?

"These results highlight the importance of early surveillance of children who are at elevated risk for ASD [autism spectrum disorder], and early initiatives should focus on early signs of the phenotype, including both movement and sensory differences (prodromal signs) prior to the emergence of diagnostic characteristics."

It was that sentence from the findings reported by Lori-Ann Sacrey and colleagues [1] (open-access available here) that caught my eye, and the idea, once again, that movement 'issues' should perhaps be considered a core feature of autism (see here) or at least more of a core feature than they currently are. I might add that I've covered other important findings from Sacrey et al on this blog previously (see here).

Although open-access, a few details might be useful: "Infants were selected at random to comprise three groups of equal size: (1) 10 non-sibling controls (LR [low risk]-control; 7 boys); (2) 10 HR [high-risk] siblings without an ASD diagnosis (i.e., with an older sibling with ASD but did not receive an ASD diagnosis themselves at 36 months; HR-N; 3 boys); and (3) 10 HR siblings with an ASD diagnosis (i.e., with an older sibling with ASD and also received an ASD diagnosis at 36 months; HR-ASD; 6 boys)." As you can see the participant numbers were fairly small but to balance this, authors did report results based on testing "for differences in reaching-to-grasp" across quite a long period (6-36 months) and utilised quite an array of psychometric testing tools pertinent to their population and study aims.

Researchers found that: "Children who were later diagnosed with ASD showed higher (worse) total scores on the reach-to-grasp movement, as well as higher scores on the components of Orient, Lift, and Pronate compared to children in the LR and HR-N groups." They concluded that: "results suggest that such movement mechanics are relevant to monitoring motor development in children at risk for or diagnosed with ASD." Ergo, there may be quite a bit to see when it comes to early surveillance for autism in respect of movement and/or sensory differences.

Just before you leave I'll also bring the findings reported by Emilia Biffi and colleagues [2] to your attention. Theirs wasn't so much a study of the possible early 'prodromal' signs of autism with a focus on movement patterns but rather another finding suggesting that such movement issues may be persistent in relation to autism and can be readily tested for. Utilising some pretty nifty movement capture technology - "an immersive virtual environment using a 3-D motion analysis system with a dual-belt, instrumented treadmill" - Biffi et al reported that their findings "depicted gait peculiarities in children with ASD, including both kinetic and kinematic features." Movement and gait issues it seems, may very well be a vitally important part of autism...

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[1] Sacrey LR. et al. The reach-to-grasp movement in infants later diagnosed with autism spectrum disorder: a high-risk sibling cohort study. J Neurodev Disord. 2018 Dec 27;10(1):41.

[2] Biffi E. et al. Gait Pattern and Motor Performance During Discrete Gait Perturbation in Children With Autism Spectrum Disorders. Front Psychol. 2018;9:2530.

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Screening for autism 'symptom complexes' among residents in secure children's homes

A secure children's home (SCH) mentioned in the title of this post typically refers to a place where care and accommodation is given to "children and young people who have been detained or sentenced by the Youth Justice Board (YJB) and those who have been remanded to secure Local Authority (LA) accommodation." The paper published by P.J. Kennedy and colleagues [1] provides some interesting details about the prevalence of autism or "symptom complexes compatible with ASD [autism spectrum disorder]" among young people residing in two SCHs here in Blighty, alongside some initial demographic data around those detected.

Over 110 adolescents housed in SCHs were included for study, where their support workers completed the Social Communication Questionnaire (SCQ) on their behalf. The SCQ is one of the more important autism screening questionnaires. It's not however considered 'diagnostic' and is not without it's issues (see here), hence the use of the words "Symptom Complexes Compatible with Autistic Spectrum Disorder" by Kennedy et al. The results suggested that approaching 15% of their cohort were judged to present with symptoms/traits compatible with a diagnosis of ASD. Authors also mentioned how certain 'aspects' of positive screeners might also be important; for example, "differences in gender, legal status and a history of Child Sexual Exploitation (CSE)." There's also mention of an important word - 'vulnerability' - in the Kennedy paper, which I've often said is still very much under-used when it comes to the autism spectrum (see here and see here for examples).

Whilst further work is required on autism (whether in diagnosis or 'symptom complexes') in the context of SCHs, the suggestion that autism or autistic traits may be over-represented among SCH residents is an important one. I should add that whilst SCHs house those who have been 'detained or sentenced by the Youth Justice Board' they do also cater for quite a wide range of issues/difficulties outside of those presenting with offending behaviour. This includes those who may be at risk to themselves and others alongside those with mental health difficulties. This is an important detail in the context that I don't want to promulgate the idea that towards 15% of 'offenders' have an undiagnosed autism spectrum disorder (ASD). We don't yet know this, and need to keep in mind other important issues such as the growing realisation that autism rarely exists in a diagnostic vacuum (see here) and what that might mean for those on the autism spectrum who do offend (see here).

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[1] Kennedy PJ. et al. Brief Report: Using the Social Communication Questionnaire to Identify Young People Residing in Secure Children's Homes with Symptom Complexes Compatible with Autistic Spectrum Disorder. J Autism Dev Disord. 2018 Jul 17.

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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'.

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[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.

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Mortality patterns in older adults with learning disability

"Older adults with ID [intellectual disability] in Sweden carry a higher mortality risk compared with the general population, mainly attributable to respiratory, nervous and circulatory diseases."

So said the findings reported by Nawi Ng and colleagues [1] (open-access) looking at the records of some 15,000 individuals diagnosed with an intellectual (learning) disability compared with a similar number of control participants with respect to "patterns and risk of mortality." Researchers observed "a 4-fold higher mortality rate and a shorter median survival time among older adults with ID compared with the general older adult population." Such findings add to a growing body of research literature (see here and see here) suggesting that behavioural, cognitive and/or psychiatric diagnoses seem to be accompanied by some significant health inequalities too.

I could go into the details about the Ng study and the various ins-and-outs of how they arrived at their conclusions but to be honest, I'm just not minded to. I say that on the basis that the figures speak for themselves: "the mortality rate among individuals with ID was three times higher than in the control population" and: "Individuals with DS [Down's syndrome] had an 11-fold higher mortality risk than the control population." Sombre reading, perhaps partially reflecting how modern-day society treats some of its most vulnerable citizens.

The ultimate question should be: is there anything that can be done to improve this situation for those with a learning disability? Yes, is the answer; taking into account how a diagnosis of ID for example, means that some might be "more prone to cardiovascular disease risk factors, morbidity and mortality than the general population." The authors add that: "Cardiovascular disease health promotion and prevention programmes should be tailored for individuals with ID, to prevent or delay cardiovascular diseases and premature mortality in this vulnerable group." Corresponding action in relation to deaths resulting from epilepsy for example, should also (and always) be a priority.

"How a society treats its most vulnerable is always the measure of its humanity" is a phrase attributed to many speakers. On the basis of the research from Ng and other study results, society is seemingly failing many of those diagnosed with a learning disability as it is other vulnerable sections of society (see here).

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[1] Ng N. et al. Mortality patterns and risk among older men and women with intellectual disability: a Swedish national retrospective cohort study. BMC Geriatrics. 2017; 17: 269.

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NEET (not in education, employment or training) status and mental health

"NEET [not in education, employment or training] status and negative symptoms are modifiable predictors of illness trajectory across diagnostic categories and are not specific to transition to psychosis."

So said the findings reported by Shane Cross and colleagues [1] (open-access) who set out looking at the "trans-diagnostic study of rates and predictors of early transition from sub-threshold to full syndromal mental disorder" with "sub-syndromal unipolar, bipolar and psychotic disorders" in mind. This work adds to a growing body of research suggesting that "social as well as clinical characteristics of individuals presenting to youth mental health services for the first time (e.g. demography, symptom severity, functional impairment and NEET status) can help to predict the likelihood of and time to early transition across diagnostic groups."

Nearly 250 people aged 15-25 who were deemed to present with "a sub-syndromal presentation of a potentially severe mental disorder" were followed for a year to see if and whether there 'sub-syndromal' status 'transitioned' to a a full syndromal psychiatric disorder. Various measures were employed to assess current symptoms as well as researchers keeping an eye on those social factors including NEET status.

Results: around 15% of the group moved from a sub-syndromal status to "threshold caseness" during the study period: "Eleven per cent (11%) of sub-syndromal depressive cases, 40% of individuals with sub-syndromal psychosis and 22% of individuals with sub-syndromal bipolar disorder transitioned to stage 2 [threshold caseness]." Gender seemed to play a role - more females than males transitioned - and more negative symptoms - blunted affect, emotional withdrawal, motor retardation - as measured using the Brief Psychiatric Rating Scale (BPRS) seemed to show an effect also.

NEET status was also flagged up as a potentially important variable in transition: "26% of those who were categorised as NEET at baseline versus 16% of those who were not NEET had reached threshold caseness." NEET status as a variable also seemed to span various different psychiatric labels too.

What are the implications of such findings? Well, aside from providing a little more data about what factors might move someone from sub-clinical presentation of a mental health condition to full 'caseness' they also provide evidence that social factors might play a role. By saying this, I'm not going all 'biopsychosocal' on you (I think we've had quite enough of that, thank you very much) but rather stressing that both biological and social drivers probably impact on mental health as per other examples in the [growing] peer-reviewed research literature in this area (see here).

Other research from members of the Cross paper have looked at the possible drivers of NEET status [2] and where 'early intervention' might need to focus to offset risk of this social outcome (and potentially then impact on risks to mental health too) bearing in mind that intervention might need to be cross-generational [3].

I however, close with research indicating that any sweeping generalisations about those fulfilling NEET status as being 'unmotivated' to work are not warranted on the basis of the existing peer-reviewed science in this area [4] and what implications this has for mental health issues...

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[1] Cross SPM. et al. Predicting early transition from sub-syndromal presentations to major mental disorders. British Journal of Psychiatry Open. 2017; 3: (5) 223-227.

[2] Lee RSC. et al. A transdiagnostic study of education, employment, and training outcomes in young people with mental illness. Psychol Med. 2017 Sep;47(12):2061-2070.

[3] Alfieri S. et al. Young Italian NEETs (Not in Employment, Education, or Training) and the Influence of Their Family Background. Eur J Psychol. 2015 May 29;11(2):311-22.

[4] Goldman-Mellor S. et al. Committed to work but vulnerable: self-perceptions and mental health in NEET 18-year olds from a contemporary British cohort. J Child Psychol Psychiatry. 2016 Feb;57(2):196-203.

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Parent-mediated intervention for autism falls yet again

"We found minimal evidence for main effects of ART [Adapted Responsive Teaching] on child outcomes."

So said the study results reported by Linda Watson and colleagues [1] adding to a bank of studies (and meta-analyses) suggesting that parent delivered early behavioural interventions for autism or cases of 'at-risk for autism' in the most part are not seemingly cutting the scientific mustard (see here). I temper that last sentence with a number of caveats; not least that the methodological quality of the studies in this area still has some way to go and also that parent-mediated interventions covers quite a bit of ground in terms of techniques. The idea however that moves to make parents with children with autism some kind of 'super-parents' (yes, someone did use a term similar to that) to impact on their child's early presentation is not exactly borne out by the scientific data in this area. I would add that many parents of children with autism are already super-parents without any additional help, indications or guidance for the powers-that-be.

This time around nearly 90 young infants "at-risk of later ASD [autism spectrum disorder] diagnoses" were given either ART or REIM (referral to early intervention and monitoring) following other work from this authorship group on this topic [2]. ART by the way, focuses on 'relationships' over a 6 month period where aspects such as engagement, awareness and joint action between parent and child are some of the points of interest. Various facets of functioning were assessed and, assuming the equal use of other early intervention services between the groups, the time, effort and costs of ART did not seemingly provide some wildly significant gains when compared with REIM. In short, yes something like ART is a wonderful aid for things like increasing parental responsiveness to their kids but when it came to important child outcomes - including autism-related outcomes - the intervention did not seemingly fare so well.

What's more to say on this topic? Well, being careful not to hark back to the bad 'ole days where parenting behaviours were 'blamed' for the development of offspring autism, I'm not going to totally poo-poo this area of research and practice. There are some pretty good intervention strategies out there for helping parents to further *connect* with their children in the context of autism and potentially raising the potential and wellbeing of all parties concerned. My issue however is that moves to 'manualise' such interventions in the context of all autism (or rather all 'potential cases' of autism bearing in mind the use of the words 'at-risk') is not a great idea. As I've mentioned before in the context of the pluralised autisms, screening for things like inborn errors of metabolism potentially presenting with autism or autistic features seems a better first use of resources, assuming that underlying biological issues being associated with autism are probably not going to be that amenable to something like parent-mediated intervention or the like as per the example of something like phenylketonuria and autism (see here).

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[1] Watson LR. et al. Parent-Mediated Intervention for One-Year-Olds Screened as At-Risk for Autism Spectrum Disorder: A Randomized Controlled Trial. J Autism Dev Disord. 2017 Aug 31.

[2] Baranek GT. et al. Preliminary Efficacy of Adapted Responsive Teaching for Infants at Risk of Autism Spectrum Disorder in a Community Sample. Autism Research and Treatment. 2015: 386951.

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Video Interaction for Promoting Positive Parenting in autism: yes but not quite...

"Video feedback may help babies ‘at risk of autism’" went one write-up of the study results published by Jonathan Green and colleagues [1] (open-access available here). Continuing a theme of kids at risk of autism potentially 'avoiding' an autism diagnosis (see here) following the use of "a 12-session parent-mediated social communication intervention delivered between 9 and 14 months of age (Intervention in the British Autism Study of Infant Siblings-Video Interaction for Promoting Positive Parenting)" there is some degree of optimism from these latest results together with a pinch of 'not-so-fast'...

Including data from some 54 families - "28 intervention, 26 nonintervention" - researchers reported on the effects of interventions vs. no intervention on various aspects of functioning primarily the "severity of autism prodromal symptoms." Prodromal means early symptoms and is more readily associated with other labels/conditions. The authors reported that results were not completely cut-and-dried in terms of effect(s) of intervention on diagnostic outcome for example (i.e. there were "no intervention effects on diagnostic outcome") but potentially something to see when it comes to the 'severity' of autism prodromal symptoms and "parent-dyad social communication." The authors also noted that measures of communication and language did show something of a trend towards some benefit observed in the intervention group, but did not yield any significant difference when comparing intervention with no intervention over the quite long study period (39 months). This contrasts with their previous results [2] possibly indicating something rather more adverse when it came to intervention and aspects of language/communication. I might also draw your attention to the fact that from a bank of some 84 families invited to join the study, just over half actually agreed or fulfilled the criteria for joining.

I know this is an area of research that people really want to see work. Alongside other early intervention research in relation to autism (see here for example), the idea that some small adjustments to early interactions might affect the presentation of autism still enjoys quite a lot of support in various quarters. The thing is that these and other results whilst suggesting that things like 'parental responsiveness' can improve as a result of intervention(s), have so far shown that important outcomes for young children are far less impressive. This is something evident across quite a lot of the research literature in this area even when meta-analysed (see here including some chatter about effect sizes).

I'm not suggesting that we everyone just 'gives up' when it comes to early interventions like the one described by Green and colleagues. I do however think science and clinical practice needs to be a little more focused on things like potential best-responders to such interventions (as it does for many other aspects of autism science) and not so focused on creating grand media headlines. I might also throw in the idea that study design is something that needs to be improved particularly in light of other recent findings [3] talking about how "placebo-like effects represent substantial challenges for randomized controlled trials (RCTs) that use treatment as usual" (guess what many studies in this area use as their comparator?) Accepting that variables such as the plural autisms (see here) are inevitably going to affect results from such studies, I'm minded to suggest that quite a few more resources need to be committed to looking at the possible 'hows and whys' of autism coming about before any talk about early parent-mediated intervention becoming widespread. So, questions like whether screening for inborn errors of metabolism in relation to autism (see here) could be a good first step as part of the mantra 'diagnosis is a starting point not the finishing line' and then taking things from there...

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[1] Green J. et al. Randomised trial of a parent-mediated intervention for infants at high risk for autism: longitudinal outcomes to age 3 years. J Child Psychol Psychiatry. 2017 Apr 10.

[2] Green J. et al. Parent-mediated intervention versus no intervention for infants at high risk of autism: a parallel, single-blind, randomised trial. Lancet Psychiatry. 2015. Jan 22.

[3] Jones RM. et al. Placebo-like response in absence of treatment in children with Autism. Autism Res. 2017. 12 April.

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Green J, Pickles A, Pasco G, Bedford R, Wan MW, Elsabbagh M, Slonims V, Gliga T, Jones EJ, Cheung CH, Charman T, Johnson MH, & British Autism Study of Infant Siblings (BASIS) Team. (2017). Randomised trial of a parent-mediated intervention for infants at high risk for autism: longitudinal outcomes to age 3 years. Journal of child psychology and psychiatry, and allied disciplines PMID: 28393350