Anxiety symptoms are frequent in relation to childhood autism

The findings reported by Lieke Wijnhoven and colleagues [1] observing that "children with ASD [autism spectrum disorder] have a high risk to have co-occurring anxiety symptoms" are not likely to win any awards in relation to novelty. Most people, I assume, with some knowledge about autism will know that anxiety seems to be a quite consistent 'partner' to the label both in children and adults, and can for some, be absolutely disabling (see here).

But that's not to say that the Wijnhoven findings aren't important; as authors describe results both giving "an overview of the prevalence of anxiety symptoms in a clinical Dutch sample of children with ASD" and also examining "age, gender, ASD subtype, and IQ as potential risk factors for anxiety" in their sample of over 170 children diagnosed with an ASD.

Using a participant group already signed up for a "randomized controlled trial (RCT) testing the effect of an anxiety intervention for children with an ASD" [2], researchers analysed their responses to the Spence Children’s Anxiety Scale for Children and Spence Children’s Anxiety Scale for Parents (translated into Dutch). They also relied on data from cognitive testing, and just for good measure, added in data on the various comorbid diagnoses held by their participant group: "attention deficit hyperactivity disorder (45.3%), (persistent) depressive disorder (7.0%), oppositional defiant disorder (3.5%), obsessive–compulsive disorder (1.7%), reactive attachment disorder (1.7%), and posttraumatic stress disorder (1.2%)." Yes, those figures do put attention-deficit hyperactivity disorder (ADHD) at being present in over 45% of participant cases (see here).

Results: "In total, 66.3% of the participating children with ASD had child-rated subclinical or clinical anxiety symptoms on the total scale and/or on at least one subscale and 81.4% of the participating children with ASD had parent-rated subclinical or clinical anxiety symptoms on the total scale and/or on at least one subscale." Yep, just as you and I suspected, anxiety symptoms whether clinical or sub-clinical, are pretty rife in relation to autism. Additionally, girls seemed to present with more anxiety symptoms than boys; particularly when it came to "separation anxiety symptoms..., social phobia symptoms..., panic disorder/agoraphobia symptoms..., and generalized anxiety symptoms."

Age was and wasn't an issue, insofar as total anxiety symptoms being more 'intensely' reported for younger children than older children but: "Age was not a significant predictor of social phobia symptoms, specific phobia symptoms, panic disorder/agoraphobia symptoms, and generalized anxiety symptoms" based on child ratings. A similar pattern was also seen for parent-reports too.

What's more to say? Well, very little really. Anxiety once again, turns up as a frequent 'comorbidity' (if I can still - Mildred Creak - call it just comorbidity) and the challenges remain as to what can be done to minimise it and its effects (see here). Here's to hoping...

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[1] Wijnhoven LAMW. et al. Prevalence and Risk Factors of Anxiety in a Clinical Dutch Sample of Children with an Autism Spectrum Disorder. Front. Psychiatry. 2018; March 2; 9: 50.

[2] Wijnhoven LAMW. et al. The effect of the video game Mindlight on anxiety symptoms in children with an Autism Spectrum Disorder. BMC Psychiatry. 2015 Jul 1;15:138.

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"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...

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[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.

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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 drug] treatment, 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...

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[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.

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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]...

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[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.

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Yet more "lost their diagnosis" and autism research. Not for all but...

The question posed in the title of the paper by Solomon and colleagues [1] - "What will my child's future hold?" - examining the "phenotypes of autism spectrum disorder (ASD) based on trajectories of intellectual development from early (ages 2-3 ½) to middle (ages 5-8) childhood" - is an interesting one and a question that many parents/caregivers will probably ask or have asked at one point or another.

It's also an important question because throughout all the sweeping statements that have been made about the autism spectrum past and present, the generalisation that ALL autism is 'lifelong' is one of the more popular ones despite [peer-reviewed scientific] evidence pointing to the contrary (see here for example).

By saying all that I'm not trying to minimise the effect(s) that autism has on the lives of many, many people day-in and day-out throughout their lives and the varying requirements for suitable support. Just that, as per the notion 'if you've met one autistic person, you've met one person with autism' (or words to that effect), the experience(s) of continually hitting the diagnostic thresholds across the lifespan is likely to be different for different people as a function of many, many different factors. I say this acknowledging for example, the rise of 'compensation' in the context of autism recently (see here).

Solomon et al drew on data derived from the Autism Phenome Project including over 100 children "initially diagnosed with ASD." Researchers were particularly interested in cognitive trajectories as measured by IQ between 2 and 8 years of age and whether autistic and other related symptoms/traits were also affected by any changes to intellectual functioning. As it happens, they might be...

"A four class model best represented the data" meaning that participants typically fell into one of four 'patterns' with regards to their intellectual functions/trajectories. This included: "High Challenges (25.5%), Stable Low (17.6%), Changers (35.3%), and Lesser Challenges (21.6%) groups." As per the title of this post, I'm particularly interested in those described as 'Changers' or 'Lesser Challenges' who "demonstrated the most significant IQ change that was accompanied by adaptive communication improvement and declining externalizing symptoms" and "showed a significant reduction in ASD symptom severity" respectively. Indeed, within the Lesser Challenges group we are told that "by age 8, 14% of them no longer met ADOS-2 criteria for ASD." In other words, they did not reach cutoffs for the diagnostic criteria for an autism spectrum disorder (ASD) using a gold-standard assessment instrument and so could be considered not autistic by diagnostic standards.

Also important to the Solomon findings was the observation that: "Intervention history was not associated with group status." I'm not going to say too much more about this at the present time, but if replicated, the implications are pretty huge particularly where the current drive towards early intervention in autism is leading us (see here).

Although not always welcomed by everyone, the idea that a diagnosis of autism is permanent and immutable for all does not stand up well to scientific scrutiny. The best guess estimates currently suggest that somewhere between 9 and 12% of children/adults will 'lose their diagnosis' (see here and see here); also potentially affecting the presence of some important over-represented comorbidity too (see here). The old 'they weren't autistic in the first place' argument is a typical response from some nay-sayers on this topic; something which unfortunately contributes to the denigration of some important parts of the autism spectrum. Certainly a part of the autism spectrum that we can learn a lot from as the Solomon results are starting to show.

Indeed, given the other 'biological' focuses of the Autism Phenone Project [2] I'm hoping that we'll eventually see further results from this initiative providing important information on possible biological correlates linked to those who "no longer met ADOS-2 criteria for ASD". If ever there was a research study needed on autism, it is one including a little more biological and genetic information about those who move from autism to not-autism and what it could mean for the wider autism spectrum and particularly the concept of 'the plural autisms'...

To close, 'I want a deep fried turkey'....

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[1] Solomon M. et al. What will my child's future hold? phenotypes of intellectual development in 2-8-year-olds with autism spectrum disorder. Autism Res. 2017 Oct 27.

[2] Onore CE. et al. Levels of soluble platelet endothelial cell adhesion molecule-1 and P-selectin are decreased in children with autism spectrum disorder. Biol Psychiatry. 2012 Dec 15;72(12):1020-5.

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With great [intellectual] power comes enhanced health risks?

"Intelligence research most often focuses on the flashes of lightning seen in this rare population, however in order to serve this group of individuals fully, we must not neglect to acknowledge the rumbles of thunder that follow in the wake of their brilliance."

There was something rather poetic in the above sentence concluding the paper by Ruth Karpinski and colleagues [1] talking about "high IQ [intelligence quotient] as being a potential risk factor for affective disorders, ADHD [attention-deficit hyperactivity disorder], ASD [autism spectrum disorder], and for increased incidence of disease related to immune dysregulation." The idea being that "those with a high intellectual capacity (hyper brain) possess overexcitabilities in various domains that may predispose them to certain psychological disorders as well as physiological conditions involving elevated sensory, and altered immune and inflammatory responses (hyper body)."

I have to say that I was/am slightly unimpressed with the terms 'hyper brain' and 'hyper body' - it sounds like something from a movie I watched a while back - but am genuinely interested in the possibility of an intersection between the brain and other body functions particularly in the context of risk for specific health-related labels.

So, examining some 3700 members - "the majority of participants were older, male, and European American" - of American Mensa, Ltd. researchers sifted through responses to various questions about psychological and somatic health answered by participants. The on-line questionnaire used as the self-report tool (yes, self-report tool) included items covering both "diagnosed and suspected" in terms of various diagnoses, and results were compared against national average data covering quite a bit of clinical ground.

Results: an interesting pattern of both suspected and diagnosed comorbidities emerged from the high IQers [self-report] data. I've already quoted the authors in terms of an over-representation of autism, ADHD and affective disorders (mood and anxiety disorders). The degree of over-representation of such diagnoses was not insignificant: for autism for example "When comparing diagnosed patients, there was 1.2 times the risk within the high intelligence group compared with national averages (a 20% increase). However, an additional 5.1% suspected that they should be diagnosed with ASD, for a total combined risk of 6.3 times the national average, an increase of 530%." This perhaps ties into other independent research too (see here) bearing in mind that diagnosing autism is probably best left to the professionals (see here).

But alongside, there was also a somatic angle to consider: for 'environmental' allergies for example we are told that: "Overall, there was 3.13 times the risk of being diagnosed with an environmental allergy, an increase of 213%, for those with high cognitive ability. When included self-diagnoses, there was 4.33 times the risk, for an increase of 333%." Asthma and autoimmune diseases also registered. The same caveat about caution in self-report and self-diagnosing coming into play too.

There is quite a bit of data to absorb in the Karpinski paper and I would encourage readers to plough through it. One detail that particularly struck me in their "Hyper Brain/Hyper Body: a theoretical framework" diagram was where the authors chose to place autism - in the hyperbody side of things - and their comments: "that one such plausible genetic component to consider is that of high IQ which may be responsible for a hyper physiological response to these insults and a resulting development of ASD." I can't say if they're right or wrong about this but certainly the connections made between [some] autism and things like neuroinflammation (see here) and immune function (see here) are not to be forgotten or glossed over. More so when one considers what something like [acute] inflammation *might* be able to do in the context of psychological processes (see here).

So what implications do the Karpinski results have for clinical practice for example? Again, harking back to the opening sentence, an appreciation that with great intellectual power may come the potential for enhanced health risks is worthwhile reflecting on and what it means for preferential screening for example, alongside healthcare planning. I say this bearing in mind that correlation and causation are not one and the same, and also that the reliance on self-report used in the Karpinski study is, by no means, to be put to one side. If one however assumes that a measure like IQ has a significant genetic loading behind it, one might also speculate that the same genes (or expression of genes) governing any such association might also have the ability to affect parameters such as autistic and/or ADHD traits, the presence of depression and anxiety and also immune function in relation to things like 'environmental' allergies or autoimmune conditions. In the same way that autism genes are probably not just 'genes for autism' (see here) so a wider picture seemingly emerges with IQ potentially in mind...

To close, and without trying to trivialise the subject matter today, I wonder if people like Stan Lee and other 'Marvel'ous folk had it right when they portray great power often being balanced with a seeming lack of power?

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[1] Karpinski RI. et al. High intelligence: A risk factor for psychological and physiological overexcitabilities. Intelligence. 2017. Oct 8.

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"sufficient evidence supporting an association between developmental PBDE exposure and reduced IQ"

The results of the systematic review and meta-analysis published by Juleen Lam and colleagues [1] (open-access available here) make for interesting if rather worrying reading. Looking at the body of research examining whether developmental exposure to PBDEs - polybrominated diphenyl ethers - might have some effect on either developmental/behavioural outcomes of offspring or IQ (Intelligence Quotient), authors concluded that there was "sufficient evidence supporting an association between developmental PBDE exposure and reduced IQ." Such a specific conclusion was reached on the basis of four studies measuring something called BDE-47 in maternal serum during pregnancy or at birth that also looked at full scale intelligence quotient in offspring between 4 and 7 years of age and found a possible *association*.

When looking at the possibility that PBDE exposure might also be linked to "Attention Deficit/Hyperactivity Disorder (ADHD) and attention-related behavioral conditions in humans" the authors concluded that the available data was not up to the same standard as that connecting PBDE exposure and IQ.

"Preventing developmental exposure to PBDEs could help prevent loss of human intelligence." Such a conclusion might seem rather dramatic insofar as words such as a 'loss of human intelligence'. The implication being that like various other exposure events at critical times of development that can and do affect aspects of cognition - think lead for example - our environment seems to shape some important human functions. Despite the fact that PBDEs are apparently being phased out, there is still continuing cause for concern as a consequence of their quite excessive historic use, their ability to persist in the environment as well as their propensity to "bioaccumulate up the food chain."

And whilst we're on the topic of PBDEs and behavioural correlates, I might also draw your attention to other research that has been covered on this blog (see here) talking about the possible results of on-going PBDE exposure.

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[1] Lam J. et al. Developmental PBDE Exposure and IQ/ADHD in Childhood: A Systematic Review and Meta-analysis. Environ Health Perspect. 2017 Aug 3;125(8):086001.

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How helpful is a 'geek index'?

A quote to begin: "male offspring of older fathers had higher ‘geek index’ scores, a composite measure of high IQ, strong focus on the subject of interest and social aloofness."

So said the findings published by Magdelena Janecka and colleagues [1] (open-access) who set out to determine whether "having an older father is associated with certain beneficial traits" in offspring. Their use of the term 'geek index' (GI) was derived from a "composite measure of non-verbal intelligence, restrictive interests and reduced need to fit in with the peer group" based on data derived from the TEDS (Twin Early Development Study) initiative (something that has cropped up before on this blog). As one might imagine, use of the term 'geek index' in a science article was always likely to make some media headlines (see here for example).

In terms of study design and numbers, this was a biggie with study participants in the thousands. The geek index was derived from scores "of (i) non-verbal intelligence, (ii) restrictive and repetitive behaviours (RRBs) and (iii) social aloofness." Further: "Scores on the Raven’s Standard Progressive Matrices test were used to obtain (i). Childhood Autism Spectrum Test (CAST) scores were used to obtain both (ii) and (iii)." Various statistical 'transformations' were conducted on said scores to give that geek index sum and, not forgetting the parental age bit, paternal age was also thrown into the statistical mix.

As per the opening sentence, those children born to older fathers (but not older mothers) seemed to more frequently present with a higher geek index. This association persisted after controlling for various potentially confounding variables: "maternal age, sex, zygosity and SES [socio-economic status]." Researchers further observed that: "GI was positively linked with future academic attainment—including the key predictors of future SES—suggesting a phenotypic advantage in the offspring of older fathers."

These are interesting results and notwithstanding some study limitations i.e. "It was not possible to determine whether the advantageous effects of GI extend beyond secondary education, and correlate with future SES" require further independent investigation. Offspring being born to older fathers has generally been associated with various less-than-positive outcomes so this article kinda paints a more positive picture for children and families. Indeed, one of the commentators talking about these findings suggests that "perhaps we are destined for future society of geniuses that are going to help us solve all the world's problems." One would hope so.

As per the title of this post, I would however question how useful/helpful the term 'geek index' is when it comes to outcomes and implications. Yes, I know there is such a thing as 'geek chic' these days, but let's not forget that the word 'geek' has it's primary origins as a term of ridicule in many languages. To quote one definition: "the word typically connotes an expert or enthusiast or a person obsessed with a hobby or intellectual pursuit, with a general pejorative meaning of a "peculiar person, especially one who is perceived to be overly intellectual, unfashionable, or socially awkward."" I'm not so sure that every child (youngster or teenager) would be particularly happy to be labelled as scoring high on a geek index. Surely something a little more scientific could replace such a term?

Going also back to those study caveats provided by the authors, I might also raise the idea that just because someone shows an intellectual advantage when it comes to something like STEM (science, technology, engineering and mathematics) subjects does not necessarily mean that their future is going to be a rosy one in terms of employment, income or other markers of SES. “If you look at who does well in life right now, it’s geeks” is one of the quotes attributed to the first author of the paper; and with it as massive a sweeping generalisation as you will ever see.

If we for example, assume that strengths in STEM might be over-represented when it comes to the autism spectrum (see here) we should be seeing lots and lots of people either diagnosed with autism or possessing significant autistic traits thriving in such roles and in life in general. The reality however is that skills pertinent to STEM often do not appear in a vacuum (see here) as I would put forward the suggestion that future research might also consider the possibility of a relationship between the geek index (or other term) and the presentation of something like anxiety or depression and how that might also impact on later adult outcomes for example. The additional idea that social aloofness also makes up part of the geek index is something else that needs quite a lot more work on as part of any 'advantage' arguments being put forward...

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[1] Janecka M. et al. Advantageous developmental outcomes of advancing paternal age. Translational Psychiatry. 2017. 7; e1156.

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Prevalence of learning disability and autism in Western Australia

"The prevalence of ID [intellectual disability] in WA [Western Australia] has increased over the past 10 years compared with previous estimates... This increase is associated in a large part with an increased prevalence of ASDs [autism spectrum disorder] for whom 70% had comorbid ID or an unknown level of ID."

Those were some of the findings reported by Jenny Bourke and colleagues [1] (open-access available here). Drawing on data derived from the Intellectual Disability Exploring Answers (IDEA) database, a resource designed to 'provide high-quality complete and population-based information on Western Australians with an intellectual disability', authors set about looking at cases of ID for those born between 1983 and 2010. Intellectual disability (ID) - sometimes called learning disability here in Blighty - is typically diagnosed when IQ is assessed as being below 70 where a score of between 55-69 denotes mild ID, a score of between 40-54 denotes moderate ID and a score below 40 denotes severe ID. Authors were also able to cross-reference cases with information in other databases in terms of race, gender and location of birth.

Results: covering a total of nearly 750,000 live births during the period of inspection, some 10,000 infants "were identified with an ID by 2010." This equated to a total prevalence of ID of 17 per 1,000 live births. Most cases of ID were defined as being mild or moderate in terms of IQ scores (where available) and when compared to previous data from this authorship group [2] authors reported "an overall increase in prevalence of ID of 19% from 1999 to 2010."

Insofar as the possible causes of ID, various factors are reported to be potentially contributory including ID accompanying Down's syndrome, ID linked to various other genetic/chromosomal issues, birth defects and infection(s). Increasing preterm birth and survival rates are also suggested to be another contributory factor. The authors also add: "It is also possible that a proportion of the observed increase in mild or moderate ID may be attributable to un-diagnosed Fetal Alcohol Syndrome."

The link between autism and ID is also discussed by Bourke et al. On the basis of other research (see here) suggesting that approximately 30-40% of cases of autism will also include a degree of ID, I was pretty interested to see the authors of this latest research suggesting something a little bit different. To quote: "Of the 2307 [diagnosed with an ASD], 675 (29.3%) definitely did not have an ID." I've underlined the word 'not' because the implication is that up to 70% of those with autism did have some level of ID. I say this bearing in mind that Bourke did include children diagnosed with an ASD where "children with an autism diagnosis but an unknown level of ID were classified within the comorbid ASD and ID group." But how far will the true figure of autism and ID combined fall by excluding such unknowns?

There is just one more detail of the results that I want to draw your attention to with regards to ID: "The prevalence for Aboriginal children was 39.0/1000 compared with 15.7/1000 for non-Aboriginal children." The idea of disparities in rates of ID among Indigenous Australians and other groups is not necessarily a new one as per other research [3] and strengthen calls for a lot more research focus on this and other groups [4] from a variety of different clinical perspectives.

In terms of what to make of these combined findings, I'd like to think there are some important issues requiring further study. The idea that autism and ID can and do frequently co-exist is paramount to discussions. We can talk and discuss about the hows and whys until the cows come home but the link remains strong and indeed, among different populations, might be more variable [5] than previously suggested. Also, for many years in autism research circles, there have been discussions upon discussions about how the quite spectacular rise in autism cases (including that in Australia) might have been at the expense of diagnostic switching from categories such as ID. The Bourke data seem to suggest that not everywhere in the world is necessarily experiencing a corresponding 'drop' in cases of ID supportive of this diagnostic switching argument. Indeed, I'm minded to suggest that one has to be quite careful about explaining away any 'real increase' in autism cases solely using the ID switching argument (see here)...

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[1] Bourke J. et al. Population-Based Prevalence of Intellectual Disability and Autism Spectrum Disorders in Western Australia: A Comparison With Previous Estimates. Medicine (Baltimore). 2016 May;95(21):e3737.

[2] Leonard H. et al. Prevalence of intellectual disability in Western Australia. Paediatr Perinat Epidemiol. 2003 Jan;17(1):58-67.

[3] Leonard H. et al. Autism and intellectual disability are differentially related to sociodemographic background at birth. PLoS One. 2011 Mar 30;6(3):e17875.

[4] Bennett M. & Hodgson V. The missing voices of Indigenous Australians with autism in research. Autism. 2016 May 25. pii: 1362361316643696.

[5] Postorino V. et al. Intellectual disability in Autism Spectrum Disorder: Investigation of prevalence in an Italian sample of children and adolescents. Research in Developmental Disabilities. 2016; 48: 193-201.

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Bourke J, de Klerk N, Smith T, & Leonard H (2016). Population-Based Prevalence of Intellectual Disability and Autism Spectrum Disorders in Western Australia: A Comparison With Previous Estimates. Medicine, 95 (21) PMID: 27227936

Autism + depression = more medical issues?

I wanted to draw your attention to the paper by Greenlee and colleagues [1] today, talking about how: (a) "Co-occurring depression is a particularly common problem in higher-functioning older children" with autism, and (b) "children with ASD [autism spectrum disorder] and a history of a depression diagnosis are more likely to also have co-occurring medical problems" at least in their cohort.

Published as part of a supplement about autism in the journal Pediatrics (see here), the Greenlee paper describes findings based on the examination of over 1200 children and young adults diagnosed with an ASD derived from the "Autism Speaks Autism Treatment Network consortium." Looking at non-depressed (n=1183) and 'ever' depressed (n=89) parent or caregiver reports of offspring, researchers reported a few important details.

As per those non- and ever-depressed figures, the experience of depression or at least some of the symptoms of depression is not uncommon in paediatric autism. Drilling down into further detail, the authors reported that around a fifth of teens/young adults (13-17 years) were reported to have a history of depression. The added suggestion that "higher IQ, and Asperger disorder diagnosis" (authors words not mine) might be important correlates taps into other independent findings (see here).

And then something a little more new... "After controlling for age, IQ, and within-spectrum categorical diagnosis, the ever-depressed group exhibited significantly greater rates of seizure disorders... and gastrointestinal problems... and trend-level differences in aggression, somatic complaints, and social impairments. The groups did not differ in autism severity, repetitive behaviors, sleep problems, eating problems, self-injurious behavior, or current intervention use."

These are interesting findings despite the need for further replication and validation. That depression might also 'correlate' with somatic issues such as seizure disorders such as epilepsy or gut issues is something I'm particularly interested in. Outside of the idea that depression might not be entirely unexpected alongside the presentation of epilepsy for example (see here), the suggestion that bowel issues might also correlate in relation to autism, taps into some preliminary independent work previously covered on this blog (see here). I might also bring in some more general work looking at how labels such as depression have been noted to be over-represented when it comes to specific GI complaints such as irritable bowel syndrome (IBS) for example (see here) as further fodder for thought.

The nature of the relationship between autism, depression and something like bowel issues remains the stuff of speculation, particularly the question of what comes first. I might provide some ideas for future research directions with a view to the overlap with anxiety (see here) as a start. I could even suggest that further efforts might be needed to look into whether more external agents might play a role for some (see here) including those trillions of wee beasties that call us all home (see here). But this would only be speculation, and taking into account the plurality of autism (see here), science needs to do a lot more work on these important comorbidities, particularly given the heightened risk of adverse outcomes potentially linked to the experience of depression and how a relationship between autism and depression may even stretch into older age [2]...

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[1] Greenlee JL. et al. Medical and Behavioral Correlates of Depression History in Children and Adolescents With Autism Spectrum Disorder. Pediatrics. 2016 Feb;137 Suppl 2:S105-14.

[2] Wallace GL. et al. Aging and autism spectrum disorder: Evidence from the broad autism phenotype. Autism Res. 2016 Mar 11.

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Greenlee JL, Mosley AS, Shui AM, Veenstra-VanderWeele J, & Gotham KO (2016). Medical and Behavioral Correlates of Depression History in Children and Adolescents With Autism Spectrum Disorder. Pediatrics, 137 Suppl 2 PMID: 26908466

Autism genes and cognitive ability

Autism IS linked to higher intelligence: People with genes related to the condition 'scored better in mental ability tests' was one of the media headlines reporting on the study by Toni-Kim Clarke and colleagues [1].

Clarke et al reported results based on a pretty good sample size (in the thousands) whereby autism-associated genes and cognitive ability were examined in several cohorts including those taking part in The Generation Scotland : Scottish Family Health Study (GS:SFHS) (see here for further information). Polygenic risk for autism spectrum disorder (ASD), that is risk governed by several genes, "is positively correlated with general cognitive ability" was a primary finding. Ergo, among the general population omong those not diagnosed with autism, carrying some of the proposed genetic risk factors for the condition might confer something of a cognitive advantage albeit only a slight advantage. The same could not be said for the relationship between polygenic risk for ADHD (attention deficit hyperactivity disorder) and cognitive ability also reported on by the authors.

These are potentially important findings covered pretty well by the NHS Choices website (see here) which concluded that "The study is likely to be of interest to researchers, but does not have any obvious practical implications for individuals." Aside from the idea that certain genes linked to autism might not necessarily just be solely linked to 'disability' and *might* offer some explanation for the islets of ability reported in some on the autism spectrum [2], the Clarke findings could also be interpreted in a number of other ways. They could for example, be taken as evidence that to talk about 'autism-related genes' might actually be more accurately done so as referring to them as being autism-cognition related genes stressing the link between presented traits and cognitive ability. They may also suggest that carrying said risk genes does not automatically equate as receiving a label of autism as per the authors focus on those who never developed autism yet presented with the risk versions of the genes. Accepting also that 'autism genes' refers to a complicated and ever-increasing bank of risk genes, this might also open the door to other mechanisms at work related to risk of autism, perhaps other, more environmentally driven factors also having some interactive effect?

I could spend all day talking about the genetics of cognitive ability on the back of studies such as the one from Plomin & Deary [3]. Among the important points made with such research in mind is that genes linked to concepts such as intelligence or cognitive ability are also likely to similarly impact on other traits too. The paper from Eva Krapohl and colleagues [4] hinted at this with regards to education achievement and test performance scores, and how one has to take quite a wide view when it comes to the genetics of something like cognition or autism. The days of one gene = one condition / one trait are seemingly long gone. Oh, and that gene function outside of structural genomics might also be important [5] is worth mentioning...

Without wishing to dilute the positive message to come from the Clarke findings, I feel I should also raise the important issue of how enhanced cognitive ability does not necessarily automatically translate into better life outcomes. I kinda touched upon this in a post a few years back talking about outcome and autism (see here) and how we live in an age where some truly intellectually gifted individuals live among us, but this does not necessarily mean that they live the life they want or deserve. The quite depressing figures on the rates of employment for those with autism [6] who can and want to work are for example, a stark reminder of how societal and other factors play an important role irrespective of any cognitive prowess.

And of course, there may be other factors at work...

Music: Setting Sun by The Chemical Brothers. Particularly apt for today (see here).

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[1] Clarke T-K. et al. Common polygenic risk for autism spectrum disorder (ASD) is associated with cognitive ability in the general population. Molecular Psychiatry. 2015. March 10.

[2] Shah A. & Frith U. An islet of ability in autistic children: a research note. J Child Psychol Psychiatry. 1983 Oct;24(4):613-20.

[3] Plomin R. & Deary IJ. Genetics and intelligence differences: five special findings. Mol Psychiatry. 2015 Feb;20(1):98-108.

[4] Krapohl E. et al. The high heritability of educational achievement reflects many genetically influenced traits, not just intelligence. Proc Natl Acad Sci U S A. 2014 Oct 21;111(42):15273-8.

[5] Haggarty P. et al. Human Intelligence and Polymorphisms in the DNA Methyltransferase Genes Involved in Epigenetic Marking. PLoS ONE. 2010;5(6):e11329.

[6] Taylor JL. & Seltzer MM. Employment and post-secondary educational activities for young adults with autism spectrum disorders during the transition to adulthood. J Autism Dev Disord. 2011 May;41(5):566-74.

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Clarke TK, Lupton MK, Fernandez-Pujals AM, Starr J, Davies G, Cox S, Pattie A, Liewald DC, Hall LS, MacIntyre DJ, Smith BH, Hocking LJ, Padmanabhan S, Thomson PA, Hayward C, Hansell NK, Montgomery GW, Medland SE, Martin NG, Wright MJ, Porteous DJ, Deary IJ, & McIntosh AM (2015). Common polygenic risk for autism spectrum disorder (ASD) is associated with cognitive ability in the general population. Molecular psychiatry PMID: 25754080

The label of autism rarely exists in a diagnostic vacuum

"Most young ASD [autism spectrum disorder] children met the criteria for additional psychopathology." That was the primary conclusion reported by Fernando Salazar and colleagues [1].

At the risk of sounding like a broken record going on and on about how the diagnosis/label of autism very rarely exists in a diagnostic vacuum when it comes to comorbidity, I did think it important that the findings of Salazar et al were [briefly] brought to your attention. I've talked a few times on this blog about the ESSENCE around autism (see here) and autism plus (see here) as putting some flesh on the scientific bones that the presentation of autism is often only one part of behaviour in those diagnosed as being on the autism spectrum. That and the plurality of autism...

"Most common diagnoses were: generalized anxiety disorder (66.5 %), specific phobias (52.7 %) and attention deficit hyperactivity disorder (59.1 %)." The sorts of comorbid diagnoses listed most frequently by Salazar and colleagues are no strangers to autism comorbidity research as per some of my other musings on anxiety (see here) and ADHD (attention deficit hyperactivity disorder) (see here).

Anxiety in particular, has been something in receipt of quite a bit of research attention, whether it be through discussions on possible reasons why (see here) or associations made with more physical features also known to be over-represented following a diagnosis of autism (see here). I don't doubt that the hows and whys connecting autism and anxiety are likely to be complicated and quite individual. Indeed, from Salazar et al: "Higher IQ was associated with anxiety disorders" which kinda taps into some other work on the effect of insight on the presentation of anxiety (see here) for example.

There's little more for me to say about the Salazar paper aside from pointing out the impressive authorship roll call included on the paper, including those who've also looked at more somatic comorbidity alongside the diagnosis of autism (see here) and horror of horrors, gut barrier issues appearing in some children on the spectrum (see here). Oh, and that comorbidity occurring alongside a diagnosis of autism doesn't always have to be psychological/behavioural is an important point to raise too...

Music to close: Golden Brown by The Stranglers.

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[1] Salazar F. et al. Co-occurring Psychiatric Disorders in Preschool and Elementary School-Aged Children with Autism Spectrum Disorder. J Autism Dev Disord. 2015. March 4.

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Salazar, F., Baird, G., Chandler, S., Tseng, E., O’sullivan, T., Howlin, P., Pickles, A., & Simonoff, E. (2015). Co-occurring Psychiatric Disorders in Preschool and Elementary School-Aged Children with Autism Spectrum Disorder Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-015-2361-5

Optimal outcome and autism: a role for intervention?

Optimal outcome and autism.

Not here you don't @ Wikipedia 

I'm sure most people with an eye on autism research and practice will have come across this issue. The idea is that in amongst the various developmental trajectories which are being realised in these days of autisms over autism, there may be some children previously diagnosed with an autism spectrum disorder (ASD) who move outside of the diagnostic boundaries of the condition.

There is still lots of debate about the hows and whys of this scenario [1], and in particular, whether leaving the autism diagnostic label behind means everything about autism is left behind (see here). But certainly it is getting more and more difficult to dispute the fact that [some of] the signs and symptoms of autism are anything but static [2] and for some at least, the diagnostic label of autism might not be as lifelong as previously thought. Even the recent IMFAR conference saw some continued interest in this issue (see here).

Today I want to introduce a couple of papers which add to the literature on optimal outcome (OO) and autism, and in particular move away from just description to looking at what factors might potentially influence optimal outcome and specifically a possible role for intervention. You might consider this post an extension of an entry not-so-long-ago (see here) talking about the findings from Deborah Anderson and colleagues [3].

The paper by Nahit Motavalli Mukaddes and colleagues [4] (open-access) adds to the increasing literature on optimal outcome and autism with their assertion that: "High IQ and the development of communicative and language skills at an early age could be the most powerful factors contributing to an optimal outcome". The paper is open-access but a few points are noteworthy:

• Based in Turkey, this was a descriptive study of some 39 children "who previously received a diagnosis of ASD and who did not meet the criteria for any ASD in the final examination". Importantly, the authors held pretty detailed records on this group based on their initial assessment and diagnosis for autism including "an in-depth psychiatric examination of the child" which meant plenty of face-to-face contact accompanied by an analysis of medical history. 
• They also followed children "every 3-4 months" following their referral to an education program "inspired by Pivotal Response Training (PRT)". Most children followed PRT although 2 children "were able to attend ABA [Applied Behaviour Analysis] programs with frequencies ranging from as low as 8 hours per week up to the recommended 20 hours per week".
• Optimal outcome was specifically defined in this study based on the paper by Helt and colleagues [5] slightly modified. This included both abatement of autistic symptoms and IQ also being measured in the 'normal' range.
• Results: Well, aside from talking about communication and IQ as being potentially important factors related to optimal outcome: "The time from baseline to optimal outcome was 2.71 ± 1.76 years (range: 0.5-8 years)". The mean age at optimal outcome was round about 5 years old although there was some variation around these variables.

The authors provide quite a bit more detail on their study and why their results might be considered credible. I note they also suggest that comorbid medical disorders such as epilepsy were largely absent from this group and might "be another factor that influences outcomes". I'd chime in here and agree with that sentiment in light of what we know about the autism-epilepsy relationship (see here) and specifically the growing realisation that IQ or cognitive ability seems to be an important factor, confirmed by Jokiranta and colleagues [6]. The issue of intervention type and specifically whether something like ABA might play a role in optimal outcomes leads me on to the next study.

The paper by Alyssa Orinstein and colleagues [7] adds even further to the collected literature in this area, daring again to talk about what intervention might show involvement with a small group of optimal outcomers compared with those categorised as being high-functioning autism (HFA). Deborah Fein, the godmother of optimal outcome is also a co-author on this study.

So:

• "The current study examined intervention histories in 25 individuals with OO and 34 individuals with HFA (current age, 8-21 years), who did not differ on age, sex, nonverbal intelligence, or family income. Intervention history was collected through detailed parent questionnaires". 
• Those letters A-B-A were again mentioned in the results: "Substantially more children with OO than HFA received applied behavior analysis (ABA) therapy, although for children who received ABA, the intensity did not differ between the groups".
• Likewise that issue of comorbid conditions likely rears its head in this study too: "Children in the HFA group were more likely to have received medication, especially antipsychotics and antidepressants".
• One final quote to make at the risk of plagiarising the whole abstract: "There were no group differences in the percent of children receiving special diets or supplements".

ABA seems to do rather well in both the Mukaddes and Orinstein studies in relation to optimal outcome. I know that as an intervention it's not everyone's cup of tea, particularly with some rather chequered history, but there are 'moderates' out there who support the principles of ABA (see here) and the evidence base is not bad compared to lots of other interventions put for improving outcome in relation to autism. Without nailing my colours to any particular mast, I'd echo the sentiments of Orinstein et al and their suggestion of more to do - prospective studies - in this area. I might also draw your attention to other findings on PRT and ABA which might also be pertinent [8].

I'll also pass some comment on the use of the words 'special diets' when it comes to the Orinstein paper. I assume special diets includes things like the gluten- and casein-free (GFCF) diet and goes some way to addressing the notion that the optimal outcome group are not over-represented by those following such an intervention. I'd agree with that sentiment knowing what I think I know about this particular intervention. There is of course another way of looking at this insofar as there being best responders to something like a GFCF diet included in the optimal outcome group... but let's not get too carried away just yet.

'Optimal outcome' with autism in mind still has the ability to divide opinion. Reading again the editorial by Sally Ozonoff (see here) which accompanied the original Fein study and the description from Uta Frith on "a variant that is temporary" (see here) makes me realise that sometimes the bigger job of science is not actually doing and reporting the work, but altering long and often passionately held views and opinions as a result of that new knowledge. As intimated on a previous post talking about the economics of autism (see here), although I am not a great fan of talking about 'what autism costs' and the potentially unhelpful way that headlines like 'Autism costs '£32bn per year' in UK' can be construed, the findings from the Mukaddes and Orinstein studies should perhaps be the topic of further autism research. Not only because they might further highlight who is most likely to fall into the OO category and how they might arrive there but as per the paper by Barrett and colleagues [9] the onward implications to public finances with the aim to: "leverage investment in education and intervention to mitigate aspects of autism spectrum disorder that negatively impact individuals with the disorder and their families".

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[1] Bölte S. Is autism curable? Dev Med Child Neurol. 2014 May 20.

[2] Wodka EL. et al. Predictors of phrase and fluent speech in children with autism and severe language delay. Pediatrics. 2014; 131: e1128-e1134.

[3] Anderson DK. et al. Predicting young adult outcome among more and less cognitively able individuals with autism spectrum disorders. J Child Psychol Psychiatry. 2014 May;55(5):485-94.

[4] Mukaddes NH. et al. Characteristics of Children Who Lost the Diagnosis of Autism: A Sample from Istanbul, Turkey. Autism Res Treatment. 2014: 472120.

[5] Helt M. et al. Can children with autism recover? If so, how? Neuropsychol Rev. 2008 Dec;18(4):339-66.

[6] Jokiranta E. et al. Epilepsy Among Children and Adolescents with Autism Spectrum Disorders: A Population-Based Study. J Autism Dev Disord. 2014 May 7.

[7] Orinstein AJ. et al. Intervention for optimal outcome in children and adolescents with a history of autism. J Dev Behav Pediatr. 2014 May;35(4):247-56.

[8] Mohammadzaheri F. et al. A Randomized Clinical Trial Comparison Between Pivotal Response Treatment (PRT) and Structured Applied Behavior Analysis (ABA) Intervention for Children with Autism. J Autism Dev Disord. 2014 May 20.

[9] Barrett B. et al. Comparing service use and costs among adolescents with autism spectrum disorders, special needs and typical development. Autism. 2014 Jun 9.

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Mukaddes, N., Tutkunkardas, M., Sari, O., Aydin, A., & Kozanoglu, P. (2014). Characteristics of Children Who Lost the Diagnosis of Autism: A Sample from Istanbul, Turkey Autism Research and Treatment, 2014, 1-10 DOI: 10.1155/2014/472120



Orinstein AJ, Helt M, Troyb E, Tyson KE, Barton ML, Eigsti IM, Naigles L, & Fein DA (2014). Intervention for optimal outcome in children and adolescents with a history of autism. Journal of developmental and behavioral pediatrics : JDBP, 35 (4), 247-56 PMID: 24799263