Lactobacillus plantarum PS128 "ameliorated opposition/defiance behaviors" in boys with autism?

There was something potentially rather special about the results published by Yen-Wenn Liu and colleagues [1] suggesting that use of a probiotic - Lactobacillus plantarum PS128 - might, under "randomized, double-blind, placebo-controlled" conditions, have some important effects with some young people diagnosed with an autism spectrum disorder. Special because, if such results are eventually replicated and borne out, some of the more 'disruptive' behaviours that can sometimes be observed alongside a diagnosis of autism - "opposition/defiance behaviors" - might be amenable to quite a simple intervention. That could be important for many, many different reasons.

The basics: PS128 containing "3 × 1010 CFU/capsule of PS128 with microcrystalline cellulose as the carrier" was the compound under investigation, pitted against a placebo that "only contained microcrystalline cellulose." Eighty participants, all boys diagnosed with an autism spectrum disorder (ASD) were recruited for study; 39 were assigned to receive PS128 and 41 receiving the placebo for a period of 4 weeks. Various different schedules and questionnaires were used to measure behaviour at baseline and week 4 between the groups. With a fairly small attrition rate - data for 36 participants in the PS128 and 35 in the placebo group were analysed - the results were pretty interesting.

Results: first and foremost we are told that no adverse events were reported during the study. That's important. Next, for the vast majority of measures used when straight comparing of PS128 and placebo, no significant difference was noted. The authors even mention how a clinician rated scale, the CGI-I, basically said that "both groups were equivalent to "minimally improved""  between baseline and study end. It was only when results were stratified for age that things started to 'happen' as various behaviours around anxiety, rule-breaking, inattention and opposition/defiance showed something like a 'nominal' reduction in the PS128 group compared with placebo, particularly for those aged between 7-12 years. As per the use of the word 'nominal' to denote a small 'change' the results were not spectacular.

Caveats? Well, this was a 4-week study of boys on the autism spectrum. Not a long time in anyone's book but longer than other studies on other interventions that did show a statistically significant effect (see here for example). The Liu study was also a study that exclusively relied on behavioural observation measures, so we can't say anything about how something like PS128 might have impacted on gut bacteria for example. Other, less methodologically sound studies have been more comprehensive (see here).

But there are strengths to the Liu study; strengths around the design and use of a placebo condition. And if there is a chance that something like Lactobacillus plantarum PS128 or other preparations (see here and see here) or related techniques (see here) *might* help improve quality of life for young and old people on the autism spectrum minus any significant side-effects, they should be explored an awful lot more...

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[1] Liu Y-W. et al. Effects of Lactobacillus plantarum PS128 on Children with Autism Spectrum Disorder in Taiwan: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2019; 11: 820.

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Estimated autism prevalence in Northern Ireland: 3.3% for 2018-2019

The BBC news headline reading "Autistic children in NI schools trebles in a decade" provides the blogging fodder today.

NI refers to Northern Ireland, and the news report relates to the publication of further findings from the Department of Health in NI [1] on the topic of autism prevalence among school-aged children.

I've covered the NI 'autism in school children' figures for quite a few years on this blog (see here and see here). The stats have gone from 2.3% in 2015/2016 to 2.5% in 2016/2017 to 2.9% in 2017/2018 to the most recent figures of 3.3% in 2018/2019. The report and news coverage focus on how that recent 3.3% figure compared with 1.2% back in 2008/2009. That's quite a shift in the space of just a decade.

A few details are worthy of further mention. First, Northern Ireland seems to be taking a bit of a lead in collecting information about rates of autism in school-aged children (see here). Indeed, many of the 'home countries' making up the United Kingdom (UK) are starting to ask the questions that England, unfortunately, is seemingly not yet asking (see here).

Second, we are told that: "The increase in prevalence of children with autism can be attributed to an annual average increase in the number of children identified with autism of 12% between 2009/10 and 2018/19, against a background of a relatively static school population." This means that the rates of autism in school-aged children are not simply increasing because the school population as a whole is increasing. Indeed, with other not-so-long-ago chatter about long waiting lists for assessment in places like Northern Ireland (see here), one could argue that the current figures are an under-estimate.

Third, with regards to the sex ratio (boys:girls), the 2018/2019 figures suggest that "5.1% of males were identified with autism compared to 1.5% of females." The same figures a decade ago (2008/2009) were 1.9% and 0.4% respectively. I don't however necessarily agree with the: "Autism could therefore be considered to be an extreme of the normal male profile" sentiments expressed by the author to account for this difference but...

Fourth, the rate of the increase across the decade (2008/2009 compared with 2018/2019) was present in every school year. The author focuses in on the fact that nearly 4% of those in Year 6 (the end of primary school) were "identified with autism". He also mentions that most identification of autism in school is occurring when children are aged between 5 and 10 years old. Primary school, it seems, is an important time for the identification of autism.

Fifth: something approaching grading a child for autism 'severity' is also discussed. I know 'severity' is still a contentious issue (someone actually suggested 'severe autism' should be replaced by 'profound autism' which sounds rather sensible). Special educational need (SEN) assessment is a process via which a child's needs are graded. More details about this process applied to Northern Ireland can be found here. SEN stage 4 and SEN stage 5 indicate that a child requires support from school but also that "the education authority shares responsibility with the school." Nearly two-thirds of children identified with autism were at SEN stage 5. This was however down from previous years with the main 'growth' being among those who were gauged at SEN stage 2 and stage 3. The authors caution that such figures are only a snapshot (children can move up and down the SEN stages for example).

Whichever way you cut it, the recent figures out of Northern Ireland show the increasing trend for autism in school-aged children (see here). We can add such figures to those which have recently come out of the United States (see here and see here), Canada (see here) and various other parts of the world. We can quibble about the old 'better awareness' arguments and even diagnostic switching as being primary causes of the increase. I personally do not believe that such explanations even come close to the final reasons for the increase in cases that have been noted and continue to be seen (see here). What I do know is that further finance and resources are required to meet the often complex needs of these children and young adults to allow them to reach their potential.

And minus any emotive language (i.e. tsunami), let's remember that children turn to adults, and many of these children will require on-going help and support into their later years. The question is: are we prepared?

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[1] Waugh I. The Prevalence of Autism (including Asperger Syndrome) in School Age Children in Northern Ireland 2019. Northern Ireland Department of Health. 2019. May 10.

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"people on the autism spectrum have a high prevalence of physical and mental health conditions in midlife and old age"

Should anyone really be that surprised by the findings reported by Lauren Bishop-Fitzpatrick & Eric Rubenstein [1] talking about "a high prevalence of physical and mental health conditions in midlife and old age" when it comes to autism?

Well, yes and no. No, because things like 'psychiatric symptoms and disorders' have already been talked about with regards to older age adults with autism [2] (see here also), alongside various other 'medical comorbidity' being noted in this group (see here). But also yes, because the scale of the physical and mental health conditions identified by Bishop-Fitzpatrick & Rubenstein is quite literally jaw-dropping: "immune conditions (70.6%), cardiovascular disease (49.0%) and its risk factors (46.2%), sleep disorders (85.3%), gastrointestinal disorders (49.7%), neurologic conditions (55.9%), and psychiatric disorders (72.0%) were highly prevalent in our full sample." Said full sample consisted of "de-identified Medicaid claims data for 143 adults with a recorded autism spectrum disorder diagnosis aged 40–88 years."

Researchers also mention how 44% of their sample had an intellectual (learning) disability. This kinda accords with various other data on this topic (see here). Other observations mentioned by the authors also complement existing (peer-reviewed scientific) knowledge that: (a) intellectual (learning) disability seems to bring about an increased risk of epilepsy appearing alongside autism (see here), and (b) depression and anxiety prevalence seems to be particularly elevated in those with autism without any accompanying learning disability (see here) (assuming that depression and/or anxiety are actually being screened for in those with autism + learning disability).

What do the collected data imply? Well, screening is important. Screen and screen and screen and screen. Screen for lots of things, and if something turns up, treat / manage it. If your average Jane or Joe turned up at their Doctors office with a sleep disorder or the symptoms of cardiovascular disease, medical professionals would do something about it. If the Doctor also knew that Jane / Joe might, for example, be more likely than usual to be in receipt of certain classes of medicines that potentially elevates such risks further, they'd be even more keen to screen and intervene. So it should be the same if Joe or Jane is diagnosed with autism or an autism spectrum disorder (ASD).

I'd also suggest that such data should really be leading to a lot more questioning about why? Why do people on the autism spectrum seem to be at particularly high risk of 'immune conditions' or 'digestive disorders'? Are there potential genetic links between autism and such conditions as per the notion that 'autism genes aren't necessarily just genes for autism' (see here) or that such genes might also affect other biological systems as well as the grey-pink matter floating around the skull (see here for example)? Are there other intricate connections between such classes of conditions as per the idea that sleep problems seem to follow gut problems for some (see here)? Why? Pain, discomfort, something else? And don't even get me started on the whole 'immune system - autism' connection (see here for example) which has been known about for many, many, many years. Known about but brushed under the carpet by some.

And whilst talking about the research tag-team that is Bishop-Fitzpatrick & Rubenstein, I once again would direct you to another important paper of theirs [3] about how we need to be very careful about using the word 'comorbidity' when referring to the various mental and physical issues that are over-represented around autism. As we've seen from other research (see here and see here), the core features of autism may very well predispose to a lot more than just autism and, in that respect, this might go way beyond just comorbidity...

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[1] Bishop-Fitzpatrick L. & Rubenstein E. The physical and mental health of middle aged and older adults on the autism spectrum and the impact of intellectual disability. Research in Autism Spectrum Disorders. 2019. Jan 29.

[2] Lugo-Marín J. et al. Prevalence of psychiatric disorders in adults with autism spectrum disorder: A systematic review and meta-analysis. Research in Autism Spectrum Disorders. 2019; 59: 22-33.

[3] Rubenstein E. & Bishop-Fitzpatrick L. A matter of time: The necessity of temporal language in research on health conditions that present with autism spectrum disorder. Autism Res. 2019 Jan;12(1):20-25.

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"the incidence of ADHD, ASD, and DD significantly increased after TBI events in early childhood"

TBI mentioned in the title of this post refers to traumatic brain injury, and represents the 'target variable' examined by Hsuan-Kan Chang and colleagues [1] in the context of rates of "attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and developmental delay (DD)."

Consistent with various other research published by this authorship group, the fantastic but sadly now defunct National Health Insurance Research Database (NHIRD) in Taiwan was the resource used by Chang et al in pursuit of their research goal. And the participant numbers under study reflected the use of the NHIRD: "A total of 7,801 and 31,204 children were enrolled in the TBI and control cohorts, respectively."

As well as instances of TBI being listed in the NHIRD "from 1998-2008", researchers also had access to "the incidence of subsequent ADHD, ASD, or DD (according to ICD-9 criteria)." They observed that: "The TBI cohort exhibited a higher incidence of subsequent ADHD, ASD, or DD than the controls" and that said developmental diagnoses tended to be made "at a younger age compared with the controls" (non-TBI controls). They concluded that TBI seemed to increase the risk of each developmental diagnosis and that "severe TBI, repeated TBI events, and TBI at a younger age" were all (variably) potentially important factors for the labels.

This is interesting and thought-provoking research. It does require some 'treading carefully' sentiments; not least with the idea that within the huge heterogeneity and variability of labels such as ADHD and autism (ASD), TBI *might* be a route or part of a possible route towards a diagnosis. Whilst not discounting the idea that sub-clinical signs and symptoms of developmental disorders could actually put someone at greater risk for TBI (see here for example), the possibility that TBI 'might lead to' a developmental diagnosis should not be shied away from. Indeed, other independent findings might also be important (see here). I say that mentioning that TBI is a general term that says nothing about the reason for the injury, the type of injury or what specific part of the brain may be affected. If one however takes autism as an example, it's not beyond the realms of possibility that certain TBIs could 'mimic' effects seen in other examples of 'acquired autism' where brain injury is part-and-parcel of the clinical picture (see here and see here). Indeed, similar sentiments have been expressed in relation to ADHD too (see here).

Whatever the relationship and mechanisms involved, the Chang findings imply that further investigations are needed in this area. Also, far greater efforts need to go into first preventing and then managing TBI...

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[1] Chang HK. et al. Traumatic Brain Injury in Early Childhood and Risk of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder: A Nationwide Longitudinal Study. J Clin Psychiatry. 2018 Oct 16;79(6). pii: 17m11857.

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Relative age and ADHD: more data and a meta-analysis

So, relative age and ADHD. The observation that in amongst the various pathways that might lead someone to a diagnosis of attention-deficit hyperactivity disorder (ADHD), "the youngest children within a school class are at a disadvantage in many aspects compared with their older classmates" including increasing "the probability of having ADHD-related symptoms... or other psychopathology..., of receiving a diagnosis of ADHD... or being treated with stimulant medications."

I've talked about this issue a few times on this blog (see here and see here) and am blogging today about a couple of other studies that add to the literature in this area. The first investigation was undertaken by Janine Wendt and colleagues [1] and concluded that: "Using a prospective study design and comprehensive adjustment for confounding and baseline symptoms, we confirmed prior evidence of the association between young ASE [age at school entry] and teacher-reported ADHD symptoms in primary school." The second study was published by Josephine Holland & Kapil Sayal [2] who, following a systematic review of the peer-reviewed science literature on this topic, concluded that "the majority of studies show evidence of a relative age effect influencing both the diagnosis of and receipt of medication for ADHD."

Both studies are open-access so really don't require too much explanation from me. The Wendt study relied on data collected from over 120 "Rudolf Steiner Schools (Waldorf Schools) located within Germany" (Waldorf schools are based on the philosophy of producing "free, morally responsible, and integrated individuals equipped with a high degree of social competence") covering over 3000 children. We are told that this prospective study gathered data via parent- and teacher- reports: "ADHD-related symptoms were assessed at school entry and second and fourth grades by parent-reported and teacher-reported versions of the Strengths and Difficulties Questionnaire (Hyperactivity-Inattention Subscale)." Their results found a possible *association* between age and school entry (ASE) and teacher-reported ADHD symptoms using the SDQ: "ASE was negatively associated with ADHD-related symptoms in the second grade... and fourth grade. Associations remained after adjusting for potential confounders and pre-existing symptoms at baseline." Those 'potential confounders' included "gender, time of observation and source of information." I'm also inclined to point out that the prevalence of possible ADHD overall in the Wendt study was pretty high in some scenarios: "The frequency of ADHD indications ranged from 3.7% (girls, second grade, parent reports) to 25.0% (boys, second grade, teacher reports)."

Then to the Holland-Sayal study. This was a systematic review of the existing research literature pertinent to the questions: "Is there an association between younger relative age, defined as being in the second half of the academic year, and: (1) the presence of high levels of ADHD symptoms, (2) receiving a clinical diagnosis of ADHD and (3) receiving medication for ADHD?" Based on an examination of the literature "published from the 1st of January 2000 to the search date of the 7th September 2017" and including 20 papers for review, the answer: yes, generally-speaking, there is more evidence for a relative age effect in relation to ADHD symptoms, diagnosis or receipt of medication for ADHD than against it.

Holland & Sayal do caution that their findings were not totally unambiguous. They discuss how differences across the various studies included for analysis might be important to the final outcome determined. So: "studies differed by sample size, years studied, ages studied and methods of reporting and recording ADHD diagnosis and medication." They also noted that: "The culture of diagnostic practice within a country’s health system may have an influence on the relative age effects found" implying that the willingness to diagnose ADHD in a particular country or region could very well have had an effect on the main findings.

Overall however, these studies add to the existing research-based message observing that age and maturation may be important 'influencers' of reported ADHD symptoms, diagnosis and/or receipt of ADHD medicines.

The big question now is 'what is science and clinical practice going to do about it? bearing in mind that there may be 'redshirting' models to follow [3]...

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[1] Wendt J. et al. Young age at school entry and attention-deficit hyperactivity disorder-related symptoms during primary school: results of a prospective cohort study conducted at German Rudolf Steiner Schools. BMJ Open. 2018;8:e020820.

[2] Holland J. & Sayal K. Relative age and ADHD symptoms, diagnosis and medication: a systematic review. European Child & Adolescent Psychiatry. 2018. Oct 6.

[3] Whitely M. et al. Attention deficit hyperactivity disorder late birthdate effect common in both high and low prescribing international jurisdictions: systematic review. J Child Psychol Psychiatry. 2018 Oct 14.

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Long-term health conditions and autism: a Scottish perspective

There were a few things that raised my eyebrow (Roger Moore style) in the paper published by Ewelina Rydzewska and colleagues [1]. The primary finding that: "Comorbidity is substantially greater in adults with reported autism than in other people" was one of the eyebrow raisers. But also the observation that: "Scotland’s Census is one of the few country censuses that asks every person in the country whether or not they have autism, indeed it may be unique in this regard" was another. There were others too...

Back to the first point and the primary purpose of the Rydzewska study: "to investigate the prevalence and predictors of deafness or partial hearing loss, blindness or partial sight loss, intellectual disabilities, mental health conditions, physical disability and other condition, in a whole country population of adults with reported autism aged 25+ compared with their peers without autism." Said whole country was somewhere not a million miles away from where I write this post - Scotland - and results based on Scotland's Census 2011. The Census did what Census (I don't know what the plural should be!) are normally designed to do: to provide details on the population (N=5 295 403) covering everyone "whether living in communal establishments (such as care homes and student halls of residence) or private households." As mentioned, I wasn't aware that Scotland asked about whether someone has autism or not as part of the Census but I'm impressed that they do. As to the authors' testing the idea that autism is rarely a stand-along diagnosis, well let's just say that this has already been discussed a few times in the peer-reviewed science arena (see here for example) so we kinda had some clues as to what might have been observed.

Results: "There were 6649/3 746 584 (0.2%) adults aged 25+ recorded to have autism as defined here, 4610 (69.3%) of whom were men and 2039 (30.7%) women compared with 1 776 845 (47.5%) men and 1 963 090 (52.5%) women in the adult population without autism." Let me just say that again: in the Scottish 2011 Census, that covered both private households and 'communal establishments' only 0.2% of the respondents above 25 years of age were reported to have a diagnosis of a "developmental disorder (eg, autistic spectrum disorder or Asperger’s syndrome)." Interesting.

Continuing: "The rate of autism was lowest in the oldest age groups (autism may be associated with reduced life expectancy)." 'Autism may be associated with reduced life expectancy' is another important detail mentioned in the Rydzewska study and something that taps into a wealth of other science (see here for example) observing that the diagnosis of autism can, very much, be a life-limiting label for some.

Then to the main event: lots of different diagnoses/labels were seemingly over-represented alongside a diagnosis of autism. Indeed, pretty much all of the ones enquired about by researchers fell into that category. A third of participants for example, reported experiencing 'something' under the heading of "a mental health condition"; a finding also fairly consistently stretching across individual analyses based on different age bandings. When it came also to the category titled 'intellectual disabilities' (also known as learning disability here in Blighty) the figures stood out: "A high rate of intellectual disabilities in children with autism has been described previously; we have now quantified the extent of this—29% (25%–32% depending on age group; 22%–35% for men and 31%–42% for women)—in a much larger study of adults." This [roughly] accords with other independent data too (see here).

What's more to say? Well yet again, it's all about not looking at autism as some sort of 'stand alone' label given the over-representation of some pretty significant categories of health issues, covering both the somatic (physical) and the psychological. I don't think anyone would disagree with such an observation in this day and age as the words 'Autism Plus' are also mentioned in the Rydzewska paper. Once again, this also has implications for preferential screening when a diagnosis of autism is received and also the treatment/management of any issues that are detected (see here and see here for examples).

As for that 0.2% adult (over 25 years old) prevalence figure noted by the authors, I'm not going to say too much more about that for now. Aside that is, from dropping in some discussions about another adult autism prevalence study (see here) which reported that figures were potentially climbing in line with the childhood autism prevalence figures (see here). I'm sure that there are multiple discussions that could be generated around such figures but not here, not now, and not to distract from the important observation that autism rarely appears in a diagnostic vacuum...

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[1] Rydzewska E. et al. Prevalence of long-term health conditions in adults with autism: observational study of a whole country population. BMJ Open. 2018;8:e023945.

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Autistic traits carrying a 'cognitive cost' into old age?

I don't think anyone should be too alarmed at the findings reported by Gavin Stewart and colleagues [1]. But their observation that "autism traits as measured by the BAPQ [Broad Autism Phenotype Questionnaire] may confer additional risk of cognitive decline in aging" represents something that requires quite a bit of further investigation.

Some twenty 'older' adults who were questioned and deemed to have met criteria for the broader autism phenotype (BAP) were tested on skills related to executive function alongside episodic memory. Their results were compared with twenty 'older' adults who did not reach criteria for the BAP. Authors reported that: "Despite no differences in age, sex ratio, educational history or IQ, the BAP group demonstrated poorer performance on measures of executive function and episodic memory compared to the COA [control older adults] group." They interpret this in the context of that 'additional risk of cognitive decline in aging'.

The numbers of participants in the Stewart study were low and imply that one has to be quite careful about making any sweeping generalisations as a result. Bear also in mind that the BAP does not necessarily equal autism or autism spectrum disorder (ASD) as a function of it describing sub-threshold autistic traits (sub-threshold for a diagnosis). Traits, I might add, that are seemingly not just potentially representative of autism (see here for one example).

But set within a 'gap' in the research base looking at autism in older adults (see here), there is a scheme of work to follow. If for example, the Stewart 'trend' does overlap with the experiences of older adults on the autism spectrum in terms of 'cognitive decline', there is a whole barrage of potentially important implications to consider. More so when one considers that the autism prevalence data continues to head in only one direction (see here) and what this means for societal financial and resource planning.

Just before I go, one more detail was revealed in the Stewart paper: "Older adults who met the BAP criteria also reported higher levels of depression and anxiety." Continuing a theme on this blog that various over-represented issues/diagnoses in relation to autism might not be best described as just being 'comorbid' (see here and see here and see here), I believe that this finding adds further weight to the notion that autistic traits (clinical and sub-clinical) might have some important 'direct' relationships with other psychopathology. Not necessarily a welcome opinion in some quarters, but something that also requires a lot more investigation.

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[1] Stewart GR. et al. Aging with elevated autistic traits: Cognitive functioning among older adults with the broad autism phenotype. Research in Autism Spectrum Disorders. 2018; 54: 27-36.

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One in five 8-year olds "received a psychiatric diagnosis"

"Question: What is the cumulative incidence of psychiatric diagnosis and use of psychotropic medications in a Medicaid-insured birth cohort by age 8 years?"

Answer: About 1 in 5 children were in receipt of a psychiatric diagnosis at age 8, and about 10% were in receipt of psychotropic medication.

So said the findings reported by Dinci Pennap and colleagues [1] who relied on "Medicaid claims data for newborns in a mid-Atlantic state in 2007... and followed up for 96 months or less through December 31, 2014." As per the focus on Medicaid - an initiative that 'helps with medical costs for some people with limited income and resources' - this was a study conducted in the United States, and included data for over 35,000 infants/children. The sorts of psychiatric diagnoses examined by Pennap et al included "ADHD [attention-deficit hyperactivity disorder], disruptive disorders, learning disorder (LD), adjustment disorder, anxiety disorders, depression, ASD [autism spectrum disorder], and other psychiatric diagnoses" all diagnosed by a clinician, but also requiring "2 or more diagnosis claims on separate days."

Venturing further into the study results, we learn some potentially important details. So, across the years of study, approaching two-thirds of the diagnoses received were defined as 'behavioural'. As probably expected (see here), a diagnosis of ADHD was the most popular label - "accounted for 43.9% (1999 of 4550)" - followed by a learning disorder (disability) diagnosis received by just over 30% of the group. White children were seemingly more likely to receive any psychiatric diagnosis than African American children or Hispanic children, and there were some important sex/gender differences noted across various diagnostic labels. If I'm also reading the results correctly with regards to the label of ASD (autism spectrum disorder) (see here), it looks like about 2-2.5% of boys had received a diagnosis, bearing in mind that this is a figure showing as a percentage of those who had received a psychiatric diagnosis. As a function of the entire cohort (N=35,244), the cumulative incidence of ASD across the years (2007-2014) and across the genders was 0.89%.

Then to the issue of pharmacotherapy or medication prescription. Bear in mind that Pennap and colleagues were looking at psychotropic medication being delivered to infants and young children; a group where even greater caution than usual should be expected. They reported that just over 10% of the entire cohort had some history of psychotropic medication use. Alongside those stats on ADHD as a diagnosis, so the medicines classed as stimulants (indicated for ADHD) made up the biggest class of medication used. The authors also zoomed in on a few particular parts of their medication findings. First: "girls were twice as likely as boys to initiate treatment with anxiolytics and hypnotics (25.2% [173 of 686] vs 13.2% [199 of 1510]; P < .001)", also noting that "there is insufficient evidence to support the use of anxiolytics and hypnotics as first-line treatment for pediatric mental health conditions." Second, they discuss evidence suggesting that: "antipsychotics are largely used for off-label behavioral management in the birth cohort, highlighting the need for a delicate benefit-risk balance." Yes, indeed there is a need for exploring that 'delicate benefit-risk balance' (see here and see here). The other rather important finding concerned the use of more than one psychotropic medicine over a prolonged period of time: "approximately 20% of medicated children (433 of 2196 [percentage adjusted for right censoring]) received 2 or more classes concomitantly for 60 days or more." Remember again, these were young children that were under study.

The picture painted by Pennap et al is an important one. It adds to other independent evidence to suggest that across different geographies, psychiatric disorders including behaviourally and emotionally-defined conditions, are prevalent, dare I even say frequent (see here and see here). I'd also add in the 'yet newer' recent US CDC 'estimates' of autism in 8-year olds in this context too (see here).

In relation to the medication side of things, well, 10% of their total population have had some exposure to psychotropic medication, which is important. Accepting that (very) careful medicines management is required given the young age of the group, I'm gonna stick to a line that I've mentioned before regarding the clinical need for such medicines [generally] outweighing the risk(s). I say this on the basis that prescribing clinicians know their clinical population and know something about the risk-benefit profile of the medicines they're administering. I'd also add that when it comes to something like stimulants as a class of medicines, the clinical profile of such medicines is typically 'safe' (benefits outweighing risks) and can, in a few cases, literally be a life-saver (see here and see here). But all that does not mean that science shouldn't be looking to other avenues for intervention for various labels (see here and see here for examples), alongside keeping a sharp eye on ways and means of making such medicines even safer for such younger populations...

And just in case you thought the figure 1 in 5 only holds for the United States, you're wrong and resources and services here in Blighty are seemingly still struggling...

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[1] Pennap D. et al. Patterns of Early Mental Health Diagnosis and Medication Treatment in a Medicaid-Insured Birth Cohort. JAMA Pediatrics. 2018. April 30.

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"Gluten-free prescribing is in a state of flux"

Consider this off-core-topic post an extension of previous other off-topic chatter on this blog talking about the prescription of gluten-free foods here in Blighty (see here). On that previous blogging occasion, I discussed a 'head-to-head' debate on whether the prescription of gluten-free foods for conditions such as coeliac disease was still 'relevant' in an age when supermarkets have shelves loaded with gluten-free products as part of a societal fascination with 'going gluten-free'. Whether there may be other models - such as the use of a voucher scheme - that could save time and money yet still ensure that the important use of a gluten-free diet in relation to coeliac disease is maintained and supported.

Well, the recent findings reported by Alex Walker and colleagues [1] add to this debate, and their look at "long-term national trends in gluten-free prescribing, and practice and Clinical Commissioning Group (CCG) level monthly variation in the rate of gluten-free prescribing (per 1000 patients) over time." CCGs by the way, are groups here in England "responsible for the planning and commissioning of health care services for their local area."

Walker et al relied on a retrospective cohort study design that analysed prescribing and spending data from various sources, and covered various geographical areas of England in relation to gluten-free prescribing. Alongside, other potentially pertinent data were included in the statistical mix, for example: "Index of Multiple Deprivation (IMD) score; patients with a long-term health condition (%); patients over 65 (%) and whether each practice is a ‘dispensing practice’ with an in-house pharmacy service (yes or no)."

Results: including data from over 7600 medical practices, authors reported that between July 2012 and June 2013, some 1.8 million prescriptions for gluten-free products were dispensed costing around £25.4 million. Fast forward to the period July 2016 - June 2017 and fewer prescriptions were made: "1.3 million gluten-free prescriptions nationally... with a total expenditure of £18.7 million." This, bearing in mind, that rates of diagnosed coeliac disease are seemingly only going in one direction - up [2].

Researchers also reported that there was "substantial variation in prescribing rates among practices" which was captured by some other reporting on the Walker paper as per bylines such as: "Prescribing of gluten-free products in England differs largely and “without good reason”, researchers have concluded." Indeed Walker and colleagues concluded that much of the geographical discrepancy in the gluten-free prescribing rates was "driven at the CCG level, where there is also a great deal of variation." For some CCGs, the decision was to provide gluten-free prescriptions; for others, there seems to be "a partial or complete withdrawal of prescriptions." A bit of a postcode lottery if you like.

As to those other variables included in the analysis, a few other important details emerged. So: "practices in the most deprived areas had a significantly lower rate of gluten-free prescribing than those in less deprived areas." Further: "We also found that percentage of patients over 65 is strongly associated with gluten-free prescribing, which is unsurprising given that coeliac disease prevalence increases with age." That first finding in relation to deprivation *might* be linked to things like an under-diagnosis of something like coeliac disease in those areas. But it could point to other factors potentially coming into play as well...

At the time of writing / publishing this post, we are still living in the age of austerity here in Blighty. Government in particular, [still] wants to 'balance the books' yet is still expecting national services such as health to provide for the population they serve. Set within that context, and also how health budgets are having to deal with more people with more complex needs, it's probably not surprising that for some geographical areas, 'low hanging fruit' such as gluten-free prescriptions are seen as fair game when it comes to balancing the books. It shouldn't, but there you go.

I do stand by the idea that if things are seemingly 'on the downward slide' in terms of gluten-free prescribing patterns, there may be other models to look at that could help (i.e. that voucher scheme idea). Patients and their relevant organisations need to have a voice in this process to ensure that gluten-free diets are maintained and health does not unduly suffer. Food, for people with coeliac disease - gluten-free food - is medicine, and one should never forget that and the absolute requirement to provide such medical provision.

To close, and entirely unrelated to today's post, I see Belgium have some historical and/or statistical advantage when it comes to the World Cup starting soon...

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[1] Walker AJ. et al. Trends, geographical variation and factors associated with prescribing of gluten-free foods in English primary care: a cross-sectional study. BMJ Open. 2018 Apr 16;8(3):e021312.

[2] Holmes GKT. & Muirhead A. Epidemiology of coeliac disease in a single centre in Southern Derbyshire 1958-2014. BMJ Open Gastroenterol. 2017 Apr 1;4(1):e000137.

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The headline: "One in nine young people in Scotland have attempted suicide"

I have to say that I drew a sharp intake of breath when I read the media headline titling this post - "One in nine young people in Scotland have attempted suicide" - based on the findings reported by Rory O'Connor and colleagues [1]. The idea that, from a sample of some 3500 young people in Scotland, some 10% and 15% of respondents to the questions: "Have you ever made an attempt to take your life, by taking an overdose of tablets or in some other way?’ and ‘Have you ever deliberately harmed yourself in any way but not with the intention of killing yourself? (i.e. self-harm)" answered in the affirmative, seemed pretty important. Not least with the question 'why?' in mind.

OK, media headlines aside, the O'Connor findings require some dissection. The reasoning behind studying this issue was not only to look at the very complicated topic of suicide in a part of the UK (Scotland) that authors write "has a higher suicide rate than England", but also to try and understand how non-suicidal self-injury (NSSI) or non-suicidal self-harm (NSSH) presents in young adults and whether there is something important linking NSSH and suicidal thoughts and/or attempts.

The participant group was drawn from "a representative sample of young people aged 18–34 years from across Scotland" who were recruited to the Scottish Wellbeing Study. Lots of measures were completed by participants as part of the wider study initiative but we are told that "only the prevalence of NSSH and suicide attempts information is reported" in the O'Connor article on this occasion. I might also add that participants were compensated to the tune of £25 (pounds sterling) for their time and participation.

Alongside those headline findings on self-reported attempted suicide and self-harm, a few other important trends were observed. So: "More than 20% reported lifetime suicidal thoughts, 2.4% reported that they last thought about suicide in the past week and 10.4% reported they last thought about suicide in the past 12 months." Around 6% of respondents reported that they had both attempted suicide and also engaged in self-injury suggesting that professionals should "routinely enquire about history of self-injurious behaviour, especially as past behaviour is such a strong predictor of suicide." Also: "Earlier age at NSSH or suicide attempt onset was associated with more frequent lifetime NSSH and suicide attempts." And finally: "The prevalence of NSSH and suicide attempts was significantly higher among those classified as unemployed... and economically inactive... compared with those who were employed." Age, societal and environmental factors seem to play some roles too.

Then to another important set of questions: (a) why? and (b) what can be done to reduce these headline-grabbing statistics? Well, there are no easy answers to such questions I'm afraid. The authors do note that: "From a public health perspective, the unemployment and economic inactivity findings are noteworthy" and perhaps suggest that there are some modifiable variables that could influence suicidal thoughts and/or actions focused on getting people into employment and the benefits that this brings (wide-ranging benefits by all accounts). But this probably only covers one side of the issue, as discussions inevitably turn to what role psychiatric and/or behavioural comorbidity might play in such reporting (see here and see here and see here) and whether there may be a need for (a) something like enhanced screening for suicidal thoughts or other 'risks' among selected populations and/or (b) the [careful] use of 'preventative' strategies in such cases (see here and see here). I say all that accepting that diagnoses around mental health probably play an important role in suicide-related behaviours but are not necessarily a pre-requisite...

As always, there is always someone to talk to if needed...

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[1] O'Connor RC. et al. Suicide attempts and non-suicidal self-harm: national prevalence study of young adults. BJPsych Open. 2018; 4: 142-148.

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"Health inequalities in relation to people with learning disabilities": LeDeR reports.

LeDeR mentioned in the title of this post, refers to the Learning Disabilities Mortality Review, an English initiative designed to "make improvements to the lives of people with learning disabilities." Part of that 'make improvements' statement covers the important area of health inequality and some truly shocking early mortality risks that seems to follow a diagnosis of learning (intellectual) disability. To quote: "Today, people with learning disabilities die, on average, 15-20 years sooner than people in the general population, with some of those deaths identified as being potentially amenable to good quality healthcare." Remind me what century we live in again...

I've covered early mortality in the context of learning disability before on this blog (see here and see here) and how various factors seem to 'converge' to place someone diagnosed with a learning disability at some significant disadvantage when it comes to living a healthy life or being faced with an early death. So things like an acknowledgement that various physical conditions seems to be 'over-represented' alongside learning disability and the idea that diagnostic overshadowing is quite prevalent are some key points to consider (see here). Minus any sweeping generalisations, I should also mention that the quality of the care received (or sometimes not received) by some people diagnosed with a learning disability is also sometimes part of the picture too (see here).

The LeDeR report covering 2017 [1] once again paints a pretty grim picture of how we, as a society, treat some of how most vulnerable members. Some media coverage of the publication of the report can be seen here and other bloggers have dissected some of the observations (see here). The report notes from the period 1st July 2016 to 30th November 2017 there were over 1300 deaths reported to the LeDeR programme. Also: "The median age at death of people with learning disabilities (aged four years and over) was 58 years (range 4-97 years). For males it was 59; for females 56." And: "More than a quarter (28%) of deaths were of people aged under 50 years." More than a quarter of deaths were noted in those under 50 years of age. Let that sink in, as it appears that being diagnosed with a learning disability impacts on how long you're likely to live. Perhaps just as important was another observation made: "People with profound or multiple disabilities had a median age at death of 41 years; those with mild or moderate learning disabilities had a median age at death of 63 years." There appears to be a dose-related relationship between mortality and how disabled a person was.

Details on the cause of death also revealed some important patterns. Respiratory illness was mentioned on the death certificate of some 30% of people - the most frequently cited cause - and diseases of the circulatory system in around 15%. In more detail, these categorisations covered specific diagnoses such as pneumonia and sepsis. I should also mention that epilepsy was also mentioned as a cause of death in around 4-6% of cases.

Where next? Well, the report does make some recommendations to try and reduce/eliminate such health inequalities in the context of learning disability. Obviously, not every death recorded could have been avoided, but there are potential ways and means in which care might (should!) be improved to help lessen the risk of early mortality for some. Outside of things like 'strengthening collaboration and information sharing' noted in the report, I was drawn to a few other recommendations including one stating that "all people with learning disabilities with two or more long term conditions (related to either physical or mental health) should have a local, named health care coordinator" and another that: "There should be a national focus on pneumonia and sepsis in people with learning disabilities, to raise awareness about their prevention, identification and early treatment." I can't disagree with such future directions assuming that is, that the money required to set in motion such recommendations, also follows suit.

I'm becoming increasingly aware that there is a real issue present in the care of many different groups of people, specifically where a learning, developmental or psychiatric diagnosis is mentioned. People with a learning disability are at a heightened risk of early mortality. People diagnosed with a developmental disorder such as autism are at a heightened risk of early mortality (see here and see here). People diagnosed with a psychiatric disorder such as schizophrenia are at a heightened risk of early mortality (see here and see here). It strikes me that the time may be right to set up an independent commission covering these (often, very often, overlapping) diagnostic areas, and look at putting into action new ways of ensuring that such diagnoses are not a gateway to an early death.

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[1] The Learning Disabilities Mortality Review (LeDeR) Programme. 2018. Annual Report December 2017.

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Estimated autism prevalence in Canada in 2015: 1 in 66

"On March 29, 2018, the Public Health Agency of Canada published the first comprehensive review of the prevalence of autism spectrum disorder (ASD) in Canada."

So began the 'what did we find' summary (see here) covering the "Made in Canada" findings detailed in the Canadian National Autism Spectrum Disorder Surveillance System (NASS) 2018 Report (see here) [1]. Pertinent to the year 2015 and including some 88% of the children and young adults living in various participating Provinces and Territory, data was gathered from various sources (education, social services, health) onward to the estimated prevalence of diagnosed autism in Canada.

Their results: "Among children and youth 5–17 years old across seven provinces and territory, the combined prevalence of ASD for the year 2015 is 1 in 66 (15.2 per 1,000)" (bold text added by me).

Details, details, details... Such an estimate applies to children and young adults (youth) diagnosed with autism and does not say anything about the number of adults diagnosed with autism. It only covers those diagnosed with autism based on strict criteria: "The diagnosis of ASD is provided or confirmed by a licensed health care professional(s)... [and] The diagnosis of ASD is based on the clinical criteria in the Diagnostic and Statistical Manual (DSM) for Mental Disorders or the case is identified as ASD in the International Classification for Diseases (ICD)." It does not provide any information on how many people *might* be autistic but not yet in receipt of a diagnosis. Males made up the lion's share of those diagnosed. Most had been diagnosed by the age of 8 years (72%). Oh, and not every Province or Territory showed the same estimated prevalence rate for various potential reasons. And rest.

Also pretty important to the reported findings is the comparison with earlier years estimates: for 3 geographic locations in Canada we see the characteristic 'upward trend' in the estimated prevalence of ASD noted in other sample data from other countries, from around 4-6 per 1,000 in 2003 to between 16-20 per 1,000 in 2015. And when compared with a neighbour to the South (USA) and their estimated autism prevalence stats covering 2012 (see here) coming up with a figure of 1 in 68, the Canadian estimates are not a million miles away,. This, bearing in mind, some differences in the way the different country figures were arrived at and also the time periods covered. That also reminds me, we should be seeing the latest US stats on estimated autism prevalence from the CDC at some point in the (very) near future, and the promise that "the ADDM Network will be able to estimate ASD case status on the basis of both DSM-5 and DSM-IV-TR." Those comparisons should be rather interesting in light of other preliminary data (see here).

What else it there to say? Diagnosed autism is fairly prevalent across Canada (who have some important history in relation to the autism 'numbers game') and I assume we'll be seeing more on their tracking of the diagnosis in future times. Preparation is an important part of the figures being discussed; preparation of education, social and health services to support the numbers of children and young adults being diagnosed now and who, I assume, will eventually be transitioning to adult services. And on the topic of adult services, I'll refer you to Harold Doherty's blog and some of his opinions on adult services in a Canadian setting (see here).

Finally, is the question of 'why' the increase? Well, let's wait and see what those US CDC figures say first and how useful they might be to answering 'why' in the Canadian and other contexts too. I say this accepting that those 'better awareness', 'diagnostic switching' and 'broader criteria' arguments that have long been trumpeted as 'fact' are probably not all there is to see in this area (see here and see here).

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[1] Autism Spectrum Disorder among children and youth in Canada 2018. Public Health Agency of Canada. 2018. March 2018.

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ATEC (Autism Treatment Evaluation Checklist) still rising

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

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

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

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

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

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

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

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

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

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"ASD characteristics in adulthood are differently perceived across age, sex, and informants"

The research tag-team that is Anne Lever and Hilde Geurts have provided peer-reviewed fodder for this blog before (see here and see here). Without wishing to cajole their research interests into a specific box, quite a bit of their time seems to be taken up by looking at autism in the context of ageing, alongside how the label of autism does not seem to have a monopoly on the presentation of certain autistic traits.

A recent paper published by this team [1] provides yet more blogging material, specifically focused on testing "the association between age and ASD [autism spectrum disorder] characteristics, including empathy and sensory sensitivity, in adults aged 19–79 years." A scientific hat-tip is offered to other research in this area [2] that previously observed that: "older age was associated with higher ratings of ASD traits and better cognitive performance."

Drawing on data derived from a participant group numbering above 400 (N=237 with autism and N=198 without autism) spanning the age ranges, a variety of self-report and informant-report (family members, friends, other significant others) were utilised. I should point out that the autism participant group seemed to be represented by the 'more able' part of the autism spectrum (I don't use the term 'functioning') insofar as most either being diagnosed with Asperger syndrome or PDD-NOS (pervasive developmental disorder - not otherwise specified), being predominantly independent or living with a partner or housemate in residential status terms and also with that reliance on self-report used throughout the study kept in mind. This is worth knowing given other discussions on under-represented groups when it comes to scientific study (see here) and how representative autism research may or may not be to the entire spectrum.

Among the measures included for analysis we have an old favourite - the Autism-Spectrum Quotient (AQ) - as well as the Interpersonal Reactivity Index (IRI) (measuring various aspects of empathy) and the Sensory Sensitivity Questionnaire (SSQ) (examining sensory hyper- or hyposensitivity). Obtained results were collated and subjected to quite a few statistical analyses.

Results: noted as a 'group difference' findings were reported observing that: "Adults with ASD reported higher scores on the SSQ and on all subscales of the AQ than adults without ASD." This is pretty much what would be expected, despite any qualms I might have about what the AQ actually measures (see here for more of them). Sensory issues being reported as being greater in those with a diagnosis of autism also ties in well with their inclusion in the DSM-5 schedule for diagnosing autism or ASD (see here).

Then: "Within the ASD group, age-related differences were observed in self-reported ASD traits and sensory sensitivity, with a peak among middle-aged adults." Alongside that previously 'hat-tipped' study, the authors conclude that "ASD characteristics are more heavily experienced in middle adulthood than in younger or older adults." This is interesting from quite a few perspectives; bearing in mind that such findings say nothing about the expression of autism in childhood and early adulthood. Appreciating that the self-report of autism or sensory traits may not be the same as everyday autism expression, such findings *might* have some relevance to various issues such as the rise and rise of adult autism diagnoses being given and indeed, how a diagnosis of autism for some (a few?) might not be a 'lifelong' issue (see here). I know that last point raises blood pressure in some quarters as words like 'masking' are banded around (with the need for far greater study), but there is good reason to think that like many other conditions/labels, autistic behaviours and/or traits ebb and flow according to environment and perhaps other factors, such as the presentation of comorbidity for example (as per the author's other work [3] already mentioned). In short, the presentation of autism is probably dynamic and fluidic, rather than just a static thing.

Onward: "we replicated earlier findings that females with ASD had more sensory issues and reported more ASD characteristics than males... whereas females without ASD manifested fewer ASD traits than non-ASD males.". Females with ASD (74 females vs. 163 males) 'reported more ASD characteristics than males'? Intriguing - "ASD females reported higher scores than ASD males on the AQ total score" - to say the least in light of other [childhood] findings [4] but not without cautions. I go back once again the question of what the AQ is actually measuring and whether for example, the typically higher rate of mood disorders generally noted in females could be a potential confounder when it comes to AQ scores in the context of that previous reference [3] from the authors. This area requires further investigation.

Finally: "Overall, the current results show poor to fair agreement between self- and other-reports of well-known proxies, even though the agreement of the overall group was similar to those previously reported for social responsiveness." Again, some potentially important lessons to be learned here insofar as the 'meaning of autism' to a person and those around them. Indeed I note the authors' offer one explanation: "the self may be more accurate about traits that describe unobservable thoughts and feelings due to privileged access (e.g. feelings of empathy and sensory sensitivity), whereas an informant would be more accurate about observable behavior (e.g., ASD traits)." Again, jumping back into 'hot potato' territory, such a finding may have implications for the whole 'self-diagnosed vs. formal diagnosis' debate that still continues at a pace (see here).

There is quite a bit more to take in from this latest paper from Lever & Geurts and definitely some food for thought. I'll leave you however with one final quote from the authors that is perhaps one of the more important take-away points from their study: "it is important to repeatedly assess self-reported ASD characteristics during adulthood." Who would argue with that in terms of getting wants, wishes, needs and requirements accurate and up-to-date?

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[1] Lever AG. & Geurts HM. Is Older Age Associated with Higher Self- and Other-Rated ASD Characteristics? Journal of Autism & Developmental Disorders. 2018. Jan 18.

[2] Happé FG. et al. Demographic and Cognitive Profile of Individuals Seeking a Diagnosis of Autism Spectrum Disorder in Adulthood. J Autism Dev Disord. 2016 Nov;46(11):3469-3480.

[3] Geurts HM. et al. Autism Characteristics in Older Adults with Depressive Disorders. The American Journal of Geriatric Psychiatry. 2016; 24: 164-169.

[4] Øien RA. et al. Sex-Differences in Children Referred for Assessment: An Exploratory Analysis of the Autism Mental Status Exam (AMSE). J Autism Dev Disord. 2018. Feb 8.

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Is there a bidirectional relationship between autism core symptoms and anxiety?

"Our results do not support a bidirectional relationship between the ASD [autism spectrum disorder] core symptom domains and anxiety" said the findings reported by Jorieke Duvekot and colleagues [1].

Initially including 130 children diagnosed with an ASD who were then whittled down to 79 some 2 years later, researchers wanted to find out more about the "potential differential relationships of the two core symptom domains of ASD - social communication impairment and restricted, repetitive behavior - with anxiety over time." This based on the fact that anxiety disorders seem to be very much over-represented when it comes to autism (see here) and can be absolutely disabling for both the person concerned and for those significant others around them. I might add that this research group have some 'research form' when it comes to longitudinal autism research [2] coinciding with this latest publication.

The chosen method of analysis was the use of a crossed-lagged model which typically involves studying two or more variables over two or more occasions to ascertain any association(s) or not. After adding the variables under investigation into the statistical mix, authors observed that "anxiety symptoms predicted social communication impairment over time" but not the other way around. They also reported no bidirectional relationship between anxiety and restricted, repetitive behaviours, again over time.

I have to say that I was a little confused by these results. Confused because, as someone on Twitter pointed out (thanks Frank), the quite young (mean) age group of the cohort (6.7 years) might be an important variable when it comes to both the presentation and measurement of something like anxiety. I'm not saying that anxiety is not a feature of early childhood autism - indeed again this research group have some peer-reviewed experience in this area [3] - just that it would probably be a lot easier to spot and diagnose when clinical in older children/young adults assuming the correct instrument is used. To say therefore that there was no support for a bidirectional relationship between core autism symptoms and anxiety might not exactly be accurate across the autism spectrum age-groupings.

That's not the only thing that confused me: the lack of any type of relationship between anxiety and those restricted, repetitive behaviours (I'll call them RRBs for short) detailed by Duvekot et al is seemingly contrary to other research in this area [4] albeit research looking at core symptoms and anxiety over a similar time frame. Take for example the findings reported by Vicki Bitsika & Christopher Sharpley [5] (see here for my take) who observed among other things that "experiencing difficulty in changes in routine was associated with a 10-fold increase in risk of GAD [generalised anxiety disorder]." Yes, the focus was on the use of the "GAD subscale of the Child and Adolescent Symptom Inventory (CASI-4 GAD)" and one has to be careful with causality, but it does make some sense to suggest that the 'stress' of something impacting on RRBs might be enough to induce not just anxiety, but clinical anxiety even in the longer term. I'll also throw in the findings reported by Ashwood and colleagues [5] for good measure too, illustrating how one of the premier 'are you autistic?' screens (yes, the AQ) has some real problems when it comes to things like GAD mimicking ASD and potentially inflating AQ scores "leading to false positives." Such work implies that the core facets of autism might be very much interlinked with the core facets of anxiety (and vice-versa); something that I would also expect to see manifest over a longer time period. I await more research on this important topic.

To close, and related to today's content on core symptoms and comorbid conditions, I want to refer you to the article published by Ginny Russell and colleagues [6] and the importance of engaging with the community your are studying. To quote: "While treating autism per se. was seen as problematic by some, treating specific co-occurring problems was seen as helpful in some circumstances." My question: what happens if and when by treating co-occurring issues, one does start to impact on core symptoms or vice-versa? Indeed, if one assumes that some of the most debilitating and 'life-changing' aspects of autism may very well be tied into the presentation of core symptoms (see here and see here for examples), what then happens to such 'problematic' views? Difficult questions with no easy answers...

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[1] Duvekot J. et al. Examining bidirectional effects between the autism spectrum disorder (ASD) core symptom domains and anxiety in children with ASD. J Child Psychol Psychiatry. 2017 Oct 27.

[2] Duvekot J. et al. Design and Cohort Characteristics of the Social Spectrum Study: A Multicenter Study of the Autism Spectrum Among Clinically Referred Children. J Autism Dev Disord. 2017 Jan;47(1):33-48.

[3] Duvekot J. et al. Symptoms of autism spectrum disorder and anxiety: shared familial transmission and cross-assortative mating. J Child Psychol Psychiatry. 2016 Jun;57(6):759-69.

[4] Rodgers J. et al. The relationship between anxiety and repetitive behaviours in autism spectrum disorder. J Autism Dev Disord. 2012 Nov;42(11):2404-9.

[5] Ashwood KL. et al. Predicting the diagnosis of autism in adults using the Autism-Spectrum Quotient (AQ) questionnaire. Psychological Medicine. 2016;46(12):2595-2604.

[6] Russell G. et al. Selective patient and public involvement: The promise and perils of pharmaceutical intervention for autism. Health Expect. 2017 Oct 31.

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