Saturday, 18 November 2017

Probiotics degrading gluten peptides - part 4

Here we go again. Probiotics degrading gluten peptides part 4 adds to previous posts on this topic (see part 1 here, part 2 here and part 3 here).

The difference this time around? People. People actually eating a a test meal containing gluten - "a porridge containing 0.5 g gluten" - and being given a potential gluten-degrading preparation - "Aspergillus niger-derived prolyl endoprotease (AN-PEP)" - or a placebo whilst their gastric and duodenal content was sampled for gluten concentrations over a 3-hour period after. So described the results published by Julia König and colleagues [1] continuing a research theme from this group [2].

AN-PEP was the product under the research spotlight following some previous scientific findings [3] suggesting that unlike various other digestive enzyme supplements, this stuff showed some pretty good actions/effects on immunogenic gluten peptides. Following a "randomized placebo-controlled crossover study" design, researchers followed 16 participants "with self-reported gluten sensitivity" (but not coeliac disease or wheat allergy) across 3 test days when on each day either a high dose of AN-PEP was given, or a low dose of AN-PEP was given or a placebo was given. Details of the high and low doses included: "The low dose tablets provided 83300 Protease Picomol International (PPI), and the high dose 166700 PPI of AN-PEP enzyme (1 PPI is the amount of enzyme that releases one picomole of p-nitroaniline per second under defined assay conditions)."

This was quite an invasive study as researchers had to gain access to parts of the gastrointestinal (GI) tract of participants and so: "Subjects attended each test day after an overnight fast, and a multi-lumen nasoduodenal catheter was placed with one lumen tip in the gastric antrum and one lumen tip 15 cm lower in the duodenum." It was then a case of drawing off stomach and duodenal samples and analysing for gluten content. Further: "success of AN-PEP in degrading gluten was defined as at least 50% gluten degradation compared to placebo, calculated as area under the curve (AUC) over 180 min."

Results: "It actually works" was a quote from one of the authors of the paper in previous media attention of this study before peer-reviewed publication. "In the stomach, gluten levels were reduced from 176.9 to 22.0 in the high dose and to 25.4 μg × min/ml in the low dose. In the duodenum, gluten levels were reduced from 14.1 in the placebo to 6.3 in the high dose and to 7.4 μg × min/ml in the low dose." AN-PEP appeared to be doing its designated job. Importantly too: "No severe adverse events were reported" over the course of the study period.

Scientific replication is the name of the game following the König results. Replication with larger sample numbers and also potentially looking at whether such a preparation might be useful for those diagnosed with something like coeliac disease or other accepted immune-related pathology linked to gluten consumption. I say that acknowledging that a gluten-free diet is the best that science and medicine currently has for the management of coeliac disease. The authors also note that they "did not perform a double-blinded placebo-controlled gluten challenge as sometimes suggested to confirm the diagnosis of gluten sensitivity" in their participants. This kinda intersects with the continuing discussions about what non-coeliac gluten/wheat sensitivity actually is (see here).

"In conclusion, our study showed that the AN-PEP enzyme is effective in degrading small amounts of gluten as part of a complex meal in the stomach. Even though the use of AN-PEP is not intended to replace a gluten-free diet in gluten-related disorders, it appears to be effective as a digestive aid protecting against the unintentional intake of gluten." I can't argue with that and look forward to seeing more on this topic in future.


[1] König J. et al. Randomized clinical trial: Effective gluten degradation by Aspergillus niger-derived enzyme in a complex meal setting. Sci Rep. 2017 Oct 12;7(1):13100.

[2] Salden BN. et al. Randomised clinical study: Aspergillus niger-derived enzyme digests gluten in the stomach of healthy volunteers. Aliment Pharmacol Ther. 2015 Aug;42(3):273-85.

[3] Janssen G. et al. Ineffective degradation of immunogenic gluten epitopes by currently available digestive enzyme supplements. PLoS One. 2015 Jun 1;10(6):e0128065.


Friday, 17 November 2017

On iron and vitamin D and autism

"This study suggests that deficiency of iron and Vitamin D as well as anemia were more common in autistic compared to control children."

'This study' refers to the findings reported by Abdulbari Bener and colleagues [1] (open-access available here) who set out to "investigate iron deficiency anemia and Vitamin D deficiency among autism children" in Qatar, a part of the world not renowned for its 'lack of sunshine' (a source material for the production of vitamin D).

Looking at some 300 children diagnosed with an autism spectrum disorder (ASD) and an equal number of controls, not-autism controls "who visited the primary health-care centers", researchers concluded that as a group, those with autism were more likely to present with low serum iron levels (and various related measures) and further that: "Vitamin D deficiency was considerably more common among autistic children." The authors provide some background details on what constitutes vitamin D deficiency and other 'levels': "Participants were classified into four categories: (1) severe Vitamin D deficiency, 25OHD <10 ng/ml; (2) moderate deficiency, 25OHD 10–19 ng/ml; (3) mild deficiency, 25OHD 20–29 ng/ml; and normal/optimal level is between 30 and 80 ng/ml."

When attempting to ascertain what factors might be important to the autism vs. not-autism participants, researchers reported that: "serum iron deficiency, serum calcium levels, serum Vitamin D levels; ferritin, reduced physical activity; child order, body mass index percentiles, and parental consanguinity can all be considered strong predictors and major factors associated with autism spectrum disorders." I might add that consanguinity defined as "unions between couples who share at least one common ancestor" is perhaps something more 'culturally-relevant' to autism in certain countries and societies [2] but not necessarily widely applicable...

What's more to say about the Bener findings? Well, given that issues with iron (see here) and issues with vitamin D (see here) are no strangers to the autism research landscape, there is little novelty in the conclusions reached even if being "the first report on an establishing level of iron deficiency in children with autism in Qatar and in Arabian Gulf Countries." The implication is again that preferential screening and treatment of such issues should be offered when a diagnosis of autism is received, save any further health inequalities arising. Whether or not treating something like iron deficiency and/or vitamin D issues will impact on behavioural presentation (see here) is perhaps an issue for another day. I say this bearing in mind the sentiments expressed in the recent paper by Philippe Autier and colleagues [3] examining the collected data on vitamin D supplementation "on non-skeletal disorders" and results seemingly "strengthening the hypothesis that low vitamin D status is a consequence of ill health, rather than its cause."


[1] Bener A. et al. Iron and vitamin D levels among autism spectrum disorders children. Ann Afr Med. 2017 Oct-Dec;16(4):186-191.

[2] Mahajnah M. et al. Clinical characteristics of autism spectrum disorder in Israel: impact of ethnic and social diversities. Biomed Res Int. 2015;2015:962093.

[3] Autier P. et al. Effect of vitamin D supplementation on non-skeletal disorders: a systematic review of meta-analyses and randomised trials. Lancet Diabetes Endocrinol. 2017 Oct 25. pii: S2213-8587(17)30357-1.


Thursday, 16 November 2017

Sleep and gut issues in autism: a clinically relevant subtype?

"Autistic children with gastrointestinal or/and sleep problems may represent clinically relevant subtypes of ASD [autism spectrum disorder], for which targeted treatments may be needed."

That was one of the conclusions reached by Xiao-Lei Yang and colleagues [1] looking at an interesting combination of symptoms/conditions that have featured before on this blog (see here and see here): gastrointestinal (GI) and sleep issues with autism in mind.

Surveying around 170 children diagnosed with an autism spectrum disorder (ASD) and a similar number of "healthy children" (authors words, most definitely not mine), researchers sought to estimate the prevalence of GI and sleep issues among their cohort(s). Perhaps unsurprisingly "GI and sleep problems were prevalent in Chinese ASD children." Interestingly too: "ASD children with GI symptoms reported more severe ASD core symptoms than others." Those with sleeping issues also showed "lower performance in daily living skills, social cognition, social communication and intellectual development" than the children with ASD who did not present with sleeping issues.

The implications of such observations? Several. Not least that when one talks about GI issues  - whether functional or more pathological - being over-represented in relation to autism, one has some confidence that such 'over-representation' seems to cross different ethnicities and different countries and is not just derived from or based on Western research findings. This adds further weight to the notion that at least some types/phenotypes of autism may have a significant bowel-related component to them for whatever reason(s).

Next, the suggestion that children with autism who also present with GI symptoms might present with a more 'severe ASD core symptoms' profile provides some truly tantalising clinical and research opportunities. Not least that said bowel symptoms might be able to affect some aspects of behaviour and onward the question: what happens when bowel symptoms are effectively treated? I know such sentiments are not necessarily welcomed in some quarters ('autism symptoms are lifelong and immutable' so the saying goes) but for others, particularly those suffering with bowel symptoms (yes, I did say suffering), there are some potentially interesting consequences following intervention. Assuming also that pain and discomfort are key parts of 'suffering' from bowel issues in autism as they are when present in not-autism, we arrive at a situation whereby certain autistic traits may be at least 'heightened' when pain is present. Such a proposition is not necessarily new news to the peer-reviewed autism research (see here and see here). And if one was to assume that something like 'inflammation' might be part and parcel of said GI issues and pain in relation to autism, we arrive at yet another testable hypothesis (see here)...

Finally, sleep issues in relation to the autism spectrum. What's more to say? They are pretty prevalent throughout children and adults on the autism spectrum and probably contribute to the various 'quality of life' disparities that have been shown in relation to autism (see here). There are things that can be 'tried' in relation to intervention (see here and see here for examples) but by no means is there some 'magic wand' that helps every single sleep issue for every single person. The idea that sleep issues, like GI issues, might also impact on certain behavioural aspects linked to autism is probably not unexpected but I would like to see a lot more research done in this area before any grand sweeping generalisations are made. Not least recognising that certain over-represented behavioural comorbidity such as attention-deficit hyperactivity disorder (ADHD) is rising through the sleep research ranks (see here) and what that might mean for autistic traits in these ESSENCE-like times...


[1] Yang X-L. et al. Are Gastrointestinal and Sleep Problems Associated with Behavioral Symptoms of Autism Spectrum Disorder? Psychiatry Research. 2017. Oct 24.


Wednesday, 15 November 2017

Loneliness --> low self-esteem ---> depression?

It was the findings reported by James McCauley and colleagues [1] that prompted today's post. Working on the basis that "there have been few comprehensive investigations of self-esteem in children and adolescents with autism spectrum disorder (ASD)" researchers set out "to assess how youth with ASD rate their self-esteem compared to age-matched TYP [typically developing] youth." Further, how levels of self-esteem (or not) might onward influence "internalizing psychopathology", the fancy phrase for issues such as depression and anxiety.

I don't typically go for grand theories and sweeping generalisations on this blog, particularly when referencing the very large and very diverse autism spectrum. I've not moved over to the 'dark side' of generalisation in this post but am particularly interested in the some of the *associations* talked about my McCauley et al.

Specifically how: "youth with ASD rated their self-esteem significantly lower than did TYP youth" and how self-esteem was "strongly related to depression." Add in the findings reported by Micah Mazurek [2] who observed that "loneliness was associated with increased depression and anxiety and decreased life satisfaction and self-esteem" and some potentially important processes emerge as per the equation titling this post: Loneliness --> low self-esteem ---> depression?

McCauley and colleagues do also talk about how Theory of Mind (ToM) also showed some possible *associations* to elements of their results but I'm not really minded to go into this part of their findings with any great detail. It's not that I don't believe that ToM might not be an issue for some on the autism spectrum, but rather as other results have suggested [3], questions still remain about what ToM actually means and whether other issues (i.e. alexithymia) might predominate in relation to some autism [4] (where the stress is on 'some').

I don't doubt that there are several other important elements potentially influencing things like self-esteem in relation to autism and how it can lead to issues such as depression (see here). Further studies are needed on this topic, including drawing on the autism-not-specifically-mentioned research literature [5]. But insofar as the simplistic relationship set out in the post, there is an obvious area ripe for intervention: loneliness. And on that point, there are options available (see here) if and when desired; accepting that not everyone wants (or needs) lots of people around them all of the time. This perhaps is also where the online world (in moderation) can also come into it's own [6] (I repeat 'in moderation').

Finally, I'll be coming to the findings reported by Cage and colleagues [7] in the not-too-distant-future talking about how "personal acceptance significantly predicted depression" in the context of autism and what role self-esteem might play here too (minus too much psychological fluff and ToM chatter)...


[1] McCauley JB. et al. Self-Esteem, Internalizing Symptoms, and Theory of Mind in Youth With Autism Spectrum Disorder. J Clin Child Adolesc Psychol. 2017 Oct 19:1-12.

[2] Mazurek MO. Loneliness, friendship, and well-being in adults with autism spectrum disorders. Autism. 2014 Apr;18(3):223-32.

[3] Oakley BF. et al. Theory of mind is not theory of emotion: A cautionary note on the Reading the Mind in the Eyes Test. J Abnorm Psychol. 2016 Aug;125(6):818-23.

[4] Trevisan DA. et al. Alexithymia, but not autism spectrum disorder, may be related to the production of emotional facial expressions. Mol Autism. 2016 Nov 11;7:46.

[5] Sowislo JF. & Orth U. Does low self-esteem predict depression and anxiety? A meta-analysis of longitudinal studies. Psychol Bull. 2013 Jan;139(1):213-240.

[6] Sundberg M. Online gaming, loneliness and friendships among adolescents and adults with ASD. Computers in Human Behavior. 2017. Nov 1.

[7] Cage E. et al. Experiences of Autism Acceptance and Mental Health in Autistic Adults. J Autism Dev Disord. 2017 Oct 25.


Tuesday, 14 November 2017

Breastfeeding and autism meta-analysed

"This meta-analysis provides evidence that breastfeeding (exclusively or including additional supplements) may protect against ASD [autism spectrum disorder]. Prospective longitudinal research is required to disentangle the complex relationships and to explore potential pathophysiological mechanisms."

So said the systematic review and meta-analysis published by Ping-Tao Tseng and colleagues [1] covering a [complicated] topic that has been discussed on this blog before (see here). I should mention that I was part of the 'and colleagues' bit to this latest paper; something that will in no way interfere with my hopefully critical musings on this latest publication.

Bearing in mind "a controversial relationship between ASD and breastfeeding" that exists in the peer-reviewed literature and the strong requirement not to make new mums feel bad just because they don't want to or can't breastfeed, the aim of the meta-analysing game was to synthesise the collected research literature into something like a coherent 'where we're at' statement. Seven studies out of a possible 20 were included for review, together including nearly 1500 children diagnosed with ASD and nearly 1200 not-diagnosed-with-autism controls.

Results: "Cumulatively, children with ASD, either in the form of clinical diagnosis or self-report, were significantly less likely to have been breastfed than children without ASD." I should add that 'self-report' refers to parents reporting on their child receiving a diagnosis of autism but not necessarily being independently confirmed by researchers or medical records. The strength of the association/effect was not to be sniffed at; with results even holding up when taking into account those "who were breastfed with additional supplementation."

Another important quote: "one should note the observational nature of these preliminary findings, whereby causation can clearly not be determined." What this means is that whilst variable A (breastfeeding) and variable B (autism or ASD) might be *associated* it is nigh on impossible to definitively say whether variable A *causes* or *protects against* variable B on the basis of the studies analysed. I might also suggest that the call for 'prospective longitudinal research' is also not likely to provide a definitive answer any time soon either, when taking into account how many other variables might be associated with risk of offspring autism and indeed, the plurality of the label and some related discussions on that topic (see here and see here). It's also noteworthy that autism rarely exists in some sort of diagnostic vacuum (see here) and how breastfeeding trends might be important there too [2] thus complicating any 'causative' picture.

Still, the Tseng results do provide some further information about this issue and a reiteration of the value of breastfeeding for many different reasons. Other studies have arrived at a similar conclusion insofar as the impact that breastfeeding *might* have on 'autistic traits' [3]; again, with more research to do.

Mechanisms of effect? Well, once again we're faced with a 'we don't know yet' scenario. Tseng et al speculated on various possible factors linked to breastfeeding and breast milk 'ingredients' that may be important (neurotrophic factors, oxytocin, fatty acid constitution, casomorphins) and could conceivably impact on risk of offspring autism. I'm also minded to add in the idea that the early presentation of autism in the first months of life [for some] could also potentially affect breastfeeding patterns; perhaps making breastfeeding practices more difficult and/or contributing to the early cessation of breastfeeding in some cases. Relevant mechanisms are likely to be complicated.

I appreciate that not everyone is going to be enthralled with this study or topic - no, it doesn't say that a lack of breastfeeding causes all autism - particularly when words like "protect against ASD" are also included in the text. All I can say is that we faithfully looked at the existing peer-reviewed research available to us in this area and went where the data instructed us to do so without fear or favour...


[1] Tseng P-T. et al. Maternal breastfeeding and autism spectrum disorder in children: A systematic review and meta-analysis. Nutritional Neuroscience. 2017. Oct 18.

[2] Bar S. et al. Long-term neurodevelopmental benefits of breastfeeding. Curr Opin Pediatr. 2016 Aug;28(4):559-66.

[3] Boucher O. et al. Association between breastfeeding duration and cognitive development, autistic traits and ADHD symptoms: a multicenter study in Spain. Pediatr Res. 2017 Mar;81(3):434-442.


Monday, 13 November 2017

Who speaks for who in relation to autism?

I'm probably stirring up a hornet's nest by writing this post around the findings reported by Karin Jongsma and colleagues [1] touching on the subject of 'who speaks for who' in autism advocacy, but thought it an important topic to approach. Not least because in some quarters, there are some quite heated discussions being had (mainly, and unsurprisingly, across social media and related platforms) concerning representation across various organisations and initiatives with a focus on autism. The question at the heart of such debates is: 'Who should be the primary voice(s)?' when it comes to things like decision-making about research and policy in the context of autism, both at an individual and group level? It's not a new debate by any means and such discussions will likely be part of the autism landscape forever more...


"The inclusion of people with a 'neuro-psychiatric' condition poses a particular challenge for the organizational processes and political representation of such collectives" was the starting point for Jongsma et al. I'm not very philosophically literate so can't really tell you too much about the use of 'epistemic injustice' as a framework by Jongsma, outside of it being an idea that includes 'testimonial injustice' meaning "prejudices that cause one to "give a deflated level of credibility to a speaker's word".

The authors conducted interviews with a number of patient organisation (PO) representatives and concluded that: "persistent stereotypes hamper the inclusion of affected members both within POs and on the health political level." Further: "Being affected causes distrust in having the 'capacity to know' in a two-fold way; it is assumed that those who can represent themselves are "not affected enough" to present valuable insights into the condition and those who have difficulties to express themselves due to their condition are excluded because of their affectedness."

That last sentence kinda hits the nail slap-bang on the head when it comes to many of the discussions around 'who speaks for who' in the context of autism. Remembering that autism is about as heterogeneous as it comes with regards to the huge range of abilities and disabilities covered under the spectrum label, many, if not all, arguments about representation stem from perspectives on whether the so-called 'able' are able/allowed/qualified to speak for the so-called 'not so able' and the apparent lack of the 'not so able' to have an appropriate voice, thus relying on proxy voices such as their parents and/or primary caregivers. The bold emphasis was added by me just in case you ask. Such issues are also positioned in the context of tenets such as: 'if you've met one person with autism, you've met one autistic person' (or words to that effect) and older adages about 'mother (or father) knowing [their child] best'. The fact that Jongsma et al also included dementia in their study - another condition/label/state where ability and disability is pretty heterogeneous - is also worth noting.

I'd advance the idea that there is no right or wrong answer in the debate on who speaks for who when it comes to autism. Certainly, further grand sweeping generalisations in relation to autism are not required. The moves to encourage greater participation by #actuallyautistic people are to be welcomed and reflect many factors such as the rise and rise of numbers of people being diagnosed with autism (some rather late in life) and how again, social media in particular, is providing an important tool to voice wants, needs, hopes, fears, concerns, vision and lots more when it comes to the lives of those on the autism spectrum. Various different sorts of group identities are emerging/have emerged as many, particularly adults with autism / autistic adults (see here), have come together. Sometimes this is under the banner of neurodiversity and the principles which it includes; other times not, or with more specific issues in mind. Without getting too 'reflective' on the topic, the autism/autistic group identities emerging probably also help fill an important gap, taking into account all the chatter down the years about how loneliness and isolation are very much over-represented and onward how the desire to 'belong' has been too long neglected in the context of autism.

It's also fair to say that not everyone diagnosed on the autism spectrum is 'part of the conversation' bearing in mind the 'nothing about us without us' mantra. There are many children and adults with autism for whom such debates on advocacy are probably not as big a concern as overcoming various day-to-day issues; be they based on the effects of core autism presentation or other important comorbidities such as epilepsy or gastrointestinal (GI) issues. For many of this group, their voice is their parents and/or primary caregivers and will be for the rest of their lives. By saying all that I'm not falling into the whole 'high' and 'low' functioning narrative about 'who's the more disabled'. I'm simply acknowledging that some people on the autism spectrum can't and probably won't ever participate in discussions about 'who speaks for them' and therefore their own voices are heard only through their parents/caregivers, siblings or significant others. I know some people will say that we aren't trying hard enough to give this section of the autism spectrum a voice, but right or wrong, that's where we currently stand.

What can be done to improve the situation and perhaps bridge any gulf between voices from the spectrum and proxy voices from the spectrum? Well, there's no easy fix because yet again, heterogeneity rules. It would be unwise to assume that every actually autistic adult who can vocalise or communicate wants the same thing for themselves or any group they feel allied to, just as any sweeping generalisations that every non-communicating person with autism (I don't know how else to describe this group) or parent/primary caregiver wants the same thing are likely untrue. I think this is an important point to raise particularly when for example, the social model of disability - "disability is caused by the way society is organised, rather than by a person’s impairment or difference" - can too often be assumed to be a significant part of the vocal autism agenda, seemingly at the expense of acknowledging some very real disabilities. It's not, for example, difficult to imagine how such an extreme sentiment might sound to the parent or caregiver of a child/adult who requires significant day-to-day care and is very much disabled as a result of their autism and the issues it brings, irrespective of societal organisation. This also goes for those 'autism as a superpower' and related statement(s) which have been mentioned down the years. How such sweeping generalisations, seemingly contrary to the diagnostic tenets of autism, may well reflect individual perceptions and abilities of autism, but often do very little to forward the agenda of those severely impacted by their autism and their representation (including in the lay media).

There are substantial benefits to be had from listening to the many voices from the autism spectrum particularly when it comes to outcomes and events that will likely impact them as individuals and/or other groups on the spectrum. Similar sentiments are being discussed with other labels in mind too. I note for example, there are quite a few autistic voices that provide both informative and compassionate 'middle-ground' on many topics related to the details included in this post and the Jongsma paper. Importantly too that some are also not afraid to critique some of the tenets of neurodiversity (and by virtue, the misnomer of 'neurotypical' that has seemingly pervaded autism science and practice). These are important voices not just because of the accounts and experiences they provide, but also because theirs provides a hint of what challenges/successes might be 'more likely to occur' when a person is diagnosed with autism. Further, they do to some extent, provide an opportunity to positively act on such issues for the benefit of the person themselves and others who may not be in such a fortunate [communicative] position.

But also there is no reason why autistic voices cannot be complemented by hearing the equally important messages that parents and primary caregivers - the people who raise and mould children - can bring to the discussion table too. This also includes the 'teachings' of a rapidly emerging group who offer a really unique perspective: the rise and rise of autistic parents raising children with autism.

I suppose the bottom line is that everyone deserves to be heard no matter what section of the autism community they are allied to, and autism research and practice is all the richer for have such a diverse set of voices on the topic of autism. But this does not mean that conflict(s) are going to be so easily solved given the multitude of opinions, viewpoints and experiences included with autism in mind. How, the very individual nature of autism, is probably never going to lend itself particularly well to favouring one specific viewpoint over any others...


[1] Jongsma K. et al. Epistemic injustice in dementia and autism patient organizations - an empirical analysis. AJOB Empir Bioeth. 2017 Nov 8:0.


Saturday, 11 November 2017

Relative age and ADHD continued

"In a health service system with low prescribing rates for ADHD [attention-deficit hyperactivity disorder], a younger relative age is associated with an increased likelihood of receiving a clinical diagnosis of ADHD."

So said the findings published by Kapil Sayal and colleagues [1] (open-access available here) adding to an important body of peer-reviewed research evidence suggesting that younger relative age - relative age compared with other children in the same school year - does seem to be a factor in both receipt of a diagnosis of ADHD (see here) and use of medication purposed for ADHD (see here). I might also direct your attention to another paper also recently published by Sayal and colleagues [2] discussing ADHD in a more general sense.

The Sayal study represents yet another large population being used to analyse any such link; this time relying on "nationwide population-based registers to identify all Finnish children born between Jan 1, 1991, and Dec 31, 2004, who were diagnosed with ADHD from age 7 years onwards (age of starting school)." They found over 6000 children diagnosed with ADHD, and as well as looking at relative age compared to other children in the school year, also examined the important variable of year of diagnosis - "(1998-2003 vs 2004-11)" - to ascertain whether changes in diagnostic practices might be contributory to this issue.

As per the opening line, there was consistency in the Sayal findings with the other occasions that this issue has been examined. So: "Compared with the oldest children in the school year (ie, those born between January and April), the cumulative incidence of an ADHD diagnosis was greatest for the youngest children (ie, those born between September and December)." Sex/gender did not seem to show any differences in this trend. Also relevant: "This effect has increased in recent years."

If all that wasn't enough, the results published by Boland and colleagues [3] (open-access available here) also add to the data on relative age and ADHD by observing that: "Attention deficit hyperactivity disorder was the only identified relative age association" in their study utilising "electronic health record data from 6 sites representing 10.5 million individuals in 3 countries (United States, South Korea, and Taiwan)." The more general research brief for Boland et al to examine "Birth month and climate impact lifetime disease risk" took into account lots and lots of diagnoses not just ADHD concluding that: "children younger than their peers [are] experiencing greater ADHD risk."

Other coverage of the Sayal study (see here) caution about the 'applicability' of the results particularly in the context of school and ADHD here in Blighty. I agree that the study does not 'prove' relative age is directly linked to ADHD diagnosis (and/or medication use for ADHD) but in the context of this not being the first time that such a link has been made and the strength of the accumulating evidence, I find it difficult to suggest that any relationship is just a spurious one.

Finally, to quote from Sayal: "In terms of clinical and educational implications, these findings suggest that key adults (teachers and parents) might interpret behaviour differently of children who are younger than their classmates." Translation: one should be careful not to mis-classify 'developmental immaturity' with a diagnosis of ADHD [4] and that ideas discussing greater flexibility on school age start dates perhaps come into their own...

To close, lest we forget today of all days...


[1] Sayal K. et al. Relative age within the school year and diagnosis of attention-deficit hyperactivity disorder: a nationwide population-based study. Lancet Psychiatry. 2017 Oct 9. pii: S2215-0366(17)30394-2.

[2] Sayal K. et al. ADHD in children and young people: prevalence, care pathways, and service provision. Lancet Psychiatry. 2017 Oct 9. pii: S2215-0366(17)30167-0.

[3] Boland MR. et al. Uncovering exposures responsible for birth season - disease effects: a global study. J Am Med Inform Assoc. 2017 Sep 28.

[4] Efron D. The role of schools in the diagnosis of ADHD. Lancet Psychiatry. 2017 Oct 9. pii: S2215-0366(17)30406-6.


Friday, 10 November 2017

"abnormalities in mitochondrial activity in the lower GI tract of children with ASD"

The findings reported by Shannon Rose and colleagues [1] (open-access) continue a research theme by [some of] this authorship group looking at how mitochondrial dysfunction seems to be part and parcel of at least some autism (see here). Indeed, how when one talks about mitochondrial issues potentially accompanying [some] autism, one really needs to look at it in the context of other issues potentially also 'over-represented' in relation to autism (see here).

This time around, Rose et al set out to "determine whether mitochondrial dysfunction may contribute to GI [gastrointestinal] symptoms in children with ASD [autism spectrum disorder]" on the basis that GI symptoms (whether functional or more pathological) are no stranger to autism (see here). With this in mind, I note the name Tim Buie is included as part of the Rose paper authorship team and so should reference some of the sterling work he and his team have done on the topic of GI issues and autism and its importance down the years.

Researchers analysed mitochondrial function(s) in rectal and cecum mucosal biopsies in a small sample of children diagnosed with ASD (n=10) and compared results with those from "10 children with Crohn’s disease and 10 neurotypical children with nonspecific GI complaints." There are two points for me to make here: first, although it is an invasive procedure to collect them, those biopsies used for study were extracted on a clinical basis as part of "elective diagnostic colonoscopy." This was not a case of 'experimenting' on children for the sake of an experiment; rather that children were already undergoing investigations for their significant bowel issues, save any health inequalities appearing "just 'cos they were autistic" for example. Second, although the authors have chosen to use the term 'neurotypical' to reflect not-autism, I myself still find this terminology to be scientifically problematic (see here) in the context that no brain is seemingly typical or atypical according to current scientific evidence. Not least also on the basis that immune-based conditions such as inflammatory bowel diseases do seem to carry an increased 'risk' of psychiatric issues (see here) and what that might [eventually] mean for those children diagnosed with Crohn's disease (an inflammatory bowel disease) for example. Anyhow, two approaches are described in connection with the study of mitochondria in those biopsy samples looking at both the quantity and activity of various electron transport chain (ETC) complexes. Yet again, I can profess no serious expertise on the various elements of mitochondria but there is some good reading out there in the peer-reviewed science domain on the topic.

Results: "Differences in mitochondrial function were found in children with ASD as compared to the other control groups across several ETC complexes suggesting a difference in overall mitochondrial function rather than a change in one specific mitochondrial enzyme." Accepting the small participant numbers included for study, these are potentially important results. Not least because other work looking at such mitochondrial issues in relation to [some] autism has been predominantly based on activity in muscle; now it appears extending "this observation to altered ETC complex activity in the GI mucosa" too.

Then to some speculation: "The fact that increased ETC complex protein content was primarily seen in the cecum, an area where enteric microbiome fermentation products such as PPA [propionic acid] and BUT [butyrateare abundant, suggests a role for the enteric microbiome in the evolution of mitochondrial abnormalities in children with ASD." An interesting perspective indeed and in need of some further investigation. Butyrate has, in recent years, been elevated to almost scientific sainthood (see here for example) so one has to perhaps be a little cautious about sweeping statements in the context of autism or any other label. I say this with particular relevance to an 'autism colon' discussed by the authors (see here) which I also think is perhaps a little premature to speculate on.

No mind, the results are what they are and add to the growing literature discussing mitochondria in the context of [some] autism. The implication once again is to screen for such issues within the context that a diagnosis of autism should represent a starting point for further investigations not the finishing line.

And finally, to another author on the Rose paper, I'm still waiting to read about some of your results...


[1] Rose S. et al. Mitochondrial dysfunction in the gastrointestinal mucosa of children with autism: A blinded case-control study. PLoS One. 2017 Oct 13;12(10):e0186377.


Thursday, 9 November 2017

On antipsychotic treatment failure when both psychosis and autism present together

"Children with first-episode psychosis and comorbid autism spectrum disorders at first presentation are less likely to have a beneficial response to antipsychotics."

So said the results reported by Johnny Downs and colleagues [1] based on their analysis of historical health records for over 630 children and young adults "referred to mental health services in South London, United Kingdom" between 2008 and 2014. Researchers looked for evidence of "multiple treatment failure" (MTF) - defined as "the initiation of a third trial of a novel antipsychotic due to insufficient response, intolerable adverse effects, or nonadherence to prior antipsychotic treatment" - among their cohort as a function of a diagnosis of an autism spectrum disorder (ASD) and other neurodevelopmental labels such as "hyperkinetic disorders (ICD-10 F90) and intellectual disability (ICD-10 F70–9)." The hypothesis being that those with at least one mention of psychosis in their health records alongside comorbid ASD "would be more likely to experience treatment failure" as a consequence of other findings talking about "psychopharmacologic effectiveness [being] lower in populations with coexisting ASD." The reasoning for that hypothesis seemingly comes from other research such as that from Politte and colleagues [2] and is set in the context of the NICE guidance here in Blighty on the subject of antipsychotics and 'core' autism (see here).

Results: 114 of the 638 participants (~18%) studied also had a diagnosis of ASD. This kinda reiterates that psychosis and other conditions characterised by psychosis are probably not strangers when it comes to the clinical profile of [some] autism (see here and see here). Some 20% of their total cohort developed MTF during the study follow-up period. After adjusting for various potentially confounding variables researchers observed that: "ASD comorbidity was associated with a 2-fold increased risk of MTF" and further: "28% of those with comorbid ASD compared to 11% of non-ASD children had a persistently insufficient response to antipsychotics." Autism or possibly something about autism or linked to autism, seemed to potentially affect response to antipsychotics where psychosis was present.

There are a couple of other observations to make about the Downs data. When comparing the ASD - first episode psychosis (FEP) group with the not ASD - FEP group, the former showed an increased frequency of both hyperkinetic disorders a.k.a attention-deficit hyperactivity disorder (ADHD) and intellectual (learning) disability. This tallies with quite a bit of other research looking at other over-represented labels in the context of autism (see here and see here respectively). Also: "Children with ASD showed higher rates of the “persistent insufficient response” or the “insufficient response–adverse effect” trajectory but lower rates of adherence-related reasons relative to those without ASD." The adherence bit kinda suggests that for example, not taking the antipsychotic medicine when required to, was not a core reason for MTF where ASD is mentioned.

Insofar as the important questions of 'how and why' in relation to the Downs results, the authors pop into 'speculating mode'. They talk for example, about how findings "may be explained by specific neurobiological profiles related to psychosis-ASD comorbidity" mentioning things like dopamine as being important. Equally as speculative, I might add in a few ideas that could also be pertinent. The first is that some effect on immune function could be a complementary pathway in relation to the action of specific antipsychotics (see here). The second is another 'sexy' area of research with a proposed 'epigenetic' action (see here); antipsychotics potentially acting on targets linked to gene expression for example. Both areas - immune function and/or epigenetics - have some 'research form' in both psychosis and autism investigations (see here for example). Both areas require a lot more investigation in this context.

I'm going to finish with another important quote from the Downs paper: "Our results are consistent with the evidence that shows psychotic illness experienced by children and adults with ASD may be different from non-ASD samples." I think the authors might be on to something here as per other observations on important psychiatric comorbidity in relation to autism such as the presentation of bipolar disorder (see here) for example. The idea being that such 'atypical' psychosis presentation and seemingly poor(er) response to recognised treatments for such psychiatric issues could denote that either a novel phenotype may be at work or indeed, that alongside anxiety and depression (see here and see here) being present in cases of autism, psychotic and other symptoms might be seen as more 'core' features of some autism? Once again, I hark back to the [sadly forgotten] writings of Mildred Creak and colleagues [3] as a possible framework for further study...


[1] Downs JM. et al. The Association Between Comorbid Autism Spectrum Disorders and Antipsychotic Treatment Failure in Early-Onset Psychosis. Journal of Clinical Psychiatry. 2017.

[2] Politte LC. et al. Psychopharmacological interventions in autism spectrum disorder. Harv Rev Psychiatry. 2014 Mar-Apr;22(2):76-92.

[3] Evans B. How autism became autism: The radical transformation of a central concept of child development in Britain. Hist Human Sci. 2013 Jul;26(3):3-31.


Wednesday, 8 November 2017

Incontinence in autism: systematically reviewed

I appreciate that incontinence - urinary and bowel incontinence - is not exactly great dinner table conversation. When talking about such issues in the context of specific labels, there's also the possibility that stigma can result, which in turn can affect the outward view of that label. But incontinence can be a life-changing prospect for many people (and labels); realising the scale of the issue is the first step towards providing appropriate screening and also management onward to improving quality of life...

With such an issue in mind, I'm introducing the paper published by Justine Niemczyk and colleagues [1] who took a look at the collected peer-reviewed research literature covering "the co-occurrence of nocturnal enuresis (NE), daytime urinary incontinence (DUI), and fecal incontinence (FI) in ASD [autism spectrum disorder], and vice versa, of ASD in children with incontinence." I might add that this research group are no strangers to this topic (see here).

After picking out over 30 publications, authors managed to 'boil down' the literature to a few principal statements, most importantly including "The published literature implies a higher prevalence of incontinence in children with ASD compared to typically developing children." They also noted that: "ASD symptoms are found in incontinent children" but caution that "no study included a non-ASD control sample."

Acceptance that autism and the bowel for example, represent an important pairing for quite a few people (see here and see here) is growing as the years pass by. It's no longer a 'taboo' point to say that both functional and potentially more pathological bowel symptoms/conditions are over-represented in relation to a diagnosis of autism and appropriate screening and management should be in place save any further health inequalities appearing. Clinical practice however, still has some 'catching up' to do when it comes to those points about screening and treating such issues; specifically, not just assuming that 'it's all down to their autism' or providing some fluffy psychological explanation when it comes to the appearance of such issues. A diagnosis of autism is seemingly protective of nothing (see here for an example) and the onus is to screen and rule out first before making any grand judgements...

Alongside there is also quite a bit more to do in this whole area as Niemczyk and colleagues note, both to improve the quantity and quality of investigations in relation to incontinence and autism. In the meantime, there is guidance out there for potentially dealing with such incontinence issues as and when they arise (see here) with the added proviso that seeking professional help is a must in this area bearing in mind the variety of 'causes' potentially behind such issues [2] which might need to be examined.


[1] Niemczyk J. et al. Incontinence in autism spectrum disorder: a systematic review. Eur Child Adolesc Psychiatry. 2017 Oct 10.

[2] Afzal N. et al. Constipation with acquired megarectum in children with autism. Pediatrics. 2003 Oct;112(4):939-42.


Tuesday, 7 November 2017

'Childhood adversity' and chronic fatigue syndrome: comorbidity might count...

"The data suggests that previous studies showing a relationship between childhood adversity and CFS [chronic fatigue syndromemay be attributable to the confounding effects of co-morbid or misdiagnosed depressive disorder."

So said the findings reported by James Clark and colleagues [1], inviting a 'rethink' about the suggested role of childhood adversity when it comes to CFS. Childhood adversity can cover quite a bit of clinical ground but typically includes things like interpersonal loss (death or separation from a loved one), parental maladjustment, maltreatment and other health or social 'mountains to climb' [2]. Clark et al relied on the use of the Childhood Trauma Questionnaire (CTQ) for their study, which focuses more specifically on things like abuse and neglect in childhood over and above loss or those other social and health-related variables like poverty and ill-health.

Said questionnaire was delivered to over 50 people diagnosed with CFS who importantly had "depression comprehensively excluded" from their clinical picture. Compared with CTQ responses from a smaller - "did not meet criteria for a psychiatric disorder" - control group, authors found little to separate the CFS and control groups. They concluded that whilst there was a small increased risk of CTQ defined adversity being linked to CFS, "much of this risk is mediated by the concomitant development of major depression."

This is rather interesting work. Obviously, we need more independent research to see if such trends hold water following replication, but there may be some important implications.

First, is the whole idea that childhood trauma might be a risk factor for CFS [3]. For those who've followed the ups-and-downs of certain 'biopsychosocial' discussions with CFS in mind (see here), the Clark results represent a bit of a blow to the fluffy psychological thinking that CFS is somehow some kind of 'response' to such adverse events. I'm not saying that childhood adversity can't potentially manifest as a psychiatric disorder (whether contributory in whole or in part) but this latest data perhaps fits with other observations [4] where confounding by "comorbid psychopathology" is to be more typically assumed in the context of CFS. I might also add that CFS is NOT a psychiatric disorder just in case you didn't know...

A second point to make is in relation to how CFS and something like depression are probably linked but not necessarily 'centrally' linked. I've touched upon this before on this blog (see here), where depression can most definitely be part of the clinical picture with CFS in mind [5] but one should not assume that depression is either causative of, or specifically inter-related to the aetiology or pathology of CFS. If, for example, having been a previously active person you are struck down with a condition that blights your life for years and years and potentially leaves you bed bound for extended periods of time, one could argue that your risk of developing something like depression or depressive symptoms is probably going to be elevated. Add in other issues such as loneliness for example, and the risk becomes heightened. A case in point is this piece and the quote: "Every night I’d have these incredibly kinetic dreams. I was flying or running up mountains. I’d wake up in the morning and realise that I was still in the same bedroom, and many mornings felt really disappointed that I was still alive." The crux of the matter is that depression in such a case is a 'reactive' scenario and needs to be treated independently; also evidenced by the fact that not everyone with CFS will suffer with depression [6]...

Finally, I also want to mention the difference between CFS and 'chronic fatigue' as being something potentially important. As noted on other blogging occasions (see here) there has been a tendency among certain researchers to use the term 'chronic fatigue' and this has also extended to research looking at "childhood psychological factors" too [7]. I'm not here to question findings that suggest that "children whose mothers experience anxiety and/or depression between pregnancy and child's age 6 years have an increased risk of developing chronic disabling fatigue in early adolescence" (bearing in mind correlation is not the same as causation), just that 'chronic disabling fatigue' is not necessarily the same as CFS and hence one should not assume the same overlap might pertain. One of the key differences to consider is PEM - post-extertional malaise; an integral component of CFS and something that needs a lot more recognition in the research and clinical literature in general.

I'm going to reiterate the opening sentence to this post from the Clark paper to end things: "The data suggests that previous studies showing a relationship between childhood adversity and CFS may be attributable to the confounding effects of co-morbid or misdiagnosed depressive disorder." Just in case. And also that the continuing focus on potential psychological/psychiatric 'explanations' for CFS is too often at the expense of some rather more concrete science that is emerging (see here) at least for some (see here)...


[1] Devendorf AR. et al. Defining and measuring recovery from myalgic encephalomyelitis and chronic fatigue syndrome: the physician perspective. Disabil Rehabil. 2017 Oct 5:1-8.

[2] Kessler RC. et al. Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys. Br J Psychiatry. 2010 Nov;197(5):378-85.

[3] Heim C. et al. Early adverse experience and risk for chronic fatigue syndrome: results from a population-based study. Arch Gen Psychiatry. 2006 Nov;63(11):1258-66.

[4] Clark C. et al. Premorbid risk markers for chronic fatigue syndrome in the 1958 British birth cohort. Br J Psychiatry. 2011 Oct;199(4):323-9.

[5] Loades ME. et al. The presence of co-morbid mental health problems in a cohort of adolescents with chronic fatigue syndrome. Clin Child Psychol Psychiatry. 2017 Oct 1:1359104517736357.

[6] Daniels J. et al. Anxiety and depression in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): Examining the incidence of health anxiety in CFS/ME. Psychol Psychother. 2017 Sep;90(3):502-509.

[7] Collin SM. et al. Maternal and childhood psychological factors predict chronic disabling fatigue at age 13 years. J Adolesc Health. 2015 Feb;56(2):181-7.


Monday, 6 November 2017

What does 'recovery from myalgic encephalomyelitis / chronic fatigue syndrome' look like?

The title of this post reflects the material included in the paper by Andrew Devendorf and colleagues [1] who sought "an operationalised definition of recovery from myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) for research and practice."

Although perhaps at first sight being a rather simple question to answer - Q: What does recovery look like in relation to ME/CFS? A: Complete remission of symptoms -  there's a lot more behind such a query than you might expect. I'm particularly thinking about how 'recovery' has been a real source of discussion/debate/argument (delete as appropriate) in the context of ME/CFS in recent 'PACE' times (see here and see here).

Ten experts on ME/CFS were quizzed about their views specifically on recovery from the condition(s). As probably expected: "Physicians conceptualised recovery as complete symptom remission and a return to premorbid functioning (adjusted for with age)." No surprises there then. Insofar as the term 'significant improvement', experts also quite sensibly reported that this should be 'operationalised' as "a substantial reduction in symptoms with considerable functional gains, where patients may operate in daily life but still must cope or be treated." Again, not really that earth-shattering to be honest.

'Recovery' in the context of ME/CFS has been discussed in the peer-reviewed domain before [2] with views to "recommend a consistent definition that captures a broad-based return to health with assessments of both fatigue and function as well as the patient's perceptions of his/her recovery status." Although not everyone agreed with all that was said by Adamowicz and colleagues [3], there  is a general consensus that recovery represents an absolute term where 'complete symptom remission' is the important feature. Everything else outside of recovery falls into 'a spectrum of improvement' (substantial, significant, so-so, etc) through to no change or even potential symptom worsening.

The task facing ME/CFS research and practice now: how best to measure the recovery / non-recovery spectrum? I agree that questionnaires about fatigue and (very) important clinical signs like post-exertional malaise (PEM) need to be part and parcel of such measurements. As with any condition that is [currently] diagnosed solely on the basis of presented symptoms with no genetic or biological test yet able to distinguish cases from not-cases, questionnaires and interviews are always going to be important in terms of how symptoms change/evolve over time either naturally or as a result of some specific intervention(s). But research and practice really need more than that; they need some objectivity too...

So, physical activity levels: well, I've often gone on (and on!) about the great potential of actigraphy in the context of several research areas. You want data on rest and activity cycles for a condition characterised by rest and activity cycles? There's plenty of technology out there in the marketplace to measure such cycles and associated measures that could be used in a complementary fashion (see here). How do you define 'recovery' based on such data? Well, typically (at the moment where such tech are still relatively new) there probably won't be 'before and after' data as noted in other examples of such tech use (see here) so a reliance of general population data is the next best thing. Yes, by doing so we're moving from individual data to more generalised data as a comparator, but when such generalised data runs into the thousands or even millions of people (see here for one example) you can start to build up a picture based on 'expected' physical activity levels taking into account sex/gender, age and other important variables. The important point is that one element of recovery in CFS/ME is going to be a restoration of physical activity levels (and perhaps even sleep cycles?) and there are easy ways to measure that minus any subjectivity issues potentially included in questionnaires or interviews. I say all of that acknowledging that levels of typical day-to-day tasks such as work, shopping, socialising and other pastimes/activities which generally require physical exertion can also be to some extent ascertained via a questionnaire.

PEM? I'm not so sure about how to measure this outside of some limited research in this area [4] talking about a "change in complement C4a level and the increase in pain and fatigue 24 h following the self-paced, physiologically limited exercise support the use of C4a as a marker for postexertional malaise in people with ME⁄CFS." Complement C4a by the way, is something of a 'mediator of local inflammatory processes' and has cropped up on this blog before (see here). In light of other work also suggesting that PEM might have cognitive effects [5] too, I'm sure a little more scientific inquiry could bring together a suite of fairly cost-effective ways and means to objectively measure PEM both in terms of biology and also cognitive prowess. Yes, there are details to be worked out but...

Other things to be included in recovery criteria? Well, it depends on whether you're going to go down the sole 'core' symptoms pathway or going to include elements that may potentially be more peripheral [6] yet still impact on notions of recovery in CFS/ME (hyperacuity anyone?). That's not my call I'm afraid, although given what has been discussed with regards to health-related quality of life and ME/CFS (see here), the addition of something like the EQ-5D-3L to any protocol might not also go amiss as part of any measurement of recovery with CFS/ME in mind...


[1] Devendorf AR. et al. Defining and measuring recovery from myalgic encephalomyelitis and chronic fatigue syndrome: the physician perspective. Disabil Rehabil. 2017 Oct 5:1-8.

[2] Adamowicz JL. et al. Defining recovery in chronic fatigue syndrome: a critical review. Qual Life Res. 2014 Nov;23(9):2407-16.

[3] Twisk FN. A definition of recovery in myalgic encephalomyelitis and chronic fatigue syndrome should be based upon objective measures. Qual Life Res. 2014 Nov;23(9):2417-8.

[4] Nijs J. et al. Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and interleukin-1beta. J Intern Med. 2010 Apr;267(4):418-35.

[5] Cook DB. et al. Neural consequences of post-exertion malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Brain, Behavior, and Immunity. 2017; 62: 87-99.

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


Saturday, 4 November 2017

Maternal immune history and autism (social) symptom severity

"Pregnant mothers' asthma and allergies linked to more severe autism in their children" went one of the media headlines discussing the findings reported by Patel and colleagues [1]. Drawing on data derived from the "Western Australian Autism Biological Registry (WAABR)" researchers set out to examine whether "having an immune or autoimmune-driven MIA [maternal immune activationis associated with increased severity of ASD [autism spectrum disorder] symptoms for the child."

The conclusions arrived at: "a positive immune history (allergies or asthma) was associated with increased severity of social symptoms in child." Said data derived from 220 families/children who were quizzed about "the medical history of the biological mother, where details regarding any diagnosed illnesses or chronic conditions were reported, along with age of any diagnosis" alongside the use of more direct measures to ascertain autistic traits in children: Autism Diagnostic Observation Schedule-Generic (ADOS-G) and the Social Responsiveness Scale (SRS).

One obviously has to be a little cautious about such results where the study was conducted 'retrospectively' and what this could mean in terms of recall [2] (although, I hasten to add, other studies of maternal recall vs. medical records in the context of autism are actually quite promising). That no objective confirmation of the presence of allergy or autoimmune disease via direct testing for example, were included in this publication is also something to be a little careful about (I'm pretty sure however, someone would know if they had received a diagnosis of coeliac disease or not for example).

So what do the results mean and what are the implications? Well, MIA - maternal immune activation - in the context of offspring autism risk is not something new (see here and see here for examples) as the authors mention in their paper. Added to work talking about how inflammation, a process that is part-and-parcel of immune function, might have the ability to 'affect' social cognitive processing (see here) one might see further evidence for how the immune system seems to be doing quite a bit more than just protecting us from the odd pathogen or two. This might be particularly relevant during pregnancy; a time when a reprogrammed immune system is in place to prevent mum's body from 'rejecting' the developing foetus and associated systems.

"Findings support the role of an immune system-mediated subtype in ASD, which may be driven by MIA and changes in levels immune markers. Identification of such a subtype in ASD will enable more streamlined diagnosis and management in clinical environments." Yes, alongside acknowledgement that there may be an 'immune phenotype' of autism (see here), the authors do mention the potential future use of "immune-modulating pharmacotherapies" in the context of the growing evidence base for MIA and risk of offspring autism. Such options are already being explored in the animal research domain as per those findings from Vuillermot and colleagues [3] and how "early dietary supplementation with vitamin D may open new avenues for a successful attenuation or even prevention of neurodevelopmental disorders following maternal inflammation during pregnancy." Vitamin D and autism is already quite a hot topic (see here for example). And things don't just stop at vitamin D neither (see here for another example) as further investigations are warranted with the hope that children with possible 'MIA autism' (if I can use that term) are "able to function and integrate into the world... [and] have a level of independence" required to do so successfully (and of course, happily).


[1] Patel S. et al. Social impairments in autism spectrum disorder are related to maternal immune history profile. Molecular Psychiatry. 2017. Oct 10.

[2] Ozonoff S. et al. Reliability of parent recall of symptom onset and timing in autism spectrum disorder. Autism. 2017 Sep 1:1362361317710798.

[3] Vuillermot S. et al. Vitamin D treatment during pregnancy prevents autism-related phenotypes in a mouse model of maternal immune activation. Mol Autism. 2017 Mar 7;8:9.


Friday, 3 November 2017

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 quotientas 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?


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