Wednesday 31 October 2018

Unrecognised autism in epilepsy

"All children with epilepsy, particularly those with IQ[less than or equal to] 50, irrespective of age of onset of epilepsy, seizure type, frequency of seizures, or intractability of epilepsy, should be screened for ASD [autism spectrum disorder]."

So said the findings reported by Monica Juneja and colleagues [1] continuing an important research theme on how autism and epilepsy seem to be very, very closely linked (see here and see here).

Researchers "randomly selected" over 100 children with epilepsy "(defined as two or more epileptic seizures unprovoked by any immediate identifiable cause...)" who were first screened for using Social Communication Questionnaire (SCQ) for autism and then for some, given a more detailed diagnostic work-up. They reported that about 8% of their cohort (9/106) 'screened positive' on the SCQ - "had [a] SCQ score of ≥15" - and 8 of those 9 subsequently went on to meet the criteria for an ASD based on the DSM-IV. They conclude that: "The prevalence of unrecognized ASD was 7.5/100."

This is important work. It adds to an increasing body of peer-reviewed research literature that sees both autism as a risk factor for epilepsy (see here) and epilepsy as a risk factor for autism. The authors also make reference in their findings that they: "add to the growing body of evidence that epilepsy, autism, and ID [intellectual disability] are different clinical manifestations of neurological damage that disrupts the normal neuronal pathways in the developing brain." Accepting that 'neurological damage' is perhaps rather too sweeping a term to apply to the entire autism spectrum (see here), I do think such a conclusion by Juneja et al is worthy of further investigation. I say that from the point of view that the term 'epileptogenic brain lesions' is no stranger to the research literature [2] and that the use of the term 'comorbidity' referencing epilepsy appearing alongside autism, might not always be entirely accurate (see here)...


[1] Juneja M. et al. Prevalence of Unrecognized Autism Spectrum Disorders in Epilepsy: A Clinic-Based Study. Journal of Pediatric Neurosciences. 2018;13(3):308-312.

[2] Kreilkamp BAK. et al. Neuroradiological findings in patients with "non-lesional" focal epilepsy revealed by research protocol. Clin Radiol. 2018 Sep 28. pii: S0009-9260(18)30519-1.


Tuesday 30 October 2018

On the link between academic achievement and drug abuse: stay in school kids!

"These results provide empirical support for efforts to improve academic achievement as a means to reduce risk of drug abuse."

So said the findings reported by Kenneth Kendler and colleagues [1] who aimed to answer the research question: "To what extent is the known association between poor academic achievement and risk of drug abuse influenced by causal processes?" This follows a scheme of other research from authors on this topic [2].

I'll admit to being slightly outside of my research comfort zone with the topic under investigation and methods used by Kendler et al. I'm aware of the observation that higher academic achievement *might* reduce the risk of drug abuse but I'm not particularly au fait with the scientific literature looking at this relationship. No mind, the Kendler paper is another example of good value for [scientific] money insofar as authors reporting on the use of two different methodologies - "using instrumental variable and co-relative analysis designs" - to try and answer the 'causal' question. Sweden was the research starting point, and some rather impressive study cohort figures: "instrumental variable analysis included 934 462 participants (478 341 males and 456 121 females" followed for nearly 20 years and: "Co-relative analyses were conducted in pairs of cousins (263 222 pairs), full siblings (154 295), and monozygotic twins (1623) discordant for AA [academic achievement]." Alongside looking at academic achievement as a function of month of birth, they also had access to data on a history of drug abuse as per: "Drug abuse registration in national medical, criminal, or pharmacy registries."

The combined results suggested that there is a "significant association observed between AA at 16 years of age and risk of DA [drug abuse] into middle adulthood" and that the link "may be causal". They stress how keeping kids/young adults in school and learning and (hopefully) achieving could provide some important protection against the development of drug abuse. Accepting that drug abuse often has wider implications and effects than for just individuals, I don't doubt that the message 'stay in school' might also impact more extensively too.

And minus any sweeping generalisations, the findings presented by Mochrie and colleagues [3] offer at least one clinical direction where efforts might need to be especially focused...


[1] Kendler KS. et al. Academic Achievement and Drug Abuse Risk Assessed Using Instrumental Variable Analysis and Co-relative Designs. JAMA Psychiatry. 2018. Sept 5.

[2] Kendler KS. et al. Social and economic consequences of alcohol use disorder: a longitudinal cohort and co-relative analysis. Psychol Med. 2017 Apr;47(5):925-935.

[3] Mochrie KD. et al. ADHD, depression, and substance abuse risk among beginning college students. J Am Coll Health. 2018 Sep 26:1-5.


Monday 29 October 2018

"a neurodevelopmental abnormality possibly associated with congenital Zika virus infection"

I'm a little late getting to the findings reported by Marion Rice and colleagues [1] (open-access available here) but I did want to cover them because of their current importance and perhaps future implications. The topic in question was the Zika virus and specifically the research efforts of the U.S. Zika Pregnancy and Infant Registry (USZPIR) used to track those infants exposed to the virus during the important nine months than made them. Just in case you didn't follow the hows-and-whys of the Zika virus outbreak and its effects a while back, some background can be found here.

Rice et al report findings for nearly 1500 children "of mothers with laboratory evidence of confirmed or possible Zika virus infection during pregnancy" in terms of their level of care and clinical follow-up and also "to identify Zika-associated birth defects and neurodevelopmental abnormalities possibly associated with congenital Zika virus infection." Aside from reporting that the majority of their cohort had "some follow-up care reported" ('some' that included very basic "length/height, weight, or head circumference measurements and date of measurements" reported back to the USZPIR), a few other observations were also made. This included findings such as: "approximately one in seven (14%) were identified during infancy or early childhood as having either a Zika-associated birth defect, a neurodevelopmental abnormality possibly associated with congenital Zika virus infection, or both."

Although the talk about birth defects is important to Zika virus exposure (microcephaly being only one part of this), I was specifically interested in the 'neurodevelopmental' side of things reported in the Rice paper as affecting 9-10% of the cohort depending on what laboratory testing for Zika virus exposure was carried out. Bearing in mind the age group of the cohort (1 year old and above), and that such neurodevelopmental issues covered a lot of clinical ground (e.g. "hearing abnormalities; congenital contractures; seizures; body tone abnormalities; movement abnormalities; swallowing abnormalities; possible developmental delay; possible visual impairment; and/or postnatal-onset microcephaly") it's important to understand how infections such as Zika might have the ability to affect cognitive and/or neurodevelopmental outcomes. What's also important too is the realisation that given the young age of the cohort, "the full spectrum of adverse outcomes related to congenital Zika virus infection is not yet known." So developmental delay for example, *could* eventually develop into something else, and why appropriate monitoring will continue through initiatives like the USZPIR.

From a cold, objective science perspective and without wishing to diminish the very human effects associated with this event, the 2016 Zika outbreak that struck the Americas provides an ideal opportunity to study our important interaction with the environment around us. It emphasises how facets of our environment can very much influence both physical and psychological health, particularly at critical times of development. A lesson that perhaps is transferable to many different neurodevelopmental labels [2]...


[1] Rice ME. et al. Vital Signs: Zika-Associated Birth Defects and Neurodevelopmental Abnormalities Possibly Associated with Congenital Zika Virus Infection - U.S. Territories and Freely Associated States, 2018. MMWR Morb Mortal Wkly Rep. 2018 Aug 10;67(31):858-867.

[2] Lydholm CN. et al. Parental infections before, during and after pregnancy as risk factors for mental disorders in childhood and adolescence – a nationwide Danish study. Biological Psychiatry. 2018. Oct 1.


Saturday 27 October 2018

On 'definite ADHD' and an "overall increase in caseness"

Consider this post a short continuation of an entry not-so-long-ago (see here) talking about the rates of attention-deficit hyperactivity disorder (ADHD) in the United States (US) going in only one direction. The findings reported by MinKyoung Song and colleagues [1] observed a similar trend - an increase in rates of ADHD - but added that the trend was noted in "Definite" ADHD" caseness: ""Definite" ADHD in caseness in 2007/2008 was 4.04%, increasing to 5.49% in 2011/2012."

The definition of 'definite' ADHD caseness? Authors "stratified identification of ADHD by current status, severity, psychiatric comorbidity, and ADHD medication usage". Alongside, they also talk about 'probable, doubtful and no' ADHD using data from the (US) National Survey of Children's Health (NSCH), an initiative that "provides rich data on multiple, intersecting aspects of children’s lives—including physical and mental health, access to quality health care, and the child’s family, neighborhood, school, and social context."

Accepting that different information sources are perhaps likely to produce slightly different results, the Song findings based on the NSCH don't exactly overlap with the Xu findings [2] previously blogged about, derived from the National Health Interview Survey (NHIS). The Song 'definite' ADHD caseness figures for 2007/2008 came in at about 4%. The rival Xu figures were more like 8%. The Song figures for 2011-2012 were 5.5%. The Xu figures for that period were approaching 10%. You can perhaps see the differences and trend.

Either way you can however still see that the direction of the figures - up - and once again perhaps appreciate that with data showing that a diagnosis of ADHD is associated with greater odds of various adverse life events occurring (see here and see here), so it's imperative that those who are diagnosed receive all the support that they need. I'd also suggest that science should be doing its utmost to focus on why the figures are increasing and what can be done to curb them.


[1] Song M. et al. Addressing Discrepancies Between ADHD Prevalence and Case Identification Estimates Among U.S. Children Utilizing NSCH 2007-2012. J Atten Disord. 2018 Sep 28:1087054718799930.

[2] Xu G. et al. Twenty-Year Trends in Diagnosed Attention-Deficit/Hyperactivity Disorder Among US Children and Adolescents, 1997-2016. JAMA Network Open. 2018; 1: e181471.


Friday 26 October 2018

"greater autism severity predicted greater pain response"

Among the many pressing topics that require [significant] research funds and attention when it comes to autism, I can think of only a few (one actually) that top the observation that pain *might* be something particularly important when it comes to autism (see here). It is with this in mind that I briefly bring the findings reported by Domingo Garcia-Villamisar and colleagues [1] to the blogging table, and their conclusion that: "greater autism severity predicted greater pain response" that "was partially mediated by anxiety and depression."

Authors describe how they 'observed' over 40 adults diagnosed with autism and "intellectual delay" whilst they were undergoing either vaccination or dental cleaning. We are told that "their pain behaviours [were] coded and measures of autism symptom severity, anxiety, depression and obsessivity taken." When the data was gathered and analysed, authors observed that *association* between the intensity/severity of autistic signs and symptoms and the expression of pain. They concluded also that: "Mood must therefore be considered in future research on pain in ASD [autism spectrum disorder] as well as clinical pain management."

Accepting that 'pain coding' is something that requires a little more research, particularly in the context of autism, I'm willing to accept the authors' findings as a road-map to further investigations in this area. Given that conditions/states/symptoms like depression and anxiety are no strangers to autism (see here) it's perhaps implied that they may have quite a large bearing on pain expression in the context of autism.

And if something like anxiety and depression might be 'mediators' of the pain response, shouldn't we doing everything we can to alleviate such issues in the context of autism? Even if that means targeting core symptoms (see here and see here)?


[1] Garcia-Villamisar D. et al. Internalizing Symptoms Mediate the Relation Between Acute Pain and Autism in Adults. J Autism Dev Disord. 2018 Sep 27.


Thursday 25 October 2018

Participatory research in autism continued

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

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

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

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

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

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

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

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


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

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


Wednesday 24 October 2018

"A high prevalence of disordered eating in individuals with ADHD was observed"

The quote heading this post - "A high prevalence of disordered eating in individuals with ADHD [attention-deficit hyperactivity disorder] was observed" - comes from the study results published by Louis Jacob and colleagues [1].

Drawing on information derived from the 2007 Adult Psychiatric Morbidity Survey (APMS) here in Blighty (an initiative that has been talked about previously on this blog), researchers looked at the data for 'screened for' ADHD signs and symptoms using the Adult ADHD Self-Report Scale (ASRS) Screener as well as data derived from "the five-item SCOFF screening instrument" relevant to eating disorders (ED) completed by over 7000 adults.

Researchers reported that: "The prevalence of possible eating disorder (ED) was much higher among those with ADHD symptoms (ASRS score ≥14) compared to those without ADHD symptoms (19.2 vs. 5.7%)." They also noted that issues such as anxiety and the presence of borderline personality disorder (BPD) also might have an important influence on disordered eating as measured by the SCOFF. ADHD plus anxiety linked to a heightened increased risk of another condition presenting? I've heard that before (see here).

Accepting the fact that use of the ASRS in initiatives such as the APMS is not without potential 'limitations' (see here), and the important word 'possible' when it comes to the presence of an eating disorder based on SCOFF results alone, these are potentially important results. I say that on the basis that a connection between food/diet and ADHD has a long history from many different perspectives (see here and see here and see here for examples). I should also add that this is not the first time that ADHD and eating disorders have been talked about in the peer-reviewed research literature (see here and see here).

Other implications aside from the potential need for preferential screening for eating disorders as and when ADHD or ADHD-type behaviours feature? Well, I'd be minded to suggest that including another label/diagnosis/constellation of symptoms into future research proceedings might be useful. I speak of autism or autistic traits and the ideas that: (i) autism and ADHD occurring together is not unheard of (see here) and (ii) there is some increasing interest regarding the presence of autistic traits in relation to those diagnosed with an eating disorder (see here and see here).


[1] Jacob L. et al. Attention deficit hyperactivity disorder symptoms and disordered eating in the English general population. Int J Eat Disord. 2018 Sep 6.


Tuesday 23 October 2018

The Scotland Census 2011 and autism again: focus on children and young adults

Consider this post an extension of some previous chatter on this blog (see here). That previous chatter was based on the work published by Ewelina Rydzewska and colleagues [1] talking about how (a) Scotland seems to be pretty unique insofar as 'asking about autism' in their population Census, and (b) how examination of such a query, alongside asking a few other questions, represents an important research resource particularly pertinent to the idea that autism rarely appears in some sort of diagnostic vacuum (see here).

Now there's more from Rydzewska and colleagues [2] and their analysis of the Scotland 2011 Census. This time the specific focus was on under 25 year olds (their previous research was dedicated to looking at "the prevalence of comorbid mental health conditions and physical disabilities in a whole country population of adults aged 25+ with and without reported autism").

Researchers report that 1.6% of their population (25,063/1,548,819) were reported to have (or someone on their behalf) ticked the box to the question 'have any of the following conditions' that was labelled 'Developmental disorder (for example, Autistic Spectrum Disorder or Asperger's Syndrome)'. This was quite a bit higher than the 0.2% of adults (over 25 years old) that was previously reported on. They also reported that the traditional 4:1 male:female ratio regarding autism was intact as other recent population (estimated) prevalence studies have also indicated (see here and see here).

Then to the main event: "Autism had an odds ratio of 5.4 (5.1–5.6) for predicting deafness/partial hearing loss, odds ratio of 8.9 (8.1–9.7) for blindness/partial sight loss, odds ratio of 49.7 (38.1–64.9) for intellectual disabilities, odds ratio of 15.7 (13.4–18.5) for mental health conditions, odds ratio of 15.8 (14.1–17.8) for physical disability and odds ratio of 3.9 (3.8–4.0) for other conditions."

It's worthwhile reiterating some of those observations made by Rydzewska et al: the chances (odds ratio) of intellectual or learning disability appearing alongside autism in under 25 year olds was about 50 times more likely than in those not ticking that 'Developmental disorder' option. In terms of specific percentage frequencies, the figures for learning disability in the age groups 0-15 years (children) and 16-24 years (young adults) where autism was mentioned were 13-14% and 18% respectively. This was contrasted against percentages of 0.3% and 0.4% in similar non-autistic age groupings. I'm also minded to include the observation that girls with autism across both age groups seemed to be at some elevated risk of learning disability when compared to boys. The next highest risk values came in for the presence of a mental health condition where again girls with autism seemed to shoulder the highest risk (a divide that seemingly grew as children aged into young adults). The conclusion yet again is that for quite a few people, autism is not a stand-alone condition/label and that such "conditions are disabling and have a significant impact on long-term quality of life; their coexistence with autism adds extra complexity."

On the last blogging occasion when the first research paper from Rydzewska using the Scotland Census 2011 data was discussed, I held back from commenting too much on the adult prevalence figure picked up by authors. This time I'm not going to, because the difference between children/young adults with autism (or a developmental disorder) (1.6%) and autistic adults (0.2%) is too stark not to mention. I appreciate that there may be many variables/factors contributory to such figures, and that such figures are perhaps prone to some degree of error (bearing in mind the legal requirements behind completing a Census), but the disparity between them cannot be just brushed under the scientific carpet. They show that for the year 2011 in Scotland, autism - all forms of autism - was quite significantly over-represented in children and young adults compared with autism in over 25 year old adults. They show that arguments about the prevalence of adult autism potentially being on a par with childhood autism were/are wrong. They show that autism is disproportionately affecting children/young adults and by inference, the trend in autism being diagnosed is an upward one primarily stemming from childhood/young adulthood diagnoses and not from the late diagnosis of adults.

By saying that I'm not ruling out the idea that there may be adults in Scotland in 2011 who had slipped through the diagnostic net with autism in mind. I'm not saying that some 7 years later, things haven't moved on with regards to autism awareness and the like. But I do find it extremely unlikely that there were literally thousands and thousands of 'hidden' people 'undiagnosed' in Scotland in 2011 however much some people have inferred, and continue to infer, that this is true. The peer-reviewed evidence for this phenomenon is just not there, and certainly nowhere near there when it comes to those with 'very visible' autism who for example, require significant day-to-day social and health care support (see here and see here for examples).

I am hoping that when the next Scottish Census (2021) results eventually come in we might see more from this fabulous research opportunity with autism in mind. Even better would be for other countries to follow the Scottish lead in their questioning of their nation and perhaps provide a more accurate picture of the rates of autism across the age groupings.


[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 Sep 1;8(8):e023945.

[2] Rydzewska E. et al. Prevalence of sensory impairments, physical and intellectual disabilities, and mental health in children and young people with self/proxy-reported autism: Observational study of a whole country population. Autism. 2018 Oct 17:1362361318791279.


Monday 22 October 2018

"Omega-3 polyunsaturated fatty acid treatment for anxiety might be effective in clinical settings"

Today I present the findings of yet another systematic review and meta-analysis as per the publication from Kuan-Pin Su and colleagues [1] that concluded: "omega-3 PUFAs [polyunsaturated fatty acids] might help to reduce the symptoms of clinical anxiety." A finding that may have some quite profound implications for lots and lots of different diagnoses/conditions/labels where anxiety seems to be particularly over-represented and life-draining (see here and see here for examples).

So, the starting hypothesis was that "omega-3 PUFAs might have anxiolytic effects in patients with significant anxiety- and fear-related symptoms." Various studies, both in animals and humans, have implicated fatty acids in 'emotional states', particularly the so-called 'good fatty acids' including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The authors reported that "there have been no systematic reviews of this topic to date" so decided to remedy the situation.

Trawling through various repositories and databases of peer-reviewed science, they searched for relevant science on the topic of fatty acid supplementation and anxiety measurement. From little over a hundred possible science articles, they whittled the numbers down to 19 studies including over 1200 participants "with omega-3 PUFA treatment (mean age, 43.7 years; mean female proportion, 55.0%; mean omega-3 PUFA dosage, 1605.7 mg/d)" and "1037 participants without omega-3 PUFA treatment (mean age, 40.6 years; mean female proportion, 55.0%)." Taking into account that some studies (most) included a placebo element to their design, different dosages and formulations of PUFAs were used and that various different tools and schedules were used to 'measure anxiety', there were some boiled-down messages to emerge.

First: "The overall findings revealed modest anxiolytic effects of omega-3 PUFAs in individuals with various neuropsychiatric or major physical illnesses." That's not to say that every study was 'positive' in terms of PUFA effects on anxiety, but generally speaking the evidence tended to side more with an effect rather than no effect. Second, dose and formulation seemed to matter: "Participants treated with a daily dose of 2000 mg or more of omega-3 PUFAs showed a significantly greater association of treatment with reduced anxiety symptoms." Third: "the association of omega-3 PUFA treatment with reduced anxiety symptoms was significantly stronger in subgroups with specific clinical diagnoses than in subgroups without specific clinical conditions." So the effect of PUFA supplementation was stronger in those with a clinical diagnosis of something like anxiety than those who didn't have one.

Downsides? Well, there are of course limitations to the data included in the Su study; for example, "the significant heterogeneity among the included studies... with potential influence by some outlier studies" and these should not be underestimated. I'm also minded to bring in the [still emerging] issue that meta-analyses are only as good as the data that they are based on (see here and see here for examples). And I'd also mention that side-effects are something not discussed too heavily in the Su study but one shouldn't assume that just because we're talking about a fish oil so this is somehow side-effect free for everyone...

Given the low cost of fatty acid supplements and their wide, very wide, availability, the Su results provide some pretty good support to suggest that 'giving it a go' could be an option for at least some people diagnosed with an anxiety disorder. Please don't however take that as me giving anyone medical or clinical advice; I'm merely following what the results say and the media coverage that has followed (see here).

And since we're on the topic of food and mood, I note the recent meta-analysis from Camille Lassale and colleagues [2] suggesting that "adhering to a healthy diet, in particular a traditional Mediterranean diet, or avoiding a pro-inflammatory diet appears to confer some protection against depression in observational studies" has been garnering news headlines (see here). These studies combined suggest that diet might have an important effect of mood and well being. Now, where have I heard that before (see here)...?


[1] Su K-P. et al. Association of Use of Omega-3 Polyunsaturated Fatty Acids With Changes in Severity of Anxiety Symptoms. JAMA Network Open. 2018;1(5):e182327.

[2] Lassale C. et al. Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies. Molecular Psychiatry. 2018. Sept 26.


Friday 19 October 2018

Helminthic Trichuris Suis Ova vs. placebo for repetitive behaviours in adult autism

The trial results published by Eric Hollander and colleagues [1] were not entirely unexpected. I had previously mentioned their study on the "use of the immunomodulator Trichuris Suis Ova (TSO)" with autism in mind in another post (see here) but, at that time, still awaited the peer-reviewed publication version to appear. I wait no longer.

OK, Trichuris suis (T. suis) is a parasite. It makes its home in the deepest, darkest recesses of other creatures, apparently also having the rather important evolutionary advantage of being able to stay in egg form for quite a long time 'awaiting ingestion'. But just before you turn away John Hurt style (no, I'm not going to link to the 'chest-buster' scene), this particular parasite might not be 'all bad'. I'm specifically talking about some preliminary data suggesting that T. suis *might* have some important immunological effects [2] when ingested in a controlled manner under certain clinical circumstances.

Hollander et al took things one stage further by their insinuation of a link between use of an "immunomodulator" such as T. suis and their study to determine "the effect sizes for TSO vs. placebo on repetitive behaviors, irritability and global functioning in adults with ASD [autism spectrum disorder]." And just before you question the idea that immune function might be something important to some overt behaviour(s), there is other research out there discussing the possibility of such an effect (see here and see here) specifically with autism in mind.

"A 28-week double-blind, randomized two-period crossover study of TSO vs. placebo in 10 ASD adults, ages 17 to 35, was completed, with a 4-week washout between each 12-week period." This was a 'gold-standard' trial design albeit with a very, very small participant group who represented only a specific 'part' of the autism spectrum [3]. The trial was also registered for all to see the proposed hows-and-whys (see here) including the detail: "Have a personal or family history of allergies" as part of the inclusion criteria.

Results: "Differences between treatment groups did not reach statistical significance." This is an important point highlighting how use of T. suis ("the eggs of intestinal helminthes (trichuris suis ova) administered as 2500 ova doses every two weeks") did not translate into statistically significant group differences across measures looking at the social communication aspects of autism for example. I say this bearing in mind that the Hollander study was a cross-over trial too.

But... "Large effect sizes for improvement in repetitive behaviors (d = 1.0), restricted interests (d = 0.82), rigidity (d = 0.79), and irritability (d = 0.78) were observed after 12 weeks of treatment." What this means is that when comparing participants using T. suis vs. their baseline measurements, they seemed to do better on the T. suis portion of the trial across various different types of behaviour. Importantly too we are told that "TSO had only minimal, non-serious side effects" bearing in mind this included various gastrointestinal (GI) side-effects (and knowing that GI issues are already 'a thing' when it comes to autism).

So, there we have it. The results of the first (small scale) clinical trial using Trichuris Suis Ova (TSO) helminthic style with autism in mind. Obviously a lot more research is required before this type of intervention goes anything like 'mainstream'. Alongside there is also the 'acceptability' factor to consider: how many people would actually want to ingest a parasite such as T. suis? Indeed, one of the next courses of study is perhaps to see 'why' such helminthic therapy has the effect that it has on behaviour, and whether such an effect can be replicated in a medicine or other formulation rather than ingesting a parasite?


[1] Hollander E. et al. Randomized Crossover Feasibility Trial of Helminthic Trichuris Suis Ova vs. Placebo for Repetitive Behaviors in Adult Autism Spectrum Disorder. World J Biol Psychiatry. 2018 Sep 19:1-25.

[2] Jouvin MH. & Kinet JP. Trichuris suis ova: testing a helminth-based therapy as an extension of the hygiene hypothesis. J Allergy Clin Immunol. 2012 Jul;130(1):3-10.

[3] Hollander E. et al. Trichuris Suis Ova (TSO) as an immune-inflammatory treatment for repetitive behaviors in ASD. European Neuropsychopharmacology. 2016; 26: 891.


Thursday 18 October 2018

"contrary to its findings, there is no evidence that graded exercise therapy is effective" for myalgic encephalomyelitis / chronic fatigue syndrome

Things can sometimes move pretty fast in the world of peer-reviewed science. I had originally scheduled this post to appear in November (2018) but there's been some recent 'movement' in this area (see here) so I've decided to publish it now.

The original post is shown below. And below that are a few extra thoughts in light of the reported decision to remove the Larun article (at least for now)...


The re-analysis paper published by Mark Vink & Alexandra Vink-Niese [1] makes for some really interesting reading. Not only because it adds to other voices in the peer-reviewed domain (see here) questioning the usefulness and safety of the intervention known as graded exercise therapy (GET) 'for' myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but also because it kinda fits in with a narrative suggesting that 'trusted evidence' is almost always open to interpretation (see here).

So, graded exercise therapy (GET) and ME/CFS. I have to say that out of all the interventions / treatments that I've come across down the years that have been indicated for various diagnostic labels, GET is probably one of the most reviled by the population it is supposed to be aimed at. The reasons for such a scenario are multiple and complex, but one of the more vocal arguments seems to be the lack of regard for harm caused by the use of a stepped physical activity schedule on a population whose illness is defined by boom-bust symptom profiles caused by physical exertion. Of particular importance to this line of thinking is the idea that post-exertional malaise (PEM) needs to have a lot more prominence attached to it when it comes to ME/CFS, minus any psychobabble 'deconditioning' chatter or related explanations.

The Vink-Vink-Niese paper is based on a Cochrane review paper of GET published by Lillebeth Larun and colleagues [2]. Yes, the same Cochrane that is going through a bit of turmoil at the moment. The Larun paper concluded a few things such as: "Exercise therapy did not worsen symptoms for people with CFS" and "Moderate‐quality evidence showed exercise therapy was more effective at reducing fatigue compared to ‘passive’ treatment or no treatment." This based on the examination of "eight randomised controlled studies" with "reported data from 1518 participants." To be fair to the Larun review paper, the authors did also mention that: "Serious side effects were rare in all groups, but limited information makes it difficult to draw firm conclusions about the safety of exercise therapy" and "further studies should be carried out to discover what type of exercise is most beneficial for people affected by CFS, which intensity is best, the optimal length, as well as the most beneficial delivery method." This, on the basis that CFS/ME is best described as a heterogeneous condition and accepting that exercise can come in various different forms, some of which might be more applicable than others when it comes to individuals with fatigue-related labels (see here for example) minus any sweeping generalisations.

Some familiar themes crop up in the Vink re-review paper - "Entry score requirements were not sufficiently strict" and "The review used subjective fatigue measured by questionnaires as the primary outcome" - which have quite notably hindered the research in this area. I note also that authors mention about attrition (dropout) rates in the reviewed studies and how, in some studies, over a third of participants placed in exercise conditions withdrew from such investigations. Such statistics will no doubt have an important influence on any final results, as well as providing an important clue that such an intervention might not be sufficiently well tolerated by quite a few [3].

Vink concludes by saying that: "The GET trials reviewed here are inherently biased: use of exercise may attract only the mildly affected and may deter the more disabled patients from participating" and that: "The flaws in the review and the trials... all created a bias in favour of the exercise intervention."

On the basis of their interpretation of the scientific data, I'm in agreement with Vink & Vink-Niese that the evidence base for the universal application of GET to ME/CFS is by no means indicated. You might well say that GET is not universally rolled out for everyone with ME/CFS but, as things currently stand at the time of writing, it is still part of the clinical guidance for the condition(s) here in Blighty (for now) and hence potentially something that can be suggested for anyone diagnosed with ME/CFS. The ethos behind GET also being tied into another biopsychosocial (BPS) favourite - CBT - also makes for a good reason why psychology really shouldn't be let anywhere near such clinical issues, particularly when the evidence against such 'interventions' is seemingly mounting (see here). Indeed, although little comfort to those currently living with ME/CFS, I'm sure one day we'll look back at the whole BPS 'involvement' with ME/CFS and truly say WTF?

And finally, whilst on the topic of 'not listening to your target population' I would also draw your attention to the recent findings from McManimen and colleagues [4] highlighting what could happen when those with ME/CFS face stigma (and dogma). Oh, and because the Cochrane name is part-and-parcel of today's post, I'll also draw your attention to an important message concerning some of their other advice pertinent to CFS...


What else to add to this post? Well, a quote appearing in that Reuters report on the decision to temporarily withdraw the Larun review suggesting that "the withdrawal decision set a worrying precedent for scientific evidence being over-ridden by the opinions of activists" is, to my mind, inappropriate. Aside from the feedback received regarding the Larun article (see here) the Vink paper for example, is peer-reviewed science and published peer-reviewed science at that. It's not some activist randomly throwing around allegations and the like on social media or blogs(!). It's published peer-reviewed-science that calmly calls into question the conclusions of the original Larun analysis. Indeed, it's part of a trend for serious scientific conversations being held in the peer-reviewed science domain concerning some of the science and clinical practice around ME/CFS (see here). Nothing vexatious.

As I mentioned, given that other Cochrane reviews covering the topic of CFS have also been recently withdrawn [5] (see here for more on the withdrawal notice) it strikes me that Cochrane is perhaps also wisely ensuring that it's previous high standards are maintained and confidence restored in its 'evidence-based' name particularly when it comes to research into ME/CFS. Given also the turbulent few weeks that have just passed (see here) and seemingly, are still continuing (see here) for the 'collaboration', it's also a timely reappraisal that fits the important narrative that ME/CFS is a long-term physical health condition (see here) and not a mental disorder or worse. And intervention options need to recognise this fact...


[1] Vink M. & Vink-Niese A. Graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective and unsafe. Re-analysis of a Cochrane review. Health Psychology Open. 2018;5(2):2055102918805187.

[2] Larun L. et al. Exercise therapy for chronic fatigue syndrome. Cochrane Database Syst Rev. 2016 Jun 24;(6):CD003200.

[3] Cheshire A. et al. Guided graded Exercise Self-help for chronic fatigue syndrome: patient experiences and perceptions. Disabil Rehabil. 2018 Oct 16:1-10.

[4] McManimen SL. et al. Effects of unsupportive social interactions, stigma, and symptoms on patients with myalgic encephalomyelitis and chronic fatigue syndrome. J Community Psychol. 2018 Nov;46(8):959-971.

[5] Adams D. et al. WITHDRAWN: Traditional Chinese medicinal herbs for the treatment of idiopathic chronic fatigue and chronic fatigue syndrome. Cochrane Database Syst Rev. 2018 Oct 15;10:CD006348.


Wednesday 17 October 2018

"maternal pre-pregnancy obesity is associated with autism-like behaviors in offspring"

The results reported by Kandice Varcin and colleagues [1] concluding that "maternal pre-pregnancy obesity is associated with autism-like behaviors in offspring" continue and extend a research theme (see here and see here). A research theme that highlights a potentially important relationship between maternal weight (and/or related parameters) and offspring development across various, potentially intertwined, variables (see here).

Including the notable name of Andrew Whitehouse on the authorship team (see here and see here for some examples of his other research), researchers set about to explore whether "pre-pregnancy weight was related to autistic-like traits among offspring not diagnosed with ASD [autism spectrum disorder]." I added the bold highlight to the word 'not' to emphasise how this work was set slightly apart from the other research that has observed an *association* between maternal weight before or during pregnancy and a risk of a formal diagnosis of autism in offspring. Pregnant women in their second trimester of pregnancy were recruited and "had their height measured." They also "reported their pre-pregnancy weight" which combined with the height measurements to give the measure known as the body mass index (BMI). And also: "At 19-20 years of age, 1238 offspring of these women completed a measure of autistic-like traits, the Autism-Spectrum Quotient (AQ)." Keep those issues in mind for now.

Results: "Regression analyses identified a positive association between increasing maternal pre-pregnancy BMI and increasing AQ Total Score amongst offspring; this association was maintained even after controlling for a range of variables including maternal/obstetric factors (age at conception, education, smoking, alcohol consumption, hypertensive diseases, diabetes, threatened abortion), paternal BMI at pregnancy, and child factors (parity, sex)." Sorry for the large quote, but the authors said it better than I ever could. Authors also reported that those women defined as being obese before pregnancy, according to their BMI measurement, were quite a bit more likely to "have offspring with high scores (≥26) on the AQ." This then lead them to conclude that "maternal pre-pregnancy obesity is associated with autism-like behaviors in offspring."

Caveats? Well, yes, a few. Height measured in the second trimester but participants "reported their pre-pregnancy weight"? I can see a few complications there in terms of accuracy of recall and perhaps the possibility of some bias creeping in. Having said that, many mums-to-be do have records of their weight during that 'special time' and some probably before as part of their regular clinical care or just as a result of how health conscious everyone is being these days. That and the fact that most people roughly know their typical weight (outside of pregnancy).

But also the AQ... the AQ. Regular readers probably already know that I have some qualms about the AQ and it's 'specificity' when it comes to autism and autistic traits (see here and see here). I know it's often seen as one of the internet's premier 'are you autistic?' instruments, but sometimes I think it's done more harm than good by way of it's probable link to the rise and rise of the 'self diagnosis' (see here) for example. I could go on about this, but I won't. Instead I'll just mention that 'autism-like' behaviours as judged by the AQ is probably the correct phrase to use in the context of the Varcin paper. Indeed, one might easily suggest that in a non-clinical population, AQ might also be tapping into other labels and traits [2]: "Higher AQ scores were associated with higher scores of loneliness, social anxiety, depression, and anxiety, as well as with lower scores of quality of life (QoL)." So unless one accepts that depression and/or anxiety might potentially be core features of autism (see here and see here), AQ might be picking up other things other than autism.

Still, I can't argue with the *association* talked about by Varcin et al, and what it might mean for the quite spectacular rise and rise in the numbers of people being diagnosed with an autism spectrum disorder (see here). No, not by any means the only factor to account for the increase in diagnoses, but potentially an important part of the story...


[1] Varcin KJ. et al. Maternal pre-pregnancy weight and autistic-like traits among offspring in the general population. Autism Res. 2018 Sep 19.

[2] Reed P. et al. Loneliness and Social Anxiety Mediate the Relationship between Autism Quotient and Quality of Life in University Students. Journal of Developmental and Physical Disabilities. 2016; 28: 723-733.


Tuesday 16 October 2018

Prevalence of autism in preterm infants meta-analysed

"The prevalence of ASD [autism spectrum disorder] is significantly high in the preterm population. Adequate resources are needed to improve the outcomes of these children."

So said the findings reported by Sachin Agrawal and colleagues [1] who present the results of yet another meta-analysis with autism in mind; yet again on a topic that has filled quite a few peer-reviewed science column inches (see here and see here for examples).

'Preterm' typically refers to babies who are born alive but before completing the usual 37 weeks of gestation. It is further sub-categorised into extremely (less than 28 weeks), very (born between 28 and 32 weeks gestation) and moderate-to-late (born between 32 and 37 weeks gestation) preterm. The risk of a wide variety of 'adverse' outcomes seems to be significantly heightened following preterm birth, covering both physical (somatic) and psychological/developmental domains. Outside of the very final outcome that is early mortality, longer-term issues, particularly associated with brain development occurring outside of the womb, have been a feature of several results. Autism has also been mentioned in this context (see here).

Agrawal et al set about analysing the data pertinent to autism risk and preterm birth. They talk about the scenario of a 'perfect storm' whereby "whatever initiates the preterm birth process might also initiate abnormal pathways of brain development" as being potentially pertinent to autism. Covering the research literature up to May 2017, some 18 studies including over 3300 preterm infants were included for analysis. They specifically included studies that utilised known diagnostic tests for autism or ASD (ADOS, ADI, DAWBA) rather than those that used only "ASD screening tools" and looked up the cumulative prevalence rate for autism.

Results: 7%. That was the overall autism prevalence rate among preterm infants included in the various studies analysed. There was quite a bit of variation across the studies and the prevalence figure fluctuated to some degree as and when children with disabilities were included or not, but the 7% figure seemed to be an accurate one. Authors also put the 7% figure into some 'real world' perspective too: "This equates to ∼900 000 additional children each year who will develop ASD given that globally ∼15 million infants are born preterm (before 37 weeks’ gestation), of whom 13 million survive." Kinda takes your breath away doesn't it?

A couple of other important details are worthwhile mentioning too. So: "Our meta-regression analysis revealed no significant association between gestational age, birth weight, and prevalence of ASD in preterm infants." This doesn't totally rule out such factors as exerting an effect, but...

What else to say? Well preferential screening for autism or ASD in cases of preterm birth could be indicated. The allocation of further research resources into how and why preterm birth occurs could also be useful, focusing on how and why the infant brain seems to be so sensitive to maturation outside of mum's body. And then in relation to all those 'we don't know what causes autism' sentiments that continue to be expressed, well, add prematurity to the growing list of strong possibilities (see here and see here for other examples).

Oh and minus any medical or clinical advice being given or intended, it appears that nutrition, particularly omega-3 fatty acid levels, *might* play 'some' role in some preterm births [2] with some intriguing possibilities for supplementation (minus sweeping generalisations)...


[1] Agrawal S. et al. Prevalence of Autism Spectrum Disorder in Preterm Infants: A Meta-analysis. Pediatrics. 2018 Aug 3. pii: e20180134.

[2] Olsen SF. et al. Plasma Concentrations of Long Chain N-3 Fatty Acids in Early and Mid-Pregnancy and Risk of Early Preterm Birth. EBioMedicine. 2018 Aug 2. pii: S2352-3964(18)30252-4.


Monday 15 October 2018

Autism research really needs to study the prevalence and treatment of scurvy in autism

The results published by Melinda Saavedra and colleagues [1] describing another case report where scurvy was [eventually] diagnosed as appearing alongside autism represents yet another 'call to action' on this topic.

I've covered this issue quite a few times before on this blog (see here and see here and see here), and quite frankly it's reached the point where autism research really needs to step up and formally study the prevalence of scurvy in relation to autism. Indeed given the almost universal reports of medical science not initially recognising that scurvy can be no stranger to autism, the time has also come to "announce [to] the pediatrician and other professionals dedicated to primary health care about scurvy as a potential consequence of restrictive diets in children with autism spectrum disorders."

This time around the clinical focus was on a 4 year old boy who was brought to clinical attention as a result of "hip pain and refusal to walk, associated with petechiae and bruising of the lower limbs." The clues were all there that scurvy could be a cause of such symptoms, but it was only when it was revealed that the child had "selective feeding habit" that the penny seemed to finally drop. Indeed: "Levels of Vitamin C in blood were measured and without waiting for results he started treatment with 300 mg per day of ascorbic acid." Lo and behold, his vitamin C results were found to be low, and vitamin C supplementation eventually did the trick. Of vital importance, the pain associated with scurvy also showed improvement and he was discharged from clinical care with a maintenance dose of vitamin C and some nutritional advice.

'Selective feeding patterns', 'picky eating' or whatever you want to call it, is an issue that is not stranger to autism (see here). It's reasonable to assume that where such feeding issues continue into the longer-term, and dependent on what foods are consumed as part of such a restrictive pattern, there are likely to be biological consequences for the person concerned as a function of what nutritional inadequacies follow. Indeed, I daresay that such a pattern follows what is being noticed in connection with other food-related conditions in the longer term (see here). Set in this context, a lot more research and importantly, clinical practice, needs to focus on the hows-and-whys of such behaviours and their remediation. There is no longer any excuse for allowing diseases of the past such as scurvy and also others like rickets, to plague the children of today, vulnerable children of today, where healthy food in most parts of the world, is not in short supply.

Oh, and bear in mind that 'picky eating' might not be the only reason why scurvy might appear alongside autism [2]. We need lots more data.

And also, as I write this [3]...


[1] Saavedra MJ. et al. Scurvy due to restrictive diet in a child with autism spectrum disorder: case report. Arch Argent Pediatr. 2018 Oct 1;116(5):e684-e687

[2] Hasan Al-Breiki S. et al. Scurvy as the tip of the iceberg. Journal of Dermatology & Dermatologic Surgery. 2014; 18: 46-48.

[3] Caldwell KJ. et al. Child With Autism and a Limp. Ann Emerg Med. 2018 Oct;72(4):493-495.


Saturday 13 October 2018

Regressive vs. non-regressive autism: limited chemical differences noted

The paper published by Antonio Gomez-Fernandez and colleagues [1] examining whether or not there may be some potentially important biological differences as a function of reported regression vs. no regression in autism provides the blogging fodder today. Not for the first time has the immune system and 'regressive autism' been mentioned in the peer-reviewed science literature (see here and see here), but the current work focuses on the examination of various immune system and other related compounds: in a seemingly well-defined cohort: "Analyses of plasma molecules, such as cathepsin, IL1β, IL6, IL8, MPO, RANTES, MCP, BDNF, PAI NCAM, sICAM, sVCAM and NGF."

"Fifty-four children (45 males and nine females) aged 2-6, who were diagnosed with ASD [autism spectrum disorder], and a control group of 54 typically-developing children of similar ages were selected." Authors relied on quite an extensive battery of assessments looking at behaviour, alongside their use of the DSM-5 diagnostic criteria for autism (see here). Also accompanying physical examination "with a special emphasis on neurological and nutritional status", authors garnered blood samples from participants (overnight fasting) for their immune system and related functioning evaluations.

"The group of ASD children was further divided into two subgroups based on the presence or absence of neurodevelopmental regression during the first two years of life, which was assessed using a five-item questionnaire following the guidelines used by the Autism Diagnostic Interview-Revised (ADI-R) for the evaluation of this process." The ADI-R has been previously discussed on this blog in relation to regression in autism (see here). And just in case you might not be totally convinced that regression can be part of a pathway to autism, here's some more evidence for you (see here)...

Results: "there were 20 children included in the AMR [neurodevelopmental regression] subgroup and 32 in the ANMR [without neurodevelopmental regression] subgroup; two children could not be classified in these subgroups because they were adoptees, allocated by a national adoption agency." Bearing in mind that we cannot rule out any recruitment bias that might have leaned towards including those with regressive autism on the Gomez-Fernandez study, the figure of approaching 40% of their cohort showing such a regressive profile is notable. I'd also draw your attention to the finding that the behavioural profile for the regressive group (AMR) was also significantly different from the non-regressive group (ANMR) insofar as perhaps painting a picture of greater [group] autism severity...

Interestingly, the study did not show too many immune system and other compound differences between those diagnosed with autism and the asymptomatic (for autism) control group. So: "No differences were found between the two groups in terms of the cytokine and adhesion molecule levels studied, except for NGF [nerve growth factor], in which the group of ASD children was found to have twice the plasma levels compared to the control group." NGF is no stranger to autism research, and other studies have come to a similar conclusion [2].

When it came to examining results based on comparing the regressive (AMR) and non-regressive (ANMR) groupings, things got slightly more interesting but again no complicated pattern of difference was noted. So, for the ANMR (non regression) grouping: "lower plasma levels of the NCAM adhesion molecule were detected compared to the levels in the AMR subgroup and the control group. This ANMR group also exhibited higher NGF levels than the typically-developing children, which could indicate an alteration in neuronal development." Again, adhesion molecules have been mentioned in other autism research (see here).

"In conclusion, the results of this study show that there is not a typical profile for the expression of relevant plasma cytokines, adhesion molecules or growth factors in children with ASD compared with that in typically-developing children." OK, there are caveats to the phrasing used by the authors; not least that the participant numbers were quite small in the Gomez-Fernandez study and the idea that within the very heterogeneous autism spectrum, there may be smaller groupings (phenotypes) that perhaps show a tendency to greater immune system and related 'issues' (see here). But there are also some strengths attached to the Gomez-Fernandez study; not least the study "benefits from a careful selection of children of similar ages, as well as the complete diagnosis of ASD with multiple tests, clinical follow-up and associated complementary tests."

Questions still remain. Perhaps an important one is the question around why some children show a regressive pattern of behaviour as part of their path to a diagnosis of autism? Yes, issues such as infection do seem to be part-and-parcel of the clinical profile for some (see here and see here for examples) and perhaps more detailed focus is required in such areas. But much like a group showing the opposite of regressive autism - those who seemed to 'grow out' of autism - currently thought to include as many as one in ten (see here), a wider range of biological as well as psychometric measures are required to help pick out potentially important mechanisms pertinent to the idea that autism is not necessarily 'hard-wired' for all...


[1] Gomez-Fernandez A. et al. Children With Autism Spectrum Disorder With Regression Exhibit a Different Profile in Plasma Cytokines and Adhesion Molecules Compared to Children Without Such Regression. Front. Pediatr. 2018. September 26.

[2] Dinçel N. et al. Serum nerve growth factor levels in autistic children in Turkish population: a preliminary study. Indian J Med Res. 2013 Dec;138(6):900-3.


Friday 12 October 2018

Pervasive refusal syndrome and autism: autistic traits 'speeding up the recovery process'?

Before reading the case report paper by Emily Bond & Rosalind Oliphant [1], I have to admit that I knew next to nothing about the label known as pervasive refusal syndrome (PRS). PRS, a condition manifesting as 'refusal to eat, weight loss, social withdrawal and school refusal', is not currently recognised in any of the major diagnostic manuals (DSM, ICD) but does seem to have a following in certain circles [2].

Bond & Oliphant detail a case report of a 9-year old boy who came to clinical attention "due to concerns regarding minimal dietary intake." He had previously been diagnosed with an autism spectrum disorder (ASD) as well as attention-deficit hyperactivity disorder (ADHD) following a trend these days (see here). He was subsequently detained under the Mental Health Act as a consequence of "his resistance of treatment in the community" and also him "lacking Gillick competence." The authors detail his clinical journey, and how, with the right support and accommodations, he was eventually discharged from hospital care with the expectation for him to "make a full recovery to his premorbid functioning with support in the community."

Among the various issues raised in the Bond/Oliphant paper, one of the most striking points made by the authors was in the sentence: "It is possible that the ASD [autism spectrum disorder] symptoms such as literal thinking and concrete processing have actually aided in speeding up the recovery process." The idea that certain autistic traits might actually have had a positive benefit to getting someone through treatment for PRS...

I'm slightly careful here not to go off on the 'autism is a superpower' tangent that some people have previously spoken about (particularly on social media). For this young man, autism for him included communication issues ("His sole method of communication was typing on an iPad to his mother")  and various other traits (e.g. "struggling with understanding abstract questions, complex reasoning, and problem solving skills") which probably didn't impart any superpower for him. He did have an interest in superheros and dressing up in costumes however...

Authors mention how his recovery from PRS - he was discharged after 4 months - was significantly quicker than is typically expected (around 12 months "from previous literature"). They noted that: "The clinical team working with our case quickly found that he responded very well to rules, boundaries, and clear consequences of behaviour." This is perhaps even more notable in the context of his autism-ADHD diagnostic combination.

It did get me wondering whether further research might be revealing into how autism or specific autistic traits might positively impact on other treatment/management scenarios. I'm specifically thinking about more psychologically-inclined interventions, for example, dealing with something like anxiety (see here) where talking therapy is something that is being particularly pushed forward. Whether or not I agree that such therapy is going to be all that useful in the longer-term if for example, one considers that anxiety might be intricately related to some core functions in relation to autism (see here) is irrelevant. Whether certain autistic traits might be a critical variable in intervention success however requires much further study...


[1] Bond EC. & Oliphant RYK. Pervasive Refusal Syndrome in Autistic Spectrum Disorder. Case Rep Psychiatry. 2018 Jun 7;2018:5049818.

[2] Nunn KP. et al. Pervasive refusal syndrome (PRS) 21 years on: a re-conceptualisation and a renaming. Eur Child Adolesc Psychiatry. 2014 Mar;23(3):163-72.