Monday, 30 April 2018

"children with ASD who experience GI symptoms have an imbalance in their immune response"

The findings reported by Destanie Rose and colleagues [1] piqued my interest recently for a variety of reasons. Not only was there an emphasis on gastrointestinal (GI) issues in relation to autism (see here) but mention of the words 'microbiota composition' and 'impaired gut barrier function' make an important reference to something of a new triad in relation to [some] autism (see here).

First things first, as well as being another welcome research publication from the MIND Institute, the name Destanie Rose has appeared before on this blog with reference to maternal immune activation (MIA) and 'Old World monkeys' (see here). This work illustrated how infection during pregnancy can, under certain circumstances and at critical times, have a bearing on offspring development and behaviour; keeping in mind, that is, the possibility of logical fallacies (see here) when it comes to extrapolating from animal studies.

This latest time around, and including other notable names on the authorship list including Alessio Fasano (zonulin man) and Paul Ashwood (gut and immune system man), the focus shifted to immune function in the context of real life autism with the aim to "determine whether there are biological signatures in terms of immune dysfunction and microbiota composition in children with ASD with GI symptoms."

Four groups of children diagnosed with an autism spectrum disorder (ASD) participated in the study, including those with and without a diagnosis of ASD and with and without "current or previous GI symptoms." Both blood and stool samples were donated by study participants and subject to various analyses pertinent to assessing 'cytokine production' (cytokines are chemical signallers of the immune system) and ahem, the 'microbial composition' of poo(p) samples.

Results: those in the ASD + GI symptoms group showed "increased levels of mucosa-relevant cytokines including IL-5, IL-15 and IL-17" under "Toll-Like receptor (TLR)-4 stimulation" compared with those diagnosed with autism but with no bowel symptoms. TLR-4 is a protein that, as one of its duties, "plays a fundamental role in pathogen recognition and activation of innate immunity." Artificial stimulation of TLR-4 kinda mimics what would happen in real life as and when the body comes across a pathogen such as bacteria and needs to activate those immune defences.

Alongside other findings suggestive of "differences in microbiome composition between ASD and TD [typically developing] children with GI symptoms", authors also observed some interesting findings pertinent to impaired gut barrier function too. So: "The ASDGI also showed an over-representation of the gene encoding zonulin, a molecule regulating gut permeability, compared to the other groups." The gene in question is something called HP or Haptoglobin, and specifically HP2 which refers to a "common polymorphism consisting of two structural alleles: HP1 and HP2" [2]. As per the Vanuytsel paper [2], the HP2 allele is described as a risk allele for things like inflammatory bowel disease (IBD).

Bearing in mind that symptoms such as functional bowel issues (such as constipation and diarrhoea) are not necessarily the same as pathological bowel conditions such as the IBDs, I was interested in one of the figures included in the Vanuytsel paper on how HP2 links into gut permeability issues. In particular how "it is not unlikely that carriers of the zonulin gene (i.e., individuals with genotype HP21 or HP22) could possibly have an increased risk to develop IBD, because of the permeating effect of zonulin on the intestinal barrier." Zonulin has been something else of interest to this blog in the context of autism and so-called 'leaky gut' (see here) hence the interest in "a propensity to impaired gut barrier function which may contribute to their [gastrointestinal] symptoms and clinical outcome."

From what I gather, there was an over-representation of the HP2 allele (HP22 genotype) and under-representation of the HP1 allele in the ASDGI group examined in the Rose study, but things were not [statistically] completely cut-and-dried. This however, has to be set in the context of a seemingly increased risk of IBD as and when autism is diagnosed (see here).

What are the take-away messages from the Rose findings? Well bowel symptoms - functional bowel symptoms - occurring alongside autism probably have quite a complicated series of genetic and biological processes going on behind them. Both the mucosal immune system and the wider immune system are probably going to show 'some kind of relationship' to such chronic symptoms and, unsurprisingly, those trillions of wee beasties known as the gut microbiota are also probably involved/affected. The "propensity to impaired gut barrier function" associated with autism + bowel issues is also mentioned by Rose, and offers further testable hypotheses regarding the possibility of a gut-brain axis in relation to [some] autism (see here) and indeed, what measures might ease the pressures of such bowel issues. Also, whether bowel symptoms *might* show a connection to certain presented behaviour (see here) is another important area of further investigation...


[1] Rose DR. et al. Differential immune responses and microbiota profiles in children with autism spectrum disorders and co-morbid gastrointestinal symptoms. Brain, Behavior, and Immunity. 2018. March 20.

[2] Vanuytsel T. et al. The role of Haptoglobin and its related protein, Zonulin, in inflammatory bowel disease. Tissue Barriers. 2013;1(5):e27321.


Saturday, 28 April 2018

Risk of coercive sexual victimization *associated* with neurodevelopmental disorders

The paper by Vide Ohlsson Gotby and colleagues [1] represents an important contribution to the idea that 'vulnerability' is very much part and parcel of various childhood neurodevelopmental disorders (NDDs), and such vulnerability can have some pretty serious outcomes.

Relying on data from the Child and Adolescent Twin Study in Sweden (CATSS) - an initiative that is no stranger to discussions on this blog (see here for example) - researchers set about looking at any *association* between NDD status and risk of "being sexually victimized." Sexual victimisation was defined as "lifetime experiences of coercive sexual touching and/or coercive sex." Importantly, the Ohlsson Gotby results only covered "coercive sexual victimization up to age 18".

Their findings are worrying; as per one example: "In females, ASD [autism spectrum disorder] was associated with an almost threefolded increased risk of coercive sexual victimization." Following further analysis on whether "the association is driven by a general NDD phenotype versus specific diagnoses" authors concluded that: "General NDD symptom load, rather than specific ASD or ADHD [attention-deficit hyperactivity disorder] symptoms, seems to be a moderate vulnerability factor for coercive sexual victimization."

I appreciate that this is an uncomfortable topic. In light of all the talk about 'female autism' (see here) and issues such as camouflaging and the like (see here) potentially impacting on the rates of autism in girls and women, added to the age limit imposed by authors, it's highly likely that the Ohlsson Gotby findings are only the tip of the iceberg. Further investigation is required to see how prevalent such issues are across a lifetime, and importantly, what protective factors there might be against such a vulnerability. Whether also, minus any sweeping generalisations, there may be an intergenerational 'effect' (see here) is also an important question to answer. And having mentioned the word 'vulnerability' quite a bit already, more evidence is emerging on this topic [2].

Another important point to mention about the data derived from Ohlsson Gotby et al is their focus on boys as well as girls. They discuss how the [statistical] magnitude of the results obtained looking at males was not the same as with girls, but I'm inclined to again suggest that there may be some under-reporting of such issues. Being male and being diagnosed with autism and/or ADHD is not likely to be a protective factor against sexual victimisation.

And finally something rather shocking from the authors: "We speculate that an evocative gene-environment correlation might account for this observation [general NDD symptom load being related to sexual victimisation], such that sexual perpetrators actively target NDD individuals." Parents, caregivers and others with a vested interest in the care of those with NDD need to be particularly vigilant it seems.


[1] Ohlsson Gotby V. et al. Childhood neurodevelopmental disorders and risk of coercive sexual victimization in childhood and adolescence - a population-based prospective twin study. J Child Psychol Psychiatry. 2018 Mar 23.

[2] Williams DM. et al. Can you spot a liar? Deception, mindreading, and the case of autism spectrum disorder. Autism Res. 2018 Apr 27.


Friday, 27 April 2018

"... and now believe their pet has canine autism"

A recent tweet from the account of one of the most popular TV breakfast shows here in Blighty made some waves (international waves no less) for a couple of reasons. Leaving aside the insinuation that vaccination *might* correlate with certain behavioural changes in domestic pets, the idea that autism might not be something exclusive to humans was also implied from said tweet.

Needless to say that quite a few people took exception to the idea of 'canine autism'; even the British Veterinary Association (BVA) insisted that "there is currently no scientific evidence to suggest autism in dogs." But is that actually scientifically accurate? And more widely, is it possible for a non-human to have autism or present with significant autistic features?

Before progressing through the evidence around this question, I think it's worthwhile getting a few things straight. First, I appreciate that whilst autism is a label or diagnosis denoting a set of behavioural characteristics that 'significantly impact on day-to-day life' according to current diagnostic schedules, it's also a label of identity for some people. One therefore needs to be sensitive to the effect that discussions about animals also potentially 'having that label' would have to those who associate with an autistic identity. Second, there is a long, very long, history in peer-reviewed research circles, where animals have been used to model aspects of autism. Take for example, the increasingly important research emerging on a role for prenatal valproate exposure as a route to potentially increasing the risk of autism and other neurodevelopmental conditions being diagnosed (see here); an area that has also included discussions of a valproate-treated rodent model of autism (see here) being used in research. Of course, one needs to be aware that modelling autistic features in animals is not the same as autism and all its complexity presenting in humans (including the idea that autism rarely appears in some sort of diagnostic vacuum) and the resulting 'logical fallacies' that can arise (see here). But the assumption is that elements of certain core features of autism can potentially present in non-humans too, and could provide important clues as to the underlying nature of autism.

Going back to that 'no scientific evidence' statement made by the BVA in the lay press, you might be surprised to hear that actually, dogs have been the topic of some research interest in relation to their presenting with some of the features of autism. In an article titled: 'Can Dogs Have Autism?' some of that research was discussed. Starting from an article published way back in 1966 [1] observing behaviour in a dog "resembling human infantile autism" up to more recent peer-reviewed studies [2], several commentators have speculated on facets of autism being present in certain dogs and perhaps being more readily presented in certain breeds of dog. I've actually covered this topic previously in another post on this blog (see here) based on other research [3] reporting on shared biochemical parameters noted in some children and some canines: "tail-chasing Bull Terriers." This, on the basis that from a behavioural and biological point of view, humans are not a million miles away from canines and vice-verse. In short, there is a small scientific evidence base pursuing the notion that facets of autism may present in non-humans too.

Minus too many deep, philosophical musings about our relationship with animals and any evolutionary *connections* between human and animal behaviours, this topic did get me thinking about quite a few other things. It got me wondering whether there may be other behaviours and/or behaviourally-defined conditions / labels that are readily diagnosed in humans but that might also present in non-humans too. I also started to wonder about the myriad of animal-assisted 'interventions' that have been mentioned with autism in mind down the years (see here) and whether other possible research connections could be made as a result. Are we being too presumptuous by saying that the essence of autism is a uniquely human state?

And without trying to trivialise or make light of what autism means to many, many people, there is a long history of speculation when it comes to cats and autism...


[1] Fox MW. A syndrome in the dog resembling human infantile autism. J Am Vet Med Assoc. 1966 Jun 1;148(11):1387-90.

[2] Zamzow RM. et al. Characterizing autism-relevant social behavior in poodles (Canis familiaris) via owner report. J Comp Psychol. 2017 May;131(2):139-149.

[3] Tsilioni I. et al. Elevated serum neurotensin and CRH levels in children with autistic spectrum disorders and tail-chasing Bull Terriers with a phenotype similar to autism. Transl Psychiatry. 2014 Oct 14;4:e466.


Thursday, 26 April 2018

The yet newer CDC estimated autism prevalence rate: 1 in 59 8-years olds with autism in 2014

The report detailing the latest autism prevalence estimates from the US CDC has at last been published [1] coinciding with some other information on the findings. These figures were expected, given the two years that have flown past since the last report put the estimated figure at a stabilised 1 in 68 8-year olds being diagnosed with an autism spectrum disorder (ASD) in 2012 (see here) similar to the report before that which covered the year 2010 (see here).

The latest estimate by Jon Baio and colleagues covering the period 2014 is: 1 in 59 otherwise recorded as 16.8 per 1,000 (1.7%) 8-year-olds diagnosed with an autism spectrum disorder (ASD). Media reporting of the latest figures focuses on the headline finding of that increase in the estimated rate (see here) alongside the 'we don't know why' sentiments voiced by some important authority figures (see here).

So, what other details do the statistics hold and what do they mean?

Well, first and foremost the 'stabilising' of figures noted two years ago at 1 in 68 did not seemingly tell the whole story. I know quite a few people made the most of those non-changing estimates to say that 'autism awareness' and 'changes to diagnostic criteria' and 'diagnostic substitution' were the drivers of the increase and the stabilisation was solely reflective of those factors taking their course. Well, I guess not. Indeed, the restarting of the upward trend kinda suggests that there's probably a lot more going on. It also adds to increasing evidence of a possible 'real' increase in autism (see here). But stand by for the 'it can't be a real increase' sentiments to fly in thick and fast...

Second, as mentioned in the last report from the CDC, we are now presented with not one, but two diagnostic systems to characterise autism or ASD, as the DSM-5 enters service. DSM-5, if you'll remember, is the new classification system that is slowly starting to replace the older DSM-IV criteria. It's also the schedule that *seemed* to be a little more 'selective' in who did and did not qualify for a diagnosis of autism according to other external findings (see here). Did it exert an effect on the most recent autism prevalence estimates? Well, yes it did, as authors noted that: "ASD prevalence was approximately 4% higher based on the historical DSM-IV-TR case definition compared with the new DSM-5 case definition." Although the overall effect was probably not a great one, the more selective case definition provided by DSM-5 in the direction of potentially reducing numbers, contrasts with the upward trend reported. It should also be noted that authors mention how there was "approximately 86% overlap between the two case definitions." But... no mention of the other categorisation called Social Communication Disorder (SCD) (see here) was however included in the latest figures.

Other details are also mentioned in the new report that are worthwhile noting. Almost a third of the children with autism identified in the latest data, who had intellectual functioning data available, were reported to present with an intellectual or learning disability. This tallies with quite a lot of other independent data on the overlap of learning disability with autism. The 4:1 male:female ratio of autism also seemed to hold true in the latest figures. Also: "While a higher percentage of white children were identified with autism compared to black children, and even more so compared to Hispanic children, these disparities were smaller when compared with estimates from previous years." Autism practice it seems, is starting to reach some traditionally under-served populations, that probably contributed in part to the increased estimate noted. I stress the words 'in part' in that last sentence, just in case more sweeping generalisations are put out there to explain away any 'real' increase in the estimated numbers just to better detection of autism in non-white groups.

So, there you have it. An approximate 15% increase in autism estimates in 8-year olds compared with previous figures. As one news report put it: "a 150% increase since 2000." The authors of this most recent CDC report conclude by saying: "ASD is an urgent public health concern that could benefit from enhanced strategies to help identify ASD earlier; to determine possible risk factors; and to address the growing behavioral, educational, residential and occupational needs of this population." I really can't disagree with any of those sentiments.


[1] Baio J. et al. Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years — Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2014. Morbidity and Mortality Weekly Report (MMWR). 2018; 67(6): 1-23.


Effects of pregnancy vitamin D deficiency on social behaviours of offspring rats

I note the findings reported by Nathanael Yates and colleagues [1] have garnered a few lay and science media headlines recently (see here) as authors concluded that "early life levels of vitamin D are an important consideration for maternal behavioural adaptations as well as offspring neuropsychiatry." Further coverage of their findings is provided in a helpful article for The Conversation (see here), where some authors - including the autism research powerhouse that is Andrew Whitehouse - provide a little more interpretation of their findings. I might also add that Whitehouse is no stranger to the vitamin D - autism research story (see here).

So, what's all the current discussion about?

Well, vitamin D - the 'sunshine' vitamin/hormone - is front and centre of this latest research, and some investigation into "how early life vitamin D deficiency during rat pregnancy and lactation alters maternal care and influences neurodevelopment and affective, cognitive and social behaviours in male adult offspring." This is set within the context that vitamin D seems to be doing a lot more than just contributing to bone health (see here). You'll of course note the use of the word 'rat' in the above text, and in particular what happened to offspring baby rats in terms of "offspring neurodevelopmental markers, ultrasonic vocalisations and adult behavioural outcomes including social, cognitive and affective-like behaviours" when mummy rat diets are loaded up with enough vitamin D as opposed to those mummy rats who were provided with a vitamin D deficient diet. The theory behind those vitamin D loaded vs. vitamin D deficient mummy rat diets is that: "In both humans and rats, a baby developing in the womb is completely reliant on the mother’s vitamin D stores." Probably something to do with the lack of sunlight exposure in the womb(!)...

Results: there did seem to be some difference across various 'test a rat / test an offspring rat' measures as a function of vitamin D status, looking across behaviour, brain scans (yes, rats did meet some MRI equipment) and also "plasma corticosterone levels and neural expression of genes associated with language, dopamine and glucocorticoid exposure." So for example, authors describe how "males that had been exposed to vitamin D deficiency in early life exhibited decreased social behaviour, impaired learning and memory outcomes and increased grooming behaviour, but unaltered affective behaviours." It's not difficult to see the 'decreased social behaviour' links that *could* be made with a condition / label / diagnosis like autism; particularly when vitamin D has quite the peer-reviewed research history with autism in mind (see here).

Interestingly too, but not made too much of in the chatter about this study for obvious reasons, were the observations made around maternal care as a function of vitamin D status, bearing in mind that vitamin D deficiency will probably impact both mummy rat and baby rat. So: "the quality of maternal care was decreased in dams consuming a vitamin D-deficient diet." Mmm...

Whilst this is important work, and adds to our understanding that appropriate nutrition throughout the lifespan is important to various aspects of functioning, I'll reiterate that this was research using rats. Rats not humans. It is perhaps timely that at around the same time that the Yates paper was published, I also chanced upon some discussion over at Spectrum on how we all need to be a little bit careful when talking about modelling autism in various animals (see here) and their relevance to real, often much more complicated, people (see here) and their [multiple] labels (see here).

I note that in their piece for the The Conversation, authors caution that their findings don't mean everyone who is pregnant (or could become pregnant) should rush out and load up on vitamin D so as to potentially influence offspring developmental course. I would second that view; but would also direct your attention to some Government advice quite recently (at least here in Blighty) that we should perhaps all be thinking about vitamin D supplementation (see here) and the many and varied ways that this vitamin/hormone *might* impact on our physiology and beyond (see here).


[1] Yates NJ. et al. Vitamin D is crucial for maternal care and offspring social behaviour in rats. J Endocrinol. 2018 May;237(2):73-85.


Wednesday, 25 April 2018

Autistic traits in adult schizophrenia

"Results of this study indicate the existence, in a sample of patients with a diagnosis of schizophrenia, of a distinct group of subjects with ASD [autism spectrum disorder] features, characterized by specific symptomatological and cognitive profile."

So said the findings reported by Stefano Barlati and colleagues [1] continuing a research theme from this group [2] looking at the potential overlap between autism spectrum disorder and schizophrenia.

Reiterating my interest in how the autism and schizophrenia spectrums can and do collide (see here) both at a condition and trait level, the Barlati findings provide some pretty in-depth analysis of what autism *might* look like in the context of schizophrenia. They report evaluation of their cohort - "Seventy-five schizophrenia patients (20 females, mean age 42 ± 12)" - with two of the gold-standard autism assessment instruments: the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R) alongside other "clinical, neuropsychological, and psychosocial functioning measures."

It's important to say that, in these days of pluralisation of behavioural and/or psychiatric labels (see here and see here), quite a few participants (47/75) assessed as part of the Barlati study turned up "negative to all the autism scales administered." This tells us that it's not necessarily a straight-forward nor universal relationship when it comes to autism and schizophrenia (and vice-versa). More likely is the possibility that there either may be subgroups within the diagnosis of schizophrenia that present with significant autistic traits or possibly even that the timing or severity or grading of schizophrenia and its symptoms may predispose to autistic traits being more or less likely to be presented. That last point relies on the idea that various traits or characteristics of labels like schizophrenia and autism might not be as immutable as many people believe...

For however the participants diagnosed with schizophrenia who turned up clinically significant autistic traits in one or other or total domains/scores using the ADOS and ADI, further research is indicated. Further research on what this phenotype might look like longitudinally, how frequent it might manifest, and whether there may be unique challenges associated with it. It also might have some implications for intervention too (see here).

And yet again, such findings provide more fodder for the idea that autistic traits are not exclusively just part and parcel of a diagnosis of autism (see here), and the pressing need for formal, professional assessment when autism is suspected...

Oh, and then there's more...


[1] Barlati S. et al. Autistic traits in a sample of adult patients with schizophrenia: prevalence and correlates. Psychol Med. 2018 Mar 20:1-9.

[2] Barlati S. et al. Autism Spectrum Disorder and Schizophrenia: Do They Overlap? International Journal of Emergency Mental Health and Human Resilience. 2016; 18: 760-763.


Tuesday, 24 April 2018

Suicide risk in ADHD (based on a selective review)

The paper by Giancarlo Giupponi and colleagues [1] makes for pretty sombre reading in relation to the question of suicide risk in attention-deficit hyperactivity disorder (ADHD). Accepting that there were methodological differences among the various peer-reviewed studies included for [selective] review, authors' findings were along similar lines to what has previously been reported: "many studies indicate an association between ADHD and suicidal behavior."

I'm not going to say too much about the Giupponi findings on this blogging occasion, because they kinda speak for themselves. As well as covering quite a bit of research talking about suicidal behaviour in the context of child/adolescent and adult ADHD and the issue of "whether there is a direct relationship or whether the association depends on the increased prevalence of pre-existing comorbid conditions and individual and family dysfunctional factors", authors also mention the important role played by various medicines clinically indicated for ADHD as potentially being protective against suicidal behaviour(s) (see here). From a methodological perspective, I would have liked to have seen a table or something illustrating all the studies included in the Giupponi 'selective review' but oh-um...

The authors conclude by recommending that "patients with ADHD should be routinely screened for suicidal behavior, and early intervention protocols should be established in order to detect and reduce suicidal ideation and behavior and to improve the quality of life." I don't think anyone would disagree with such sentiments, added to what is already becoming known about suicidal behaviour in a more general context (see here). Given also the increasingly close proximity of ADHD to another label / conditions / diagnosis frequently discussed on this blog (see here) also including some enhanced suicide risk too (see here), I daresay that routine screening might extend much further than some might realise...


[1] Giupponi G. et al. Suicide risk in attention-deficit/hyperactivity disorder. Psychiatr Danub. 2018 Mar;30(1):2-10.


Monday, 23 April 2018

Anxiety symptoms are frequent in relation to childhood autism

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

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

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

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

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

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


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

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


Saturday, 21 April 2018

"a subset of patients with ME/CFS who have sensitivity to wheat and related cereals in the absence of coeliac disease"

The findings reported by Melanie Uhde and colleagues [1] make for some interesting conversation today, with their observation that: "there may be a subset of patients with ME/CFS [myalgic encephalomyelitis/chronic fatigue syndromewho have sensitivity to wheat and related cereals in the absence of coeliac disease, with potential relevance to some of their symptoms."

OK, first things first. Coeliac disease (CD) in case you don't know, is the archetypal 'gluten is the baddie' autoimmune condition. I don't want to dwell too much on the genetic and biological details of CD but it basically involves a certain type of genetics linked to a certain type of immune response being 'activated' and 'super-charged' by ingestion of gluten. Treatment/management is currently via a lifelong gluten-free diet (currently!) Outside of CD, there is growing recognition of a suite of other gluten-related conditions that are not quite CD but something similar. Indeed, Uhde and colleagues have been quite involved in looking at this so-called non-coeliac gluten/wheat sensitivity (see here) previously.

ME/CFS represents a diagnosis characterised by fatigue and in particular, persistent and unrelenting fatigue that does not disappear with rest. Post-exertional malaise (PEM) is also an important part of the condition too (see here). ME/CFS is a condition just starting to move out from the 'biopsychosocial' shadows (see here) with much greater recognition that this is an organic condition (set of conditions) and not something that typically appears or is perpetuated by 'having the wrong mindset' as some people have historically opined.

Uhde et al on this most recent research occasion considered "whether a subset of patients with ME/CFS may exhibit serologic markers associated with NCWS [non-coeliac wheat sensitivity], which might explain some of the corresponding symptoms." They report results based on the screening of some "131 patients with ME/CFS and 86 healthy controls" using the panel of serological markers discussed in their previous study [2]. Alongside: "Questionnaires were used to assess GI [gastrointestinal] symptoms within the past 6 months, including abdominal pain, bloating and nausea" onwards to a summed score of GI issues.

Results: using data from their previous study as a sort of control/comparison, a few notable observations were made. First: "one (0.76%) patient with ME/CFS and two (2.3%) control subjects as belonging to the coeliac disease group." Second: "20 (15.3%) patients with ME/CFS and 4 (4.6%) control subjects were categorised in the NCWS group" when taking into account their statistics aiming to categorise participants as "NCWS, coeliac disease.. [or] healthy control." Finally: "There was also a significant correlation between the calculated NCWS probability and the GI symptom severity total score in patients with ME/CFS" although I'm minded to suggest that the stats related to this finding weren't exactly 'up there' with the best.

No mind, this is interesting data and cries out for larger, more controlled studies. It potentially adds some 'serological' flesh on to the bones of at least some observations of dietary and nutritional interventions being useful for some with ME/CFS (see here) and indeed, some related protocols for intervention (see here). More than that, if it is shown that dietary intervention such as the implementation of a gluten-free diet might *treat' some ME/CFS, it provides further evidence for that all-important shift in moving ME/CFS away from more psychosomatic explanations. Whether however such dietary intervention will be funded by the State is another question...

Oh, and the focus on 'subsets of patients with ME/CFS' kinda taps into a growing realisation that ME/CFS might not be just 'one thing' in identity or severity [3]...


[1] Uhde M. et al. Markers of non-coeliac wheat sensitivity in patients with myalgic encephalomyelitis/chronic fatigue syndrome. Gut. 2018. March 17.

[2] Uhde M. et al. Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease. Gut. 2016. 65: 1930-1937.

[3] Richardson AM. et al. Weighting of orthostatic intolerance time measurements with standing difficulty score stratifies ME/CFS symptom severity and analyte detection. J Transl Med. 2018 Apr 12;16(1):97.


Friday, 20 April 2018

ALSPAC examines... pregnancy risk factors and oppositional-defiant disorder (ODD) and conduct disorder

ALSPAC mentioned in the title of this post refers to the Avon Longitudinal Study of Parent and Children, something of quite a regular feature on this blog by all accounts (see here and see here for examples). On this blogging occasion, I'm talking about ALSPAC in relation to the research paper published by I. Hyun Ruisch and colleagues [1] who reported that: "Common and potentially preventable pregnancy risk factors were independently related to both offspring ODD [oppositional-defiant disorderand CD [conduct disorder] symptomatology in children from the general population."

ODD and CD represent a couple of the most prevalent 'disruptive behavioural' conditions seen nowadays. Whilst subtly different from one and another both in scope and severity, both represent conditions where control and in particular, self-control in accordance with cultural rules and norms, is perhaps not as it should be. I've mentioned one or other of these conditions in previous posts on this blog (see here for example) and the heightened risk of future adverse outcomes seemingly associated with them.

As with many (nay, all) behavioural and psychiatric conditions, science is still at a bit of a loss as to how they come about, accepting that they all probably [variably] include genetic and non-genetic factors working differently in different people. Ruisch et al set about utilising data from ALSPAC to ascertain if and whether "a broad range of pregnancy factors" might play some [statistically significant] role. Their results are quite revealing...

So: "Higher ODD symptom scores were linked to paracetamol use... and life events stress... during pregnancy." Further: "Higher CD symptom scores were linked to maternal smoking..., life events stress... and depressive symptoms... during pregnancy."

It should be noted that ODD and CD symptoms scores were gathered via the Development and Well-Being Assessment (DAWBA) as per other ALSPAC research occasions (see here). Researchers also quizzed both mothers and teachers of their children; thus providing two potentially different snapshots of functioning and their related factors.

In relation to that sentence on "Common and potentially preventable pregnancy risk factors were independently related to both offspring ODD and CD symptomatology in children" my eye was immediately drawn to two variables reported as being connected to said diagnoses: pregnancy paracetamol use and maternal smoking; both of which have appeared with increasing regularity in relation to adverse offspring developmental outcomes.

First, paracetamol also known as acetaminophen to our cousins across the Pond and other parts of the world. What can I say? It seems to be going from bad to worse for this go-to over-the-counter medicine with regards to pregnancy use *associations* and offspring developmental factors (see here). Yes, I appreciate that more studies need to be done on the possible pregnancy effects of this medicine, but the emerging peer-reviewed science is starting to look quite consistent. And many of the studies pointing the finger at paracetamol, like ALSPAC, are not to be under-estimated in size or power...

Second, maternal tobacco smoking during pregnancy. Again, something that has been talked about before on this blog (see here) in the context of related clinical labels. We can't yet say that 'pregnancy smoking causes offspring CD' because proof of cause-and-effect are rarely established by such observational studies. But much like the paracetamol story, the data is becoming more and more consistent for a possible effect of pregnancy smoking on child development. And for various other reasons, smoking during pregnancy is generally not thought of being a great thing for the developing child.

More investigations are indicated but clues are starting to emerge.


[1] Ruisch IH. et al. Pregnancy risk factors in relation to oppositional-defiant and conduct disorder symptoms in the Avon Longitudinal Study of Parents and Children. J Psychiatr Res. 2018 Feb 23;101:63-71.


Thursday, 19 April 2018

Hans Asperger "was actively involved in the Nazi regime's euthanasia programme in Austria"

Credit: The BBC News website 19 April 2018
Many people will already have seen the headlines (see here for example) covering the paper by Herwig Czech [1] that concluded that: "The narrative of [Hans] Asperger as a principled opponent of National Socialism and a courageous defender of his patients against Nazi ‘euthanasia’ and other race hygiene measures does not hold up in the face of the historical evidence."

It makes for particularly difficult reading insofar as dispelling other highly-cited accounts of Asperger as being some sort of 'hero' - "the narrative of Asperger as an Oskar Schindler-like protector of children with autism" - who claimed "to have shielded his patients from the Nazi regime." Instead, as also acknowledged in an accompanying editorial on the Czech findings [2], the evidence uncovered seems to point to something rather more approaching: "that Asperger was not just doing his best to survive in intolerable conditions but was also complicit with his Nazi superiors in targeting society’s most vulnerable people." The main assertions seem to be around Asperger "referring children both directly and indirectly to Am Spiegelgrund", a notorious clinic that summed up the utter disdain that the Nazi regime had for the beautiful heterogeneity of life.

I don't really want to say too much more on this topic because I'm sure that discussions will go on with regards to the Czech findings and their implications. I do want to raise two points that may be pertinent however.

First, the question of 'does it matter?' that Asperger had such a past is bound to be raised. Yes, it does matter. As a previous opinion piece published just before the Czech article (see here) mentions: "To medical ethics, it does. Naming a disorder after someone is meant to credit and commend, and Asperger merited neither." That author, who also has a book coming out on this topic, went as far as suggesting that: "We should stop saying “Asperger.” It’s one way to honor the children killed in his name as well as those still labeled with it."

Second, and related to the first point, is the 'flack' that has been taken by the most recent Diagnostic and Statistical Manual (DSM) (version 5) when it dropped the term 'Asperger syndrome'. Instead, the authors of this 'diagnostic bible' chose to go down the more generic 'autism' route; something that also looks likely in the context of the ICD-11 proposals too (see here). In view of the Czech findings and bearing in mind that issue of 'medical ethics' it looks like this was a correct decision. I appreciate that this may have knock-on effects for those diagnosed and identifying as having Asperger syndrome - ""No-one with a diagnosis of Asperger syndrome should feel in any way tainted by this very troubling history," Carol Povey, director at the Centre of Autism for the UK's National Autistic Society, said in a statement to the BBC" - but with these new revelations must come some sort of change in thinking.

The Czech findings matter because lives matter. They matter because they paint a picture of a man who lived and worked in very difficult times but a man "that the Nazi authorities saw... in an increasingly positive light, including as someone willing to go along with their ideas of race hygiene."


[1] Czech H. Hans Asperger, National Socialism, and “race hygiene” in Nazi-era Vienna. Molecular Autism. 2018; 9: 29.

[2] Baron-Cohen S. et al. Did Hans Asperger actively assist the Nazi euthanasia program? Molecular Autism. 2018; 9: 28.


"adult patients with CFS report few autistic traits in the self-report instrument, the AQ"

The findings reported by Indre Bilevicute-Ljunger and colleagues [1] tap into something of a developing interest I have on this blog: whether there is 'clinical overlap' between the diagnosis of chronic fatigue syndrome (CFS) (also known as ME or myalgic encephalomyelitis) and the diagnosis of autism or autism spectrum disorder (ASD) (see here).

Just before anyone gets the wrong end of the stick here, I'm not at all insinuating that CFS/ME and autism are one and the same. They are not. As per a previous research foray into the diagnostic borderlands of CFS/ME [2] I have however long been struck by how there may be some 'shared' symptoms relevant to both labels; particularly with reference to the presence of perceptual and motor issues ("auditory hyperacuity", "problems of balance", "walking problems"). Added also to a number of anecdotal reports suggesting that a diagnosis of autism is seemingly not protective against receipt of a diagnosis of CFS/ME, and it strikes me that there could be more investigations required in this area. At the time of writing however, there is very little in the peer-reviewed research domain examining any such 'overlap'.

Bilevicute-Ljunger et al - including the notable name of Susanne Bejerot on the authorship list (see here) - set out to examine any potential 'relationship' between autism and CFS by means of assessing three participant groups with everyone's favourite 'are you autistic?' self-report measure, the Autism-Spectrum Quotient (AQ). Said groups included those diagnosed with CFS (n=59) , those diagnosed with autism (n=50) and a group headed under the rather uninformative label of 'healthy controls' (HC) (n=53). The presented results showed that those diagnosed with ASD "scored significantly higher on the AQ than the CFS group and the HC group" and that: "No differences in AQ scores were found between the CFS and HC groups." Authors therefore concluded that: "Despite clinical observations of symptom overlap between ASD and CFS, adult patients with CFS report few autistic traits in the self-report instrument, the AQ."

Sounds pretty straight-forward eh? Well, hold on just a moment...

"The choice of instrument to assess autistic traits may influence the results." That was another line included in the Bilevicute-Ljunger paper, in conjunction with the idea that the AQ may very well be 'testing for' something in the context of autism, but that doesn't mean it is without issues in terms of things like specificity for autism (see here and see here). Indeed, I'll also take you back to a recent blog post (see here) which kinda said everything that needed to be said in terms of the [general] current state of adult questionnaires and screening measures for autism [3] including the AQ: "Evidence suggests some utility of diagnostic measures in identifying autism spectrum disorder among clinic referrals, although specificity for diagnosis was relatively low." Ergo, it is not completely unlikely that scoring high on the AQ and various other instruments *might* not necessarily mean just autism is present. I'll be coming back to the issue of AQ yet again on this blog quite soon.

Without trying to sound like someone who has a bee in their bonnet about the AQ not being a particularly great 'autism-specific' measure, I would like to see some further work done looking at any overlap between symptom presentation in CFS/ME and the same with regards to autism. I'd perhaps be minded to suggest that science starts to look at CFS/ME symptoms in autism rather than the other way around first and foremost. This would provide a baseline to see how prevalent CFS/ME in diagnosis or traits might be when an autism diagnosis is in the frame, particularly extending into adulthood. It might also provide some 'clues' as to whether shared or overlapping genetics / biology / physiology could be further investigated (hint: immune functions such as autoimmunity, oxidative stress, gut microbiota, etc. might be places to look) minus the psychobabble that both conditions have had to endure over the years. I'd similarly be interested in the idea that the sex ratios are seemingly opposing when it comes to ME/CFS and autism, and what that might mean for ensuring that screening for autism or autistic traits in relation to ME/CFS takes account of the chatter about sex/gender *potentially* influencing symptoms profiles (see here) and things like the female camouflage effect (see here)...


[1] Bilevicute-Ljunger, I. et al. Patients with chronic fatigue syndrome do not score higher on the Autism-apectrum quotient than healthy controls: comparison with autism spectrum disorder. Scandinavian Journal of Psychology. 2018.  May 8.


Wednesday, 18 April 2018

"Comprehensive Nutritional and Dietary Intervention for Autism Spectrum Disorder"

It's been a while coming but the paper by Jim Adams and colleagues [1] detailing the effects of a "comprehensive nutritional and dietary intervention for autism spectrum disorder" has finally seen the peer-reviewed light of day. I say 'a while coming' because as per the entry for this research (see here), it was seemingly scheduled to start back in 2011 and be completed by 2013, I assume, without taking 5 years to write up and be published. But better late than never I suppose.

Anyhow, the nutritional and dietary intervention scheduled adopted by Adams et al was rather a complicated affair as per the study description. So: "Day 0: Vitamin/Mineral supplementation begins. Day 30: Essential Fatty Acid supplementation begins. Day 60: Epsom salt baths begin. Day 90: Carnitine Supplementation begins. Day 180: Digestive Enzyme supplementation begins. Day 210: Healthy, casein-free, gluten-free diet [HGCSF] begins." Quite a few of those individual intervention elements have been fodder for this blog before (see here and see here for examples); also reflecting other research interests from Adams and colleagues (see here). Talk about a gluten- and casein-free diet is also music to my [research] ears (see here), as is the welcome inclusion of sulfate / sulphate back into autism research proceedings (see here).

Results of that nutritional and dietary schedule are reported for a starting pool of 67 children diagnosed with an autism spectrum disorder (ASD), where 28 participants completed the 'treatment' arm and some 27 participants completed a non-treatment arm (where no new intervention(s) were reported for the 12 months of the study). Additional findings for 50 not-autism controls (I don't like the word 'neurotypical' and its rather sweeping connotations) are also reported. The study duration was a year, and the sorts of measures examined over the course of the intervention were quite comprehensive, covering both behaviour and cognition and also physiological parameters.

Results: it's always refreshing to see a study first and foremost reports any adverse effects based on the tenet 'first, do no harm'. Authors note that: "A few adverse effects were reported for some treatments" and go on to list what happened over the course of each element of the intervention. They talk for example, how: "One parent reported that implementation of the diet [healthy, gluten- and casein-free diet] in a strict manner resulted in increased aggression towards peers, inability to problem solve, and increased spinning behavior, probably due to frustration in regards to removal of favorite foods." Thankfully, most of the adverse effects noted over the study period were relatively minor and certainly not life threatening. Once again, first, do no harm.

With levels of compliance regarding the various study elements also reported as being quite high, the authors report that across the various behavioural assessments - including the CARS, SRS, VABS, and ATEC - significant effects in favour of intervention were found. Based on blinded evaluations using something called the Reynolds Intellectual Assessment Scales (RIAS), authors reported "a significant improvement in nonverbal intellectual ability in the treatment group compared to the non-treatment group." By contrast, blinded use of the gold-standard assessment instrument known as ADOS revealed "no significant change on the ADOS scores for either treatment or non-treatment group." Interestingly, when parents were asked to rate the effectiveness of each part of the intervention, results revealed that: "The highest rated treatments were the vitamin/mineral supplement and the essential fatty acids, followed by the Healthy HGCSF diets, followed by the carnitine, digestive enzymes, and Epsom salt baths."

Adams and colleagues also provide further details on "3 exceptional cases of improvement during the study, all of which occurred in the treatment group." For one participant it appears that the introduction of a carnitine supplement was associated with some quite remarkable improvements in relation to strength and energy levels in particular. The authors note that: "low carnitine seems likely to have contributed to her challenges, and carnitine supplementation seems to have helped." There could be some interesting tie-ups there with regards to previous peer-reviewed results too (see here for example). For another participant it seemed that the introduction of a HGCSF diet *correlated* with the resolution of urination problems, where a dairy-free diet removed the need for "intermittent catheterization" and resolution of associated problems. OK, these examples don't so much focus on the core issues associated with autism, but I'm pretty sure that they were factors that would have influenced quality of life.

There is quite a bit more to see in the Adams paper and I would encourage readers to take the time to read it in its entirety. Despite the fact that not every measure showed significant effects from such an intervention regime, I like the idea that authors didn't just focus on one intervention but rather, in a systematic way, looked at a whole suite of interventions focused on nutritional and dietary factors. I believe this is more 'naturalistic' in terms of what parents/caregivers tend to report. Indeed the authors themselves discuss how: "A limitation of this study is that all participants received all treatments, whereas probably only a subset are likely to benefit from any single intervention (for example, only participants with low carnitine are likely to benefit from carnitine supplementation)." Yup.


[1] Adams JB. et al. Comprehensive Nutritional and Dietary Intervention for Autism Spectrum Disorder—A Randomized, Controlled 12-Month Trial. Nutrients. 2018; 10(3): 369.


Tuesday, 17 April 2018

Low grade inflammation in acute psychiatric inpatients

I was interested to read the findings reported by Emanuele Osimo and colleagues [1] (open-access available here) recently, and their observation that: "Evidence of low-grade inflammation was present in all major diagnostic groups, with prevalences ranging from 12 to 40% depending on the measure."

'Major diagnostic groups' included in the Osimo paper, included "acutely unwell psychiatric inpatients from all major ICD-10 diagnostic groups" covering labels such as psychotic disorder, schizophrenia, mood disorders, personality disorders and organic mental disorders.

Authors - including the notable name of Golam Khandaker who has published work previously covered on this blog (see here and see here for examples) - conducted an "anonymised search of the electronic patient records" for those hospitalised in a specialist mental health department for the treatment of a mental health / psychiatric condition between 2013 and 2016. Alongside, they had to have "a blood test result for CRP [C-reactive proteinor for WBC [total white cell count] [that] had been recorded on the electronic medical notes system within 14 days of admission" yielding almost 600 participants. In effect, a blood test pertinent to the measurement of compounds reflective of immune system processes such as inflammation.

As per the opening sentences to this post, and using CRP and/or WBC as a measure of inflammation, authors identified some quite notable prevalences of low-grade inflammation in their patient group. So: "The prevalence of inflammation in the major ICD-10 diagnostic groups of psychotic disorders (F20–29), mood disorders (F30–39), neurotic disorders (F40–48) and personality disorders (F60–69) was 32%, 21%, 22% and 42%, respectively." Various other variables also seemed to be *associated* with the presence of such inflammation too. Authors note for example that: "Patients with medical comorbidities were more likely to be inflamed" alongside various other factors also potentially exerting an effect: "older age, black ethnicity, being single, self-harm, diagnoses of schizophrenia, bipolar disorder, current treatments with antidepressants, [and] benzodiazepines" were all associated with low-grade inflammation.

Such findings add to the ever-growing amount of research that suggests a role for the immune system in relation to various psychiatric / behavioural diagnoses (see here). Further, that with a little more focus on the somatic as well as the psychiatric (see here) when it comes to such conditions, potentially relevant clues may emerge pertinent to treatment options. I might finally also draw your attention to some work previously discussed on this blog dealing with the idea that inflammation *might* have the ability to affect social cognitive processing (see here). Such a finding, focused on symptoms rather than labels, could offer a few alternative directions for intervention given the widespread nature of social cognitive issues across a wide variety of psychiatric conditions.


[1] Osimo EF. et al. Prevalence and correlates of low-grade systemic inflammation in adult psychiatric inpatients: An electronic health record-based study. Psychoneuroendocrinology. 2018 Mar 1. pii: S0306-4530(17)31581-0.


Monday, 16 April 2018

Immunoadsorption and ME/CFS: observations from a small proof of concept study

Immunoadsorption refers to "an alternative blood purification technique... used to eliminate pathogenic antibodies." I'll freely admit that I don't know an awful lot about this procedure, so approach the findings reported by Carmen Scheibenbogen and colleagues [1] with a degree of naivety with regards to 'usefulness' and also important issues such as safety.

Authors report preliminary findings from their 'proof of concept' study, using immunoadsorption (IA) on a small group of adults (N=10) diagnosed with Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS / ME) who also presented with "infection-triggered disease onset, disease severity according to the Bell scale of ≤ 50 of 100, and elevated levels of ß2 antibodies." The Bell scale by the way, seems to refer to a scale developed by David Bell with scores ranging from 0 to 100 to denote fatigue symptoms, post-exertional malaise (PEM) and 'ability to work full-time'. A lower score denotes more severe symptoms. The description "elevated levels of ß2 antibodies" refers to antibodies against ß2 adrenergic receptors; receptors which are found throughout the body and are involved in various biological tasks including smooth muscle relaxation and regulating certain cardiac functions. As the authors note: "Antibodies to ß2... receptors had been reported in various other diseases including dilatative cardiomyopathy, postural tachycardia, regional pain syndrome, Alzheimer, Sjögren’s syndrome, asthma and others." The 'antibodies' bit implies that the body is failing to recognise these receptors as 'self' and instead wrongly mounts an immune response against them.

Scheibenbogen et al mention that during their other studies on ME/CFS [2] they noted "a sustained decline of pretreatment elevated ß2 antibody levels in clinical responders to rituximab treatment." The rituximab bit refers to some initially encouraging results [3] from the use of this treatment that, unfortunately, do not seem to have weathered more rigorous scientific scrutiny (see here). Authors further hypothesised that IA might be a route to "removing autoantibodies" and specifically those "elevated antibodies against β2."

Results: "Prior to IA all patients had elevated antibodies against β2, in addition 7 patients against ß1 adrenergic receptors and 6 patients against both M3 and M4 acetylcholine receptors." Autoantibodies in many of the participants included for study went beyond just those against β2.

Following quite a few cycles of IA - "IA was conducted in 5 cycles on days 1–3 and 6–7 with 2 to 2.5-fold plasma volume filtered" - authors reported that: "Levels of ß2 adrenergic antibodies were low to undetectable in 9 of 10 patients." This is kinda what would be expected following IA (bearing also in mind that: "After the 5th IA cycle all patients received 25 g IgG i.v." also known as IVIG).

Insofar as the clinical course of participants' presented symptoms, well, it was a bit of a mixed bag. So: "A rapid improvement of several symptoms was reported by 7 of these 9 patients during IA. However, none of the patients completely recovered and 5 patients had worsening of fatigue towards the end of treatment despite improvement of other symptoms." I'm happy to report that the authors did utilise the wonderful technology headed under the term actigraphy (activity monitoring) as per their assessing participants step counts "by a Vivofit activity tracker." Such objective activity monitoring is sadly lacking from many other studies on ME/CFS (see here for example). Again however, the step counts reflect an initial 'good start' for IA followed by a not-so-good finish...

"Taken together, this pilot study provides evidence that IA can effectively remove ß2 and M3/M4 autoantibodies in CFS/ME and can result in rapid moderate to marked symptom improvement." I wouldn't disagree with the authors' conclusions but would perhaps suggest that the current results as they stand don't yet provide authoritative evidence for a beneficial effect of IM in the longer term. More [controlled] study is required.


[1] Scheibenbogen C. et al. Immunoadsorption to remove ß2 adrenergic receptor antibodies in Chronic Fatigue Syndrome CFS/ME. PLoS One. 2018 Mar 15;13(3):e0193672.

[2] Loebel M. et al. Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome. Brain, Behavior, and Immunity. 2016; 52: 32-39.

[3] Fluge Ø. et al. B-Lymphocyte Depletion in Myalgic Encephalopathy/ Chronic Fatigue Syndrome. An Open-Label Phase II Study with Rituximab Maintenance Treatment. PLoS One. 2015 Jul 1;10(7):e0129898.


Saturday, 14 April 2018

Autistic traits and risk of suicidality: ALSPAC opines...

The findings reported by Iryna Culpin and colleagues [1] observing that: "Social communication impairments are an important autistic trait in relation to suicidality" return me back to a topic that features much too frequently on this blog: suicide risk and autism.

Drawing on data from the Avon Longitudinal Study of Parents and Children (ALSPAC) initiative, that continues to provide some important insights on labels like autism (see here for example), researchers sought to answer a couple of important research questions: "1. Is an autism diagnosis and/or autistic traits associated with suicidal ideation (suicidal thoughts and plans) and suicidal behaviour (self-harm with and without suicidal intent) by age 16 years? 2. Are any of the observed associations explained by depressive symptoms in early adolescence?"

The question of whether autism or autistic traits are *associated* with suicide (ideation and/or behaviour) is something that has entered the peer-reviewed research psyche quite a bit in recent times. I've talked for example, about data from 'big data' Taiwan on this topic (see here) who concluded that: "ASD [autism spectrum disorder] was an independent risk factor of attempted suicide" [2] based on the analysis of over 5000 young people diagnosed with autism and some 22, 000 not-autism controls.

The numbers included in the Culpin study were a little less impressive - "5,031 members of the UK-based birth cohort study-the Avon Longitudinal Study of Parents and Children" - but ALSPAC does have the advantages of "long-term follow-up, the availability of data on several outcomes, as well as rich data on confounders, and longitudinal design that enables to examine mediating pathways." Indeed, as well as focusing on a diagnosis of autism, Culpin et al also had some 'rich data' on the presence of "four dichotomised ASD traits (social communication, pragmatic language, repetitive behaviour, sociability)." This enabled them to both observe any findings based on a diagnosis / label of autism or ASD and also traits pertinent to a diagnosis of autism or ASD. Issues such as self-harm and/or suicidal thoughts or plans were similarly sought from participants at age 16 years based on answers to questions such as "Have you ever hurt yourself on purpose in any way (e.g., by taking an overdose of pills or by cutting yourself?)" and "On any of the occasions when you have hurt yourself on purpose, have you ever seriously wanted to kill yourself?"

Results: as per the opening sentence, authors observed that "social communication difficulties may be important in relation to suicidality." They interpret this by suggesting that their results tally with others where "social impairments and difficulties in establishing interpersonal relationships are triggers for suicidal behaviour."

But... when it came to examining the diagnosis of autism or ASD in relation to suicidality, they reported that there was: "no evidence of an association between ASD diagnosis and any of the outcomes." They caution however that the numbers of those with a diagnosis were "very low and confidence intervals wide." I also note that data on the numbers of those with a diagnosis of ASD with self-harm with or without suicidal intent are shown as 'censored' to "prevent disclosure due to small cell counts."

Finally, it's worthwhile noting another part of the Culpin study analysis looking at a role for depressive symptoms on the observations made. We are told that "data from the Short Mood and Feelings Questionnaire (SMFQ), a 13-item instrument used to evaluate core depressive symptomatology in children aged 8 to 18 years" was also analysed. Authors report on "evidence of an indirect pathway from impaired social cognition to self-harm via depressive symptoms" but such depressive symptoms only accounted for about a third of the "total estimated association between impaired social cognition and self-harm." Enough however for them to conclude that "addressing the mental health needs of children with autism" *might* offset some risk in this area. Who would argue with that?

There are issues with the Culpin study insofar as the focus on self-report over clinical diagnosis for something like depression or depressive symptoms and "limitations in establishing suicidal intent accompanying self-harm, particularly using self-reports which could be influenced by fluctuations in mood or change over time." I will, once again, reiterate that the report of no evidence of of an association between a diagnosis of autism or ASD and suicidality is also likely to be "imprecise due to small numbers."

A final question: by tackling and hopefully influencing "impairments in social communication" alongside other interventions, is it possible that the risk of suicidality in relation to autism can be reduced? I say this bearing in mind that future studies in this area might want to take a larger view of autism (see here) on the basis that a diagnosis of autism rarely exists in a diagnostic vacuum (see here). How also, issues such as depression like various other quality-of-life-draining facets that seem to be over-represented in relation to autism (see here), may very well be a lot more 'core' over 'comorbidity' (see here) at least for some.


[1] Culpin I. et al. Autistic Traits and Suicidal Thoughts, Plans and Self-Harm in Late Adolescence: Population-Based Cohort Study. J Am Acad Child Adolescent Psychiatry. 2018. March 14.

[2] Chen MH. et al. Risk of Suicide Attempts Among Adolescents and Young Adults With Autism Spectrum Disorder: A Nationwide Longitudinal Follow-Up Study. J Clin Psychiatry. 2017 Nov/Dec;78(9):e1174-e1179.