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.


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.