Saturday, 18 August 2018

Robot-mediated intervention and autism: fun but is it genersalisable?

For any Sci-Fi fan like me, mention of the word 'robot' conjures up various iconic images. Outside of the obvious, you have lovable robots like Twiki from the 1980s film/series that was Buck Rogers in the 25th Century. You also have the not-so-lovable robots like the Cylons from the original (and best) film/series that was Battlestar Galactica or even the spider robots designed (on screen) by a member of Kiss (yep, you heard me right). There are lots of examples.

These days the early dreams that robots might become an integral part of modern living have kinda come true albeit typically without the homicidal intent that their portrayal almost always seemed to imply. These days robots are our friends and helpers and are seemingly present in many areas of our modern infrastructure...

Set in this context the paper by Clare Huijnen and colleagues [1] provides a welcome analysis of the "roles, strengths and challenges of robot-mediated interventions using robot KASPAR [Kinesics and Synchronisation in Personal Assistant Robotics]  for children with autism spectrum disorder (ASD)." Authors concluded that there are some strengths to the application of robots to intervention with autism in mind, but also a few 'be careful' issues too...

Just in case you might not know, KASPAR is a social robot designed to "act as a social companion" to improve quality of life for children on the autism spectrum [2]. He/she/it is a little jarring to initially see (Leatherface sprung to mind) but works on the premise that as a robot he's 'safe and predictable' and because of that predictability, he might provide a good opportunity to help children on the spectrum learn certain skills, particularly around social interaction and communication. Noble sentiments.

Huijnen and colleagues decided to ask various care and education professionals - presumably with an interest in autism - about their views on KASPAR. Specifically: what role he/she/it might play, alongside the strengths and potential challenges around the use of such technology. The results were interesting insofar as positives like "personalisation possibilities, its playfulness... its neutral expression,... and repetitive application of actions." There's potentially lots that a robot could do that might be useful for some children, particularly children who crave predictability.

But just as interesting and important were the down-sides to such robot use, and in particular: "difficulties with generalisation or transfer and finally potential dependence on KASPAR." In other words, we're not yet living in the 'I, Robot' world where autonomous robots walk among us, and so one has to be quite careful that children aren't just being 'trained' to interact with KASPAR or similar robots rather than real people.

I've watched the emerging 'robots for autism' scene play out in the peer-reviewed science domain. I've watched various groups proudly showcase their technology and the promises that it holds. It's great to see this embracing of tech in many areas of autism research and practice but it has, I have to admit, always left me with niggling questions and doubts. Questions/doubts about whether this is just 'cosmetic' research or whether there is real potential for such technology...

I am particularly concerned that using robot-mediated intervention in the context of autism does one thing and one thing only: it 'teaches' children to interact with a robot. It provides a false reality that, whilst initially, might produce some gains for some children, does not in the longer-term prepare children for the very complicated social world. Interacting with a robot is not the same as interacting with children in a school playground or later, interacting with people in the workplace and beyond. Interacting with a robot is not the same as sitting in a job interview or interacting with the human face(s) of our very complicated social benefits systems to ensure suitable allowances are (rightfully) provided. Interacting with a robot is, well, interacting with a robot.

I'm not totally poo-pooing this work. There may yet be potential from such robot interactions that may provide transferable skills. At the moment however, we have little to no scientific data to backup the idea that robot-mediated intervention is anything more than a fun addition to the learning experience over some long-term meaningful teaching tool. Certainly, we have nothing to suggest that social interactive skills for example, are going to be significantly improved in the longer-term by sitting down and interacting with a robot.

To close, kids, don't be swayed by your robot companions...


[1] Huijnen CAGJ. et al. Roles, Strengths and Challenges of Using Robots in Interventions for Children with Autism Spectrum Disorder (ASD). J Autism Dev Disord. 2018. July 17.

[2] Huijnen CAGJ. et al.  How to Implement Robots in Interventions for Children with Autism? A Co-creation Study Involving People with Autism, Parents and Professionals. J Autism Dev Disord.  2017;47(10):3079-3096.


Friday, 17 August 2018

Even more on wandering and autism

I don't know if it's just me being more attentive but I seem to be more regularly seeing media reports of children and adults diagnosed with autism or autism spectrum disorder (ASD) wandering from their family/caregiver home or other place. Some of these media reports end happily insofar as the person being found safe and unharmed to then be reunited with their loved ones; on occasion, using some important previously learned survival skills. Other reports however, don't have such a happy ending...

The paper by Laura McLaughlin and colleagues [1] brings the topic of wandering (elopement) back into research view, observing that in their cohort of nearly 1500 parents talking about their children diagnosed with an ASD: "22.4% of the children wandered from their home or yard and 24.6% from a public place more than monthly." Such research continues a theme down the years illustrating how wandering is an important issue when it comes to autism (see here) and how for some, wandering can lead to a very, very final outcome (see here).

Researchers distributed their anonymous on-line questionnaire about various aspects related to wandering through several autism-related organisations, encouraging parents of children diagnosed with autism/ASD to respond. This wasn't your typical 'does your child wander?' questionnaire, but instead also incorporated several related items such as "the use of electronic tracking devices,... use of restraints and/or seclusion to prevent wandering at school, and receipt of guidance about wandering."

About a quarter of parents said their child wanders (and wanders quite routinely) and the effects of such behaviour seemed to be quite wide-ranging. Not only did wandering reflect a worry for many parents - "48.6% and 58.7% of parents were moderately/very worried about their child wandering from home or yard or a public place" - but almost three-quarters of parents reported that wandering concerns affected "decisions to let their child spend time with friends or family in their absence." With such sentiments being expressed, it's not difficult to see why some parents with children with autism have to announce 'why I can never die' (see here). Perhaps also surprisingly, McLaughlin et al reported that only a third of parents in their cohort "had previously received any counseling about wandering."

I still maintain that wandering represents one of the most important 'issues' linked to autism (see here). Lots more resources need to be dedicated to the hows-and-whys of such behaviour (see here) and what can be done to reduce risks all round. I also think more needs to be done to talk about wandering in the context of autism and provide parents/caregivers with the information and tools ('best available evidence') about wandering. Given also the seemingly important relationship between wandering and water safety in particular (see here), I'm minded to again vocalise the (preferential) need to teach water and swimming skills as and when a child is diagnosed...


[1] McLaughlin L. et al. Wandering by Children with Autism Spectrum Disorder: Key Clinical Factors and the Role of Schools and Pediatricians. J Dev Behav Pediatr. 2018 Jul 6.


Thursday, 16 August 2018

"aggressive behaviour is not a choice for children with autism": a legal decision with implications...

The quote heading this post - "aggressive behaviour is not a choice for children with autism" - reflects a legal ruling rather than a piece of peer-reviewed research that more typically appears on this blog. The ruling, which was reported in several media outlets (see here and see here), concerns an appeal over "a 13-year-old boy with special educational needs who had been excluded from school because of aggressive behaviour that was linked to his autism."

The details of the case concern various incidents where the boy - referred to as 'L' - struck a teaching assistant with a ruler as well as pulling her hair and punching her. As a result, the school gave L a one-and-a-half day exclusion. The exclusion was challenged on the basis that L was being denied an education as a result, in contravention of his human rights. The judge agreed and deemed the exclusion discriminatory on the basis that the presentation of such aggression was 'not a choice' but instead his "behaviour in school is a manifestation of the very condition which calls for special educational provision to be made." The National Autistic Society (NAS) here in Blighty was involved in bringing this appeal and have highlighted what it means: "all schools must make sure they have made appropriate adjustments for autistic children, or those with other disabilities, before they can resort to exclusion."

Of course this is all good news for children on the autism spectrum and their parents. It stresses that school exclusion should always be a tool of last resort as enshrined in law. It means that such 'challenging behaviours' should always be investigated as a 'sign of unmet need' and appropriate provision put in place to 'work through and manage' rather than exclude as a first reaction. This is really important and will influence many, many futures; hopefully also reversing a worrying trend (see here). It also means that schools excluding pupils or trying to exclude pupils perhaps on the basis of "their results not counting against the school" or similar sentiments, have been given notice...

But there is another side to this coin, and one that may also have equally important long-term repercussions for autism and the autism spectrum: aggression or aggressive behaviour is now inextricably *linked* to autism. And the removal of the word 'choice' from such 'tendency to physical abuse' behaviour - "through no fault of their own... akin to a spasmodic reflex" - starts to place such actions and behaviours in law in a similar position to that of various other developmental and psychiatric labels. 'Vulnerability' it seems, continues to retain it's relevance to autism (see here).

Not to carry on with casting a dark cloud over such a ruling, there is another group of people often forgotten in such cases for whom such a judgement will also likely have an important effect: teachers and teaching assistants who are often working at the 'sharp end'. Indeed, in one of the news reports on this case, there are some important points made by a union representative: "school staff members are attacked at work on a daily basis - from verbal abuse, to being spat at, kicked and punched. But they love their jobs, love the kids and want to carry on doing their best for the children. They understand these pupils can lash out and violent incidents can occur. All they ask is their school backs them up when it does happen - and takes the common sense steps needed to protect them." Such a ruling is unlikely to aid in the recruitment and retention of teaching and support staff who, just as anyone else in any other profession, also have enshrined rights at work when it comes to their health, safety and wellbeing. And without an appropriate intake of such often under-paid, under-appreciated staff, the education system, including that relevant to special educational needs, can only be put under even more stress and strain coupled to the current funding issues. A vicious cycle continues and is only likely to accelerate (see here).

Further research aplenty [1] is required on this important topic. Research on how to make school a more welcoming place for all is the primary objective and already implied. Every child deserves a decent education, and school should also be a place where happy memories are made and remembered for a lifetime. It's not an impossible task by any means; there are schools out there catering for various different needs and doing it well, if not in an 'outstanding' capacity. Good practice needs to be shared and shared widely. Minus any 'blame game' indications, such a ruling also means that some further calm and objective discussions and investigations about ways to reduce and minimise acts of physical aggression should at the same time, also be prioritised (see here and see here and see here for some possible research directions). Minus that is any psychobabble explanations, sweeping generalisations or 'one-size-fits-all' sentiments being expressed...


[1] Brede J. et al. Excluded from school: Autistic students’ experiences of school exclusion and subsequent re-integration into school. Autism. 2017. Nov 9.


Wednesday, 15 August 2018

On the question of suicide risk and chronic fatigue syndrome / myalgic encephalomyelitis continued

The paper by Andrew Devendorf and colleagues [1] brought me back to a complicated and sensitive topic previously discussed on this blog (see here) regarding the issue of suicide risk in the context of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Specifically, the Devendorf findings provide some potentially important information about the possible reasoning behind suicide risk in the context of ME/CFS: "(1) feeling trapped and (2) loss of self, loss of others, stigma and conflict."

Based on discussions with 29 people diagnosed with ME/CFS "who endorsed suicidal ideation but did not meet depression criteria" researchers, including one Leonard Jason (see here), discussed some of the hows-and-whys of such suicidal ideation. As per the 'did not meet depression criteria' sentiments of the research, this work was less about 'mental health diagnoses affecting suicide risk' and more about how thoughts, feelings and situational factors might play a role. And as per the two variables highlighted by the study - 'feeling trapped' and 'loss of self & others and the stigma and conflict' generated by this incapacitating condition(s), some clear areas for further research and clinical attention emerged.

I've covered the sensitive issue of suicide (risk, ideation, completion) quite a few times on this blog for all-manner of different reasons (see here and see here for examples). In the most part, my musings have been on research into suicide where a specific label/condition/disorder has been diagnosed, and how facets of such labels/conditions/disorders *might* at least partially, 'intrinsically' elevate the risk of suicide ideation or beyond. The Devendorf findings kinda deviate from such 'intrinsic' sentiments, insofar as examining the implications of an acquired physical disability (see here and see here) and the onward the physical (and mental) restrictions of a condition seemingly elevating the risk of suicidality. By saying all that, I'm not making any sweeping generalisations...

I don't think anyone should really be surprised by the Devendorf results. With ME/CFS you have a condition that literally steals life from people; for example, rendering previously fit and active people to sometimes being bed-bound for days and days (or even longer) at a time. Add in a 'boom-bust' pattern of symptoms (see here) and the various 'environmental' effects (to employment, finances, social life, etc) of the condition, and well, I'm often surprised how resilient people with ME/CFS are.

I noted also how the words 'stigma' and 'conflict' were also detailed in the Devendorf study, and what implications this might have for quite a few areas of current research and clinical practice in relation to ME/CFS. I'm thinking specifically about the whole 'biopsychosocial (BPS) thing' that seems to have pervaded ME/CFS thinking down the years (see here), and how psychology in particular, seems to have over-stepped it's usefulness in relation to ME/CFS. It's kind of a coincidence that as I write this post, another article including Keith Geraghty [2] on the authorship list, is published discussing how some ME/CFS patients and patient groups have been labelled as 'militant' (or similar words and phrases) on the basis of them pushing back against medical dogma as a function of their own experiences of BPS-backed 'intervention' for example (see here). Militant is one word that has been used, 'vexatious' is another (see here).

"Participants emphasized that they were not depressed, but felt trapped by the lack of treatments available." This sentence serves to reiterate that suicidality in the context of ME/CFS is perhaps not something that should necessarily be thought of as intrinsic to the condition(s). It emphasises how issues like 'hopelessness' at the state of medical knowledge about ME/CFS, about the lack of biological explanation for the condition, and the lack of intervention options (not BPS guided I might add) may play a role in thoughts and feelings related to suicidality. It also provides another rather pressing reason why less 'psychologising' and more biological science needs to be dedicated to the hows-and-whys of ME/CFS and the search for a cure...


[1] Devendorf AR. et al. Suicidal ideation in non-depressed individuals: The effects of a chronic, misunderstood illness. J Health Psychol. 2018 Jul 1:1359105318785450.


Tuesday, 14 August 2018

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

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

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

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

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

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


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


Monday, 13 August 2018

Participatory research in autism: some good ideas but who gets to participate?

I was genuinely pleased to read the article published by Sue Fletcher-Watson and colleagues [1] talking about how the incorporation of views and opinions from people with autism / autistic people can hopefully improve the relationship between autism research and clinical practice. Pleased because, as autistic voices become more prominent in many walks of life including important research agencies, so such voices can help both guide research priorities and also aid in the the important translation of research findings from dusty science books/journals to [positively] affecting real lives.

The Fletcher-Watson paper recalls the results of a "shaping autism research seminar series" held here in Blighty. We are told that the "overarching goal was to examine how autism research could become more participatory in nature" where the 'target group' aids in making research "more meaningful – that is, relevant to the community, consistent with their values, and not tokenistic in delivery." 'Nihil de nobis, sine nobis' so the [important] saying goes.

Some key themes emerged from the initiative: "Respect, Authenticity, Assumptions, Infrastructure and Empathy." All of these points serve to enhance autism research and move it away from issues like 'research solely for the benefit of researchers careers' and/or 'research for the benefit of just getting further research grants/money' which probably feature in at least some circumstances. Instead the message is about moving towards a research strategy that has tangible real life impact for those on the autism spectrum, also trying to be sensitive to the numerous wants, needs and desires. All those sweeping psychobbable explanations of autism from yesteryear really haven't served anyone well in terms of enhancing quality of life and so people want something different...

The authors accept that alongside the strengths of such an approach there are also challenges. So for example, we are told that under the category of 'authenticity' where "autism communities can shape a research agenda", one challenge is going to be that "merging perspectives of a diverse group into homogeneous outcomes can result in under-specified priority research topics." Indeed it can, and it has been talked about before in the context of consumers/producers of autism research (see here).

Whilst noble in sentiment, I have some cautions and caveats about this area; not least around the question of exactly how participatory such initiatives truly are and can be when it comes to the very heterogeneous autism spectrum and the multitude of voices to be included (see here). Are voices from the autism spectrum who for example, are critical of the concept of neurodiversity likely to be invited to participate? What about those who don't see their autism or its effects in as positive a light as others? Who are the gatekeepers deciding who is involved in "shaping autism research through meaningful participation" and what is the criteria for participating aside from a diagnosis of autism? What happens also when there are disagreements in research direction between 'professionals' and the communities they serve?

The oft-used term 'if you've met one person with autism, you've met one autistic person' always figures in my mind. It denotes that within such a heterogeneous label/diagnosis, there is huge variation in the presentation of autism and the impact that core and related symptoms have on day-to-day living, alongside lots of different views and opinions about autism and what the label means to people. And in this context, terms like 'relevant to the community' and 'consistent with their values' are difficult concepts to entertain in any universal sense because there really is no single 'autistic community' or universally shared values. Remember: if you met one person with autism... Indeed, their meaning may also likely be something slightly different to the 'under-studied' parts of the autism spectrum for example (see here), where voices seem to be currently less well heard in many different scenarios (see here).

I was also a little confused to read the word 'allies' multiple times in the Fletcher-Watson paper, denoting those who are not autistic but share the various views and opinions of those on the spectrum particularly included in the article. 'Allies' is typically a word used in the context of combat and warfare. I appreciate that there are debates/arguments on-going in the autism 'community' that sometimes look and feel like warfare. But the implication from the use of such a 'them-and-us' term, particularly in the context of a research paper, is that if you're 'for' participatory research of the specific type highlighted by the authors, you're an ally. If you're not, or if your opinion differs in terms of possible research priorities (whether you are autistic or not), then by definition, you're not an ally. This is important. Words matter, particularly in the context of 'participatory' research. I say all this also acknowledging that science should really be allegiance-free...

Without wishing to continue too much with the cautions and caveats when such inclusion efforts have noble goals, I have further points. Appreciating that some important research goals have already been published (see here) and with the rapid development of the ICF core sets for autism (see here), there are already plenty of research directions that need to be taken which prioritise people with autism / autistic people and the day-to-day challenges they face; all already including input from people on the autism spectrum. In this respect, participatory research is nothing new to autism.

Insofar as that research 'relevant to the community' (or should that be 'communities') opinion, I'd also advance the idea that 'life-saving' should perhaps represent the first tier of autism research importance to any participatory strategy, as issues such as wandering, suicide risk and early mortality (see here, see here and see here respectively) continue to remain ever-present and significantly impact on many peoples' lives - again, particularly among those who perhaps fall into that 'under-represented' categorisation of autism (see here). The alleviation of pain and suffering, whether physical (see here for one example) or otherwise (see here), should probably form the next tier of research importance. And perhaps another tier of participatory research could be devoted to giving those with autism who seemingly don't have a voice, the means to communicate their wants, needs and desires and thus enable themselves to participate further in such participatory schemes. Just my observations...

A final question I have for such participatory research is an ethical one in the context of some likes and dislikes voiced by some on the autism spectrum: if for example, by tackling such primary issues such as depression and anxiety that plague many people on the autism spectrum and often severely impact on quality of life, it actually means having to intervene on the core presentation of autism (see here and see here for other research in these areas), would such participatory research 'alliances' be brave enough to take on such an option? If for example, it mean't that something like the presence of social-communication issues showed a *connection* to the experience(s) of depression for example (see here), would such participatory research look to evidence-based strategies and possibilities to try and 'change' such core issues and behaviour? Or would the conversations just revert back to something like the tenets of the social model of disability as being the primary reason for such issues as per other examples (see here)?


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


Friday, 10 August 2018

"Risk markers for suicidality" and autism: masking or insight as a feature?

The findings reported by Sarah Cassidy and colleagues [1] continue an important research theme in relation to risk of suicide and autism (see here). The value-added bit to their research on this occasion was the observation that "there are unique factors associated with autism and autistic traits that increase risk of suicidality" and that some of these factors may be potentially modifiable.

Members of this research team have some important research history [2] when it comes to looking at suicidality and autism. This time around they report the results of an on-line survey completed by over 160 adults on the autism spectrum and a similar number of not-autistic controls. Prior to the delivery of this survey we are told that a steering group of autistic adults / adults with autism helped to target the research towards what factors might be relevant, including: "non-suicidal self-injury, mental health problems, unmet support needs, employment, satisfaction with living arrangements, self-reported autistic traits (AQ), delay in ASC [autism spectrum condition] diagnosis, and ‘camouflaging’ ASC."

"Results are consistent with previous findings that autistic adults are at significantly increased risk of suicidality compared to the general population." As worrying as that finding is, the observation that suicidality is elevated in relation to autism is nothing new. Indeed, as far back as the late 1990s, there were rumblings of 'under-reporting' of suicidality in relation to autism and related developmental disorders.

Continuing: Various psychiatric labels/conditions were identified as being present in those with autism at a greater frequency than controls. This included various 'comorbidities' previously discussed with autism in mind (see here and see here). Several of those conditions have also been identified as key risk variables when it comes to suicidality. I was also particularly drawn to the rate of personality disorder (PD) identified in this sample: 18% in females with autism compared with 3-4% in control females for example. This is interesting in light of other research explored on this blog (see here) and again, some evidence of an enhanced risk for suicide alongside such a condition. And mention of 'Myalgic encephalopathy' I assume akin to Myalgic Encephalomyelitis (ME), another mainstay topic of this blog, perhaps taps into an area that requires lots more study on the possible overlap between autism and ME/CFS (chronic fatigue syndrome) (see here). Indeed, in future posts I'll be [again] covering research on the issue of suicide in relation to ME/CFS [3] that could also be relevant to autism and ME/CFS when co-occurring, reiterating that ME/CFS is not a psychiatric or mental health diagnosis...

Onward: "These results suggest that autism diagnosis and autistic traits explain significant additional variance in suicidality beyond a range of known risk factors, and are therefore independent risk markers for suicidality." So 'autistic traits as being independent risk markers for suicidality'. This is not the first time that such peer-reviewed sentiments have been reported (see here) and probably won't be the last. The logical implications from such a finding is that a reduction in autistic traits may well impact on suicidality. This is not a sentiment that some people will find palatable, but that's the logical implication stemming from such a finding.

Finally, quite a lot has been made (on social media at least) about the issue of camouflaging (masking) and a possible connection to suicidality in relation to autism. Masking reflects the idea that some on the autism spectrum actively camouflage signs and symptoms "in order to cope in social situations." The authors report that: "Camouflaging and unmet support needs appear to be risk markers for suicidality unique to ASC [autism spectrum conditions]." I'm however slightly cautious of this at the moment when wearing my objective science hat. One has to remember that, at present, there aren't many (any?) well validated tools for objectively assessing masking in relation to autism. In this study, Cassidy and colleagues mention how: "A brief set of four questions were designed to quantify tendency to camouflage." The answers to such a small set of open questions are subject to considerable bias (particularly if the individual is active on social media and perhaps privy to all the discussions around masking on there). One also cannot discount the idea that having the fundamental ability of 'insight' to be able to mask/camouflage may itself be a risk factor for suicidality. I say this on the basis of other research talking about how a higher cognitive capacity in relation to autism seems to increase the risk of vulnerability to depression (see here) as a function of the link between depression and suicidality. Simple answers to complex questions are likely to be few and far between.

So, where next? Well, being careful not to fall into any sweeping generalisations or psychobabble explanations of suicide risk in relation to autism, it strikes me that there are a few things to think about in terms of harm reduction. Screening for something like depression and/or non-suicidal self-injury (NSSI) should be much more widespread in the context of autism. Obviously, such behaviours / diagnoses are not just 'locked in' over a lifetime, so such screening needs to be done quite regularly. I would also mention that other comorbidity seemingly over-represented when it comes to autism might also exert an important effect too (see here). Tackling 'unmet support needs' also looks to be important. I'm slightly less sure of how to go about affecting this, given that the availability of many services are seemingly at the whim of finances and resources, which continue to be in short supply in these austere times (see here). But where there's a will, there's a way. I'll also reiterate that if certain autistic traits are themselves independent risk factors for suicidality, it surely follows that moves to reduce such behaviours would impact on suicidality. Indeed, in this context, the active process of masking could be seen as a double-edged sword when it comes to suicidality and autism.

And I'm also minded to bring in some important literature where autism is talked about in the context of euthanasia and assisted suicide (see here) and what lessons could be learned from some of the accounts detailed there. It's another difficult topic to discuss but something that is becoming increasingly relevant (see here).

As always, if you need someone to talk to (or text), there are organisations available. Please use them.


[1] Cassidy S. et al. Risk markers for suicidality in autistic adults. Mol Autism. 2018 Jul 31;9:42.

[2] Cassidy S. et al. Suicidal ideation and suicide plans or attempts in adults with Asperger's syndrome attending a specialist diagnostic clinic: a clinical cohort study. Lancet Psychiatry. 2014 Jul;1(2):142-7.

[3] Devendorf AR. et al. Suicidal ideation in non-depressed individuals: The effects of a chronic, misunderstood illness. J Health Psychol. 2018 Jul 1:1359105318785450.


Thursday, 9 August 2018

On postpartum paracetamol metabolites and risk of offspring ADHD: details matter

The findings reported by Yuelong Ji and colleagues [1] provide the blogging fodder today, as once again the topic of acetaminophen (a.k.a paracetamol) use during pregnancy and offspring risk of attention deficit hyperactivity disorder (ADHD) is in the spotlight. I say 'once again' because this topic has cropped up time and time again on this blog (see here for example).

On this research occasion, the starting point was the Boston Birth Cohort (a cohort that has been mentioned before) and specifically, an analysis of "maternal plasma acetaminophen metabolites levels measured within a few days after delivery and ADHD diagnosis in the offspring" as a measure of paracetamol exposure. The metabolites in question were "unchanged acetaminophen, acetaminophen glucuronide, and 3-(N-Acetyl-l-cystein-S-yl) acetaminophen." All were measured in blood plasma using one of the gold-standard chemical analytical techniques: mass spectrometry. A diagnosis of ADHD was extracted from medical records on the basis of ICD-9 and/or ICD-10 definitions.

Results: taking into account other potential confounding variables, authors reported finding "a significant positive association between maternal blood acetaminophen metabolite levels measured within 1–3 days postpartum and ADHD diagnosis in offspring." It's perhaps however important to understand how such a finding was arrived at, bearing in mind that ADHD was not the only diagnostic fruit examined in the Ji study. So: "The main exposures analyzed in this study were maternal acetaminophen metabolite levels, which were inverse normal transformed to approximate the normal distribution." What this means is that rather than reporting the specific levels of each paracetamol metabolites across different diagnoses and a 'neurotypical group' ("Children without any diagnosis of ASD [autism spectrum disorder], ADHD, developmental delays, or intellectual disabilities were classified as neurotypical (NT)"), authors chose to covert the raw values into groupings. Groupings were based around "no detection, below median, above median of detected values." I'm not altogether sure that this is the best way to report results; certainly I would have liked to have seen the raw values for each metabolite according to group as a comparator; but that's just my research preference. Researchers mention that they did not see any association between paracetamol metabolites and any other diagnostic label, and also stressed how the association remained when other potentially confounding variables were taken into account. And when it comes to ADHD, there are a few (see here for example).

How much weight can we give these results? Well, this is probably the first time that someone has looked at actual paracetamol metabolites in mums rather than just relying on maternal or doctor records of paracetamol usage during pregnancy, and that's a good thing. Authors also mention that their study was "further strengthened by the diagnosis of ADHD by both general pediatricians and developmental specialists." Add in the prospective design of the study, and you have some potentially important evidence for a *relationship* between paracetamol use and subsequent offspring development.

But... "this study only included a one-time measurement of maternal acetaminophen metabolite levels within 1–3 days postpartum." The authors rightly acknowledge that paracetamol is pretty quickly metabolised in the body so, at best, their study really only looked at recent paracetamol use immediately during or after birth. Maybe further study of archived samples during pregnancy (at multiple points during pregnancy) would provide some further information? And comments from the authors like "women with detectable levels of acetaminophen biomarkers are likely to be more regular users" really don't have any place in a scientific paper without supporting evidence. Particularly when pain relief is going to be pretty important when it comes to the process of childbirth.

Also: "our metabolite measurement method did not include acetaminophen sulfate, which accounts for 30–44% of the total metabolites of acetaminophen under the normal dosage." I don't want to go into the nitty-gritty of paracetamol metabolism, but just going back to the research looking at sulphation (sulfation) in the context of autism (see here), it would have been useful to examine both paracetamol sulphate and paracetamol glucuronide at the same time. Certainly it would have provided a more complete picture of typical paracetamol metabolism.

Don't get me wrong, I am interested in the Ji findings and their addition to the literature on paracetamol use and offspring outcomes. This still remains an important area of investigation. I'm not however completely convinced that the evidence presented by Ji and colleagues counts as particularly strong evidence despite the important measurement of paracetamol metabolites in this context...


[1] Ji Y. et al. Maternal Biomarkers of Acetaminophen Use and Offspring Attention Deficit Hyperactivity Disorder. Brain Sci. 2018 Jul 3;8(7). pii: E127.


Wednesday, 8 August 2018

Autism prevalence in California: 1931 to 2014

Credit: Nevison et al, 2018
'Autism prevalence' is a topic of real discussion both inside and outside of autism research circles. It's not so much a debate about whether there has been an increase in the numbers of people being diagnosed with autism or autism spectrum disorder (ASD) - there has and continues to be (see here and see here) - but rather the extent of the increase and the possible reason(s) behind such an increase.

The paper published by Cynthia Nevison and colleagues [1] adds something further to the autism prevalence discussions. They focused on how much of an increase in cases of autism has been noted in one part of the United States (US) and how some notable birth years have been seemingly driving the increase.

OK, first things first, Nevison et al are no strangers to the [peer-reviewed] debates around the autism numbers (see here and see here). Their previous analyses have concluded that the increase in cases of autism in the US is NOT solely driven by changing diagnostic criteria or diagnostic switching/substitution, although these factors have probably played some role. Yes folks, there might have been a very real increase in the numbers of people being diagnosed with autism (see here).

On this most recent research occasion, Nevison and co-author Mark Blaxill are joined by a noteworthy figure in the field of autism prevalence tracking, Walter Zahorodny. Zahorodny is intricately involved in tracking autism prevalence in New Jersey (see here) and was also listed as an author on the most recent CDC stats regarding estimated autism prevalence that were quite quietly published a few months back [2]. In short, he's an expert in such matters.

Authors started with the California Department of Developmental Services (CDDS) data on autism which "provides services to eligible individuals living in California who meet the DSM diagnostic criteria for autism." In the age of the (very) wide autism spectrum, the CDDS has been pretty reserved in terms of who gets the services it offers. The term 'code 1 autism' has been used to refer to CDDS recipients eligibility, where autism or autistic disorder was typically the diagnosis listed and importantly: "individuals applying for CDDS services must demonstrate significant functional disability in 3 out of 7 life challenges, which include self-care, language, learning, mobility, self-direction, capacity for independent living and economic self-sufficiency." We are told that: "Milder subtypes such as Asperger’s syndrome and PDD-NOS [pervasive developmental disorder - not otherwise specified] have not been eligible for services unless they have another qualifying disability" (authors words not mine). With the onset of the DSM-5 description of autism, where individual diagnoses like PDD-NOS and Asperger syndrome have been 'rolled' into one definition (autism spectrum disorder), the CDDS has had to adapt and change. The years 2016 and 2017 have been particularly important for the DSM-5 change to the CDDS.

Added to their examination of the CDDS data, authors also looked at a couple of other initiatives with autism prevalence data: The Individuals with Disabilities Education Act (IDEA) and the Autism and Developmental Disabilities Monitoring (ADDM) Network. As I've already mentioned, Zahorodny has been quite 'active' in ADDM research circles for some time.

From all this [estimated] prevalence of autism data, authors set about to 'visualise' autism prevalence data extracted from the CDDS and other information sources and further examine whether "ASD is truly a constant prevalence condition" taking into account the various methods for collecting data on autism prevalence.

Credit: Nevison et al. 2018
Results: "The data are consistent across methods in showing a strong upward trend over time." The long-term trend of autism prevalence based on the CDDS data show "an apparent ~ 1000-fold increase in CDDS autism prevalence between birth year 1931, when prevalence was only ~ 0.001%, and birth year 2012, when prevalence had increased to 1.18% among 5 year-olds born in that year." Nevison et al talk about "age-resolved snapshot and constant-age tracking method[s]" as tools in their research, but the long-and-short of it is that the only way was up when it came to autism prevalence across the years. They further note: "The increase from ~ 0.001 to 1.18% in the 2012 birth cohort has occurred gradually, with a slow upward creep starting as far back as the 1940s, but with several change points along the way, around ~ 1980, ~ 1990, and ~ 2007, when the rate of growth accelerated."

I don't think there is too much more to say about the Nevison findings aside from reiterating that autism prevalence seems to have quite dramatically changed over the last 80 years or so. Insofar as those upticks in diagnoses around birth years 1980, 1990 and 2007, I'd be interested to know a little more about what factors might have been contributory to those particular years' growth or whether they are just statistical blips.

And before you say it, no, it's probably not just better awareness and the like...


[1] Nevison C. et al. California Autism Prevalence Trends from 1931 to 2014 and Comparison to National ASD Data from IDEA and ADDM. J Autism Dev Disord. 2018. July 5.

[2] 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.


Thursday, 2 August 2018

The FACE-SZ initiative: inflammation and latent Toxoplasma infection in schizophrenia

The FACE-SZ initiative mentioned in the title of this post refers to the National FondaMental Expert Center (FACE-SZ) Cohort, a French collaboration designed to further knowledge about schizophrenia (SZ). The year 2018 has already been quite a year for peer-reviewed publications stemming from this initiative (see here), previously covering some really important topics.

Today I'm discussing two papers from the FACE-SZ scheme: the first from Guillaume Fond and colleagues [1] covered the issue of latent Toxoplasma infection and schizophrenia, and the second also from Fond and colleagues [2] observed that peripheral low-grade inflammation seemed to be something over-represented when it came to "ultra resistance to treatment in schizophrenia (UTRS)." The common ground between the papers is the immune system and how 'activation' of the immune system *might* have some important connections to the presentation of schizophrenia (see here).

Toxoplasma infection is a topic that has been mentioned in the context of schizophrenia before (see here). The causative agent of such infection - Toxoplasma gondii - is most definitely one of Nature's survivors; even to the point of potentially 'making' mortal enemies 'attracted' to waste products of the other (see here). There's still some debate about the hows-and-whys of T.gondii and Toxoplasma infection in relation to schizophrenia, but the collected data is not easily ignored when it comes to an over-representation of infection in the context of schizophrenia and its symptoms (see here and see here).

The first Fond paper [1] reports data from a cohort of some 250 people diagnosed with schizophrenia and "included between 2015 and 2017 in the national FondaMental Expert Center (FACE-SZ) Cohort." Alongside looking for the presence of Toxoplasma infection - "Latent Toxoplasma infection was defined by T. gondii IgG ratio ≥0.8, equivalent to ≥10 international units" - researchers also looked for signs of peripheral inflammation as per their measurement of everyone's favourite pentraxin: highly sensitive C reactive protein (CRP). I should also mention that CRP also has quite a peer-reviewed publication history when it comes to schizophrenia (see here) albeit not always in agreement (see here).

They reported that almost three-quarters of their cohort (184/250) showed signs of latent Toxoplasma infection, equating to Toxoplasma being "almost 3 times more frequent in SZ population compared to general population in France." Not only that but such infection seemed to correlate with some important clinical measurements of schizophrenia, and "Treatments with Anti-Toxoplasmic Activity (TATA)" also correlated with lower depressive symptoms.

The second Fond paper [2] focused on 'chronic low-grade peripheral inflammation' as again, high sensitivity CRP (hs-CRP) was the analyte of choice. The focus this time around was on a sub-group classified as showing "ultra resistance to treatment in schizophrenia (UTRS)" and to see if the such inflammation was *associated* with such cases. Including a starting participant number of over 600 people all diagnosed with schizophrenia, researchers reported that about 10% fell into that UTRS grouping. Among this 10%, they reported something of important relationship between UTRS and levels of CRP as a marker of inflammation. Such a relationship also held when taking into account other, potentially influential variables: "adjustment for age, sex, current daily tobacco smoking, metabolic syndrome and antidepressant consumption." The authors opine that further studies should be directed to look at whether 'treating' such low-grade inflammation *might* have an important effect on some of the presented symptoms of schizophrenia.

Taken together, I'm hoping that readers can see the value of the FACE-SZ initiative, and what it could mean for research looking at the possible aetiology and pathology of at least some cases of schizophrenia. Yes, I appreciate that genetics and environment are going to be important to schizophrenia (as they seem to be for just about every behavioural/psychiatric label) but with that immune system 'connection' there could be lots of research opportunities including some potentially novel treatments to be examined. Once again, the immune system seems to be doing an awful lot more than just playing protector against various pathogens...

To close, and noting the mention of T.gondii in today's post, the news doesn't seem to be all that great when it comes to cat ownership...


[1] Fond G. et al. Latent toxoplasma infection in real-world schizophrenia: Results from the national FACE-SZ cohort. Schizophr Res. 2018 May 27. pii: S0920-9964(18)30265-2.

[2] Fond G. et al. Chronic low-grade peripheral inflammation is associated with ultra resistant schizophrenia. Results from the FACE-SZ cohort. Eur Arch Psychiatry Clin Neurosci. 2018 May 28


Friday, 27 July 2018

'Comprehensive metabolomics' and ME/CFS: lipid and energy production turn up again

The findings reported by Dorottya Nagy-Szakal and colleagues [1] describing the results of "biomarker discovery and topological analysis of plasma metabolomic, fecal bacterial metagenomic, and clinical data from 50 ME/CFS [myalgic encephalomyelitis/chronic fatigue syndromepatients and 50 healthy controls" provide the rather long blogging fodder today.

Just in case that opening quote sounds like gibberish, this was a study that in effect examined two quite prominent biological 'systems' alongside looking at symptom profiles of participants diagnosed with ME/CFS compared with controls. Metabolomics is a discipline that is no stranger to this blog, and is focused on the analysis of small molecule metabolities in a range of biological fluids (see here). The interface between the technology used to separate out and analyse said metabolites and the statistical analysis of the huge amounts of data generated as a result, are what make metabolomics the science that it is. 'Fecal bacterial metagenomics' also known as microbiomics (see here) refers to the science of cataloguing what bacterial species are present in poo(p) samples. Yes, bacteria have their own genomes too, and stool samples can therefore be a rather informative medium.

It's important to realise that this isn't the first time that metabolomics has been spoken in the same breath as CFS/ME (see here and see here for examples); something alluded to in the Nagy-Szakal paper. Indeed, this most recent paper adds to the authors other work in this area [2] (see here for my take) where the focus was on immune-related parameters and their *association* with CFS/ME in the context of the gut and its bacterial inhabitants. And once again, there are some eminent research names included on the authorship list as last time...

So, fifty participants diagnosed with CFS/ME were compared with 50 asymptomatic (I hate the words 'healthy control') participants, and their blood (plasma) and stool were analysed. Mass spectrometry played an important role in their metabolomic work, as over 550 compounds were initially separated out from the samples provided and identified.

Results: "Among the top plasma biomarkers differentiating ME/CFS patients from controls were decreased levels of betaine, complex lipids (lysophosphatidylcholine [LPC], phosphatidylcholine [PC]) and sphingomyelin (SM), and increased levels of triglycerides (TG), α-N-phenylacetyl-glutamine, ε-caprolactam and urobilin." I'm not going to go through all of those compounds individually as to their possible relevance but there are some important classes of compound being mentioned (i.e. lipids and triglycerides).

Authors also mention another group of compounds as also potentially being important: ceramides. You may have heard the word 'ceramide' before if you are/were a user of certain brands of shampoo in recent times (see here). Outside of any hair care role, ceramide "is a waxy lipid implicated in suppression of electron transport, insulin and leptin resistance and apoptosis." Among the many roles they play 'in' the body, there is some research literature to suggest that ceramides "may play a role in gut barrier dysfunction and increased gut permeability." Interesting (see here). And going back to the Nagy-Szakal results we are told that "patients with ME/CFS and IBS [irritable bowel syndromehave increased plasma levels of ceramide." Even more interesting.

Having mentioned the gut and gut issues in the form of IBS, it's also important to note that the authors made allowances for the presence of such gut dysfunction in their participant groups. And yes, one needs to remember that it was "based on self-reported diagnosis of IBS on the medical history form". As probably expected, the introduction of IBS (self-reported) did seem to affect the metagenomic (microbiomic) data obtained (something authors talked about in their last paper). More than that: "Chemical enrichment analysis of plasma metabolites revealed that metabolomic profiles of ME/CFS patients with IBS were distinguished from controls by levels of TG, ceramides, phosphatidylethanolmines (PE) and metabolites in the carnitine-choline pathway." Indeed also, take away the IBS bit from the ME/CFS findings and: "ME/CFS patients without IBS co-morbidity showed disturbances in PCs and carnitine-choline pathways, similar to the disturbances found in the overall ME/CFS cohort." Again, interesting.

Authors conclude that their results draw attention to a few areas already pertinent to CFS/ME, in particular, "lipid and energy metabolism." The word 'mitochondria' figures a few times in their results write-up and specifically how: "compounds in the choline-carnitine pathway were decreased in ME/CFS patients regardless of their IBS status." I've written about quite a bit of research on mitochondria and CFS/ME (see here and see here for examples) and how even if there aren't genetic reasons for mitochondrial issues (see here), this does not mean that there may not be more other issues with this system (see here).

We really need much more research in the area of metabolomics and ME/CFS. And patients really need it now, not some time later in the future...


[1] Nagy-Szakal D. et al. Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics. Sci Rep. 2018 Jul 3;8(1):10056.

[2] Nagy-Szakal D. et al. Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome. Microbiome. 2017; 5: 44.


Monday, 23 July 2018

Exposure to maternal type 1 diabetes and risk of offspring autism

"Among the 3 main types of diabetes complicating pregnancy, the risk of ASD [autism spectrum disorder] in offspring was elevated in mothers with T1D [type 1 diabetes], T2D [type 2 diabetes], and GDM [gestational diabetes mellitus] diagnosed by 26 weeks’ gestation compared with no diabetes."

So said the findings reported by Anny Xiang and colleagues [1] who undertook a look back at the records of over 400,000 children "born at 28 to 44 weeks’ gestation in Kaiser Permanente Southern California (KPSC) hospitals from January 1, 1995, through December 31, 2012." Specifically, authors were looking for a history of maternal diabetes - where diabetes refers to a state of high blood sugar levels over an extended period - as well as various potentially confounding variables as a function of a diagnosis of offspring ASD or not.

They describe how some 5800 children were diagnosed with autism over a typical follow-up period of about 7 years. Pertinent to their research question, researchers reported that relative to no exposure to maternal diabetes, various types of diabetes seemed to elevate the risk of a diagnosis of ASD. The statistics were: "the adjusted HRs [hazard ratios] for exposure to maternal diabetes were 2.36... for T1D, 1.45... for T2D, [and] 1.30... for GDM by 26 weeks’ gestation." The 'adjusted' part of those stats means that those potentially confounding variables - "birth year, maternal age at delivery, parity, education, self-reported race/ethnicity, median family household income based on residence census tract, history of comorbidity (≥1 diagnosis of heart, lung, kidney, or liver disease; cancer), and child’s sex" - were taken into consideration.

Should we be surprised by this *association*? Well, not really. On more than one occasion on this blog I've talked about how maternal diabetes seems to show 'some connection' to enhanced risk for autism in offspring (see here and see here). This work residing in a wider sphere where various conditions linked to the presentation of metabolic syndrome during pregnancy seem to show some connection to autism (see here).

Xiang et al also talk about how their T1D findings "add new information" but again, I'd be inclined to suggest that this is not the first time that T1D has cropped up with offspring autism in mind (see here). The possibility of a link with T1D does add an 'autoimmune' element to proceedings and *could* tie into other work mentioning this concept and autism (see here). Much more research in this area is indicated including that related to possible biological mechanisms.


[1] Xiang AH. et al. Maternal Type 1 Diabetes and Risk of Autism in Offspring. JAMA. 2018. June 23.


Friday, 20 July 2018

A short-term aquatic exercise intervention for (some) individuals with CFS/ME?

I have to say that I did um-and-ah about whether or not to make this blog entry on the results published by Suzanne Broadbent and colleagues [1]. In it, researchers talked about the use of "a short-term aquatic exercise programme" with a small group of women diagnosed with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

My 'in two minds' state was because the words 'exercise as intervention' and 'CFS/ME' have a rather poor history both in research and clinical terms; as proposals like 'graded exercise therapy' (GET) have the ability to invoke some rather adverse memories and reports for some/many people (see here and see here). As you can see, I did in the end decide that science should be seen and heard, even if it might be a tad uncomfortable. As hopefully you'll see, the Broadbent results might even provide some much needed focus in the area of activity and exercise with CFS/ME in mind minus any sweeping generalisations and psychobabble explanations which have typically followed such research.

Before progressing through their paper, it is worth mentioning that some of the authors on this most recent paper have some 'research form' when it comes to looking at exercise in the context of CFS/ME. Yes, there is mention of the words 'graded exercise' [2] in previous publications, but interestingly this is wrapped in the context of "immune system dysfunction in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)" and their looking at various biological aspects of exercise [3] with an immune system slant to it. This is not your regular 'de-conditioning' thinking...

Aquatic exercise was the name of the research game on this most recent occasion, and an open trial detailing various physiological and behavioural measures pre- and post-use of "an initial 20-min aquatic exercise session then two self-paced 20-min sessions per week for 4 weeks" with 11 women. As you can already see, this was not a controlled trial and there was no comparison group used; just an initial research foray looking at whether their fairly brief water-based exercise program might produce some meaningful results or not. I assume that the authors were conscious that water-based exercise has some advantages over er, not water-based activity, in relation to impact (aquatic exercise is typically termed 'low impact) and also strength-building (water resistance is much greater than air resistance). I might also add that others have been following the development of this trial with some interest (see here).

'First, do no harm' is a primary tenet in all of medicine, and on the basis of "no reports of symptom exacerbation" in their small participant cohort, the authors can tick an important item of their research checklist on this occasion. Alongside, authors detail results based on various physiological parameters: "6 min Walk Test (6MWT), perceived exertion (RPE), hand grip strength, Sit-to-Stand, Sit-Reach test, Apley's shoulder test" as well as monitoring heart rate after each session. There's even mention of "24- and 48-h post-session tiredness/pain scores" which, I assume, could be stretched to mean looking at aspects of an important symptom: post-extertional malaise (PEM). And on that basis the authors reported that many of those physiological parameters did show changes between pre- and post-intervention in relation to things like grip strength, the 6MWT and also pain ("24-h post-test tiredness and pain decreased"). Ergo, aquatic exercise was seemingly well-tolerated in their small participant group and further - more scientifically 'stronger' - investigations are perhaps indicated to substantiate this finding.

When I first tweeted about the Broadbent article, it did create some discussion (see here). I wasn't surprised by this given the nature of the trial and some of the references to other peer-reviewed research made by authors. It's not easy to put into words how much damage has been done by the widespread (universal?) advocacy of something like GET when it comes to ME/CFS. Suffice to say that for many people with CFS/ME, any study that mentions 'exercise' as an intervention is likely to be met with a degree of scepticism. Once bitten and all that. And I also note the words "raising the possibility that there could be future lawsuits from ME patients whose condition has worsened from the treatment" have recently been mentioned in relation to GET...

But I do think there is more research to be done in this area on the back of the Broadbent results. Minus hype, sweeping generalisation and again importantly without any 'psychological theory' input, further analysis of the physiological effects of exercise on those with ME/CFS is a must, particularly with something like PEM in mind. No, I'm not advocating research practices that unethically put people with CFS/ME onto exercise regimes, but rather smaller research steps starting, for example, with the greater use of actigraphy on a day-to-day basis. It's been a real point of contention that actigraphy - the (objective) study of rest and activity cycles - has not been more incorporated into CFS/ME research (see here). Particularly, when discussions about 'recovery' from ME/CFS have been prominent in many quarters (see here) seemingly without mention of objective ways and means of establishing parameters of such recovery. I'd also suggest that the authors' previous work on immune function following exercise could also be applied to further aquatic exercise research too...


[1] Broadbent S. et al. Effects of a short-term aquatic exercise intervention on symptoms and exercise capacity in individuals with chronic fatigue syndrome/myalgic encephalomyelitis: a pilot study. Eur J Appl Physiol. 2018 Jun 19.

[2] Broadbent S. & Coutts R. Intermittent and graded exercise effects on NK cell degranulation markers LAMP-1/LAMP-2 and CD8+CD38+ in chronic fatigue syndrome/myalgic encephalomyelitis. Physiol Rep. 2017 Mar;5(5). pii: e13091.

[3] Broadbent S. & Coutts R. Graded versus Intermittent Exercise Effects on Lymphocytes in Chronic Fatigue Syndrome. Med Sci Sports Exerc. 2016 Sep;48(9):1655-63.


Thursday, 19 July 2018

Probiotics for anxiety: fine if you're a (diseased) rodent, but not yet ready for mass roll-out for humans

"While probiotic administration reduces anxiety-like behavior in rodents, the current state of clinical research does not (yet) support probiotics as an efficacious treatment for anxiety."

That was the research bottom-line reported by Daniel Reis and colleagues [1] who scoured the various peer-reviewed science databases looking "to evaluate the clinical and preclinical (animal model) evidence regarding the effect of probiotic administration on anxiety."

Probiotics, in case you don't already know, describe a range of bacteria and yeasts that are touted "as having various health benefits." Most probiotics are taken orally and are thought to be acting on the multitude of wee beasties that in particular, call our gut home (gut microbiota). Anxiety represents a 'state' that manifests as various physical and psychological symptoms. I've talked a lot about anxiety on this blog in the specific context of autism (see here for example) and how absolutely disabling it can be. Mentioning anxiety in the same sentence as probiotics provides a clue that something called the 'gut-brain axis' might be important for some...

Reis et al undertook a systematic review and meta-analysis of the pertinent research literature, having previously published their intention to do so (see here). Randomised-controlled trials matching their inclusion criteria were examined up to November 2017 including both pre-clinical (animal) and clinical (human) studies. The various results were collated, examined and boiled down to a consensus on the basis of the currently available data.

Bearing in mind that the word 'probiotic' covers a lot of ground in terms of what bacteria/yeasts and what preparations are included, the results were a bit of a mixed bag. As mentioned in the opening line to this post, if you're a rodent, the chances are favourable that taking a probiotic might *reduce* anxiety-like behaviour(s). One has to be a little careful about how one defines 'animal anxiety' but compared to placebo, probiotics - specifically including Lactobacillus (L.) rhamnosus - might be something to consider. Even better if you are a 'diseased' rodent...

When it came to the research on anxiety and probiotics in humans, the current status of the research is a little more 'complicated'. So: "Combining standardized mean differences (SMDs) for the 14 included studies revealed a pooled SMD of -0.12, indicating that probiotic administration did not result in a significant reduction of anxiety." The results did not alter where dose and duration were taken into account or whether 'healthy' or 'clinical' participants were observed. Ergo, the current state of the research (up to November 2017) does not generally suggest an action for probiotics in the treatment/management of anxiety in humans.

Of course that does not mean that every study on animals and humans found the same direction (or lack) of effect. We are told that: "At the level of individual trials, 12 of the 22 included animal studies found that probiotics significantly reduced anxiety-like behavior on at least one outcome measure" and "3 of the 14 included clinical studies (encompassing 1527 individuals) found that probiotics significantly reduced symptoms of anxiety." I might also direct your attention to earlier meta-analyses that found that probiotics did seem to affect psychological symptoms in people including anxiety (see here). One therefore needs to be mindful of the limitations of such systematic reviews and meta-analyses and the sweeping generalisations that are made as a result.

But... the results, as they currently stand, suggest that more investigation and perhaps less 'hype' is required around the topic of probiotics for anxiety.

And speaking of meta-analyses over-turning other meta-analyses, I'm not sure I would describe fish oils for a healthy heart as 'nonsense' as one media report did on the basis of a new review. Particularly when other reviews not-so-long ago along similar lines, came to a slightly different opinion with regards to some groups of people...


[1] Reis DJ. et al. The anxiolytic effect of probiotics: A systematic review and meta-analysis of the clinical and preclinical literature. PLoS ONE. 2018; 13(6): e0199041.