Friday 31 May 2019

Baclofen is back: "Baclofen as an adjuvant therapy for autism"

"Our data support [the] safety and efficacy of baclofen as an adjuvant to risperidone for improvement of hyperactivity symptoms in children with ASD [autism spectrum disorder]."

So said the findings reported by Seyedeh-Mahsa Mahdavinasab and colleagues [1] talking about the use of baclofen as an add-on medicine in the context of risperidone use in relation to autism. Baclofen by the way, is typically known as "a gamma-aminobutyric acid (GABA) agonist" (binds to the GABA receptors and activates them) which accounts for its use as "a skeletal muscle relaxant" given the inhibitory function of GABA and GABA receptors.

Why the 'baclofen is back' sentiment expressed in the title of this post? Well, a few years back there was some excitement about a compound called STX209 otherwise known as arbaclofen in the context of a genetic condition manifesting autistic signs and symptoms (see here) and autism itself. Arbaclofen is an enantiomer (mirror image in a chemical sense) of baclofen, but unfortunately fell by the wayside after some less than impressive results emerged from clinical trials (see here). Arbaclofen might have been kicked into the long grass for now but baclofen it seems, is still on the autism research agenda...

Researchers report results based on a "10-week randomized-controlled study aimed at evaluating the potential of baclofen as an adjuvant therapy to enhance the effect of risperidone in children with ASD." Risperidone is an antipsychotic which is indicated for selective use with children with autism (see here) specifically to treat/manage aggressive and challenging behaviours. They reported that several outcome measures saw a change - a positive change - specifically in relation to hyperactivity behaviours which can often accompany aggression. Importantly, they also noted that during and after 10 weeks of add-on baclofen use, adverse events were reported to be at a minimum.

There is more to do in this area before any sweeping generalisations are made. I personally would like to see more data on potential best- and non-responders in the context that GABA is still a topic of interest to autism research (see here). I know also that some people might be a little put-out by the idea that more medication is added to the lives of young children with autism and worries about how this might impact them in later years. We need a lot more data.


[1] Mahdavinasab SM. et al. Baclofen as an adjuvant therapy for autism: a randomized, double-blind, placebo-controlled trial. Eur Child Adolesc Psychiatry. 2019 Apr 12.


Thursday 30 May 2019

What's potentially behind self-injury coincidental to autism?

"Alexithymia, depression, anxiety and sensory differences may place some autistic individuals at especial risk of self-injury."

Those were some of the conclusions reached in the paper published by Rachel Moseley and colleagues [1] (open-access) following their investigation of an important topic - non-suicidal self-injury (NSSI) - in relation to autism "without intellectual disability." Self-injurious behaviour (SIB) is not a pleasant topic to talk about, but is important to quite a few people diagnosed as being on the autism spectrum (see here and see here).

Drawing on data provided by over one hundred adults with autism (autistic adults if you prefer), half of whom were categorised as 'current self-harmers', a quarter of whom were 'historic self-harmers' and a quarter of whom were 'non self-harmers', researchers set to work "to examine alexithymia, mentalising impairments, autistic traits and sensory differences" as possible important variables for NSSI. Alexithymia by the way, is described as "the subclinical inability to identify and describe emotions in the self." Researchers utilised several different questionnaires including a tool specifically designed to test for NSSI: The Non-Suicidal Self-Injury Assessment Tool (NSSI-AT), a "comprehensive instrument [that] documents the nature and bodily location of any self-injurious behaviours; their functional utility; their recency, frequency and likelihood of reoccurrence; the age of onset of self-injury; the severity of injuries" among other things. Results were collated and analysed.

Alongside the headline finding that was included in the opening sentence to this post, other interesting details also emerged from the data. So: "Of the 76 current and historic self-harmers, 60 could recall the onset of self-injury at an average age of 15.1 years." Bearing in mind that 15.1 years was an average age of onset, such a finding potentially provides a developmental window when self-harming could maybe be screened for and interventions put in place. Indeed, from what I understand, this is a fairly typical time of onset for self-injury in the general population minus any sweeping generalisations.

Also: "The most common function of NSSI was the regulation of low-energy affective states (depression, dissociation), followed by the regulation of high-energy states such as anger and anxiety." There's an important word in that last sentence - regulation - that needs a lot more inquiry. It implies that self-injury is not just mindless violence against self but might actually serve some sort of purpose. Indeed, other recent papers have also mentioned regulation in the context of self-injury [2] too. Allied to other research suggesting that 'challenging behvaiours' might for example, under some circumstances, also serve a purpose (see here) and how self-injury could present in a variety of ways (see here), and there are leads to follow. Indeed, it could imply that teaching regulatory processes such as those linked to exercise (see here) or the use of meditative techniques (see here) could be worthwhile for some at least.

And just before I leave this topic, I'm minded to bring in another issue that could be investigated in the context of self-injury: interoception and body awareness in the context of autism (see here). Minus any psychobabble, interoception represents "the sense of the physiological condition of the body." It strikes me as possible that a reduced capacity for interoception in relation to autism, as has been talked about in other independent study [3], could be another important variable in the cycle of self-injury and another point of intervention...


[1] Moseley RL. et al. A ‘choice’, an ‘addiction’, a way ‘out of the lost’: exploring self-injury in autistic people without intellectual disability. Molecular Autism. 2019; 10: 18.

[2] Weiner L. et al. A case study of suicidality presenting as a restricted interest in autism spectrum disorder. BMC Psychiatry. 2019; 19: 126.

[3] Fiene L. & Brownlow C. Investigating interoception and body awareness in adults with and without autism spectrum disorder. Autism Res. 2015 Dec;8(6):709-16.


Wednesday 29 May 2019

Probiotics for autism systematically reviewed

"Our review includes two randomized controlled trials, which showed improvement of ASD [autism spectrum disorder] behaviors, and three open trials, all which exhibited a trend of improvement."

So said the findings reported by Jun Liu and colleagues [1] and the results of their "updated systematic review" on the topic of probiotic 'therapy' in the context of behaviour and gastrointestinal (GI) functioning in autism.

The current scientific outlook for probiotic use in the context of autism looked to be pretty good on the basis of the Liu findings. They corroborate quite a few individual study results that have been fodder for this blog (see here and see here) and fit in well with an emerging pattern of research suggesting that the trillions of wee beasties that inhabit the gastrointestinal (GI) tract might be doing a lot more than just helping us digest food (see here and see here).

What else is required? Well Liu et al talk about more "rigorous trials" to answer questions like who on the autism spectrum might be a best responder to this type of intervention and what bacterial species might be most important. I'd also like to see a little more research on the hows-and-whys of such intervention (see here for example) and whether probiotics are as harmless as many have made them out to be.



[1] Liu J. et al. Probiotic Therapy for Treating Behavioral and Gastrointestinal Symptoms in Autism Spectrum Disorder: A Systematic Review of Clinical Trials. Curr Med Sci. 2019 Apr;39(2):173-184.


Tuesday 28 May 2019

Breastfeeding and autism continued

"We found that the percentage of mothers who started breastfeeding was similar between the two groups, but mothers of children with ASD [autism spectrum disorder] breastfed for a shorter amount of time compared to mothers of children without ASD."

So said the findings reported by Gnakub Soke and colleagues [1] continuing a research theme that I've had some professional interest in down the years (see here) on whether breastfeeding (use, duration, etc) *might* have some important *links* to risk of offspring autism and/or related conditions (see here). The same caveats mention in some of my other musings on this topic come into effect when talking (briefly) about the Soke findings (i.e. no-one is saying that a lack of breastfeeding 'causes' autism). That being said, there might still however be some important science to do on how breastfeeding and/or the constituents of breast milk might have some important biological effects for the developing child (minus any psychobabble explanations).

The Study to Explore Early Development or SEED was the starting point for the Soke study (continuing an autism research theme), and specifically investigation into the: "associations between ASD and breastfeeding initiation (yes/no) and duration (months categorized in tertiles)." The findings suggested that (a) breastfeeding rates (initiation rates) were high in mums of children with ASD compared to not-autism controls (85% vs. 90%), and (b) "mothers of children with ASD were less likely to report duration of breastfeeding in the high (≥12 months) versus low tertile (<6 months)... or the middle (6-<12 months) versus low tertile."

I don't want to dwell too much on the whys-and-wherefores of the Soke findings but there are some important questions that need answering. Not least the question of why breastfeeding seems to end quicker for those mums of children who were subsequently diagnosed as having an ASD. Were these infants more difficult to feed (something which Kanner might have picked up on in his seminal paper describing autism)? What role does the presentation of the 'broader autism phenotype' (BAP) in mothers mentioned by Soke et al play in such findings? That last point in particular, draws on the need for lots more research into the experience of pregnancy and motherhood with the BAP (see here) and/or autism in mind (see here).


[1] Soke GN. et al. Association Between Breastfeeding Initiation and Duration and Autism Spectrum Disorder in Preschool Children Enrolled in the Study to Explore Early Development. Autism Res. 2019 Mar 9.


Monday 27 May 2019

A gluten-free diet for "schizophrenia positive for antigliadin antibodies (AGA IgG)"

Short post alert...

"This feasibility study suggests that removal of gluten from the diet is associated with improvement in psychiatric and gastrointestinal symptoms in people with schizophrenia or schizoaffective disorder."

So said the findings reported by Deanna Kelly and colleagues [1] as the conference abstract [2] of their study finally hits the peer-reviewed science literature (see here).

As per my previous musings on this study, this was the "first double-blind clinical trial of gluten-free versus gluten-containing diets in a subset of patients with schizophrenia who were positive for AGA [anti-gliadin antibodies] IgG." Results were interesting insofar as "participants on the gluten-free diet showed improvement on the Clinical Global Impressions scale... and in negative symptoms." Net result: encouraging findings with the need for more study; also with a nice focus on effect sizes too...

'Nuff said.


[1] Kelly DL. et al. Randomized controlled trial of a gluten-free diet in patients with schizophrenia positive for antigliadin antibodies (AGA IgG): a pilot feasibility study. J Psychiatry Neurosci. 2019 Mar 27;44(3):1-9.

[2] Kelly D. et al. Randomized double-blind feasibility study of a gluten-free diet in people with schizophrenia and elevated antigliadin antibodies (AGA IgG). Schizophrenia Bulletin. 2018; 44: S190.


Saturday 25 May 2019

"There is broad parent interest in a genetic/epigenetic test for ASD"

The quote heading this post - "There is broad parent interest in a genetic/epigenetic test for ASD [autism spectrum disorder]" - comes from the findings reported by Kayla Wagner and colleagues [1]. As per the observation that most parents of those diagnosed with an ASD, or developmental delay (DD) or asymptomatic controls "had positive perceptions toward genetic/epigenetic research in ASD", far from being the 'danger' that it is sometimes portrayed as, the science of genetics seems to have an important standing among many parents.

The Wagner results came about as a result of this research group publishing studies "that demonstrate the utility of RNA sequencing technology (non-coding RNA) to identify children with ASD." They did what few genetic studies have done: asked parents participating in their studies whether what they were doing/finding was of interest to them. This was achieved via the use of a questionnaire which included six themes: "(1) reasons for participating in the epigenetic study; (2) prior knowledge of genetics/epigenetics, and the source of this information; (3) overall interest in genetic/epigenetic testing for ASD; (4) concerns about genetic/epigenetic testing for ASD; (5) preferences about the approach for genetic/epigenetic testing (including age of administration and biofluid of choice); and (6) extent of results to be returned." You'll probably have noted that alongside their use of the term 'genetics' they also talk about a still up-and-coming branch of genetics called epigenetics. I've talked about epigenetics and autism before on this blog (see here and see here) but the description Wager et al use just about says it all: "changes in gene expression, where the changes are not due to modification of the actual DNA sequence, but instead result from modifications that regulate DNA structure and expression." Gene expression seems to be particularly important to the science of epigenetics as per the notion that we don't all walk around with all our genes permanently switched to the 'on' or 'off' position.

Results: quite a few important points emerged from the obtained data. Most parents understood at least a little bit about genetics and some of the processes involved. Epigenetics wasn't as well known about or understood (something which is probably not so surprising). Other points also emerged: "There were no parents (0%, 0/244) concerned about a lack of scientific evidence supporting genetic and epigenetics." But that's not to say that some parents weren't concerned about the implications of genetics and epigenetics, as mention about issues like privacy and insurance status were raised during the Wagner study.

Also: "Nearly all parents (96%, 235/244) indicated that if there were genetic testing for ASD, they were interested in learning results about their child’s risk for ASD." And when it came to results, over three-quarters of all parents expressed a preference for "all epigenetic/genetic results, regardless of whether they were implicated in health and disease" and not just an overview or interpretation of any results. People want data not overviews.

And then to some important but potentially controversial findings: "The majority of parents (71%, 164/231) desired results of a genetic/epigenetic test for ASD when their child was 12 months of age or younger. Over half of parents were interested in receiving results at conception (34%, 78/231) or at birth (37%, 86/231), while fewer requested results at 12 months (17%, 40/231) or at 2 years of age (12%, 27/231)." You can perhaps see where this might be going - particularly 'receiving results at conception' - even if the authors seem to have chosen not to pursue it any further in their discussions.

I'm no bioethicist and so am nowhere near qualified to talk about the ins-and-outs of genetic testing in the context of autism and what implications this could have. I note other commentators have approached this subject previously based on some of the peer-reviewed science in this area (see here) and various points have been raised. One of the important things to bear in mind is that, as it currently stands, there is no single genetic test for all autism. Indeed, allied to the idea that the concept of 'a universal autism gene' is fast becoming a distant memory, genetic studies are serving to further highlight how complex autism actually is.

But there is always the possibility that some day someone will potentially deliver a genetic/epigenetic 'test for some autism'. The question then is how will it be used? What checks and balances will be in place to ensure that it is not misused?


[1] Wagner KE. et al. Parent Perspectives Towards Genetic and Epigenetic Testing for Autism Spectrum Disorder. Journal of Autism & Developmental Disorders. 2019. March 22.


Friday 24 May 2019

"The current study provides the first analysis of potential transgenerational impacts of glyphosate in mammals"

'Carefully' is a word that applies to any science in terms of 'meaning' and 'generalisation'. Don't get me wrong, I'm a big fan of science and scientific evidence when it comes to life, the universe and everything. But I also understand that science can be used/manipulated in many, many different ways, and rarely, if at all, do we see something that could be considered perfect science. Hence my use of the word 'carefully' in opening this blog post. With all that in mind, I bring the findings reported by Deepika Kubsad and colleagues [1] to the blogging table and the proposal that: "glyphosate can induce the transgenerational inheritance of disease and germline (e.g. sperm) epimutations."

Why am I talking about such a study on a blog primarily hosting autism research? Well, a few reasons (see here and see here), predominantly based around the observations that (a) herbicides and insecticides whilst very useful, are not seemingly without a risk-benefit profile, and (b) autism (and other related labels) have been 'talked about' in the context of risk and 'exposure' to such compounds. I emphasised the words 'talked about' to ensure that the current peer-reviewed science base is not contorted into something that it is currently not (i.e. cause-and-effect). I might also add that 'transgenerational inheritance' is something that has also been discussed in the peer-reviewed science literature in the context of autism too (see here).

The basics of the Kubsad paper: "There are an increasing number of conflicting reports regarding the direct exposure toxicity (risk) of glyphosate, but no rigorous investigations on the generational actions." So, using a rodent (rat) model of study, researchers exposed mummy rats (F0 'gestating female') to glyphosate - "daily intraperitoneal injections of glyphosate" - at doses that probably would be considered 'excessive', and then followed successive generations of rats (F1, F2, F3) looking for any "transgenerational pathologies observed... including prostate disease, obesity, kidney disease, ovarian disease, and parturition (birth) abnormalities." They also included a set of control animals - "F0 generation gestating females administered vehicle control dimethyl sulfoxide (DMSO) or phosphate buffered saline (PBS)" - and whilst they were at it, checked for any germline transmission issues/differences via the inspection of sperm; specifically looking for differential DNA methylation regions (DMRs). Those DMRs are important when it comes to whether specific genes are expressing or not ('switched on' or 'off').

Results: with that word 'carefully' in mind, we are told that there were: "negligible impacts of glyphosate on the directly exposed F0 generation, or F1 generation offspring pathology." That's important because it suggests that those directly exposed and their immediate offspring don't seemingly show adverse effects.

But... "In contrast, the F2 generation grand-offspring, derived from a direct exposure F1 generation germline, had significant increases in testis disease, kidney disease, obesity, and multiple diseases in males" and: "The F2 generation females had significant increases in ovary disease, obesity, mammary gland tumors, parturition abnormalities, and multiple disease susceptibility." Researchers also reported seeing a few things in their F3 generation too, as the words "generational toxicology" entered discussions.

As to the DMRs results, well, there were some interesting findings there too: "the glyphosate lineage sperm were found to have altered DNA methylation in direct exposure F1 and F2 generations, as well as the transgenerational F3 generation." This led Kubsad et al to conclude that glyphosate exposure could "promote germline epigenetic alterations in DNA methylation" but more needs to be done on what this actually means for gene expression and whether it tied into the disease risk(s) noted in their exposed cohort and subsequent generations.

The authors mention how their study had limitations including the use of "an environmentally relevant exposure of twice the allowed industry exposure" and the use of an animal model (bearing in mind the logical fallacies that can follow). Lots more investigation is indicated before any big headlines are generated.

But... the Kubsad results are not to brushed under the scientific carpet. They add to the range of other compounds that seemingly carry transgenerational biological correlates and imply further inspection of glyphosate in that same potential category. Whether also there may be additive or interactive effects with other compounds could also be part of the research agenda.


[1] Kubsad D. et al. Assessment of Glyphosate Induced Epigenetic Transgenerational Inheritance of Pathologies and Sperm Epimutations: Generational Toxicology. Scientific Reports. 2019; 9: 6372.


Thursday 23 May 2019

The positive effects of 12 weeks of probiotics and vitamin D in chronic schizophrenia?

The findings reported by Amir Ghaderi and colleagues [1] (open-access) provide the blogging fodder today, and the results of a study looking at a "novel combination of vitamin D and probiotic on metabolic and clinical symptoms in chronic schizophrenia." Said probiotic formulation contained "Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus reuteri, and Lactobacillus fermentum (each 2 × 109)" and was delivered over a period of 12 weeks alongside a vitamin D supplement - "50,000 IU vitamin D3 every 2 weeks" - utilising a "randomized, double-blind, placebo-controlled trial" design. We are also told that the trial protocol was "retrospectively registered."

The Ghaderi study wasn't solely focused on what their combined intervention might do for the 'clinical symptoms' of schizophrenia despite this being a prominent part of the results obtained. They also wanted to examine things like "biomarkers of oxidative stress and cardiometabolic risk in chronic schizophrenia." This was done via the measurement of marker compounds pertinent to establishing total antioxidant capacity, total glutathione levels and high-sensitivity C-reactive protein (hs-CRP) among other things.

Results: first things first, vitamin D supplementation raised vitamin D levels in those who received the vitamin D + probiotic supplement. Not exactly an unexpected result I grant you, but important from the point of view that any subsequent findings *could* be linked to those increasing vitamin D levels. Further: "Vitamin D and probiotic co-supplementation was associated with a significant improvement in the general... and total PANSS scores." PANSS stands for the Positive and Negative Syndrome Scale and has some important uses in the context of schizophrenia, and the presentation of positive and negative symptoms. That all being said, the authors also mention how their supplementation combination did not seemingly affect scores on another measure included in the study - the Brief Psychiatric Rating Scale (BPRS) - which kinda demonstrates that vitamin D + probiotics is not a panacea for every aspect of schizophrenia.

Researchers also report on how their combined supplement also *correlated* with a some changes in those oxidative stress and cardiometabolic risk measures included for study in line with other study results (see here). There's quite a bit of data so I won't provide details. Suffice to say that some of them might be 'positively' important to those health inequalities that seem to follow a diagnosis of schizophrenia (see here).

What else? Well, I can't seem to find too much in the way of side-effects details in the Ghaderi paper so I'm assuming that it wasn't a significant issue. The fact that participants in the study were "being hospitalized during the intervention" means that they were, I assume, being monitored with greater assiduity than for example if they were in the community, including looking for potential side-effects.

And with that, and the requirement for further study (see here and see here), I say no more...


[1] Ghaderi A. et al. Clinical and metabolic response to vitamin D plus probiotic in schizophrenia patients. BMC Psychiatry. 2019; 19:77.


Wednesday 22 May 2019

Childhood "neuropsychiatric morbidity" and prenatal exposure to pre-eclampsia (but not autism)

"Offspring exposed prenatally to preeclampsia have a significantly higher risk of developing a neuropsychiatric morbidity during childhood."

So said the findings reported by Kira Nahum Sacks and colleagues [1] following their analysis of a whopping "253,808 singletons... that were born between 1991 and 2014 in a single regional tertiary medical center" in Israel. Such work follows a research theme from this authorship group (see here).

Pre-eclampsia is no stranger to this blog (see here for example). It's a condition appearing during pregnancy that is characterised by "the onset of high blood pressure and often a significant amount of protein in the urine." Although most cases of pre-eclampsia are mild and some signs and symptoms treatable (see here), there are risks attached to the condition; one of the most notable being the possibility of eclampsia characterised by the onset of seizures to the mother. As you might imagine, such seizures present a risk to both mother and unborn child.

Nahum Sacks et al set out to "assess whether prenatal exposure to preeclampsia increases the risk of long-term neuropsychiatric morbidity" on the basis of "contradicting findings in the current literature." Including use of their large participant cohort, researchers took into account various other, potentially confounding factors, to look at what *might* happen in the longer term to those children who were exposed to pre-eclampsia during the nine months that made them. We are told that: "3.0% were born to mothers diagnosed with mild preeclampsia (n = 7660), 0.9% with severe preeclampsia (n = 2366) and 0.03% with eclampsia (n = 81)."

Results: it was a bit of a mixed bag of results if I'm honest. Researchers mention for example, how pre-eclampsia exposure was significantly associated with offspring obstructive sleep apnoea (OSA) and epilepsy. At least one of those outcomes - epilepsy - has previously been talked about in the peer-reviewed literature [2] as being associated with prenatal exposure to pre-eclampsia and eclampsia.

But then also there was something a little bit different in the Nahum Sacks paper: "Preeclampsia exposure [was] not associated with autism or eating disorders in offspring." This is intriguing in light of some fairly strong (and meta-analysed) links previously discussed between pre-eclampsia and autism (see here). The Dachew paper [3] that was previous fodder for this blog did caution that their meta-analysis on the topic of autism and pre-eclampsia saw evidence that many studies "did not consistently adjust for important confounding factors such as maternal obesity, parity, gestational diabetes and infection during pregnancy" and what this might mean for their overall findings. Indeed, it's a big issue for research looking at pregnancy factors as affecting offspring risk of this, that and t'other: various adverse pregnancy conditions tend to 'clump together'. This makes it all the more difficult to tie any one single factor down to any one specific risk (see here).

The Nahum Sacks findings are not to be taken lightly. The large participant group included for study add weight to the their findings. Yes, it was another observational study, and yes, there could be a 1001 other variables not controlled for that may influence the appearance of offspring neuropsychiatric morbidity. But the possibility of a link between exposure to pre-eclampsia in-utero and something like the appearance of epilepsy is something that could be worthy of a lot more study...


[1] Nahum Sacks K. et al. Long-term neuropsychiatric morbidity in children exposed prenatally to preeclampsia. Early Hum Dev. 2019 Jan 31;130:96-100.

[2] Wu CS. et al. Preeclampsia and risk for epilepsy in offspring. Pediatrics. 2008 Nov;122(5):1072-8.

[3] Dachew BA. et al. Pre-eclampsia and the risk of autism-spectrum disorder in offspring: meta-analysis. Br J Psychiatry. 2018 Mar;212(3):142-147.


Tuesday 21 May 2019

"Depression, dysthymia and symptoms of anxiety and post-traumatic stress are associated with extremist sympathies"

It's a particularly poignant time to be writing this post about the findings reported by Kamaldeep Bhui and colleagues [1] on the day that news broke about events in New Zealand (see here). An all-too-familiar story of hate leading to bloodshed helped along by access to weapons; communities are left scared, confused and broken following such acts of depravity.

Although snippets of information about the events leading to the New Zealand murders are still at the time of writing coming to light, the incident is being treated as a terrorist attack. News agencies have converged on the suspect; the life behind such crimes and any possible motives. Discussions will eventually lead to inevitable questions about what motivates someone to kill innocent people under such circumstances and on such a horrific scale, and could such an act have been foreseen and potentially avoided.

The Bhui findings hopefully represent a part of that inquiry as per their focus on trying to "better understand the drivers of radicalisation and extremist attitudes more generally, and the links with symptoms of psychological and mental illnesses." I say the Bhui findings might help, but also reiterate that at the time of writing, we don't know for example, whether 'psychological and mental illness' was part-and-parcel of the motivation for the New Zealand attacks.

The basics: a study based here in Blighty, researchers recruited over 600 adults (18-45 years of age) and asked various questions and for various bits of information. They asked for information about psychiatric variables such as depression (depressive symptoms), dysthymia "(i.e. persistent mild depression, or depressive personality)", personality disorder symptoms and symptoms related to post-traumatic stress disorder (PTSD). We're also told that: "Autism symptoms were measured by using a total score on the Autism Spectrum Quotient (AQ-10), which is reported as having high discriminant validity for those with and without a clinical diagnosis." I'll come back to that sentence shortly. Alongside, participants completed something called the "'SyfoR': Sympathies for Radicalisation" tool. As the name suggests, the instrument is used to gauge sympathies to "(a) committing minor crime, (b) committing violence… in political protests, (c) organising radical terrorist groups, (d) threatening to commit terrorist actions, (e) committing terrorist actions… as a form of political protest, (f) using bombs and (g) using suicide bombs to fight against injustices." Respondents are categorised as sympathisers, condemners or neutral. It appears that Bhui has played an integral part in developing the SyfoR tool.

Results: bearing in mind this was a study of extremist beliefs, not extremist actions, and mental health, researchers observed that: "SVPT [sympathies for violent protest and terrorism] were more common in those with major depression with dysthymia..., symptoms of anxiety... or post-traumatic stress." Perhaps just as important, we are told that: "Autism and personality disorder scores were not associated with SVPT" which kinda ties in with a judgement recently (see here). I say that bearing in mind that the AQ might be picking up quite a bit more than just a possible 'clinical diagnosis' of autism (see here) and reference to the growing research literature on how vulnerability is something to consider when autism is mentioned in several contexts (see here and see here). What else? Well, age played a factor (younger people were more likely to display SVPT) and SVPT was more commonly noted in those who drank, smoked and reported having a previous criminal conviction. Also of important note was the finding that: "SVPT were shown by 15.1% of the White British and 8.1% of the Pakistani groups" taking into account that half of participants were White British and half were of Pakistani heritage.

I don't want to get too carried away with sweeping generalisations stemming from the Bhui results but one can't help but wonder about the potential implications. As the authors opine: "in the absence of links with extremist groups or histories of extremist offending, the presence of mental illnesses may add risk" when it comes to SVPT. Onward: "A more general approach to improving population mental health alongside prevention in specific populations such as those experiencing post-traumatic symptoms and younger people may be helpful." I say all that being very careful not to stigmatise any individual or any group of people.

But there are concerns too. Concerns that for example, with the data suggesting that more and more young people are suffering with mental ill-health (see here) so this *might* potentially tie into some of the Bhui conclusions minus any sweeping generalisations...


[1] Bhui K. et al. Extremism and common mental illness: cross-sectional community survey of White British and Pakistani men and women living in England. Br J Psychiatry. 2019 Mar 15:1-8.


Monday 20 May 2019

"In the milder forms I think it's just a personality variant." Temple Grandin on autism

I draw your attention today to the transcript of an interview (see here) between a Scottish broadcaster, Rona Dougall, and Dr/Prof.Temple Grandin, following Prof. Grandin's recent appearance (Spring 2019) at a conference in Scotland.

The transcript provides readers with quite a lot of insight into Prof. Grandin's views about autism; both from a personal perspective of being diagnosed with autism (and perhaps being one of the most well-known autistic people) and also with reference to some wider discussions about autism.

Alongside the important message that Grandin wants to "see people that learn differently, people that might be labelled with autism getting good jobs" one particular part of the interview stuck out for me: "Rona: How do you define and diagnose autism? Temple: In the milder forms I think it's just a personality variant. In the more severe forms, where the individual remains nonverbal, that is definitely a disability."

I was interested in the notion that 'milder forms' of autism were seen as akin to "a personality variant" by Grandin, whilst more 'severe forms' were labelled "definitely a disability." Interested because, there are some on-going debates in various circles about (a) how one should 'classify' autism from the point of view of how much of an impact symptoms have on daily living, and (b) how the presentation of autistic traits are not solely confined to a diagnosis of autism or autism spectrum disorder (ASD).

On the first point about 'classifying' autism, there is, as I say, debate about how symptoms can variably present and how best to describe the 'differences' between someone diagnosed as being on the autism spectrum who for example, is verbal, is able to navigate the social world to some degree, hold down a job and perhaps raise a family, compared with someone who has no (verbal) language, requires a high level of daily living support and who is likely to need lifelong assistance and support for sometimes simple tasks. Such heterogeneity has been present for many years under the diagnostic label of autism; further compounded by the recent-ish disappearance of Asperger syndrome in current and planned diagnostic texts (see here and see here).

The commonly used terms 'high-functioning' and 'low-functioning' don't seemingly provide the necessary words to differentiate 'levels of autism'; also being perhaps a little demeaning to those they are meant to represent. Outside of the negative connotations of 'low-functioning', one can perhaps see how 'high-functioning' as a term for 'can function' does not always convey the real-life message when it comes to the presentation of autism. I'm thinking specifically about the issue of suicidality and autism for example (see here) and the shocking statistics that continue to emerge. Likewise, to talk about autism in the context of 'severity' comes up against similar obstacles. 'Severe autism' could potentially describe anyone on the autism spectrum during moments of 'meltdown' for example. Indeed, the 'high-functioning' non-severe autistic child who just got handed a school exclusion for having an aggressive meltdown (yes, I said aggression) in class may very well be described as having severe autism in the same way that a 'low-functioning' child screaming and banging their head whilst covering their ears may thus be described. The endpoint in both cases being that autism is significantly and severely affecting both their lives at that point. I firmly believe a lot more thought needs to go into such 'classification' issues (see here) including more mention of the concept of 'profoundness' and perhaps further utilisation of the DSM-5 'support gradings' (see here) which have been installed.

Insofar as the second point covering 'mild' autism as a 'personality variant' and the issue that the label autism does not have exclusive rights to the presentation of autistic traits, another area of interest opens up. I've talked quite a bit on this blog about how autistic features / traits / symptoms are readily seen across a whole variety of different labels (see here and see here) and what this means for the concept of 'self-diagnosis' for example, that is sometimes seen / discussed on social media in particular (see here). Drawing specifically on the presentation of autistic traits in something like borderline personality disorder (BPD) [1] one could very well express an opinion that yes, autism in some cases may well be akin to a personality variant. Such a line of reasoning fits well with the (still emerging) concept of neurodiversity as applied to autism (see here) where autism is viewed as a "natural variation" [2].

But then the questions arise: at what point does autism cease to be a 'personality variant' to then becoming 'definitely a disability'? Is it just based on the acquisition of spoken language? Grandin does mention a few times in the interview about autism "in the milder forms, where the person is fully verbal" so perhaps showing an inclination towards a view that spoken language use is an important measure to differentiate differences vs. disability. But does reliance on spoken language use offer enough to make such a differentiation? Are their other facets of autism (or combinations of facets) which could better reflect any difference vs. disability arguments?

Personally, I'm not inclined to believe that there is a personality variant vs. definite disability debate to be had when it comes to autism. Formal receipt of a diagnosis is based not only on the presentation of autistic features or traits but also that such traits "cause clinically significant impairment in social, occupational, or other important areas of current functioning." If one was to say that some autism is just a personality variation, it could for example, dissipate the meaning of autism and the supports that are required. The risk of 'diluting' an important message about the need for those services and resources to ensure that people across the autism spectrum and their loved ones get the help and support they need to have a good quality of life is not a risk, in my view, worth taking.


[1] Dell'Osso L. et al. Correlates of autistic traits among patients with borderline personality disorder. Comprehensive Psychiatry. 2018; 83: 7-11.

[2] den Houting J. Neurodiversity: An insider's perspective. Autism. 2019 Feb;23(2):271-273.


Saturday 18 May 2019

Lactobacillus plantarum PS128 "ameliorated opposition/defiance behaviors" in boys with autism?

There was something potentially rather special about the results published by Yen-Wenn Liu and colleagues [1] suggesting that use of a probioticLactobacillus plantarum PS128 - might, under "randomized, double-blind, placebo-controlled" conditions, have some important effects with some young people diagnosed with an autism spectrum disorder. Special because, if such results are eventually replicated and borne out, some of the more 'disruptive' behaviours that can sometimes be observed alongside a diagnosis of autism - "opposition/defiance behaviors" - might be amenable to quite a simple intervention. That could be important for many, many different reasons.

The basics: PS128 containing "3 × 1010 CFU/capsule of PS128 with microcrystalline cellulose as the carrier" was the compound under investigation, pitted against a placebo that "only contained microcrystalline cellulose." Eighty participants, all boys diagnosed with an autism spectrum disorder (ASD) were recruited for study; 39 were assigned to receive PS128 and 41 receiving the placebo for a period of 4 weeks. Various different schedules and questionnaires were used to measure behaviour at baseline and week 4 between the groups. With a fairly small attrition rate - data for 36 participants in the PS128 and 35 in the placebo group were analysed - the results were pretty interesting.

Results: first and foremost we are told that no adverse events were reported during the study. That's important. Next, for the vast majority of measures used when straight comparing of PS128 and placebo, no significant difference was noted. The authors even mention how a clinician rated scale, the CGI-I, basically said that "both groups were equivalent to "minimally improved""  between baseline and study end. It was only when results were stratified for age that things started to 'happen' as various behaviours around anxiety, rule-breaking, inattention and opposition/defiance showed something like a 'nominal' reduction in the PS128 group compared with placebo, particularly for those aged between 7-12 years. As per the use of the word 'nominal' to denote a small 'change' the results were not spectacular.

Caveats? Well, this was a 4-week study of boys on the autism spectrum. Not a long time in anyone's book but longer than other studies on other interventions that did show a statistically significant effect (see here for example). The Liu study was also a study that exclusively relied on behavioural observation measures, so we can't say anything about how something like PS128 might have impacted on gut bacteria for example. Other, less methodologically sound studies have been more comprehensive (see here).

But there are strengths to the Liu study; strengths around the design and use of a placebo condition. And if there is a chance that something like Lactobacillus plantarum PS128 or other preparations (see here and see here) or related techniques (see here) *might* help improve quality of life for young and old people on the autism spectrum minus any significant side-effects, they should be explored an awful lot more...


[1] Liu Y-W. et al. Effects of Lactobacillus plantarum PS128 on Children with Autism Spectrum Disorder in Taiwan: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2019; 11: 820.


Friday 17 May 2019

A test "that distinguishes ASD fast response constipation from ASD persistent right-sided constipation"?

The quote heading this post - "A test that distinguishes ASD [autism spectrum disorder] fast response constipation from ASD persistent right-sided constipation" - comes from the findings reported by Stephen Walker and colleagues [1]. The Walker results continue a theme from this research group (see here) whereby some important data is being generated on how to treat some fairly prevalent bowel issues that seem to accompany quite a few diagnoses of autism (see here).

Much like other research from this authorship group, the research material examined was biopsy tissue - "ascending colon biopsy tissues" - provided by 35 children diagnosed with an autism spectrum disorder "and chronic constipation on a background of enterocolitis." I know some people don't like the word 'enterocolitis' in the context of autism (see here) but prejudices aside, there is nothing in the current research literature to suggest that a diagnosis of autism is somehow protective against the development of inflammatory bowel disease and/or its symptoms. Nothing.

Anyhow, 20 of those 35 children were categorised as 'slow responders' on the basis of showing "recurrent right-sided fecal loading requiring regular colon cleanouts during treatment for enterocolitis" and 15 were defined as 'fast responders' as a function of experiencing "a sustained state of GI [gastrointestinal] symptomatic remission while on maintenance anti-inflammatory therapy." In effect the group was divided up into those whose bowel symptoms got better (n=15) and those whose bowel symptoms did not (even after multiple attempts) (n=20). Researchers analysed those biopsy samples with the expression of genes in mind as per other research occasions [2].

Results: "Significant differences were found between the two clusters with fast responder-predominant cluster showing an upregulation of transcripts involved in the activation of immune and inflammatory response and the slow responder-predominant cluster showing significant over-representation of pathways impacting colonic motility (e.g. genes involved in tryptophan and serotonin degradation and mitochondrial dysfunction)." Apologies for the long quote taken from the Walker paper, but they said it better than I ever could. The translation: gene expression data was different between the fast and slow responder groups.

Obviously more research is needed in this area with larger participant groups and perhaps using samples from other non-autism groups who present (or don't) with various types of bowel issues, whether sensitive to treatment or not. The cluster of genes that were used in the authors' modelling did all right when it came to talk of possible 'biomakers' - "The sensitivity (sensitivity = 0.88), specificity (specificity = 0.89), and kappa (kappa = 0.77) statistics all reflect a good strength of agreement between prediction and actual assignments" - but still need more work before any big claims are made.

There are a couple of other things to mention from the Walker results. So, results suggested that: "predominantly chronic constipation in fast responders is not only related to the inflammatory status of the right colon but is likely a direct consequence of this colonic inflammation." Inflammation perhaps equalling constipation? Interesting. And it not only offers lots more avenues for further study but also some important treatment options.

Next, the amino acid tryptophan was singled out as being potentially "especially significant." I've always been interested in the aromatic amino acids in relation to some autism (see here). Tryptophan is a particularly important aromatic amino acid because it's eventually metabolised into a whole slew of important compounds from serotonin (5-HT) to melatonin and beyond, with some interesting connections to autism (see here). Walker and colleagues mention how: "In the slow responder cluster of patients, there was a significant upregulation of transcripts in each of the metabolic degradation pathways for tryptophan, serotonin, and melatonin, suggesting that TRP [tryptophan] insufficiency (and therefore 5-HT insufficiency) may be an important factor in the sustained hypomotility seen in this patient cohort." There's some much more study that one could do in this area. Particularly when 'gut hypomotility' is a potential issue for quite a few people on the autism spectrum (see here).

There are other things to consider from the Walker paper - "A third relevant theme apparent from the slow response gene expression profile involves a number of pathways that converge in the mitochondria and impact mitochondrial function" - but I'll leave that for now (see here). Suffice to say that there is enough evidence emerging in the peer-reviewed domain to say that (a) pathological bowel problems are more than present alongside a diagnosis of autism, (b) said bowel issues also overlap with functional GI symptoms such as constipation in particular, (c) there are physiological reasons for such bowel issues outside of any psychobabble explanations, and (d) lots more research is required in this area without fear or favour pertinent to improving quality of life...


[1] Walker SJ. et al. A molecular biomarker for prediction of clinical outcome in children with ASD, constipation, and intestinal inflammation. Sci Rep. 2019 Apr 12;9(1):5987.

[2] Walker SJ. et al. A Putative Blood-Based Biomarker for Autism Spectrum Disorder-Associated Ileocolitis. Sci Rep. 2016 Oct 21;6:35820.


Thursday 16 May 2019

Yes, even gait issues accompanying autism should be investigated

In today's post, I'm directing you to the case report published by Valerio Andreozzi and colleagues [1] (open-access). This paper supports the idea that the phrase 'it's just part of their autism' should always be used sparingly (see here) when it comes to the wide range of symptoms that seem to follow or overlap with a diagnosis of autism. And that includes issues with gait or walking (see here).

As I mentioned this was a case report: "An 8-year-old Caucasian boy affected by autism presented with nontraumatic knee pain." He walked with a limp and was presented for further clinical investigation as a result. Things did not run altogether smoothly however as we are told that "Clinical examination was difficult to perform, due to the strong opposition of the autistic child." Clinicians did eventually get some imaging done on his knee which revealed the presence of a rare condition called a posterior cruciate ligament (PCL) ganglion cyst. The authors mention how "only one case of pediatric ganglion cyst of the PCL has been reported in the literature." Surgery was indicated and performed and was successful.

Andreozzi et al talk about some of the hows-and-whys of this condition being noted in this particular patient. There is mention of 'traumatic origin' (no, not the psychobabble version) as being possible as per other mention of this condition in relation to sporting injuries. They also talk about how "children with ASD [autism spectrum disorder] show deficient sensory perception relative to internal or external stimuli... and highly individualized asymmetrical lower extremity angular joint positions during gait..., which may induce tripping or falling and be a cause of repeated trauma over time." Ultimately however, they aren't able to say exactly why this particular condition came to be in this particular patient.

This was a very isolated case and so one shouldn't assume every case of autism being accompanied by gait/walking issues is due to such an issue. It does however reiterate that a diagnosis of autism should not be used as an excuse not to look at other reasons why certain signs and symptoms appear alongside autism. Indeed, when it comes to joint and gait issues appearing alongside autism, there may be quite a few investigations to undertake in this area (see here and see here for example).


[1] Andreozzi V. et al. Diagnosis and Treatment of a Symptomatic Posterior Cruciate Ganglion Cyst in a Child with Autism. Case Rep Orthop. 2019 Mar 5;2019:9192347.


Wednesday 15 May 2019

"sleep and social satisfaction could be monitored to increase QoL in autistic adults"

The quote titling this brief post - "sleep and social satisfaction could be monitored to increase QoL [quality of life] in autistic adults" - comes from the findings published by Marie Deserno and colleagues [1].

Their examination of nearly 600 adults with autism (or autistic adults if you prefer) turned up quite a few important details. Not least that "sleep problems are an important predictor of later subjective QoL [quality of life]" and "may offer an important treatment target for improving QoL." I know such findings aren't exactly unexpected (see here and see here) but they do reiterate that sleep is something pretty important to mental and physical health and well being for everyone.

The additional finding on 'social satisfaction' also potentially playing a role in subjective quality of life reports in relation to autism is also not exactly novel (see here). It reiterates that participating in society, as described by other authors (see here), should be a fundamental right for all who want it.

I hasten to add that sleep and social satisfaction are not the only things that influence quality of life in the context of autism (see here) or anything else. On the basis that 'if you've met one person with autism, you've met one autistic person' if you want to know what might help a person, why not ask them.


[1] Deserno MK. et al. Sleep determines quality of life in autistic adults: A longitudinal study. Autism Res. 2019 Apr 10.


Tuesday 14 May 2019

"Ruminative thinking is the autistic dimension more strongly associated with suicidality"

The quote titling this post - "Ruminative thinking is the autistic dimension more strongly associated with suicidality" - comes from the findings published by Liliana Dell'Osso and colleagues [1] and provides something of an extension of previous work from authors on this paper (see here).

The important topic under investigation by Dell'Osso et al was suicidality; something that crops up time and time again in connection to the autism spectrum (see here). No, such a topic doesn't make for great PR 'about autism'. But if you want to talk about research/clinical priorities when it comes to the autism spectrum, I can't think of many topics that would be more pressing...

The hypothesis: those with subthreshold autistic traits (AT) and autism spectrum disorder (ASD) "will both show a higher prevalence of suicidal ideation and behaviors" when compared with asymptomatic controls. Further: "to clarify if AT do actually imply a risk factor for suicidality similar to full-blown ASD, hypothesizing that suicidal thoughts and behaviors will not differ between subjects with subthreshold autism and full-blown ASD." Similar sentiments have been previously expressed in other research results (see here and see here and see here).

I won't bore you with all the details of the hows-and-whys of Dell'Osso study (it is open-access) but do want to focus in on a few important observations made. First authors reported that they "found no differences in suicidality scores between ASD and AT groups, while both showed a higher score than HC [healthy controls]." I might add that 'HC' is a term used by the authors and wouldn't be my choice for describing a control group. This finding is important not just for autism but potentially for lots of other labels that manifest autistic traits (see here and see here) on the basis that autistic traits are not necessarily exclusive to a diagnosis of autism.

Second: "the ASD group reported significantly higher MOODS-SR total score and MOODS-SR depressive component score than the AT group, and the AT group in turn scored significantly higher than the HC." I don't think anyone should be really surprised by the finding that the symptoms of mood disorders such as depression seem to be 'over-represented' alongside a diagnosis of autism given other data on this issue (see here). Indeed, one might even say that depression could, for some autistic people, be considered a core issue over and above just being described as a comorbidity (see here).

Finally I head back to the title of this post, and how something like ruminative thinking - "a pattern of repetitive thinking, usually associated to and exacerbating anxiety and depression, often affecting problem-solving and the processing of negative feelings and leading to social isolation" - might be a particular dimension *associated* with suicidality in the context of autism or the presentation of subthreshold autistic traits. I've talked a few times about rumination in the context of autism on this blog (see here and see here). Rumination has also been talked about in the context of autism and suicide before too (see here). If research continues to point to rumination as something important, one might potentially envisage the development of interventions that could ameliorate such an issue and possibly onward *affect* the risk of something like suicidality?

I don't want anyone to get the impression that the Dell'Osso findings have *solved* the issue of suicidality in the context of autism because they haven't. As I've said many times before on this blog, suicide is a very, very complicated and deeply personal issue (see here) with no one-size-fits-all answer to the questions it raises. As part of a larger picture however, the Dell'Osso results are however important. If their application in a clinical context saves even one life, I would consider that to be infinitely worthwhile.

If anyone needs someone to talk to, there are people who will listen (see here and see here)...


[1] Dell'Osso L. et al. Mood symptoms and suicidality across the autism spectrum. Comprehensive Psychiatry. 2019. April 3.


Monday 13 May 2019

Estimated autism prevalence in Northern Ireland: 3.3% for 2018-2019

The BBC news headline reading "Autistic children in NI schools trebles in a decade" provides the blogging fodder today.

NI refers to Northern Ireland, and the news report relates to the publication of further findings from the Department of Health in NI [1] on the topic of autism prevalence among school-aged children.

I've covered the NI 'autism in school children' figures for quite a few years on this blog (see here and see here). The stats have gone from 2.3% in 2015/2016 to 2.5% in 2016/2017 to 2.9% in 2017/2018 to the most recent figures of 3.3% in 2018/2019. The report and news coverage focus on how that recent 3.3% figure compared with 1.2% back in 2008/2009. That's quite a shift in the space of just a decade.

A few details are worthy of further mention. First, Northern Ireland seems to be taking a bit of a lead in collecting information about rates of autism in school-aged children (see here). Indeed, many of the 'home countries' making up the United Kingdom (UK) are starting to ask the questions that England, unfortunately, is seemingly not yet asking (see here).

Second, we are told that: "The increase in prevalence of children with autism can be attributed to an annual average increase in the number of children identified with autism of 12% between 2009/10 and 2018/19, against a background of a relatively static school population." This means that the rates of autism in school-aged children are not simply increasing because the school population as a whole is increasing. Indeed, with other not-so-long-ago chatter about long waiting lists for assessment in places like Northern Ireland (see here), one could argue that the current figures are an under-estimate.

Third, with regards to the sex ratio (boys:girls), the 2018/2019 figures suggest that "5.1% of males were identified with autism compared to 1.5% of females." The same figures a decade ago (2008/2009) were 1.9% and 0.4% respectively. I don't however necessarily agree with the: "Autism could therefore be considered to be an extreme of the normal male profile" sentiments expressed by the author to account for this difference but...

Fourth, the rate of the increase across the decade (2008/2009 compared with 2018/2019) was present in every school year. The author focuses in on the fact that nearly 4% of those in Year 6 (the end of primary school) were "identified with autism". He also mentions that most identification of autism in school is occurring when children are aged between 5 and 10 years old. Primary school, it seems, is an important time for the identification of autism.

Fifth: something approaching grading a child for autism 'severity' is also discussed. I know 'severity' is still a contentious issue (someone actually suggested 'severe autism' should be replaced by 'profound autism' which sounds rather sensible). Special educational need (SEN) assessment is a process via which a child's needs are graded. More details about this process applied to Northern Ireland can be found here. SEN stage 4 and SEN stage 5 indicate that a child requires support from school but also that "the education authority shares responsibility with the school." Nearly two-thirds of children identified with autism were at SEN stage 5. This was however down from previous years with the main 'growth' being among those who were gauged at SEN stage 2 and stage 3. The authors caution that such figures are only a snapshot (children can move up and down the SEN stages for example).

Whichever way you cut it, the recent figures out of Northern Ireland show the increasing trend for autism in school-aged children (see here). We can add such figures to those which have recently come out of the United States (see here and see here), Canada (see here) and various other parts of the world. We can quibble about the old 'better awareness' arguments and even diagnostic switching as being primary causes of the increase. I personally do not believe that such explanations even come close to the final reasons for the increase in cases that have been noted and continue to be seen (see here). What I do know is that further finance and resources are required to meet the often complex needs of these children and young adults to allow them to reach their potential.

And minus any emotive language (i.e. tsunami), let's remember that children turn to adults, and many of these children will require on-going help and support into their later years. The question is: are we prepared?


[1] Waugh I. The Prevalence of Autism (including Asperger Syndrome) in School Age Children in Northern Ireland 2019. Northern Ireland Department of Health. 2019. May 10.


Saturday 11 May 2019

"Neurodevelopmental effects of prenatal vitamin D in humans"

The results of the systematic review and meta-analysis published by Azahara García-Serna & Eva Morales [1] provide the blogging fodder today.

Their aim was to summarise the collected peer-reviewed research evidence pertinent to "the association between 25-hydroxyvitamin D [25(OH)D] levels in maternal blood in pregnancy or newborn blood at birth and neurodevelopmental outcomes, including cognition, psychomotor performance, language development, behavioral difficulties, attention deficit and hyperactivity disorder (ADHD), and autistic traits." This coming from authors who already have some research 'form' in this area (see here).

Twenty-five studies ("articles") were included in their boiling-down-of-the-relevant-research-literature published up to May 2018. From the combined data, a few *associations* were detected: "Comparing the highest vs. the lowest category of prenatal 25(OH)D levels, the pooled beta coefficients were 0.95... for cognition, and 0.88... for psychomotor development. The pooled relative risk for ADHD was 0.72..., and the pooled odds ratio for autism-related traits was 0.42." What this meant is that measured higher levels of vitamin D in pregnant mums-to-be or in offspring newborn blood correlated with "improved cognitive development and reduced risk of ADHD and autism-related traits later in life" for offspring.

Of course one has to be careful with such data whether it comes from a meta-analysis or not. We're still talking about observational studies where one variable (vitamin D) is being analysed in the context of one or a few others (related to offspring development). Yes, researchers can control for this potential confounder or that potential confounder, but there remains a 101 other variables that likely affect the likelihood of ADHD or 'autism-related traits' appearing, not least biology and genetics.

That being said, the García-Serna / Morales are potentially important. They point to the need for further research into various possibly interlinked areas when it comes to vitamin D levels and their intake. This follows Government guidance (at least here in Blighty) suggesting that many people should be taking a vitamin D supplement already (see here). I'm also minded to suggest that future investigations should also be looking at other related areas around vitamin D such as the various genetic processes that seem to be important to vitamin D levels and the metabolism of the sunshine vitamin (see here).

And if you're still not convinced by the potential effects of vitamin D and offspring outcomes, perhaps the findings - systematic review findings - published by Janet Janbek and colleagues [2] might help sway you a little...


[1] García-Serna A. & Morales E. Neurodevelopmental effects of prenatal vitamin D in humans: systematic review and meta-analysis. Molecular Psychiatry. 2019. Jan 25.

[2] Janbek J. et al. Associations between vitamin D status in pregnancy and offspring neurodevelopment: a systematic literature review.  Nutr Rev. 2019 Feb 26. pii: nuy071.


Friday 10 May 2019

"Physical and mental health issues were highly prevalent among children with obesity..."

The quote titling this post - "Physical and mental health issues were highly prevalent among children with obesity" - comes from the findings reported by Stasia Hadjiyannakis and colleagues [1].

Researchers set out to "examine the association between BMI [body mass indexclass and EOSS-P [Edmonton Obesity Staging System for Pediatrics] stage" on the basis that measures such as BMI "do not always accurately and reliably identify children and youth with obesity-related health risks or comorbidities" [2] and issues like obesity don't typically appear in a "metabolic, mechanical, mental health and social milieu" vacuum.

As you might have already noted, Hadjiyannakis and colleagues have some 'research form' in this area. This time around data on nearly 850 children "with obesity aged 5-17 years" attending one of a number of weight management clinics were the source material. They observed that most of their cohort - about two-thirds of them - were described as having severe obesity according to their BMI score. When it came to their EOSS-P staging scores, 80% fell into the categories of a 2 or 3 denoting moderate to severe issues with regards to health issues such as metabolic complications either requiring pharmacotherapy or being described as "uncontrolled".

Of particular note to this blog and the focus on the intersection between physical and mental health parameters, researchers describe how "mental health concerns were most common" among their participant group. By 'mental health concerns' they specifically talk about anxiety and attention-deficit hyperactivity disorder (ADHD) as being present and "equally distributed across BMI classes." I was particularly intrigued with the ADHD bit because despite the focus on hyperkinetic behaviours in ADHD, the emerging research picture is suggesting that ADHD and obesity *might* actually be connected (see here) under quite a few different circumstances (see here).

What's more to say? Well, the Hadjiyannakis results perhaps imply that preferential screening for various physical and mental / behavioural are indicated when obesity is present. Specifically, and bearing in mind that "mental health risks were high across BMI classes" the results suggest that the possibility of an elevated risk of mental / behavioural diagnoses is not something confined to those with more or less severe obesity but rather, potentially, a universal issue.


[1] Hadjiyannakis S. et al. Obesity class versus the Edmonton Obesity Staging System for Pediatrics to define health risk in childhood obesity: results from the CANPWR cross-sectional study. Lancet Child Adolesc Health. 2019 Apr 2. pii: S2352-4642(19)30056-2.

[2] Hadjiyannakis S. et al. The Edmonton Obesity Staging System for Pediatrics: A proposed clinical staging system for paediatric obesity. Paediatr Child Health. 2016;21(1):21–26.