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.

----------

On unintentional drowning deaths in children with autism

Sometimes science seems to be science for the sake of science. Y'know, findings are reported and published and are met with either 'so what' or 'what does this mean for me?' sentiments, particularly when dealing with potentially abstract concepts.

The findings published by Joseph Guan and Guohua Li [1] most definitely DO NOT fall into such a category. Their covering of a topic which has potential life-limiting implications - unintentional drowning deaths - in the context of autism is worthwhile repeating again and again and again until everyone sits up and takes note. I might add that other previous research from this authorship team similarly evoke such sit-up-and-listen sentiments (see here).

What did the authors do? Well, simply put, they scanned the Lexis-Nexis® Academic database looking for all newspaper entries covering the terms autism, drowning and boy/girl from the beginning of January 2000 until May 2017 in the United States. They analysed the collected data; retrieving specific details such as "time of day and distance from residence" when it came to such reports.

Results: "During January 2000 through May 2017, US newspapers reported a total of 23 fatal unintentional drowning incidents involving children under 15 years of age with ASD [autism spectrum disorder]." Let's just reflect on that a moment. Twenty-three children / young adults with autism who drowned. Twenty-three lives tragically cut short. Twenty-three families left grieving.

Also: "Data about proximity of the water body to the victim’s residence were available for 11 (47.8%) of the incidents, with all of them within 1000 m of the victim’s residence (mean = 290.7 ± 231.5 m)." And also: "The time of day at which victims were reported missing was available for 15 (65.2%) of 23 incidents, with 2 (13.3%) being in the morning (0:00–11:59), 11 (73.3%) being in the afternoon (12:00–17:59), and 2 (13.3%) being in the evening (18:00 PM – 23:59)." And finally: "Wandering was the most commonly reported activity that led to drowning, accounting for 73.9% of the incidents."

I could go on about the limitations of this study as highlighted by the authors - "small sample size and the availability of information reported in newspaper articles" - but really I have to ask 'does it matter?' The answer: no, such study limitation don't really make too much difference to the final - very final - outcomes reported on.

The fact that wandering (elopement if you will) was a feature of many of the cases found is not new news (see here). It reiterates once again that resources aplenty need to be put into reducing incidences of wandering or at least allowing parents and law enforcement and other agencies every opportunity to locate wandering children/adults as quickly as possible. Some might worry about things like civil liberties when it comes to monitoring someones movements. But in current times, when someone can be tracked by their mobile/cell phone use for example, I'd respectively disagree with such 'civil rights are being impinged' sentiments. Imagine if you will, if one of the various 'tracking' devices currently aimed at those on the autism spectrum was given to every child / every family free of charge at the point of diagnosis? A good use of money methinks...

Water safety is another important part of the current findings. There is science out there talking about how learning to swim might have quite a lot of positives when it comes to autism [2]; perhaps the most important being learning water safety skills. Who would argue with that? And if one wanted to be proactive in this area, how about making water safety and swimming lessons a compulsory part of the learning curriculum for everyone diagnosed with an autism spectrum disorder? Again, a very good use of money methinks and you never know, there may be other benefits too.

I'm not saying that there aren't individual circumstances around every one of those drowning deaths discussed by Guan & Li. I'm not saying that every death could have been avoided. What however I do believe is that armed with the knowledge that drowning is a significant cause of premature death in the context of autism, and knowing a little more about the general circumstances around some of those deaths, there are things that can potentially be done to mitigate future risks to the autistic population and potentially save lives.

----------

[1] Guan J. & Li G. Characteristics of unintentional drowning deaths in children with autism spectrum disorder. Injury Epidemiology 2017; 4: 32.

[2] Alaniz ML. et al. The Effectiveness of Aquatic Group Therapy for Improving Water Safety and Social Interactions in Children with Autism Spectrum Disorder: A Pilot Program. J Autism Dev Disord. 2017 Dec;47(12):4006-4017.

----------

On drinking water lithium content and dementia risk

"Lithium in tap water may cut dementia" went the BBC website headline reporting the study results published by Lars Vedel Kessing and colleagues [1]. The authors relied on some of those oh-so important Scandinavian population registries and other data to examine a possible connection between drinking water lithium levels and risk of "diagnosis of dementia in a hospital inpatient or outpatient contact."

Alongside looking at data for some 70,000 people diagnosed with dementia and nearly three-quarters of a million non-diagnosed controls, researchers estimated lithium exposure via drinking water based on data from over 150 waterworks. The relationship they observed between lithium in drinking water and risk of dementia diagnosis was not altogether straight-forward as "higher long-term lithium exposure from drinking water may be associated with a lower incidence of dementia" but the relationship was described as "nonlinear." Nonlinear meant that those with drinking water levels of lithium at moderate levels - between 5.1 and 10 micrograms per litre - actually showed an increased risk of dementia compared to those who had low levels of lithium (below 5 micrograms per litre) in their drinking water. The authors add: "Nonlinear dose-response associations are often found in medicine, with a gradual increase in drug response at the lower doses and gradual leveling off in response at the highest doses."

The authors do caution about their results and the various limitations attached to the findings. Not least is their reliance on a diagnosis of dementia as a starting point and how factors such as "accessibility to health care services that vary geographically" may have influenced such results. Indeed they note: "accessibility to health care services is increased in eastern regions of Denmark, where lithium levels generally are higher, and decreased in western regions, specifically in Jutland, where lithium levels generally are lower." They also found: "a direct inverse association with increasing risk of dementia in rural areas" as part of a sensitivity analysis, and as noted in some other studies [2]. More investigation is definitely required.

But these remain interesting results. Lithium is a treatment of choice when it comes to conditions such as bipolar disorder (see here). I've also talked about this stuff in connection to some other important research looking at suicide reduction too (see here) based on quite a body of research [3] (and growing all the time [4]) but minus simplifying something like suicide ideation, attempts or completion all down to lithium 'deficiency'. In relation to the possible effects on dementia risk, this is not the first time that lithium has been discussed as per findings looking at dementia risk in cases of lithium treated bipolar disorder [5] (something else that has been discussed on this blog - see here).

Questions still however remain. The mechanism of effect(s) is still to be suitably deciphered and one also needs to keep in mind the safety profile of lithium [6] as a balance to any risk-reduction effects on dementia or anything else. This is particularly relevant to those who might be at particular risk for dementia [7]. I'll also add that any focus on lithium intake and dementia also needs to keep in mind other *associations* that have been previously discussed in the peer-reviewed research literature such as that talking about vitamin D deficiency and dementia risk for example (see here) as part of a wider research interest in vitamin D and cognitive functions in the context of ageing (see here).

----------

[1] Kessing LV. et al. Association of Lithium in Drinking Water With the Incidence of Dementia. JAMA Psychiatry. 2017 Aug 23.

[2] Contador I. et al. Childhood and Adulthood Rural Residence Increases the Risk of Dementia: NEDICES Study. Curr Alzheimer Res. 2015;12(4):350-7.

[3] Cipriani A. et al. Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis. BMJ. 2013 Jun 27;346:f3646.

[4] Kanehisa M. et al. Serum lithium levels and suicide attempts: a case-controlled comparison in lithium therapy-naive individuals. Psychopharmacology (Berl). 2017 Aug 28.

[5] Gerhard T. et al. Lithium treatment and risk for dementia in adults with bipolar disorder: population-based cohort study. Br J Psychiatry. 2015 Jul;207(1):46-51.

[6] Albert U. et al. Lithium treatment and potential long-term side effects: a systematic review of the literature. Riv Psichiatr. 2014 Jan-Feb;49(1):12-21.

[7] Holroyd S. & Rabins PV. A Retrospective Chart Review of Lithium Side Effects in a Geriatric Outpatient Population. Am J Geriatr Psychiatry. 1994 Autumn;2(4):346-351.

----------

Wandering and autism continued... yet again

I know that I'm probably starting to sound like a broken record on the topic of wandering (elopement) and autism on this blog (see here and see here and see here) but I am yet again going to briefly talk about peer-reviewed research in this area simply because it's just too damned important not to.

This time around the results from Catherine Rice and colleagues [1] are the source of my musings and the conclusion that: "wandering among children with ASD [autism spectrum disorder], regardless of intellectual disability status, is relatively common." Based on the analysis of data from The Survey of Pathways to Diagnosis and Services (SPDS) initiative, where specific questions about 'wandering and wandering prevention' are asked (see page 29) researchers reported that: "For children with special healthcare needs diagnosed with either ASD, intellectual disability, or both, wandering or becoming lost during the previous year was reported for more than 1 in 4 children." A diagnosis of ASD seemed to be a key factor in the frequency of wandering, where those with additional learning disability were the most likely to wander (37% of the sample) and figures for those without intellectual disability came in at about 32%.

As per previous occasions when I've blogged about this topic, the differences (kingdoms) that might divide various groups/people when it comes to autism tend to take second place when it comes to tackling this issue and preventing (yes, preventing) wandering from turning into something rather more ominous. After all, there are a range of measures that can be employed to reduce the frequency of wandering/elopement and, if and when it does happen, reduce the probability of 'adverse outcomes' for the wanderer. First and foremost I would say, is for more people to take note of actual accounts about wandering as per those discussed by Solomon and Lawlor [2] for example. One can learn a lot about the circumstances around why wandering occurs and the different types of wandering (including the issue of bolting) from listening to parent and caregiver accounts. They are the experts on their own children and no doubt some of those accounts might generalise to more than just one child.

Next up are the various instruments that could be used to help find wanderers in a timely fashion. I'm thinking specifically about technology such as GPS trackers and the need for science to provide some further insight into the effectiveness of such items and what needs to be done to improve their effectiveness. I appreciate that 'tracking people' might have implications for things like civil liberties but just remember that the mobile (cell) phone you're carrying might not also be bad at telling others where you are. Improving autism awareness among first responders such as police and related agencies may also help them in their efforts if and when wandering becomes an issue.

Finally and bearing in mind that 'if you've met one person with autism, you've met one autistic person' (or words to that effect) is the importance of teaching things like road and water safety to those on the autism spectrum. I appreciate that the concept of 'danger' might not be something easily taught to some children and communication issues can be barriers to effective teaching. But, one should not assume that it is impossible to do [2], alongside the strategies for making lessons like swimming classes for example 'fun' as well as potentially lifesaving. And yes, swimming lessons can be particularly fun for many children on the autism spectrum [3].

----------

[1] Rice CE. et al. Reported Wandering Behavior among Children with Autism Spectrum Disorder and/or Intellectual Disability. J Pediatr. 2016 May 2. pii: S0022-3476(16)00428-5.

[2] Call NA. et al. Clinical outcomes of behavioral treatments for elopement in individuals with autism spectrum disorder and other developmental disabilities. Autism. 2016 May 12. pii: 1362361316644732.

[3] Eversole M. et al. Leisure Activity Enjoyment of Children with Autism Spectrum Disorders. J Autism Dev Disord. 2016 Jan;46(1):10-20.

----------

Rice, C., Zablotsky, B., Avila, R., Colpe, L., Schieve, L., Pringle, B., & Blumberg, S. (2016). Reported Wandering Behavior among Children with Autism Spectrum Disorder and/or Intellectual Disability The Journal of Pediatrics DOI: 10.1016/j.jpeds.2016.03.047

Water, carbamazepine and mother-embryo transmission

"These results provide the first evidence that carbamazepine in drinking water and at typical environmental concentrations is transmitted from mother to embryo."

So said the findings reported by Gaurav Kaushik and colleagues [1] who continued a research theme looking at the possibility of an environmental 'exposome' also potentially overlapping with [some] autism (see here). The autism connection came from the a paper by Thomas & Klaper [2] who previously reported that putting fish in a tank of water containing various unmetabolized psychoactive pharmaceuticals (UPPs) including carbamazepine resulted in some changes to gene expression patterns "associated with idiopathic autism."

This time around the idea was to test whether "psychoactive pharmaceuticals (fluoxetine, venlafaxine, and carbamazepine) administered through the drinking water at environmental concentrations to pregnant mice could reach the brain of the developing embryo by crossing intestinal and placental barriers." Authors added deuterated standards (2H-isotope labelled) of the pharmaceuticals in question to the water so they were able to quantify rat embryo brain and liver levels of them in comparison with control animals. As it turns out, carbamazepine (normally used to treat epilepsy) was the only pharmaceutical detected - "using isotope ratio mass spectrometry" - in those developing embryos and led authors to that opening sentence. Combined with the previous work they suggest that "carbamazepine may be associated with ASD [autism spectrum disorders] in infants" and as such "warrant the closer examination of psychoactive pharmaceuticals in drinking water and their potential association with neurodevelopmental disorders."

There is an obvious 'shock' value to this research insofar as the suggestion that minute concentrations of certain pharmaceuticals fairly commonly found in drinking water might have repercussions when it comes to the 'risk' of offspring autism. On that basis I tread carefully in the discussion of this topic.

I should initially tackle the idea that as much as we would like to think our drinking water comes from some untouched crystal clear spring on top of a mountain, the reality is perhaps a little different. Drinking water is mostly of a pretty good standard (well, mostly) but that's not to say that some of our population habits don't have an effect on its quality. With carbamazepine specifically in mind, there is quite a body of research suggesting that very low levels of this and other medicines do turn up in drinking water [3] across various different geographies and are pretty stable in said waters [4] at least during certain points of water purification.

The issue however is one of translating the Kaushik results from lab to real-life. Not only that they report results based on fish and mouse models but also that a wide variety of prescription and perhaps even non-prescription compounds may turn up in real-life drinking water and could have many different (often opposing) effects when it comes to things like gene expression linked to various diagnoses. Combined with the idea that gene expression patterns 'linked to idiopathic autism' does not necessarily mean that it is linked to all idiopathic or other kinds of autism and as you might see, we have some way to go yet before anyone talks about water supplies increasing risk of autism or anything else. As far as I am aware, behaviours pertinent to autism were also not analysed as part of the current research in this area bearing in mind animal models are not necessarily a true reflection of any condition.

Having said all that, I do think there is more to do in this area - first and foremost with a view to independent replication of these results. I'd also like to see a little more information about the mechanisms that might be involved aiding the passage of any UPPs to the embryo and onwards the genetic (and epigenetic) effects that they may be linked to, again taking into account other work from some of the researchers discussed today [5]. We then get to possibility of some modelling with other animal sets and then studies towards how such effects could be examined with people in mind (not forgetting that water is used for quite a few purposes other than just drinking).

----------

[1] Kaushik G. et al. Maternal exposure to carbamazepine at environmental concentrations can cross intestinal and placental barriers. Biochem Biophys Res Commun. 2016 Apr 19. pii: S0006-291X(16)30594-0.

[2] Thomas MA. & Klaper RD. Psychoactive pharmaceuticals induce fish gene expression profiles associated with human idiopathic autism. PLoS One. 2012;7(6):e32917.

[3] Wu M. et al. Occurrence and fate of psychiatric pharmaceuticals in the urban water system of Shanghai, China. Chemosphere. 2015 Nov;138:486-93.

[4] Cormier G. et al. The degradation behaviour of nine diverse contaminants in urban surface water and wastewater prior to water treatment. Environ Sci Process Impacts. 2015 Dec;17(12):2051-65.

[5] Kaushik G. et al. Psychoactive pharmaceuticals as environmental contaminants may disrupt highly inter-connected nodes in an Autism-associated protein-protein interaction network. BMC Bioinformatics. 2015;16 Suppl 7:S3.

----------

Kaushik G, Huber DP, Aho K, Finney B, Bearden S, Zarbalis KS, & Thomas MA (2016). Maternal exposure to carbamazepine at environmental concentrations can cross intestinal and placental barriers. Biochemical and biophysical research communications PMID: 27105911

Autism's environmental exposome (part 2)

Back in June 2012, I posted an entry on this blog titled: 'Autism's environmental exposome: fish and pharmaceuticals' covering some work by Michael Thomas & Rebecca Klaper [1] (open-access). In it, authors suggested that unmetabolized psychoactive pharmaceuticals (UPPs) - residues from certain medicines - present in drinking (or in the case of this work, swimming) water may "induce autism-like gene expression patterns in fish."

The UPPs in question were "FLX [fluoxetine], VNX [venlafaxine], and CBZ [carbamazepine] in a 3-component mixture" and the lucky fish volunteers were fathead minnows who got to swim with those UPPs. The data were interesting insofar as the potential "ability to induce ASD-like gene expression patterns in developing brains" as a function of exposure to those UPPs, albeit with concentrations used in the Thomas/Klaper study "higher than observed environmental concentrations". The idea being that drug residues are present in the environment around us and some, either alone or in combination, may potentially host some important biological effects.

Enter then further work from this group in the form of the paper by Gaurav Kaushik and colleagues [2] (open-access) who undertook some rather interesting network analysis among other things and concluded that: "protein products from gene sets with enriched expression in fish brains and human neuronal cells, due to an exposure of psychoactive pharmaceuticals, were comparatively more inter-connected to other neighboring proteins than protein products of non-enriched gene sets." Further: "these genes are more likely to experience altered expression upon exposure to PPCPs [pharmaceuticals and personal care products], causing further dysregulation of the whole interactome due to a ripple effect."

I'll be honest with you and say that I'm not altogether au fait with all the goings-on reported by Kaushik et al and their bioinformatics approach adopted so you'll have to take my interpretation with a pinch of salt.  What they appear to be suggesting is that the effects of UPP exposure may not be just centred on the gene expression patterns they previously reported but rather having something of a wider knock-on effect on how gene products are expressed and how this might map onto something like autism. Interestingly, this time around researchers also introduced valproate (VPA) into their investigations given the growing evidence base that "VPA is known to induce ASD [autism spectrum disorder]-like phenotypes in mice" (see here for more information) as it might in people [3]. They reported some potentially important connections - "enrichment effects of clinical doses of VPA are similar to those for environmental concentrations of pharmaceutical mixtures."

Accepting how the word 'chemical' has been very wrongly demonised over the years, the idea that environmental 'exposures' either singularly or as combinations, might have important effects on development and behaviour is something that requires quite a bit more investigation when it comes to something like autism. The idea that gene expression for example, can be modified by said exposures adds an extra layer of complexity to the rather too simplistic idea of 'genes vs. environment' when it comes to autism risk. One might also be minded to take into account gender/sex (see here) too particularly in light of some of the findings reported by Werling & Geschwind [4] recently...

Oh, and UPPs might not be the only pharmaceuticals requiring further research attention with wastewater and minnows in mind...

Music: Dinosaur Jr. - Freak Scene.

----------

[1] Thomas MA. & Klaper RD. Psychoactive pharmaceuticals induce fish gene expression profiles associated with human idiopathic autism. PLoS One. 2012;7(6):e32917.

[2] Kaushik G. et al. Psychoactive pharmaceuticals as environmental contaminants may disrupt highly inter-connected nodes in an Autism-associated protein-protein interaction network. BMC Bioinformatics 2015, 16(Suppl 7): S3.

[3] Wood AG. et al. Prospective assessment of autism traits in children exposed to antiepileptic drugs during pregnancy. Epilepsia. 2015. 11 May.

[4] Werling DM. & Geschwind DH. Recurrence rates provide evidence for sex-differential, familial genetic liability for autism spectrum disorders in multiplex families and twins. Molecular Autism 2015, 6:27.

----------

Gaurav Kaushik, Michael A Thomas, & Ken A Aho (2015). Psychoactive pharmaceuticals as environmental contaminants may disrupt highly inter-connected nodes in an Autism-associated protein-protein interaction network BMC Bioinformatics

Meteorological factors and autism?

If I had a pound (inflation adjusted y'know) for every time the words 'correlation does not equal causation' were used with autism and related conditions in mind, my piggy bank would probably be rather full by now. Indeed such is the application of this term when referring to the wide (very wide) variety of associations made between this, that and t'other, that a backlash has seemingly emerged to counter its usage as per this Slate article.

Cool, clear water @ Wikipedia 

Of course that's not to say that correlation does not imply causation. Recently for example, a study appeared  in the very well respected New England Journal of Medicine (NEJM) by Franz Messerli* which concluded: "Chocolate consumption enhances cognitive function, which is a sine qua non for winning the Nobel Prize, and it closely correlates with the number of Nobel laureates in each country".

Whilst still wondering whether this is some kind of spoof article (apparently it's not) this study encapsulates everything about the notion of correlation ≠ causation given the multitude of other factors which might possibly influence citizens of a particular country winning the distinguished Nobel Prize. I am willing to concede however, should more 'direct' prospective evidence emerge, that eating chocolate might be part and parcel of Nobel Prize winning.

With this same logic I was intrigued to read the recent paper by Sophie St Hilaire and colleagues** (open-access) which based on an ecological study of autism concluded that precipitation and drinking water source might be associated with autism. Drinking water you say? Y'mean similar to the fish and pharmaceutics research and the Brick chlorination by-products paper? Well, similar at least.

In brief:

• Based on data derived from the study by Waldman and colleagues*** which concluded a possible link between annual precipitation and autism prevalence rates in the Western United States, the source of drinking water was analysed with respect to autism rates.
• The percentage of surface drinking water was thrown into the statistical mix as was population density, farming land, SES, risk of neurological disorder from air pollution, suicide rates and meteorological data.
• When analysing all this data, the authors concluded that precipitation was linked to autism rates but the source of drinking water was an important factor too.
• In among the other correlations, rates of autism also correlated with the suicide rate and negatively correlated with the unemployment rate.

There are some other interesting factoids to take from the authors findings and conclusions. Surface sources of drinking water potentially implying some role for environmental contamination was a primary association. More than that however, the authors seemed to rule out any significant association with contaminated run-off water derived for example from pesticide use and indeed urban pollution and autism rates. They leave the door open to air pollution as a possible factor and indeed pharmaceutical contamination of water sources; bearing in mind they did not test the drug residues in water hypothesis.

The negative correlation between autism rates and unemployment (as in high prevalence of autism being linked to low unemployment rates) goes back to other research in this area. That being said, I'm reminded about more recent investigation which seem to imply an opposite trend (high prevalence of autism linked to lower SES) so once again we have to be careful not to generalise too much.

There's no doubt that this is an interesting study despite the reliance on population facts and figures and our old friend correlation. Accepting another old adage on 'lies, damn lies and statistics' (see here****), there are some useful components from the St Hilaire study ripe for further testing. Not least the continuing theme that environment may very much be a part of the increase in reported cases of autism.

To finish, bird is the word (or did you not know?).

-----------

* Messerli FH. Chocolate consumption, cognitive function, and Nobel Laureates. NEJM. October 2012.

** St Hilaire S. et al. An ecological study on childhood autism. Int J Health Geographics. 2012; 11: 44.

*** Waldman M. et al. Autism prevalence and precipitation rates in California, Oregon, and Washington counties. Arch Pediatr Adolesc Med. 2008; 162: 1026-1034.

**** Bartell SM. & Lewandowski TA. Administrative censoring in ecological analyses of autism and a Bayesian solution. J Environ Public Health. 2011; 2011: 202783.

----------

Sophie St Hilaire, Victor Ezike, Henrik Stryhn, & Michael A Thomas (2012). An ecological study on childhood autism International Journal of Health Geographics

Dune, water and autism

I like my Sci-Fi films. It all started round about Star Wars and just went (downhill) from there, particularly during that golden age of TV and cinema that was the 1980s. Why the 80s? Well where else can you find Gil Gerard as Buck Rogers or Jane Badler as Diana, leader of the Visitors. And that's just TV.

The latest film being rediscovered is that David Lynch classic, Dune. I won't bore you with the film details including a North-East son, Sting appearing amongst the star-studded cast, but those in the know might recognise the words 'never one drop of rain on Arrakis'. This very tenuous link from Dune to water leads me into the main event of this post, water drinking behaviour in relation to autism and a few other conditions.

It goes without saying that we all need water to survive. Indeed whereas we can survive without food or on minimal food for some time, a few days without water and its curtains pretty quickly. I've always been a little bit interested as to why H2O is so important, after reading a small part of the very large literature on why the body needs water, and what happens when we either drink too much or too little.

There are various conditions associated with water drinking behaviour. Diabetes insipidus is one of them; whereby the passing of large volumes of urine is accompanied by excessive and prolonged thirst (polydipsia) not suitably quenched by drinking water. Conditions such as schizophrenia have also been tied into fluid intake and thirst. Indeed whilst researching this part of the post, I came across that of the late Robert Cade, inventor of Gatorade and a man close to my own research heart following his work in autism and schizophrenia.

Various medications also carry side-effects associated with thirst. Lithium for example, used in the management of conditions such as bipolar disorder carries a risk of excessive thirst as a side-effect in some cases, possibly as a result of its impact on our thirst regulation. On the other side of the pharmacotherapy fence, the neuroleptic drug risperidone has shown some promise in treating 'psychogenic' polydipsia.

With autism in mind, water has been mentioned a few times. Outside of the possible environmental drinking water connection vis-a-vis my previous post on chlorination by-products including also speculation on things like fluoride in water, a lot of the research has focused on water drinking behaviour in autism, and in particular problems such as polydipsia or excessive thirst. I should point out that like many things related to autism, there is always the possibility that the behaviour we see is there as a consequence of the core areas associated with autism. One could therefore envisage a situation where excessive drinking habits are either a learned response or part of some routine or ritual rather than having any immediate somatic or physiological undertone. I dare say that there might even be a perceptual side to excessive water drinking in autism. Possible at least.

This paper found that polydipsia was more commonly reported in autism over learning disability, corroborating quite a few case studies and first- and second-person accounts on the web of this unusual behaviour. The possible biological mechanisms behind polydipsia are a little more of a mystery, assuming that conditions such as diabetes insipidus are not co-morbid and having an effect. I was interested by some comments made in this paper about polydipsia in a learning disability population potentially being co-morbid to pica and something called Kleine-Levin syndrome. Certainly pica has perhaps more than a passing relationship to autism, although at this point I wouldn't like to speculate too much as to whether pica and polydipsia might show any causal effect on one another outside of the effect of eating things like sand and earth which may well make one thirsty.

Whilst I have, once again, only paid lip service to excessive water intake and its possible relationship to autism, there are a few details which will get even less attention in this post. Conditions such as hyponatremia, and other disorders of electrolytes are perhaps possible risk factors as a result of excessive water consumption and the limited research so far suggests more work is needed specifically for autism. One might also expect that excessive water intake might have some effect on functional bowel patterns also; indeed one might assume that in moderation, increased water intake levels could be a useful complementary strategy at least in some cases. Finally, although polydipsia has received the most research attention in autism, I do wonder about those people with autism who might demonstrate the opposite behaviour... erm, low water intake (dont' know the Greek or Latin term) and the potential effects that this might have either on autistic symptoms or well-being in general.

To end a spot of Handel and some water music to jolly up anyone's day.

Chlorinated byproducts and autism

Brick Township in New Jersey (USA) enjoys a few accolades. According to the 2003 FBI statistics, Brick Township was the 2nd safest place to live in America. It also features highly in terms of its educational provisions and is generally seen to be quite a nice place to live. Like every other place, Brick Township (BT) does however also enjoy a not-so-enviable part of its community. In the case of BT it is its history with landfill and in particular French's landfill.

Landfill is a world-wide issue in terms of the staggering amounts of waste we as a population produce and what we do with it. We, here in the UK, are unfortunately particularly wasteful still, having previously been dubbed the 'landfill dustbin of Europe'. We are getting better I might add, but still that label persists.

French's landfill in BT has been in the US Environmental Protection Agency's sights for quite a few years. So much so that there is a dedicated EPA entry on their website showing the various strategies and progress being made in cleaning up French's landfill.  It makes for unpleasant reading in terms of the types of contaminants identified and the history of potential contamination from the site.

The reason for my interest is this paper which has recently appeared in the journal NeuroToxicology. The paper by Guariglia and colleagues appears to question the outcomes from a previous report on BT drinking water and the occurrence of autism (which can be read here). They undertook to examine how water treated with compounds similarly detected in the BT municipal drinking water supply might affect specific breeds of mice. The compounds in question were trihalomethanes (THMs) and perchloroethylenes (PCEs) which carry some pretty significant risks following continued exposure including being carcinogens. The mice (and their mothers) were given the contaminated water both whilst pregnant and post-natally.

The findings, bearing in mind that this is a study based on a mouse model:

• Male mice seemed to be affected more by the cocktail given.
• Behaviours indicative of anxiety were increased. 
• Vocalisations in response to being separated from mother mouse were decreased. 
• Social behaviours were reduced.

I appreciate that undertaking such studies on mice is not really to anyone's taste. Even though mouse models are used widespread in science (including autism research) it doesn't necessarily make it right. Keeping the ethical aspects in mind, the results deliver some very interesting leads. Interesting because of the various associations made and how they link with quite a few aspects of autism including the gender preference. Of course, correlation does not imply causation.

This is not the first time that BT has cropped up on the autism research radar. Readers may remember this study from a decade ago which hinted that BT might be a 'hotspot' for autism diagnoses. I remember quite a lot of the media interest in this at the time, and the various links being made between environment, the superior schooling provisions in BT, etc. to account for the results. Nowadays, autism spectrum prevalence rates of 0.6% look positively low compared to the emerging data.

I would like to see a little more study undertaken based on the recent mice findings. Population sampling for similar metabolites present in humans might be a good start, particularly in BT; for which various methods for analysing various biological mediums are available (indeed some very sensitive methods available). Given the amount of data amassed by the EPA within BT, I would assume some very powerful results could be produced to contribute to any 'cause or association' discussions that could follow, if only to discount any relationship.

To end on a slightly happier note, Brick Township is dealing with French's landfill. Hopefully with the completion of these clean-up operations in future months, BT can focus on its more beautiful assets and turn the page on landfill and its potential environmental effects.