Blood lead levels and 'autistic behaviors in school-age children'

Lead (Pb) has been in the news quite a lot recently. The Flint water crisis (see here for some background) has brought back into stark view why science has pretty conclusive labelled lead as "a neurotoxin with no physiological functions in the human body, the ideal concentration of which in the blood is zero" [1].

I've talked about lead and behaviour quite a bit on this blog (see here and see here for example). The crux of the combined peer-reviewed research looking at lead and children is that the two don't mix well. In fact, the two don't mix at all. Not at all, and we should be doing everything possible to limit childhood exposure in particular.

So far I've tended to cover research on this blog suggesting that general behavioural 'issues' have been correlated with increasing levels of lead (as measured in blood) over and above specific types of behaviour. Autism or autism-associated behaviours has been mentioned (see here) but more speculatively than anything else, and also in conjunction with findings reporting an increased biological lead load (see here) at least for some on the spectrum.

The paper by Kyoung-Nam Kim and colleagues [2] brings autism or rather autistic traits, more squarely into the frame with lead in mind as a result of their findings: "Blood lead concentrations at 7–8 years of age (geometric mean: 1.64 μg/dL), but not at 9–10 and 11–12 years of age, were associated with more autistic behaviors at 11–12 years of age."

Looking at nearly 2500 South Korean children aged 7-8 years old (South Korea eh?), researchers measured blood lead levels and 'autistic behaviours' every 2 years until children reached 11-12 years old. The Autism Spectrum Screening Questionnaire (ASSQ) and Social Responsiveness Scale (SRS) were the tools of choice for assessing autism-related signs and symptoms. The results as I've just mentioned suggested that there might be some important *correlation* between blood lead levels at 7-8 years and offspring outcomes at 11-12 years. Indeed: "Even low blood lead concentrations at 7–8 years of age are associated with more autistic behaviors at 11–12 years of age, underscoring the need for continued efforts to reduce lead exposure."

OK, one has to be a little cautious about making too much of when one variable (blood lead level) is correlated with another (autistic traits) over the course of quite a long time. Set within the idea that there may be literally thousands of factors influencing the presentation of autism or autistic traits (or some of its important comorbidity), to pin everything just on lead is perhaps taking things a little too far. That other groups in other parts of the world have not noted any significant association between lead levels and autism [diagnosed autism] is also something else to mention (see here).

But, and it is an important point to make, it would perhaps be unwise to poo-poo the Kim results outright. We know, for example, that having a diagnosis of autism does not protect someone from lead poisoning [2] and one might even suggest that the risk is higher where autism coincides with issues such as pica [3] for example (see here). That screening for lead intoxication might also be preferentially offered to those with a diagnosis of autism for example [4] is another important point to make. Screening is the first step.

As and when lead intoxication is detected alongside autism, treatment should follow recommended guidance. If intervention *might* also have other effects linked to decreasing lead levels [5], one might reasonably ask questions about how the lead might indeed play an important role for at least some on the autism spectrum or presenting with autistic traits bearing in mind the dangers of generalising (see here)...

----------

[1] Hou S. et al. A clinical study of the effects of lead poisoning on the intelligence and neurobehavioral abilities of children. Theoretical Biology & Medical Modelling. 2013;10:13.

[2] Kim K-N. et al. Low-level lead exposure and autistic behaviors in school-age children. NeuroToxicology. 2016. Feb 11.

[3] Cohen DJ. et al. Pica and elevated blood lead level in autistic and atypical children. Am J Dis Child. 1976 Jan;130(1):47-8.

[4] Shannon M. & Graef JW. Lead intoxication in children with pervasive developmental disorders. J Toxicol Clin Toxicol. 1996;34(2):177-81.

[5] Eppright TD. et al. Attention deficit hyperactivity disorder, infantile autism, and elevated blood-lead: a possible relationship. Mo Med. 1996 Mar;93(3):136-8.

----------

Kim, K., Kwon, H., & Hong, Y. (2016). Low-level lead exposure and autistic behaviors in school-age children NeuroToxicology DOI: 10.1016/j.neuro.2016.02.004

Teeth, dentists and autism

In this post I want to cover some of the collected research looking at teeth, oral hygiene and dentists in relation to autism spectrum conditions in light of this paper by Yi-Chia Wang and colleagues* and the various indications for the use of dental anesthesia indicating paediatric autism.

I have, in passing, mentioned teeth and autism in previous posts; most notably in this post on self-injurious behaviour (SIB) and the potentially wide variety of reasons to account for instances of SIB in autism outside of just impulsivity and stereotypy (see here).

Anyone who has experienced the discomfort of toothache or those so-called wisdom teeth making a slow and protracted appearance might understand the feelings involved. Imagine if you will what potentially might happen were you not able to communicate such discomfort or get the required medical attention that you might need?

There is however so much more to this area.

Oral hygiene and trips to the dentist are often not an easy thing for many children and adults, whether diagnosed with autism (or anything else) or not. Brushing, flossing and mouth-washing have been instilled as an integral part of the daily routine across many parts of the world in order to keep our pearly whites, pearly white and reduce the instance of tooth decay (caries) and beyond. Aside from poor adherence to a good oral health regime, including watching what you eat, there are however a multitude of reasons why people in general still have issues with their teeth (see here).

The collected literature on autism and dental health is quite extensive both in topic and findings but with a few common points raised:

• Health inequality. For whatever reason, children (and adults) with autism, as in several other conditions, often have high rates of unmet dental needs as per studies like this one from Nelson and colleagues** and this one from Brickhouse and colleagues***. There are several possible reasons for this health inequality including: cost, locality and the availability of professional skills and experience of dentistry in cases of autism. I might add that such inequalities seem also to extend to other areas of healthcare too.
• Autism and anxiety. I don't think I need to say too much more about the relationship between autism, stress and anxiety that hasn't already been said before. Anxiety can happen for lots of different reasons outside of the more classical 'out of routine' line which is pretty extensively described. Doctors appointments have been mentioned as a potential source of anxiety (see here) and one has no reason to doubt that a visit to the dentist (white coats, bright lights, funny sounds and smells) might also bring about similar feelings for some, particularly if previous visits have not been altogether unadventurous. Not surprisingly papers like this one from Loo and colleagues**** add to the Wang paper and their talk about dental patients with autism as being more likely "uncooperative and required dental treatment to take place under general anesthesia". The anaesthetic bit automatically implies that the risks are heightened for some people with autism, even for what should be routine dental work.
• Dental health. There is still a degree of discussion about whether the presence of autism correlates with an increased risk of dental caries or not. The paper from Loo et al said not, as did Namal and colleagues*****. Other results say there is, as per this paper by Jaber******. There are potentially many factors influencing tooth decay so I will perhaps reserve judgement on what the main suggestion is in this area.
• Dental injuries. I've kinda touched upon this area previously in a post discussing the issue of pica and autism (the eating of non-food materials). Suffice to say that not every instance of pica will be over something soft like dirt or paper as per the bezoars and other items that have been reported in cases of autism. Rocks, coins and related hard matter are generally not good news for teeth. Allied to this area are reported instances of rumination (eat, regurgitate, re-eat) in cases of autism******* (full-text) which given the acidity of such contents is likely to be as detrimental to oral health as repeated vomiting. Finally, there is the potential effects of bruxism (gnashing of teeth) in cases of autism. I can't readily find any reliable figures about the overlap between bruxism and autism but certainly it is relationship that has been noted as per this article by Orellana and colleagues******** and when chronically present will most certainly impact on oral health. 

There are other areas which I could have talked about such as the oral effects of certain medicines, dietary patterns and habits in cases of autism and the whole sensory side of things in relation to oral health. I'm going to stop round about here though save you all getting too bored.

If there is any conclusion from the analysis of this area it is that oral health and wellbeing is an important part of healthcare in relation to autism. Understanding the issues which can follow autism is central to maintaining good oral health; not least in the provision of trained, professional dental care sensitive to those issues.

To close, the music chatter at the moment is all about Adele and the latest Bond theme tune. I have to say that out of all Daniel Craig's outings as 007, the Casino Royale theme tune was pretty good...

----------

* Wang YI. et al. Dental anesthesia for patients with special needs. Acta Anaesthesiol Taiwan. 2012; 50: 122-125.

** Nelson LP. et al. Unmet dental needs and barriers to care for children with significant special health care needs. Pediatric Dentistry. 2011; 33: 29-36.

*** Brickhouse TH. et al. Barriers to dental care for children in Virginia with autism spectrum disorders. Journal of Dentistry for Children. 2009; 76: 188-193.

**** Loo CY. et al. The caries experience and behavior of dental patients with autism spectrum disorder. Journal of the American Dental Association. 2008; 139: 1518-1524.

***** Namal N. et al. Do autistic children have higher levels of caries? A cross-sectional study in Turkish children. Journal of the Indian Society of Pedodontics & Preventive Dentistry. 2007; 25: 97-102.

****** Jaber MA. Dental caries experience, oral health status and treatment needs of dental patients with autism. Journal of Applied Oral Science. 2011; 19: 212-217.

******* Rhine D. & Tarbox J. Chewing gum as a treatment for rumination in a child with autism. JABA. 2009; 42: 381-385.

******** Orellana LM. et al. Oral manifestations in a group of adults with autism spectrum disorder. Medicina Oral, Patalogia Oral Y Cirugia Bucal. 2012; 17: e415-e419.

----------

Wang YC, Lin IH, Huang CH, & Fan SZ (2012). Dental anesthesia for patients with special needs. Acta anaesthesiologica Taiwanica : official journal of the Taiwan Society of Anesthesiologists, 50 (3), 122-5 PMID: 23026171

Takin' a peek at pica

I arrived at this post following a thought-provoking newspaper story recently with the headline: The boy who is eating his own bedroom. There is an obvious degree of journalistic flair attached to the headline but the underlying description of a young boy with autism munching his way through his bedroom is something quite notable and understandably a source of some distress to his parents.

Definition: 'pica is a pattern of eating non-food materials, such as dirt or paper'. So goes the description provided by PubMed Health. Indeed, pica is apparently not such an uncommon issue among young children and women in particular, as partners of pregnant women the world over think back to late night shopping trips for such 'inedibles' as pickled onions or marmite (just kidding).

Seriously though, pica during pregnancy can be a very real occurrence. Likewise, many parents will have probably seen something approximating pica at some point in their child's early years; whether it be that lovely wallpaper border you bought for the little darlings room (that wasn't cheap!) or that elusive missing piece of the jigsaw puzzle (which re-emerges a few days later from a galaxy far, far away in a nappy or toilet basin). I think Piaget called it the 'sensorimotor stage'.

Pica in cases of autism and related conditions has been discussed before on this blog in one of my posts on zinc. Indeed the link with zinc in cases of autism (as in, some suggestion of deficiency in quite a few cases) shares some interesting comparisons with regards to zinc deficiency and cases of pica slightly outside of autism as per studies like this one and this one. Zinc is not the only element being linked to pica as per other research on iron deficiency suggestive of a link.

Given this and other data with regards to what happens to pica when such nutritional deficiencies are remedied, one gets the impression that there may be some kind of nutritional search potentially on-going in cases of pica rather than just mindless eating. But that might not be the whole story as per my recent post touching on gustational sensitivity and autism.

Where pica is present, there are a number of potentially important issues that might need to be looked at.

• Bezoars and other foreign bodies are always going to be a concern depending on what is being eaten and its size. Various case studies litter the research environment with regards to intestinal obstructions in individual cases of autism as per these studies by Serour and colleagues* and Conyers & Efron**. I'm not quite sure about some of the suggestions put forward to stop pica behaviours such as the "minimally obtrusive, secure mask" suggested by Taylor & Walker*** and even less so for the use of aromatic ammonia examined by Rojahn and colleagues****. That's not to say however that behavioural 'training' might not have some effect on pica as per teaching about edible and non-edible items reported by Kern and colleagues*****.
• Given the material and objects that pica may include (e.g. soil) there is always a risk of either some kind of poisoning or infestation as a result. So blood levels of things like lead have been touched upon in the research literature (here) and indeed quite recently suggested to be something to watch where pica may be an issue****** (full-text). I assume other metals might also require similar monitoring. Insofar as infestation, and in particular, parasitic infestation, the research literature with autism in mind is still sparse. Certainly parasites such as Giardia lamblia causing giardiasis are known to be associated with pica and there may be others too.
• A final issue to bear in mind relates to the potential functional effect of long-term pica on teeth and dental health. I appreciate that dental health can be a tricky issue in relation to autism for lots of other different reasons not least difficulties in installing a consistent brushing routine and the effects of potential comorbidities such as bruxism (teeth grinding). If one considers that pica may include objects which are not necessarily all soft and fluffy such as stones/rocks, or may have the propensity to lead to frequent vomiting, you could see how teeth and oral health might also suffer. 

Appreciating that pica is not a part of every autistic persons behaviour, there are perhaps a few things that can be learned from pica when present. Regular readers of this blog will (hopefully) know that I am a bit of a believer in endophenotypes when it comes to autism - so subgroups are potentially apparent in the larger constellation that is know as 'autism'. The tie-up between pica and nutritional deficiencies is potentially an important clue to one of those phenotypes and dare I suggest it, a possible marker waiting in the wings?

* Serour F. et al. Intestinal obstruction in an autistic adolescent. Pediatric Emergency Care. 2008; 24: 688-690.

** Conyers R. & Efron D. Agitation and weight loss in an autistic boy. Journal of Pediatrics & Child Health. 2007; 43: 186-187

*** Taylor MB. & Walker RA. A minimally obtrusive, secure mask for prevention of access to the mouth. Clinical Rehabilition. 1997; 11: 77-79

**** Rojahn J. et al. Suppression of pica by water mist and aromatic ammonia. A comparative analysis. Behaviour Modification. 1987; 11: 65-74.

***** Kern L. et al. Reducing pica by teaching children to exchange inedible items for edibles. Behaviour Modification. 2006; 30: 135-158

****** Clark B. et al. Is lead a concern in Canadian autistic children? Pediatrics & Child Health. 2010; 15: 17-22

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.

Even Superman had problems with lead

Whilst the Man of Steel was all but impervious to bullets and explosions, he was not without his weaknesses. Kryptonite was his primary problem, but when it came to using that X-ray vision of his, another obstacle stood in his way, lead.

Lead (Pb or plumbum) has popped up here and there in a few recent posts on this blog. It was one of the factors, the reduction of which, was put forward to partially account for the drop in crime levels in the US in this post; a factor no-one can rule out in relation to the risk of being diagnosed with ADHD in this post; and also exemplified as the archetypal behaviour-changer in this post on detox. Yes sir, lead might have quite a bit to answer for.

Lead exposure is a well-known effector of health. For children with their developing brain in particular, lead exposure is not good news and can affect both physical and cognitive development. It is perhaps with these quite important effects in mind, that lead exposure has been looked at with reference to quite a few childhood conditions, including those with a developmental aspect to them such as ADHD.

The possibility that lead exposure either pre-, peri- or post-natally might be implicated in the risk of being diagnosed with an autism spectrum condition has also been the topic of some research. Studies such as this one, this one and this one have all suggested some (varying) association between lead exposure and autism, either on the basis of treatment figures or based on biological measures of detected amounts. The literature has been joined by this recent paper suggesting chronic lead toxicity in a number of children with autism resident in Saudi Arabia.

I have blogged about the Saudi research group involved in this new study already, based on their excellent publication record this year in autism research which rivals that of the MIND Institute and Prof. Jim Adams. In this latest trial, for which I only have the abstract so far, it appears that they are signalling post-natal lead toxicity as, quote ".. could represent a causative factor in the pathogenesis of autism" on the basis of some very high levels of the lead ion being detected in plasma. Don't ask me how they made the detection because I don't have the full-text paper yet, but I would hazard a guess that based on their results they might have used our old friend ICP Mass Spectrometry or possibly via atomic absorption.

I don't want to go too overboard on this latest study yet. It is interesting to note that lead poisoning in the early years can affect various brain functions including synaptogenesis and the correct functioning of the blood-brain barrier. Both of which have been implicated, to varying degrees in cases of autism and related developmental conditions. Having said that, autism does not seem to have a monopoly on these issues outside of other conditions; whether such mechanisms could so fundamentally affect a person as to 'lead' (pardon the wordplay) to autism or autistic symptoms I don't know.

There are various potential implications from any association between lead and autism. Risk issues such as the environment, the prevalence of pica in autism and the various suggestions about the use of chelating agents to remove bioaccumulated lead all might figure in any discussions. What I would perhaps like to see initially is some guidance on ruling out lead poisoning in any and all cases of developmental diagnoses as a routine measure, bearing in mind what is known about the effects of lead and the developing brain.