Autism prevalence increasing in New Jersey

A quote to begin with from the paper by Walter Zahorodny and colleagues* with special thanks to Natasa for the full-text of the paper on the prevalence of autism spectrum disorders (ASDs) in New Jersey: "Regardless of whether one acknowledges an increased ASD prevalence, all the epidemiological and administrative studies confirm that ASD is now among the most common, severe, developmental disorders".

Edison in his NJ workshop @ Wikipedia  

For me this quote encapsulates everything about the various autism prevalence (and incidence) debates which have been, and continue to be, rife particularly in cyberspace.

It kinda says, yep we don't know all the details behind the quite enormous rise in cases of autism - which lets face it, basically boils down to whether or not you believe environment in whatever form contributes to autism aetiology - but whatever the reason(s), autism is not an uncommon condition and has a huge range of implications stretching from the diagnosed individual, their families, their schools, their doctors through to society as a whole.

Indeed, the paper from Zahorodny has lots of other soundbites worthy of quoting, but just before I head out that way, a few snippets of information about the paper are in order:

• This was a study all about comparing the estimated prevalence of ASD in the New Jersey Metropolitan Area (NJMA) in 2002 with some newer data from 2006.
• The focus was on using "identical methods and procedures" between the two time points drawing on the ADDM method which included active-screening and subsequent independent case determination. 
• Children born in 1998 and residing in the study area in 2006, classified as being educated under any special education classification (equivalent to receiving a SEN) were the starting point, filtered down to those with a documented or suspected ASD diagnosis, whose data were subsequently subjected to clinician review and analysis. "Agreement between previous ASD diagnosis and ASD case status by the surveillance method was 99%".
• Results: In 2006, out of a population of 30,570 8-year olds, 3,332 child records were reviewed, 923 of which met criteria for further review, which identified 533 with study-determined ASD, equal to a prevalence of 17.4 per 1000 (1.7%). This compared with 2002 data (8-year olds born in 1994) suggestive of a prevalence rate of ASD of 10.6 per 1000 (1.1%). The data is a little confusing because two different estimates are given based on the use of curtailed and non-curtailed populations; one used a sort of comparator to assess any changes in population affecting the estimates. 
• Allowing for the slight differences, the authors determined that 1 in 57 8-year olds in NJMA in 2006 had an ASD and a "startling" 1 in 35 boys.
• Between the sexes, ASD prevalence in boys grew from 17 to 28.7 per 1000 between 2002 and 2006 and 4.1 to 5.9 per 1000 in girls. 
• Regression, that most interesting of phenomenon with autism in mind, was relatively unchanged; the rate hovering around the 20% of cases mark.
• Quite a few factors potentially influencing the numbers were also taken into account including migration. That on top of the fact that DSM-IV TR was the main assessment criteria across the time periods.

This is an interesting study for lots of reasons. Not least because using identical protocols and identical criteria, a change in the prevalence of ASD was noted over 4 years. One therefore, to quite a strong degree, also rules out changes in DSM diagnostic revisions as a cause of the changes and to some extent those arguments about widening criteria as was evidenced between DSM-III and DSM-IV. That being said, the issue of increased awareness and its impact cannot be ascertained from this data; indeed also diagnostic substitution to some extent also remains a possibility (i.e. from learning disability to autism) as does under-diagnosis of ASD in non-white groups. This last point however needs to be tempered by the authors demonstrating a 90% increase in cases of ASD among Black, non-Hispanic children but also indicating "a broadly based escalation of ASD, rather than an increase reflecting improved case-finding in specific populations".

I get the impression that the authors were hinting that the change they reported might be more administrative over real. So they say: "It is too soon to know at what point ASD prevalence will plateau", which implies to me that they are looking to the autism rate increase to somehow eventually 'bottom out' when the message finally gets through about autism awareness and what it is. I hope I don't seem too rude when I say that we've all been waiting for that plateau for quite a few years now so as to save those 'it must be better case ascertainment' arguments, but so far there is no end it sight at least according to the latest CDC estimates. I'm sure even the staunchest supporters of the better awareness et al camp would quite logically admit that at least part of the increase might not necessarily reflect just 'better awareness' and 'more diagnostic substitution' but rather some other factor or factors also being involved? Or maybe not....

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* Zahorodny W. et al. Increasing autism prevalence in metropolitan New Jersey. Autism. November 2012.

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Zahorodny, W., Shenouda, J., Howell, S., Scotto Rosato, N., Peng, B., & Mehta, U. (2012). Increasing autism prevalence in metropolitan New Jersey Autism DOI: 10.1177/1362361312463977

The continuous nature of autism symptoms

The proposed revisions to the DSM re-definition of autism becoming an actuality are fast approaching over the clinical horizon as we are told that the die has now been cast. Although there is still considerable debate about what the changes will do to the numbers of people eligible to receive a formal diagnosis of the label autism as per previous revisions, one of the more well-received changes to the criteria is the formal acceptance that autism is a spectral condition, and that the severity of presentation of the soon-to-be dyad of core symptoms, reflects as much.

Prisms @ Wikipedia  

The spectrum concept, whilst not wholly supported by everyone, provides an intellectually satisfying description of the heterogeneity present in autism but also implies a few important principles must be accepted.

One of them is the assumption that for autistic traits to become clinically relevant, there must be a start point in the same way that the visible light spectrum has a very fuzzy beginning. Following this argument, and accepting that diagnosing clinicians are still as much artists as they are physicians when it comes to autism and other developmental disorders solely reliant on observation and developmental history, the question is: where do the symptoms of autism begin?

A recent paper by Kamio and colleagues* (open-access) looked at this question and came to some very interesting conclusions.

• The name of the Kamio game was to look at the quantitative distribution of autistic traits in a rather large normative population sample of children (N=22,529) in Japan aged 6-15 years based on parental ratings of the Social Responsiveness Scale (SRS). There were also other data included in the results based on child psychiatric patients with an autism spectrum disorder (ASD) (n=257) and without (n=157) but receiving other diagnoses such as ADHD, schizophrenia and learning disability. And also a typically developing group (n=61) with no neuropsychiatric history. These latter groups were included primarily to validate and calibrate the Japanese version of the SRS. Normative data from a US sample used to validate the US version of the SRS were also included as some points.
• Results: there were quite a few of them. The main message is, as per the title of this post, that results "add substantial evidence in support of the continuous nature of autistic traits in the general population" and specifically "there was no evidence of a natural cutoff that differentiated children categorically affected from those unaffected by ASD".
• The male : female differences were also confirmatory that boys exhibit quantitatively higher autistic trait scores than girls as per other findings.
• An interesting thought is entertained based on the capability of the SRS to distinguish autism from other conditions, "autistic traits, when present, exacerbate other types of psychopathology when they cooccur with autistic traits as comorbid conditions". In effect autism might magnify the symptoms of other comorbid conditions such as ADHD.

Some of this data takes me back to my Ph.D write-up days, and what I was once told by someone involved in my studies. It went something like this: autism is a distinct condition diagnosable on the basis of that triad (soon to be dyad) of symptoms, but most if not all of the traits present in autism are to some extent also present during typical development at specific periods. I must admit that at the time I had some trouble believing this, after all autism can be associated with some very extreme characteristics and symptoms.

As the years have gone on however, I've understood that those lining up of toys, spinning of wheels, flicking of fingers, even pronoun reversal and other communicative features, are present in typically developing children too at specific times of development; autism merely describes the unusual persistence of these behaviours or quantitative differences in their presentation. Of course this takes no account of symptoms which might not necessarily be totally psychological in nature, as per what can happen when gastrointestinal symptoms are present and potentially exert an effect on behaviour for example.

With all that in mind, it's not so surprising that there is no distinguishable natural cut-off point when it comes to autism or not-autism in those border regions outside of the lines in the sand that we draw, or rather our diagnosing clinicians and clinical symptom makers impose. I assume that's why we also have the concept of the broader phenotype further illustrating these fuzzy boundaries.

That being said Kamio and colleagues do suggest that "segments of the autistic continuum may be comprised of small clusters of discrete disorders". This point really intrigues me, in that they are in effect talking about more than one type of autism; a spectral type which basically runs from typical development through to autism, and a second type which includes a number of known conditions which manifest autism, such as Fragile X syndrome and indeed, that recent in-born error of branched chain amino acid condition. The rise of the autisms indeed.

I must finally pass some comment on that comorbidity suggestion which basically theorises that autism might magnify the effects of certain comorbidities. It really is an interesting finding which is deserving of a whole lot more study, particularly in light of how much increased risk of other comorbidity such as ADHD a diagnosis of autism can convey. Readers might know that I have a bit of a thing for comorbidity and autism on this blog, and indeed how tackling comorbidity - however this manifests - can sometimes impact on core presentation. Think dietary intervention as one example.

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* Kamio Y. et al. Quantitative autistic traits ascertained in a national survey of 22 529 Japanese schoolchildren. Acta Psychiatr Scand. November 2012.

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Kamio, Y., Inada, N., Moriwaki, A., Kuroda, M., Koyama, T., Tsujii, H., Kawakubo, Y., Kuwabara, H., Tsuchiya, K., Uno, Y., & Constantino, J. (2012). Quantitative autistic traits ascertained in a national survey of 22 529 Japanese schoolchildren Acta Psychiatrica Scandinavica DOI: 10.1111/acps.12034

T.gondii and dietary gluten joining forces?

Looking back at the way this blog has taken shape over the nearly two years that its been running, certain topics have tended to predominate which I freely admit that I knew very little about before getting into this blogging malarky.

Cold cat @ Wikipedia  

Had anyone suggested that one day I would be reading and writing about critters like Toxoplasma gondii (T.gondii to its friends), I previously would have replied 'yer what?' with puzzling facial expression to match.

Nevertheless I have found myself drawn into discussing research on this survivor and in particular how it might do so much more than just infest quite a few people around the world with particular focus on its potential role in conditions like schizophrenia, or at least some cases.

Enter then another study by a familiar name to this blog, Emily Severance and colleagues* (open-access) discussing T.gondii and some interesting possibilities on how it might be able to alter the immune response to dietary gluten, in mice, with potential implications for schizophrenia and even autism.

The research of Dr Severance and colleagues, as mentioned, has appeared twice on this blog so far as per posts on gastrointestinal (GI) inflammation in cases of schizophrenia (see here) and C1q activation (see here). I was particularly impressed with the GI inflammation paper it has to be said, not least because it introduced a really interesting investigative tool (anti-Saccharomyces cerevisiae IgG antibodies) which I thought could easily be looked at with autism in mind.

To the more recent paper:

• Aside from one of our papers getting a mention (thank you!), the study aimed to look at how infection with T.gondii might impact upon the way the immune system recognises and deals with the dietary protein gluten in a mouse model, in a sort of infection-changing-immune-system type way.
• Balb/C mice were infected with T.gondii via one of three routes: intraperitoneal (IP), peroral (PO) (via oral-diet), or prenatally.
• Antibodies (IgG) to T.gondii, gluten and C1q were measured.
• Results: I seem to say this everytime, but lots of results were generated. Perhaps the most important was the finding that infection with T.gondii was 'convincingly' (author word not mine) related to the production of gluten antibodies. 
• Second in importance was the finding that prenatal exposure to T.gondii as in the offspring of female mice who were infected, showed an elevation of antibodies to T.gondii when mummy mouse was seropostive for T.gondii which also coincided with very significantly elevated antibodies to gluten and C1q. Also, the "female sex is more severely affected following T. gondii infection".
• Finally(!) there is a suggestion of some involvement for gut hyperpermeability (the so-called leaky gut) in this story, as per the question of "how T. gondii strains gain access to systemic circulation, but a para-cellular route affecting epithelial tight junction proteins is suspected". And even those words "bacterial translocation" and "zonulin" are mentioned as part and parcel of how T.gondii might be able to open up the gut membrane and potentially allow gluten peptides to come into contact with the immune system. Not a million miles away from what's been talked about with autism in mind previously.

And rest. So, we are presented with lots of potentially important statements here concerning how infection might combine to promote an immune response to an important dietary component like gluten. We are also given a hint that maternal infection might also lead/cause/be associated with an immune response to dietary gluten in offspring. Sounds to me like some quite important leads there and more than a passing relationship with other work looking at immune activation models of conditions like autism (hint: Paul Patterson and colleagues). I also wonder whether there may be other, wider considerations of maternal immune activation as per those findings on maternal antibodies to foetal brain and the transglutaminase research in autism.

With the old science hat on, I have to reiterate that this was a study of mice not humans, and as far as I can remember these results are slightly at odds with the other C1q activation and T.gondii data previously presented**. Independent replication is also required, but I'm not going to take anything away from these very, very interesting findings which perhaps mirror other findings of infection triggering antibody production*** (many thanks to Natasa for this last link).

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* Severance EG. et al. Anti-gluten immune response following Toxoplasma gondii infection in mice. PLoS ONE. 2012; 7(11): e50991.

** Severance EG. et al. Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia. Neurobiol Dis. 2012; 48: 447-453.

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Emily G. Severance, Geetha Kannan, Kristin L. Gressitt, Jianchun Xiao, Armin Alaedini, Mikhail V. Pletnikov, & Robert H. Yolken (2012). Anti-Gluten Immune Response following Toxoplasma gondii Infection in Mice PLoS ONE : doi:10.1371/journal.pone.0050991

Metal measuring and autism

Now and again, two papers of a similar ilk are published temporally close together in the great autism research melting pot so as to cumulatively make for interesting reading.

Congratulations, it's a baby T-1000 @ Wikipedia  

In the case of this post, I am referring to the paper by Jim Adams and colleagues* and the paper by Yahya Al-Farsi and colleagues** which both examined the burden of metals present in cases of autism from the perspective of two very different geographical areas of the world. Both papers are published in the same journal too.

I should say that I've covered metals, heavy and toxic, before on this blog with reference to the background to this whole area (see here) and some research on that most controversial of areas, mercury and autism (see here). As with just about every other instance of autism research, the message is a messy one, with no 'one-size-fits-all' finding, which often wrongly gets translated as either 'it must be a universal effect' or 'there must be no effect' with seemingly no middle ground where the autisms are concerned.

Anyhow, a few details about the papers:

The Adams paper:

• The hypotheses were: (a) "children with autism would have higher levels of some toxic metals in their blood and urine" (n=55) compared with asymptomatic controls (n=44), and (b) the severity of symptoms would be associated with the toxic metal burden.
• This current study formed part of a wider body of work undertaken and published by the authors*** (open-access) looking at children aged 5-16 years. This follows other work in a similar vein**** (open-access).
• Morning blood and urine samples were eventually analysed by an old favourite method (ICP mass spectrometry) and the severity of autistic symptoms assessed by various means including the ATEC.
• Results: there were quite a few of them but most notably levels of lead in red blood cells (RBC) and urine were significantly elevated in the autism group compared with the control group, alongside urinary thallium, urinary tin and urinary tungsten.
• In terms of the measured severity of autism correlating with the metals findings, a slightly complicated picture emerges which suggested that whole blood and RBC mercury concentrations showed "possibly" significant correlations with the three assessment instruments used.
• The authors conclude that their results suggest that either there is increased exposure to these metals, increased absorption of these metals or decreased (fecal) excretion of these metals or some combination of these explanations. 

The Al-Farsi paper:

• A very similar starting point by all means, testing the hypothesis that "children with ASD will show variations and deregulated levels of heavy metals and essential minerals when compared to non-ASD controls".
• Based in the Sultanate of Oman, hair samples from children with DSM-IV autism (n=27) were analysed again by ICP-MS for the presence of various heavy metals and compared with results from age- and sex-matched asymptomatic controls (n=27).
• Results: again, quite a few but generally speaking levels of heavy metals were elevated in the autism group compared to controls, and included cobalt, cadmium, chromium, aluminium and also our old friend lead.
• When also looking at levels of essential minerals, a slightly more mixed picture emerges with lower levels of calcium and copper to be present but higher zinc, iron and sulphur (to name but a few).

OK, there are a few differences to point out between these studies outside of just the ethnicity of their autism cohorts and the possible differences in geographical exposure patterns. The Adams paper looked at blood and urine, the Al-Farsi paper looked at hair. The mean ages of the groups examined were also slightly different (Adams: autism = 5.3 years; Al-Farsi: autism = 10 years). So we are not able to directly transpose results one on top of another.

That being said, there were some similarities to these results not least about those findings related to lead. Indeed, I have quite an interest in all things lead for quite a few reasons, not least that even Superman had problems with lead so why wouldn't children exposed to the stuff, and those figures from last year (2011) which listed lead reduction as being one potential candidate among many as to why the US crime figures were falling. Exposure to lead is generally speaking not a great thing for developing or developed brains/bodies.

I'll admit to not being a great expert on how hair, blood and urine samples compare when looking at metals or any other kind of chemical/compound so I can't offer too much in the way of information about the functionality of these measures and the extent to which they reflect levels of these metals or indeed evidence of storage and any on-going physiological activity / effect. I am for some reason drawn back to the very recent CHARGE findings on air pollution and autism (bearing in mind that the reduction of lead in petrol we've seen over the past few decades) as an interesting variable potentially relevant to these results but will say no more than that at this time.

Accepting the issue of hair analysis, the Al-Farsi findings revealed some interesting trends with reference to the trace minerals examined. Higher zinc, higher iron and higher sulphur raise questions about what this means in light of other research indicating lower hair zinc (see this post) for example, and indeed that body of research on iron levels in autism (see this post and this post). The curse of messy heterogeneous autism research?

Interestingly both papers seem to wade back to similar biochemical pathways in terms of the potential significance of their findings. So glutathione pops up (see this post on where glutathione sits in the current autism research world) and how glutathione is a key component in both the processes of antioxidation-oxidative stress as well as being tied into the removal of things like metals. The feeling is that the consistently lower levels of glutathione (GSH) noted in cases of autism is probably not going to be a great thing for the biological processing of such toxic metals.

Both papers end with calls for further research into this complicated (and often controversial) area. I'd like to second that call given that this is a topic which seems to be cropping up more regularly in recent years. I know that when people start talking about toxic metals and autism, specific toxic metals, some conversations instantly move into areas which make some people a little uncomfortable. Irrespective of what causes such issues to become apparent, the questions must surely be (i) what effect, if any such burdens have contributing to the presentation of autism or indeed any of its potential comorbidities and (ii) whether there is something that can be done to ease any burden and what, if any, effects this might have on symptoms.

To close, how can I not make reference to some great music following a post about metal. Take it away AC/DC.

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* Adams JB. et al. Toxicological status of children with autism vs. neurotypical children and the association with autism severity. Biol Trace Elem Res. November 2012.

** Al-Farsi YM. et al. Levels of heavy metals and essential minerals in hair samples of children with autism in Oman: a case-control study. Biol Trace Elem Res. November 2012.

*** Adams JB. et al. Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity. Nutr Metab (Lond). 2011; 8: 34.

**** Adams JB. et al. The severity of autism is associated with toxic metal body burden and red blood cell glutathione levels. J Toxicology. 2009; Article ID 532640. doi:10.1155/2009/532640

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Adams, J., Audhya, T., McDonough-Means, S., Rubin, R., Quig, D., Geis, E., Gehn, E., Loresto, M., Mitchell, J., Atwood, S., Barnhouse, S., & Lee, W. (2012). Toxicological Status of Children with Autism vs. Neurotypical Children and the Association with Autism Severity Biological Trace Element Research DOI: 10.1007/s12011-012-9551-1

Al-Farsi, Y., Waly, M., Al-Sharbati, M., Al-Shafaee, M., Al-Farsi, O., Al-Khaduri, M., Gupta, I., Ouhtit, A., Al-Adawi, S., Al-Said, M., & Deth, R. (2012). Levels of Heavy Metals and Essential Minerals in Hair Samples of Children with Autism in Oman: a Case–Control Study Biological Trace Element Research DOI: 10.1007/s12011-012-9553-z

Targeting mitochondrial dysfunction in ME/CFS?

Consider this post a bit of a follow-up to a previous one based on some interesting observations by Booth and colleagues looking at mitochondrial dysfunction in cases of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS).

Join the Stone Age dots? @ Wikipedia  

Same authorship group but this time around presenting the results of an audit of patients who underwent examination based on the ATP profile (no endorsement given) and what they did about it published by Sarah Myhill and colleagues* (open-access).

I will at this point just reiterate my caveat about not giving advice, medical or otherwise, on this blog and hence not advocating anything based on discussions about the Myhill paper. I'm just talking, nothing else.

So here goes:

• The paper is based on the same 138 participants diagnosed with ME/CFS as described on their previous paper and how, when a multi-faceted intervention regime was put in place, some of the participants fared in terms of their mitochondrial profiles and presented symptoms.
• I say that this paper describes some of the original cohort; in essence this boils down 34 of them who had more than one ATP profile "separated by some months" of which 30 followed the intervention regime with vigour and 4 participants who were a little more lax. Bear in mind this was reported as an audit not a clinical trial.
• What was the treatment regime? Well, (a) a stone age diet which I assume is similar to a Paleolithic diet(?), (b) a good sleeping routine, (c) a supplemental vitamin/mineral/other regime and (d) assuming an appropriate work-rest balance; pacing but not PACE.
• Elements of these interventions were specifically tailored for participants based on their mitochondrial and other tests of nutritional status. Interestingly the authors report on some familiar issues as per often finding "deficiencies in glutathione (GSH) and glutathione peroxidase (GSH-PX) which are needed  to protect cells from oxidative damage and to detoxify xenobiotics". Other elements that turned up on the various testing panels were slightly more contentious as per the suggestion that "High levels of heavy metals can be tackled using selective chelation therapy".
• Results: there are some case histories reported and quite a bit of data per participant per testing occasion. I'll let you draw your own conclusions from what is described but in essence, the authors observed that there was some degree of responsiveness to the interventions shown on the repeat testing profiles for some of the participants. The caveat being that there was as expected, some degree of variability in response potentially affected by lots of variables, not least because individuals are individuals, and also probably due to the intervention regime itself.
• The authors report that "All 30 of the multiple test patients who followed the treatment protocol have increases in the major parameters of mitochondrial function and in the Mitochondrial Energy Score".
• The co-factors involved in ATP production - niacinamde, L-carnitine, coenzyme Q10 - also saw some interesting changes between baseline and post-intervention testing as a function of "% within normal range" though not presented in absolute mean values (pre- and post).
• All that being said, there is little in the way of formalised description as to the presentation of symptoms, and whether and how these overlapped with such changes (perhaps reiterating the audit nature of this paper).

For those who might be rather sceptical of this area of functional medicine, mitochondria being involved in ME/CFS or even members of the authorship group themselves, it would be easy to dismiss this paper as being nothing more than an advert for the clinical services of the authors. It is not a formal study of mitochondrial function being assessed or 'modified' in cases of ME/CFS, it focuses on individuals not groups, and there are plenty of scientific holes in how and what results have been presented (or not).

But step back a little and consider a few things. ME/CFS is probably in an even worse clinical position that autism for example, is at the moment. Whereas autism (mostly) enjoys the recognition of being a biologically-based neurodevelopmental condition, ME/CFS is still, in some quarters, thought to be a purely psychiatric condition, where sufferers - yes, people do suffer from ME/CFS - are thought to be either mentally ill or perhaps just as bad, to be hypochondriacs. Labels such as yuppie flu didn't really help matters either.

The next hurdle to be faced is the fact that the presentation of ME/CFS is heterogeneous. Even the diagnostic criteria for the condition has not been fully agreed upon, or at least as a condition with universal diagnostic consensus. That even before we start talking about comorbidity and the like.

When taking these factors into account, it does start to make a little more sense as to why initial, preliminary investigations should reflect these factors. So that mitochondrial issues might be part and parcel of ME/CFS or at least some cases, that reporting and correcting mitochondrial dysfunction might involve different strategies for different people, and that sticking to an intervention regime is not always possible in an intention-to-treat analysis manner, particularly when you are dealing with a condition which impacts so centrally on a person. Don't get me wrong, I'm not standing up for the use of audits over clinical trials - randomised, controlled clinical trials - but do consider this paper, and the previous publications from the authors, to be a good first step of where further investigation should be carried out.

Of course I would very much like to see more formal study not just on what happened to biochemistry as a result of the interventions discussed by Myhill and colleagues but also on overt signs and symptoms and importantly overall quality of life (QoL) outside of just clinical measures. Dietary changes such as those discussed are no laughing matter and can, on occasion, negatively impact on QoL as a consequence of their restrictiveness. Indeed as per other mentions of diet and ME/CFS on this blog, one wonders whether there may be either certain elements of the Stone Age diet which might be more usefully connected to cases, or indeed whether underlying clinical comorbidity such as coeliac disease or non-coeliac gluten sensitivity might be important to symptoms and outcomes.

Whatever your views on this area of research or more generally the definition of what ME/CFS is or isn't, this is peer-reviewed research and therefore represents an addition to the scientific literature and a challenge to the scientific community to undertake further independent replication save any repeat of XMRV...

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* Myhill S. et al. Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) – a clinical audit. Int J Clin Exp Med 2013;6 : 1-15.

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Myhill S,, Booth NE,, & McLaren-Howard J (2013). Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) – a clinical audit International Journal of Clinical & Experimental Medicine, 6 (1), 1-15

CHARGE, traffic pollution and autism

The headline reads "Traffic fumes linked to autism". The sub-heading describes how babies who were exposed to traffic air pollution during their first year of life "are more likely to become autistic". Welcome to the study by Heather Volk and colleagues* on traffic pollution, particulate matter and risk of autism.

Motorbiking... @ Wikipedia  

Before heading into the paper, the discerning autism research reader will no doubt remember that this is a topic which has already cropped up in autism research circles, and indeed by the same authorship group** (open-access).

The difference being that on the previous occasion, the focus was on in-utero proximity to traffic-related air pollution "as a surrogate for air pollution exposure", whereas the current study looked at both gestation and first-year estimates of exposure.

A few details of the most recent study:

• Another CHARGE-related investigation, which estimated air pollution and air quality based on mum's address for the various stages of pregnancy and first year of life for 279 children diagnosed with an autism spectrum disorder (ASD) compared with 245 typically-developing controls.
• The US Environmental Protection Agency (EPA) datasets on regional air pollution were cross-indexed with addresses, and some statistical wizardry applied.
• Results: compared with control participants, exposure to traffic-related air pollution by residence was highest for the autism group particularly during the first year of life (adjusted odds ratio = 3.1). Exposure to particulates (sub 10 and 2.5 micrometres) based on regional exposure measures were also associated with autism during the first year of life.
• The authors conclude: "Exposure to traffic-related air pollution, nitrogen dioxide, PM2.5, and PM10 during pregnancy and during the first year of life was associated with autism". The possible effect being one of inflammation (quite a regular visitor to autism shores it has to be said).

One obviously has to be quite careful with such studies of association and all that 'correlation does not equal causation' jazz. On that basis I'm not going to start any great fanfare about this research despite the intricate datasets which have been compared, and the previous body of research that it follows.

That being said, neither am I going to discard these results as being just coincidence. Air pollution is a serious environmental issue related to health; potentially acting in a multitude of ways depending on what type of pollution is present, the level of exposure*** and the age of the exposee. We've seen hints that air pollutants might play some role in cases of autism as per another study of association on meteorological factors and autism recently discussed on this blog. Definitive data is however somewhat lacking including more direct measurement of airborne pollutants and any residual traces that they may leave.

Autism is also not alone in its purported link to air pollution as exemplified by this paper by Siddique and colleagues looking at air pollution and ADHD****. Other research has attempted to link air pollution to issues with cognitive abilities*****. The primary question arising from such research is to ask whether the recent Volk data may reflect any of these comorbidities/issues above and beyond an exclusive link to autism?

Outside of just traffic-related air pollution, the air that we breathe is home to lots of other things too; some things which just don't even bear thinking about (dog poo bacteria, yep you heard me right). Questions are being asked about air quality in our cities on quite a grand scale nowadays and in conditions like autism, fast becoming a 'health priority' (and not before time), the research net should be cast as wide as possible to determine the contribution of environment (if any) to the astounding number of cases of autism estimated and being diagnosed.

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* Volk HE. et al. Traffic-related air pollution, particulate matter, and autism. Arch Gen Psychiatry. November 2012.

** Volk HE. et al. Residential proximity to freeways and autism in the CHARGE study. Environ Health Perspect. 2011; 119: 873–877.

*** Valavanidis A. et al. Airborne particulate matter and human health: toxicological assessment and importance of size and composition of particles for oxidative damage and carcinogenic mechanisms. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2008; 26: 339-362.

**** Siddique S. et al. Attention-deficit hyperactivity disorder in children chronically exposed to high level of vehicular pollution. Eur J Pediatr. 2011; 170: 923-929.

***** Suglia SF. et al. Association of black carbon with cognition among children in a prospective birth cohort study. Am J Epidemiol. 2008; 167: 280-286.

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Volk, H. (2012). Traffic-Related Air Pollution, Particulate Matter, and AutismAir Pollution, Particulate Matter, and Autism Archives of General Psychiatry DOI: 10.1001/jamapsychiatry.2013.266