Wednesday 30 January 2013

Autism and the criminal justice system

I assume most people with a connection to autism, either personal or professional, will have heard about the case of Gary McKinnon and his long-running battle against extradition from the UK to the United States to face charges of alleged hacking into various US Government systems.
Order @ Wikipedia 

The politics have, over the 10-year period of this saga, tended to focus more on the extradition arrangements between the UK and US over and above the actual person, his Asperger syndrome diagnosis (and some possibly conflicting reports about his mental state) and the reasons given for his alleged actions.

I'm sure, like me, many people (but not all apparently) were happy to hear that this ordeal for Gary has now come to some kind of end with the news that he will not face charges here in the UK. When however it comes to other people such as Syed Talha Ahsan, also diagnosed with Asperger syndrome but nonetheless extradited to the US, things have not turned out so well. Indeed there has also been some debate about possible double-standards.

I'm not here to talk politics and political decisions but I did wonder if it might be time to revisit autism, or rather the autism spectrum, and the law in light of the Gary McKinnon news (and it was big news) and also the paper by Catherine Cheely and colleagues* on the prevalence of youth with an autism spectrum disorder in the criminal justice system.

Regular readers of this blog might remember a post I wrote a while back on autistic symptoms and offending. The crux of that entry was the quite generalised assertion being raised by Geluk et al** detailing autistic symptoms as being "more prevalent in childhood arrestees compared to the general population and are uniquely associated with future delinquent behavior". I hasten to add that, as in the last post, I'm not intending to generalise, demonise or any other -ise in this entry on this quite delicate topic particularly with other recent tragic events still very much in mind.

Back to the paper by Cheely:

  • The aim of the study was three-fold: (i) look at the types of charges against youths with an autism spectrum disorder (ASD), (ii) examine adjudication outcome compared with a control cohort and (iii) see what was different about those with ASD charged compared with a cohort not charged.
  • Six hundred and nine youths with an ASD were identified from the South Carolina Autism and Developmental Disabilities Monitoring Project (SC-ADDM). That's right, one of the CDC surveillance sites used to formulate things like their prevalence estimates (see the 1 in 88 post) based on 8-year olds.
  • Five percent (32/609) of the cohort had contact with the criminal justice system and were charged with 103 offences (mean 3.3 offences per child).
  • Compared with non-ASD control youths, there was a tendency for more crimes to be committed against a person over property and generally more likely to be school-based.
  • Adjudication-wise, youths with ASD were significantly more likely to have their cases diverted and less likely to be prosecuted; indeed none of the cohort were sentenced to detainment.
  • The differences between charged youths with ASD vs. controls ASD participants? Well, the presence of intellectual disability (ID) (learning disability if you will) was less likely to occur in ASD youths committing offences.

As the authors point out, there is a feeling that most of the charges made against the youths with ASD in their study seem to eminate from spontineity over pre-meditation; something perhaps reflected in the zero percent detainment rate.

That and the fact that school seemed to be a focal point for such behaviours perhaps offers further clues about factors such as stress and anxiety as being involved and combining with anger (see the study by Quek and colleagues***), even whether inclusion might be part and parcel of the issue here (see this blog post by Zoe on a recent paper published in the autism special edition of Pediatrics).

One could try and get really technical and start talking about issues with empathy and inferring mental states as also being involved in such behaviours too, but to tell you the truth I doubt any adolescent, whether diagnosed with autism or not, truly uses such functions in this type of scenario which seems more probably like 'lashing out'. I must also make mention of the issue of bullying as potentially being related to offences highlighted by the authors in light of what has been discussed in this area in recent times and continues to be talked about.

I don't want to come across as an apologist or anything like that in this post given that an individual's diagnosis of ASD has (rightly or wrongly) been discussed in relation to some very serious crimes**** (open-access) down the years, bearing in mind that we cannot tar everyone with ASD with the same brush. One also needs to put the numbers of offences linked to ASD into context with all the other crimes carried out by non-autistic people, which I'm sure impact on many, many more people and indeed the number of occasions where people with autism themselves are a victim of crime, even in some cases by those who are meant to protect and serve.

In terms of where next with this topic of research, I'd actually like to see more done in a few areas. Things like looking at long-term outcome for that 5% who committed offences in terms of developmental course, any additional comorbidity which developed and were identified and importantly whether there was any further contact with the criminal justice system would be a good start. At least then we might get some ideas about whether we are indeed talking more about individual lapses in behaviour over something more chronic as per the literature so far on this topic*****.


Additional note: The majority of this post was conceived and written in November 2012 based on the peer-reviewed research literature available at that time. I would kindly ask that any comments or opinions posted about this entry be confined to discussions about the scientific papers mentioned. Thanks.


* Cheely CA. et al. The prevalence of youth with autism spectrum disorders in the criminal justice system. J Autism Dev Disord. 2012; 42: 1856-1862.

** Geluk CA. et al. Autistic symptoms in childhood arrestees: longitudinal association with delinquent behavior. J Child Psychol Psychiatry. 2012; 53: 160-167.

*** Quek LH. et al. Co-occurring anger in young people with Asperger's syndrome. J Clin Psychol. 2012; 68: 1142-1148.

**** Haskins BG. & Arturo Silva J. Asperger's disorder and criminal behavior: forensic-psychiatric considerations. J Am Acad Psychiatry Law 2006; 34: 374-384.

***** Hippler K. et al. No increase in criminal convictions in Hans Asperger's original cohort. J Autism Dev Disord. 2010; 40: 774-780.

---------- Cheely CA, Carpenter LA, Letourneau EJ, Nicholas JS, Charles J, & King LB (2012). The prevalence of youth with autism spectrum disorders in the criminal justice system. Journal of autism and developmental disorders, 42 (9), 1856-62 PMID: 22187108

Tuesday 29 January 2013

Lipopolysaccharide and autism research

A word that I'm just coming to grips with at the moment forms the subject of this post: lipopolysaccharide, and how LPS is starting to become more and more widely used in research into autism and other developmental / psychiatric conditions. In particular, with reference to some possible involvement from maternal immune activation and risk of various behaviourally-defined conditions in offspring.

What is LPS?

Happy Days @ Wikipedia  
The paper by Raetz & Whitfield* (open-access) provides quite a comprehensive summary of LPS, the hows and whys, but a more concise version goes something like this:

LPS and immune activation

LPS is turning into quite the immune activation weapon of choice when it comes to animal research on conditions like autism and schizophrenia. Administration of LPS - mimicking gram-negative bacterial infection - is a great way of stimulating the innate immune system as per its effects on macrophage activation (yes, those bigger eaters of the immune system) via the Toll-like receptor 4 (TLR-4) - myeloid differentiation factor 2 (MD-2) complex (see here) and bringing into play all those not-so-lovely pro-inflammatory cytokines. LPS administration also seems to have a few other effects too as per this paper by Suh and colleagues** (open-access) on what happens to various amino acid chemistry when LPS is added. I'm sure there's a lot more also that it does.

With autism research in mind?

Quite a few animals have seen their fair share of LPS in the name of autism and related conditions research with some very interesting observations having been recorded:

  • Willette and colleagues*** based on a LPS model of maternal immune activation, found that offspring rhesus monkeys showed more "behavioural disturbance" and brain enlargement when compared with controls. 
  • Baharnoori and colleagues**** (open-access) concluded that offspring of LPS immune stimulated mice also showed some interesting changes to dopaminergic chemistry.
  • Nouel and colleagues***** reported an effect from prenatal LPS exposure in terms of reduced levels of glutamic acid decarboxylase 67 (GAD67) and reelin in the rat model. Both GAD67 and reelin have been the topic of previous blog posts: GAD in connection to the neurotransmitters glutamate and GABA (see here) and reelin in relation to some interesting research on organophosphates (OPs) (see here).
  • Finally, Xu and colleagues****** presented data suggestive that LPS administration might also affect levels of neurotrophin-3 (NT-3), involved in neurogenesis (and not a million miles away from an old favourite, BDNF). 

When applying LPS to media like PBMC provided by people with autism, there have also been some important results:

  • Dr Harumi Jyonouchi (a researcher previously discussed on this blog) reported an "excessive innate immune responses in a number of ASD children" following LPS administration in this paper*******. TNF-alpha production (see this post) was of particular interest.
  • Further, Dr Jyonouchi and colleagues in this paper******** went on to suggest that the response of adding LPS to PBMCs from participants with autism might also differ as a consequence of whether a gastrointestinal (GI) element was evident alongside autism.

I hope you can see why I'm so interested in LPS as a research tool when it comes to autism. The whole maternal immune activation area of autism research is definitely in the ascendancy as exemplified by the recent inflammation - offspring autism risk paper by Brown and colleagues********* discussed in this post. Indeed for science to even attempt to recreate anything approaching the conditions that *might* be linked to offspring autism with immune function in mind, LPS is a valuable tool alongside other agents such as polyinosinic:polycytidylic acid (poly I:C) highlighted in this paper by Paul Patterson and colleagues********** (open-access).

To finish, how about some Adamski (and Seal)?


* Raetz CR. & Whitfield C. Lipopolysaccharide endotoxins. Annu Rev Biochem. 2002; 71: 635–700.

** Suh JH. et al. A new metabolomic assay to examine inflammation and redox pathways following LPS challenge. Journal of Inflammation 2012, 9:37

*** Willette AA. et al. Brain enlargement and increased behavioral and cytokine reactivity in infant monkeys following acute prenatal endotoxemia. Behav Brain Res. 2011; 219: 108-115.

**** Baharnoori M. et al. Effect of maternal lipopolysaccharide administration on the development of dopaminergic receptors and transporter in the rat offspring. PLoS One. 2013; 8: e54439.

***** Nouel D. et al. Prenatal exposure to bacterial endotoxin reduces the number of GAD67- and reelin-immunoreactive neurons in the hippocampus of rat offspring. Eur Neuropsychopharmacol. 2012; 22: 300-307.

****** Xu M. et al. Aberrant cerebellar neurotrophin-3 expression induced by lipopolysaccharide exposure during brain development. Cerebellum. January 2013.

******* Jyonouchi H. et al. Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression. J Neuroimmunol. 2001; 120: 170-179.

******** Jyonouchi H. et al. Dysregulated innate immune responses in young children with autism spectrum disorders: their relationship to gastrointestinal symptoms and dietary intervention. Neuropsychobiology. 2005; 51: 77-85.

********* Brown AS. et al. Elevated maternal C-reactive protein and autism in a national birth cohort. Molecular Psychiatry. January 2013.

Sunday 27 January 2013

Autism and residential placement

It's going to be a bit of an odd blog post this one as I muse over the results reported by McGill & Poynter* on the cost of residential placement for those diagnosed with an intellectual disability (ID). Odd because I'm going to be bringing in a little bit of politics - or at least UK Government legislation - and how this intersects with current financial policy. Hopefully you'll stay tuned though as I try and remain true to the aims of this blog (autism research and other musings).

I can't say I know a great deal about the provision of residential services for people with IDs. Through some contact with a local provider of such services for young people and older adults with autism, I've picked up snippets of what's involved and indeed the various processes and red-tape to be taken on board. All I'll say is that it's not as easy as you might think and indeed neither should it be in light of recent events at Winterbourne View here in the UK.

The McGill paper details a few important things:

  • The aim of the study was to determine which factors most strongly contribute to the highest financial costs of placements for people with an ID.
  • Bearing in mind the study was conducted in probably the most expensive part of the UK to live and work (South-East England), the average placement was estimated to cost £172,000 per year (about US$275,000). 
  • To quote: "Young, male adults with learning disability, challenging behaviour and/or autism continue to receive very high cost residential support, often in out-of-area residential care". This was indicative of the fact that (a) quite a few people with IDs cannot be readily cared for in their own home, (b) indeed quite a few people with IDs can't even be cared for in the vicinity of where they were born and/are normally resident, and (c) part of the reason why residential placement is provided is because of the presence and impact of challenging behaviours (often with autism as a diagnosis). This last point on the impact of challenging behaviours fits quite well into the findings of Hodgetts and colleagues** (thanks Natasa) and how one facet of challenging behaviours in cases of autism, aggression, can have profound effects on families and caregivers (the possible causes of such aggression have been debated in a previous post).

This is not the first time that such provision has been the topic of scientific investigation as per papers like this one from Allen and colleagues*** who seemed to have arrived at similar conclusions with regards to the factors influencing the use of out-of-area residential care (autism, challenging behaviours). I don't think that this is a big surprise to anyone really - the more complicated and severe the presentation of symptoms, the greater the need for specialist, residential care and onward the higher the costs in order to provide that care. This outside of issues like aging and the question that no parent really wants to think about: what happens to my child when I'm gone?

I did say that I would bring a little politics into this post and so I am by introducing some of the provisions of the UK Autism Act 2009. I've briefly touched upon the Autism Act in previous posts (see here for example) and how as well as being the first ever disability-specific legislation in the UK, the Act road-maps what the State must offer for adults with autism including: (i) an assessment of needs, (ii) transition planning from childhood to adulthood, and (iii) planning in relation to the provision of relevant services.

It all sounds pretty good doesn't it? That and the changes to UK/English SEN provision, now (or soon) enabling parents to have a far greater say in how budgets for their child are spent and also getting rid of the cliff-edge that was being 16-years of age where services now stretch up to the age of 25 years for those in further education. Looking at all this on paper, I actually am very proud that old Blighty is taking a lead on these issues.

Not to rain on the parade however, but legislation and Politicians talking the talk is one thing, practical implementation and ensuring the funds are available to fulfil promises and commitments is another. Indeed a few stories in the press quite recently seem to unravel the purposes of why these policies have been set up. So this article in TES magazine paints a rather different picture of transition, and this article in the Guardian on what might potentially happen to specialist FE colleges in this brave new world. Indeed even some of the service providers are battling under-funding issues as per this fairly recent story (something I've heard about before). Of course I don't need to remind anyone about the current financial climate we are all faced with and for viewers (hopefully) reading this in 2020 or 2030, it is currently all rather messy. Councils and local authorities are cutting back and at the same time having to hold services and even improve them. Rather them than me.

What's the take home message from this post? Well, as per other posts, and without trying to turn people into statistics, autism costs in terms of provision and care, and the more challenging the presentation, the more the costs rise. Here in the UK we're doing pretty well in terms of legislation and getting the rules and regulations more into line with how the real world looks where autism is concerned and trying to ensure that particularly those with very complex needs are appropriately catered for by the State. I actually know a few families who have already put things like the Autism Act to good use with their children's future in mind. That being said, there seem like there are enough loop-holes (if I can use that term) present so that things still don't necessarily run smoothly when planning transition and specialist care if and when required.


* McGill P. & Poynter J. High cost residential placements for adults with intellectual disabilities. J Appl Res Intellect Disabil. 2012; 25: 584-587.

** Hodgetts S. et al. Home sweet home? Families’ experiences with aggression in children With autism spectrum disorders. Focus Autism Other Dev Disabl. January 2013.

*** Allen DG. et al. Predictors, costs and characteristics of out of area placement for people with intellectual disability and challenging behaviour. J Intellect Disabil Res. 2007; 51: 409-416.

---------- McGill P, & Poynter J (2012). High cost residential placements for adults with intellectual disabilities. Journal of applied research in intellectual disabilities : JARID, 25 (6), 584-7 PMID: 23055291

Thursday 24 January 2013

Optimal outcomes and autism continued

My word. That paper by Prof. Deborah Fein and colleagues* (open-access) which I blogged about last week has certainly made a splash both in the media and cyberspace. Opinions abound it seems about what the paper said, what the paper didn't say and what the implications of an 'optimal outcome' (OO) group might mean for autism spectrum disorders, its description, its nature and how it is perceived more generally.

I've followed quite a few of the opinion pieces on the Fein paper which have ranged from caution to enthusiasm and everything in-between. Some of the discussions it seems, have actually tended to drift away from what was actually reported in the paper into areas such as semantics and use of the words 'grow out of'. Even in one piece discussion of 'cure' (see here) which does rather stretch the Fein findings a little.

Whilst reading this body of literature, I've been constantly reminding myself of the accompanying editorial by Sally Ozonoff** and the very level way that she has presented/discussed the Fein results; well worth a read in my opinion, as is the brief response from Prof. Uta Frith on the paper (see here).

But whilst all attention was focused on the OO group paper by Fein, another smaller paper which included Fein as part of the authorship group was also published last week by Naigles and colleagues*** titled: Residual difficulties with categorical induction in children with a history of autism.

I don't necessarily want to go through this paper with a fine-toothed comb or anything because (a) I know very little about categorical induction (see here for a brief description) and (b) I have very little professional interest in categorical induction. What I perhaps do want to stress though is the suggestion from the Naigles paper - which looked at categorical induction skills in an OO group compared also with an autism and asymptomatic control group - that "even very high functioning individuals with autism, or with an OO, still exhibit residual difficulties with category knowledge and extension". I'm not by the way, getting into any debates about 'functioning' and autism.

What are the possible implications of the Naigles findings? Well, without putting words into anyones mouth and accepting that there is still more to come from the Fein OO research, one possible suggestion is that losing the diagnosis of autism - 'recovering' if I am to use the words of Dr Ozonoff - is not necessarily an absolute thing. Or in other terms, just because the diagnostic label of autism goes, does not imply that the difficulties around autism suddenly vanish into the ether.

In my post last week, I kinda eluded to the fact that autism - the autisms - or rather the presentation of autism in real-life is not necessarily just the sum of the dyad (social affect + restricted interests/repetitive behaviours). One can often also see lots of peripheral signs and symptoms, as well as heightened risk of various comorbidities, both behavioural and somatic, which can and do impact on overall quality of life. That and the fact that autism is a developmental condition, so even if symptoms are no longer present in a clinically recognisable fashion for whatever reason, still implies that development was once 'disrupted' and at the moment, no-one is able to adequately speculate on any longer term effects that this disruption may have.

What the Fein OO and Naigles findings also stress is that autism, the label autism, is just that: a label. That label, though subject to change this year (2013), is a diagnostic label and as with many generalised, compartmentalising diagnostic labels, can never really provide a true, accurate and complete reflection of all the people carrying that label, with all their heterogeneity.

A few final words are needed about those 34 children/young adults and their families in that optimal outcome group originally described by Fein. In among all the discussions on 'growing out of', 'recovery' et al and the often disapproving ways that some commentators have implied in their writings about this group, we should remember that these individuals represent perhaps one of the most important cohorts in autism research at the moment. We therefore need to show them a little more respect...


* Fein D. et al. Optimal outcome in individuals with a history of autism. Journal of Child Psychology and Psychiatry. January 2013.

** Ozonoff S. Editorial: Recovery from autism spectrum disorder (ASD) and the science of hope. J Child Psychol Psychiatry. 2013; 54: 113-114.

*** Naigles LR. et al. Residual difficulties with categorical induction in children with a history of autism. J Autism Dev Disord. January 2013.

---------- Naigles LR, Kelley E, Troyb E, & Fein D (2013). Residual Difficulties with Categorical Induction in Children with a History of Autism. Journal of autism and developmental disorders PMID: 23321802

Wednesday 23 January 2013

Maternal C-reactive protein and autism

As per my previous blog entry on the possibility of some involvement of a skin-brain axis to cases of autism (no, seriously), one of the key themes seemingly increasing in importance in autism research is the possibility of some connection with inflammation and the inflammatory processes.

Whilst sounding completely at odds with how autism is commonly described - a developmental disorder variably manifesting specific behavioural and cognitive features - there is a surprisingly long and growing interest in how physiological processes like inflammation may overlap with cases of autism. I've covered a tiny, tiny portion of that research interest in a few posts on this blog previously (here and here for example) outside of the whole gastrointestinal inflammation side of things, which for some still remains a contentious area.
Karjalanpiirakka @ Wikipedia   

I wouldn't dream of trying to offer any consistent or reliable hypothesis for how inflammation might link into at least some cases of (the) autism(s) in either a correlative or causative way because it's way outside my area of competence. Instead I'll leave it to others looking at other, possibly related, conditions to speculate on one or two suspected mechanisms.

In this post however, I would like to talk some more about inflammation and autism following the publication of a study by Alan Brown and colleagues* reporting on the possibility that inflammation or rather one particular marker of inflammation - C-reactive protein (CRP) - in autism might have at least some of its roots and effects in the very earliest days of life. Prof. Brown by the way, seems to have some interest in how early life variables might link into later life psychiatry as per his name being on the recent Lehti paper on IVF covered in this post.

Before going further I will offer a caveat or two about the Brown paper and it's emphasis on looking at maternal CRP levels during early pregnancy. Although measuring maternal inflammation (via CRP) is the name of the game, this does not mean that autism or anything else is 'caused' by such inflammation based on the current bank of evidence. Everyone seems to be 'inflammed' to some degree and for lots of different reasons but not everyone has autism. Neither does it sound any return to the parental 'blame game' of times gone by in much the same way that de novo mutations and paternal age shouldn't either.

I could be wrong but Brown and colleagues seem to have based at least part of their collected data on a Finnish initiative detailed in this paper by Lampi and colleagues** that basically aimed to examine whether there were any interesting links between "prenatal serologic factors, mediating and moderating developmental antecedents, and risk of autism spectrum disorders (ASD)". In their recent paper they report a significant association between maternal CRP levels and risk of offspring autism; especially pronounced when comparing that fifth of the population where CRP levels were highest compared with the fifth where they were lowest.

With again all caveats in active play, this is not the first time that maternal inflammation related to risk of offspring autism has been discussed. My mind wanders back to my 'you give me fever' post based on some interesting observations from the CHARGE initiative on mum's [retrospectively] reporting fever during pregnancy and offspring autism risk. Also potentially important, and again CHARGE-related, is the whole air pollution exposure - inflammation link albeit slightly more speculative at this point. And of course there are the Paul Patterson mouse studies, which to regular readers probably require little introduction, but for everyone else implies some maternal immune activation to be potentially important to offspring autism, and in need of further investigation.

Outside of the autism risk bit, this is also not the first time that elevated maternal CRP levels have been reported in relation to autism and other developmental conditions. The possibility for example that CRP levels could be related to caring for a child with autism was discussed in this post and how the stress of raising a child with behavioural difficulties might take an inflammatory toll on parents. With all due respect to the Lovell findings***, the more recent Brown paper implies that the caring aspect might not necessarily be the root cause of elevated CRP given its measurement during pregnancy which, speaking from a bystander point of view, can be a stress in itself (also not ruling out caring duties enhancing any effect or being related to other physiological measures with a stress element).

I'm also drawn back to how the Brown findings might also relate to those studies which have actually looked at CRP in people with autism. I posted on the Khakzad study a while back and how they reported some very significant elevations in CRP in their cohort of participants with autism. On the basis of that study one might think that elevated CRP is a pretty consistent finding in autism. That being said there is still a relatively small body of CRP-autism research and in some studies, such elevations were not detected compared to controls (see this post). Such is the variable nature of the autism(s).

Brown and colleagues suggest that maternal CRP measures might potentially translate into "identifying preventive strategies and pathogenic mechanisms in autism". Personally I don't think we are quite there yet in terms of determining just how elevated CRP might translate into autism or anything else given that (a) we don't really know how far back CRP goes beyond mothers as per a family history of elevated CRP and whether any other comorbidity might be connected to it****, and (b) spot determinations of CRP levels (which I assume is what they did) don't necessarily translate into chronic elevations of CRP and says very little about other relationships such as those of the cytokines.

I am however sufficiently convinced from the cumulative data on inflammation (both maternal and first-person levels) and autism that this is an area worthy of much, much, much more investigation.


* Brown AS. et al. Elevated maternal C-reactive protein and autism in a national birth cohort. Molecular Psychiatry. January 2013.

** Lampi KM. et al. Finnish Prenatal Study of Autism and Autism Spectrum Disorders (FIPS-A): overview and design. J Autism Dev Disord. 2011; 41: 1090-1096.

*** Lovell B. et al. The psychosocial, endocrine and immune consequences of caring for a child with autism or ADHD. Psychoneuroendocrinology. 2012; 37: 534-542.

**** Ridker PM. et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000; 342: 836-843.

--------- Brown, A., Sourander, A., Hinkka-Yli-Salomäki, S., McKeague, I., Sundvall, J., & Surcel, H. (2013). Elevated maternal C-reactive protein and autism in a national birth cohort Molecular Psychiatry DOI: 10.1038/mp.2012.197

Monday 21 January 2013

The skin-brain axis and autism?

I'm sure that many people with an eye on the autism research scene will have come across the term 'gut-brain axis' at some point in their reading. Denoting the suggestion of a possible relationship between what goes on in our deepest, darkest recesses and brain function (and onwards observed behaviour), the gut-brain axis has seemingly found a home particularly when looking at autism spectrum disorders.

Be it when it comes to describing the potential hows and whys of things like a gluten- and casein-free diet (potentially) showing some effects, or those quite consistent findings of elevated rates of gastrointestinal (GI) issues reported in at least a proportion of cases of autism(s), the gut-brain axis seems to be quite an enduring concept as it might also be in other conditions such as schizophrenia.

Axis not axes @ Wikipedia  
The specifics of the gut-brain axis have not however yet been fully elucidated; although quite a lot of speculation has focused on things like gut bacteria and intestinal permeability as showing some involvement; concepts which have cropped up on this blog quite regularly.

In this post I want to talk about another axis potentially relevant to autism and quite a few other developmentally defined or mental health related conditions: the skin-brain axis following the appearance of a rather interesting paper by Yaghmaie and colleagues* on mental health comorbidity in patients with atopic dermatitis.

A few points are worth noting given that I'm not able to post a link to the full-text paper:

  • This was a survey paper based on the US 2007 National Survey of Children's Health dataset (N=91,642). 
  • In short, the parents of children aged 0-17 years (0 years denoting those under 1 year old) were contacted and asked quite a few questions about the health of their children. 
  • For the purposes of this study, children with a history of atopic dermatitis (AD) as per the question: "during the past 12 months, have you been told by a doctor or other healthcare provider that XXX had eczema or any kind of skin allergy?" were asked about "provider-diagnosed mental health conditions" covering various diagnoses "previously been reported as associated with AD" and their results were compared with those without AD. Odds ratios (ORs) were calculated based on the risk derived from AD for various conditions.
  • The 12-month prevalence of AD for 2007 was 12.9%; a rise from previous estimates from data in 2003 (10.6%). Interestingly when comparing AD estimates state-by-state, California turned out to have the lowest AD prevalence (8.5%). Regular readers will know that in autism research terms, California has always been a bit of a focus (see here for example).
  • A diagnosis of AD was associated with an elevated risk of quite a few conditions: autism (OR: 3.04 CI: 2.13-4.34), ADHD (OR: 1.87 CI: 1.54-2.27) and conduct disorder (OR 1.87 CI: 1.46-2.39) among other things. All relationships were statistically significant when comparing AD and non-AD samples.
  • The authors also report that the severity of AD was also related to the likelihood of a developmental/mental health condition, in that the more severe the AD, the more likely a diagnosis was to be received.

Bearing in mind the nature and sampling methods of the Yaghmaie study, I have to say that I was taken aback by the findings of this paper and the potential implications. It's not that skin conditions have not been talked about with autism for example in mind before, as per the research base on things like psoriasis for example (see this post) and the whole autoimmunity side of things. Indeed, the atopy and allergy field has been mentioned quite a few times in autism research; alongside issues such as mast cell activation also being a source of speculation. But the implication that a skin condition like AD might actually raise the risk of developing autism or ADHD or a conduct disorder is a whole new ballgame on the mind-body relationship stakes bearing in mind the question of correlation-and-causation.

The authors also go as far as to suggest: "Strategies to prevent AD or to aggressively treat early skin inflammation might modify the risk of mental health disorders in at-risk children". This sentence really got me thinking. Thinking about inflammation and how this topic has been looked at on more than one occasion in autism research circles. Thinking about how skin and brain/behaviour might be linked, bearing in mind the source embryological material. Thinking also about the genetic - environmental factors which are linked to AD, and indeed going back to that gut-brain axis, how food might also play a role as per the link between gluten and dermatitis herpetiformis for example. Lots of thinking indeed.

The final words about the paper by Yaghmaie and colleagues should I suppose be ones of caution insofar as science needs to (a) replicate these findings, both in the US (home to participants) and outside the US, and (b) start looking in more details as to what the shared biological mechanisms and pathways could be (at least one authorship group have asked similar questions recently**).

That being said, this is yet more potential evidence for the whole-body nature of quite a few developmental and mental health conditions - remember the airways and autism research - and how autism research needs to keep expanding its scientific boundaries outside of the view that the grey (or rather pinkish) matter floating inside our skull is working completely in isolation.

Oh and perhaps I should also mention the meta-analysis by Schmitt and colleagues*** as adding more fuel to the correlation fire? And while we are on the topic of atopy, how about the paper by Chou and colleagues**** on allergic rhinitis and ADHD?

Stop now... and I will.


* Yaghmaie P. et al. Mental health comorbidity in patients with atopic dermatitis. J Allergy Clin Immunol. December 2012.

** Denda M. et al. How does epidermal pathology interact with mental state? Medical Hypotheses. 2013; 80: 194-196.

*** Schmitt J. et al. Association of atopic eczema and attention-deficit/hyperactivity disorder - meta-analysis of epidemiologic studies. Z Kinder Jugendpsychiatr Psychother. 2013; 41: 35-44.

**** Chou PH. et al. Prevalence of allergic rhinitis in patients with attention-deficit/hyperactivity disorder: a population-based study. Eur Child Adolesc Psychiatry. December 2012.

---------- Yaghmaie P, Koudelka CW, & Simpson EL (2012). Mental health comorbidity in patients with atopic dermatitis. The Journal of allergy and clinical immunology PMID: 23245818

Saturday 19 January 2013

Sex differences in autism presentation

I've been thinking quite a bit about the paper by Lai and colleagues* (open-access) looking at cognition between the sexes with autism in mind. They concluded that "ASC [autism spectrum conditions] varies with sex in some non-social cognitive domains, although not in relation to the core social cognitive difficulties".

Fair enough, there is overlap across the sexes with the characteristics of autism in mind, but potentially some other important differences, bearing in mind that I'm not really a great fan of the grand sex-gender divide when it comes to the brain and behaviour and autism (look up Cordelia Fine for a good critique).
Lamps @ Wikipedia 

The Lai paper did however get me searching around for some of the other literature on sex differences when it comes to autism, in terms of things like identification which forms the bulk of this post.

I might add that I've touched upon this important topic previously in terms of the sex ratio (see here) and savant abilities (see here) but consider this post to be slightly different as a few papers are considered including the one from Begeer and colleagues** and the one from Mandy and colleagues***.

So without further ado a few choice points from the papers:

The Begeer paper.

  • Based on responses for quite a large sample size (N=2275) of children and adults with an autism spectrum disorder, a 53-item survey questionnaire was used to ascertain various experiences of diagnostic procedures, treatment, schooling and employment.
  • The aim of the study was to analyse the questionnaire responses based on the hypothesis that there might be differences in identification and diagnostic experiences of females with autism over males.
  • The results: the mean time between first signs and symptoms of autism appearing and identification was longer for girls (2.3 years vs. 1.9 years) than boys. The authors comment on how this figure is slightly fuzzy based on the numbers of cases of autism being diagnosed in adulthood.
  • When data were separated based on children (0-18 years) and adults (18-85) (I assume that there was criteria for those people who were actually 18 years old), girls were almost 2 years delayed in getting a diagnosis of Asperger syndrome over boys.

The Mandy paper.

  • An interesting study aiming to "investigate the female ASD phenotype amongst predominantly high-functioning children and adolescents".
  • Three hundred and twenty five children with ASD (aged between 3-18 years), comprising 52 girls, were included for study based on referrals to a specialist clinic for the assessment of "high-functioning children with social communication difficulties".
  • A variety of assessment schedules were used including the 3di**** (developed by this author group) and the ADOS, complemented by measures of intelligence (IQ).
  • Results:  there were quite a few 'no differences' detected between the sexes in things like verbal and performance IQ. Core symptom presentation-wise, the new social affect superdomain likewise showed no significant differences across the sexes. Same goes for various peripheral signs and symptoms in terms of things like feeding and sleeping.
  • When it came to repetitive stereotyped behaviours (RSB), there were some differences between the sexes reflective of "milder RSB amongst females with ASD". That and females generally showing better fine motor skills; something which was pretty stable across the age-ranges of this cohort.
  • The authors conclude that a milder presentation of things like RSB might be part and parcel of under-recognition of autism in females and indeed that girls might be better at 'compensating' for their difficulties in certain situations.

Based on these collective works, there are some potentially important points to take home. That there may be a disparity between the sexes in terms of the age of getting a diagnosis (and I assume access to appropriate services) is perhaps the most important issue. Given the strong inclination towards males presenting with autism, one could argue that our screening and assessment radar is already biased in favour of picking up autism spectrum disorders in boys. That being said, don't think that it is always easy to get an assessment for boys either as per the paper by Ryan and Salisbury***** and the sentiments of 'you know what boys are like' covered in another post.

The potential reason for disparity in getting a diagnosis? The RSB domain differences are seemingly important as per the Mandy findings. Indeed looking closer at the individual items within the RSB domain, its evident that two main driver characteristics seem to be more present in boys than girls in their cohort: (a) possessing a large factual store of information and (b) oddly formal play (so for example ordering toys, etc.). So then outside of little differences in core social affect (communication and social interaction), the question is whether the strong presence, or indeed weak presence, of these behaviours is enough to red flag boys and girls at similar times?

Of course, one has to be cautious about becoming too formulaic about sex differences in autism
bearing in mind little interfering variables like comorbidity and indeed the heterogeneity that is evident across the entire autism spectrum. The future of such sex differences is also likely to be further complicated as and when the new DSM (and ICD) criteria are eventually agreed upon and published and whether, because of the various changes proposed, the same, more or less children across the sexes are likely to fit into the new developmental boxes.

And finally, the last of the famous international playboys?


* Lai MC. et al. Cognition in males and females with autism: similarities and differences. PLoS One. 2012; 7: e47198.

** Begeer S. et al. Sex differences in the timing of identification among children and adults with autism spectrum disorders. J Autism Dev Disord. September 2012.

*** Mandy W. et al. Sex differences in autism spectrum disorder: evidence from a large sample of children and adolescents. J Autism Dev Disord. 2012; 42: 1304-1313.

**** Skuse D. et al. The developmental, dimensional and diagnostic interview (3di): a novel computerized assessment for autism spectrum disorders. J Am Acad Child Adolesc Psychiatry. 2004; 43: 548-558.

***** Ryan S. & Salisbury H. 'You know what boys are like': pre-diagnosis experiences of parents of children with autism spectrum conditions. Br J Gen Pract. 2012; 62: e378-383.

---------- Begeer S, Mandell D, Wijnker-Holmes B, Venderbosch S, Rem D, Stekelenburg F, & Koot HM (2012). Sex Differences in the Timing of Identification Among Children and Adults with Autism Spectrum Disorders. Journal of autism and developmental disorders PMID: 23001766

Mandy W, Chilvers R, Chowdhury U, Salter G, Seigal A, & Skuse D (2012). Sex differences in autism spectrum disorder: evidence from a large sample of children and adolescents. Journal of autism and developmental disorders, 42 (7), 1304-13 PMID: 21947663

Wednesday 16 January 2013

Some children lose their autism diagnosis

"Autism is a lifelong condition".

That's what I was always led to believe when I was a fresh-faced undergraduate student being taught developmental disorders 101. Indeed the recent autism myths and facts tweeted by the UK National Autistic Society (NAS) confirmed this fact; to quote: "#AutismMyth: A child with autism will grow out of the condition". Having said that I was also told that every person with autism also lacked a Theory of Mind (ToM) such was the research climate of the time.
Yucca @ Wikipedia  

With this in mind, I came across a recent piece which seems rather at odds with the conventional wisdom on the lifelong aspect based on the results of the study by Deborah Fein and colleagues (open-access)*. They reported that in a small, well-defined group where a diagnosis of autism was historically recorded and subsequently confirmed by case review, the symptoms of autism had all but abated. I think we might have heard murmurs of this study previously as per this article in the Telegraph from 2009.

Regular readers might remember that I've already touched upon this rather delicate area of research in a few previous posts on this blog: the bloomers post (here) and the 'can you grow out of autism' post (here).

That and some continued speculation on the relative (in)stability of an autism diagnosis (here) as a result of papers like this one from Kleinman and colleagues** which is only likely to become more of an issue with the arrival of the DSM-V and its detailing of a level of 'severity' of presented symptoms at time of assessment.

A few observations from the Fein study based on the paper abstract and the press release:

  • "Optimal outcome" participants (n=34) previously in receipt of a diagnosis on the autism spectrum were included for study alongside matched participants (age, sex) with high-functioning autism (n=44) and those asymptomatic for autism (n=34).
  • Early diagnostic reports for the optimal outcome group were reviewed, twice it seems (one time blinded) just to make sure that they did in fact present with autistic features. Groups were compared across various parameters looking at cognitive and more autism-specific behavioural traits.
  • Results: social issues were apparently slightly milder during early infancy in the optimal outcome group but on other important measures of the triad (sorry dyad) no real differences between them and the high-functioning autism group.
  • That and the fact that the optimal group showed, at the time of testing, no specific issues which might indicate an autism spectrum diagnosis in line with their regular schooling and no autism-specific statement of SEN (as we call it here in Blighty).

I should point out as per the quote from Tom Insel current director of the US National Institute for Mental Health (NIMH) on the press release, this study seems to be part of a wider initiative which should tell us a little more about why this group of children might have lost their autistic presentation and diagnosis.

As was perhaps expected, this study has generated quite a bit of press interest as per headlines like this one and this one. I'm sure everyone has their own opinion to account for these results stretching from intervention to infection to symptom profile - the rise of the autism(s) indeed. Even Prof. Fein has previously speculated on some possible reasons why*** and here**** too.

Whilst we await further results in this area I think it is worth reiterating a few important points: (a) this was a relatively small trial in terms of participant numbers, crying out for independent replication, (b) the authors are not suggesting that everyone 'grows' out of autism as if it is some kind of passing developmental phase, and (c) autism is not just the sum of its dyad (social affect + restricted interests/repetitive behaviours) in terms of the impact of peripheral symptoms (e.g. anxiety and stress reactions) and very importantly all that elevated risk of comorbidity.

But having said all that neither am I going to take away from the potential importance of this study and its focus on endophenotypes...


Extra note (16/01/13). A quote from the paper: "The purpose of the current study was primarily to demonstrate the existence of a cohort who had clear autism at a young age and no longer demonstrated any significant autistic impairments. The data clearly support the existence of this group."


* Fein D. et al. Optimal outcome in individuals with a history of autism. Journal of Child Psychology and Psychiatry. January 2013.

** Kleinman JM. et al. Diagnostic stability in very young children with autism spectrum disorders. J Autism Dev Disord. 2008; 38: 606-615.

*** Helt M. et al. Can children with autism recover? If so, how? Neuropsychol Rev. 2008; 18: 339-366.

**** Sutera S. et al. Predictors of optimal outcome in toddlers diagnosed with autism spectrum disorders. J Autism Dev Disord. 2007; 37: 98-107.

---------- Deborah Fein, Marianne Barton, Inge-Marie Eigsti, Elizabeth Kelley, Letitia Naigles, Robert T. Schultz, Michael Stevens, Molly Helt, Alyssa Orinstein, Michael Rosenthal, Eva Troyb, & Katherine Tyson (2013). Optimal outcome in individuals with a history of autism Journal of Child Psychology and Psychiatry :

Monday 14 January 2013

Suicide, vitamins and trace minerals

I'm straying a little bit with this post. Straying from the intended autism research blogging path but hopefully not too far beyond my competence as I offer some discussion on yet another very complicated and very emotive topic: suicide.

It's not that I haven't made mention of suicide on this blog before; quite a few times in fact, in relation to issues like poisoning by pesticide as being an important method of suicide which perhaps need further regulation (see here) and how a familiar name to this blog, Toxoplasma gondii (or T.gondii to those who know it well) might very well show some relationship to some cases of suicide (see here).

One previous post in particular on cholesterol levels and autism (see here) may also be of some relevance to half of this post, focused on some potentially important findings from John Umhau and colleagues* (open-access) on vitamin D levels and their potential connection to suicide among active service military personnel. My very limited knowledge of cholesterol and vitamin D stems from articles like this one which might in turn partially explain headlines like: Vitamin D Supplements Won't Help Cholesterol Levels. That being said, I'm not an expert.

The Umhau findings are of great interest, not only because military personnel represent a 'captive audience' (if you'll pardon the pun) in terms of availability for study and the information that can be collected - see my post on schizophrenia and milk here if you don't believe me - but also because this was a study where archived serum samples had already been collected from both those who went on to commit suicide (n=495) and those used as control participants (n=495) in the study.

It wasn't as simple as saying the group mean level of vitamin D - sorry, 25-hydroxyvitamin D [25(OH)D] - calcidiol (the prehormone, as opposed to calcitriol, the active form of vitamin D) were lower in all suicide cases, given that suicide is not just a biochemical process. No, but when various factors such as season of serum collection, any history of depression and ethnicity were controlled for, there was "a statistically significant association between 25(OH)D concentrations and suicide risk, such that subjects with higher concentrations of 25(OH)D displayed a decreased risk for suicide compared to subjects in the lowest octile". The authors add: "We found that the risk for suicide was increased in the lowest octile of 25(OH)D levels, all the members of which had seasonally adjusted levels of 25(OH)D below 20 ng/mL". One perhaps has to bear in mind that active service when it comes to military employment and deployment can bring about its own set of very special circumstances.

Another paper also cropped up fairly recently adding to the possibility of a biochemical factor potentially being related to suicide. Victor Blüml and colleagues** reported again, some interesting findings on how lithium in the water supply might be potentially related to suicide rates in the US State of Texas; to quote: "The findings provide confirmatory evidence that higher lithium levels in the public drinking water are associated with lower suicide rates". I'm not going to go too far into the hows and whys of this paper for a couple of reasons: (a) I don't yet have the full-text version of the paper so am solely reliant on what the abstract says, and (b) there are many others far more competent than I who have talked about lithium and psychiatry before; one of them being Dr Emily Deans and a post she wrote in January 2012 about lithium which offers much more information than I could. All I could add as a sort of peripheral factoid is reference to a paper by Singh and colleagues*** which suggested that lithium might not be the only target compound of future interest bearing in mind its safety profile.

Suicide is not just a biochemical process and neither is it a uniform process with I assume, lots of different factors converging to influence the steps a person takes before reaching such an ultimate decision to take their own life. The studies highlighted in this post offer some interesting correlates related to suicide which at best suggest we should be looking at environment - the physical environment - as a potential player in how some people reach such a point, but not simply to replace the multitude of other important variables which might come into play.

Just in case anyone in the UK needs to talk to someone, the Samaritans are always good listeners (most other countries have similar services).


* Umhau JC. et al. Low vitamin d status and suicide: a case-control study of active duty military service members. PLoS One. 2013; 8: e51543.

** Blüml V. et al. Lithium in the public water supply and suicide mortality in Texas. J Psychiatr Res. January 2013.

*** Singh N. et al. A safe lithium mimetic for bipolar disorder. Nature Comms. 2013; 4.

---------- Umhau JC, George DT, Heaney RP, Lewis MD, Ursano RJ, Heilig M, Hibbeln JR, & Schwandt ML (2013). Low vitamin d status and suicide: a case-control study of active duty military service members. PloS one, 8 (1) PMID: 23308099

Saturday 12 January 2013

Join the autism research dots?

A very, very short post this one...

I don't want to make too much of the paper by Heberling and colleagues* with the grand title: Hypothesis for a systems connectivity model of autism spectrum disorder pathogenesis: Links to gut bacteria, oxidative stress, and intestinal permeability because it is, as the title suggests, a hypothesis join-the-research-dots type of manuscript rather than a novel scientific experiment paper.

Published also in a journal that has had its fair share of controversy down the years, which depending on your point of view, is either a good forum for some blue-sky thinking or an outlet for some very different kind of thinking. I make no value judgement by the way.

All that being said, I am suitably intrigued that this team from the University of Delaware have gone to the effort to try and unite some of the various research findings reported in cases of autism spectrum disorders (ASDs) into a coherent document. Indeed, included in the Heberling paper are various areas of research which have to varying degrees appeared on this blog and remain of some personal research interest to me: oxidative stress, sulphation issues, gluten, bacterial issues (itself the issue of an even more recent paper by Mulle and colleagues**) and gut permeability (leaky gut).

A quote from the paper: ".. oxidative stress and sulfur metabolic deficiencies could cause changes in colonic bacterial composition; and environmental bacterial contaminants could lead to elevated oxidative stress in individual".


And while you are thinking/discussing, why not listen to Kermit singing about his happy feet.


* Heberling CA. et al. Hypothesis for a systems connectivity model of autism spectrum disorder pathogenesis: Links to gut bacteria, oxidative stress, and intestinal permeability. Med Hypotheses. December 2012.

** Mulle JG. et al. The gut microbiome: a new frontier in autism research. Curr Psychiatry Rep. 2013; 15: 337.

---------- Heberling CA, Dhurjati PS, & Sasser M (2012). Hypothesis for a systems connectivity model of autism spectrum disorder pathogenesis: Links to gut bacteria, oxidative stress, and intestinal permeability. Medical hypotheses PMID: 23273906

Thursday 10 January 2013

Reelin' in OPs in autism

Get that pinch of salt ready again, as hopefully I'm not straying too far outside my area of competence with this post.

A recent entry on the SFARI blog talked about the potential pitfalls associated with too heavy reliance on animal models of autism spectrum disorders (ASDs) from the point of view of replication and reproducibility. Without wishing to strike up the 'I've talked about that before' orchestra, I've talked about similar things before(!) on this blog with specific reference to one particularly interesting mouse model of autism - the BTBR dangermouse.

Bearing in mind that we really shouldn't be putting all our research eggs into the mouse model basket for autism or any other condition under investigation, I was drawn to the paper by Brian Mullen and colleagues* (open-access) discussing their findings based on a Reeler mutant mouse model - mice not producing as much reelin as they should be - exposed to chlorpyrifos oxon (CPO), a metabolite of the organophosphate (OP) pesticide, chlorpyrifos. Quite a while back I had started to talk about OPs and autism (see here) and some curious findings in relation to the use of galantamine. Keep that compound in mind for now.

OK, perhaps it would be best if I provided a few descriptions first before venturing in the nitty-gritty of the Reeler OP exposed mouse.

Wikipedia provides quite a good overview of the Reelin gene and reelin protein findings so far in autism. Suffice to say that it is a complicated picture but basically boils down to (a) the neuronal tasks undertaken by reelin potentially overlapping with some of the ideas of how autism - some autism - might come about and (b) the positioning of the Reelin gene - human chromosome 7q22 - thought to be an autism gene 'hotspot' (something which is coming back into vogue recently as per the paper by Michaelson and colleagues** on regional hypermutation hotspots in autism). This paper from Persico and colleagues*** (open-access) from a few years back is as good an introduction as any to the hows and whys of reelin and autism.

Chlorpyrifos? Well, quite a good description about this OP can be found here. As with many pesticides - OPs in particular - chlorpyrifos works by inhibiting the break down of the neurotransmitter acetylcholine (ACh) by binding to the active site of the acetylcholinesterase (AChE) enzyme. In animals (and humans) this eventually leads to a build up of ACh which leads to things like neurotoxicity and death. It is with this mechanism in mind that quite unfortunately a few nerve agents also work in a similar fashion.

So then the Mullen paper is open-access, but here are a few highlights:

  • Reeler mice (heterozygous for the Reeler gene - RI +/-) became romantically involved with wild-type males. A few drinks, some flirting, some Isaac Hayes music... no, not really, but Reeler females conceived and at a specific time during pregnancy, a special pump was fitted delivering a set concentration of CPO to some mouse mothers-to-be at a critical time of cortical activity and development.
  • Various combinations of offspring mice were created which were either heterozygous (+/-) or homozygous (+/+) for the Reeler gene and either received CPO or were "vehicle-treated" (placebo).
  • Several lines of investigation were carried out based on offspring survival, AChE activity, mouse behaviour and various anatomical studies.
  • Results: Prenatal CPO did not affect embryo survival rates. That being said, more boy mice were present in the CPO treated litters (bearing in mind the relatively small litter numbers). CPO administration affected AChE activity as one might expect, reducing it by about "85% of the starting value". In contrast, CPO administration seemed to have a "protective effect on reelin protein" which brought reelin levels up in the +/- group.
  • Mouse behaviour was interesting and not exactly in line with what the authors expect (they predicted that the reduced reelin expression combined with CPO exposure would increase autistic-like behaviours). Yes they saw some changes in the +/- CPO combination but more often than not it was rather more mixed and indeed suggested some potential mitigating effect. Also "combined CPO exposure and loss of reelin expression seemed to have more of an effect in female mice rather than male mice". Mmm...
  • Same goes for brain anatomy... indeed the authors again actually suggest that each variable (reelin expression or use of CPO) seemed to mitigate one and another rather than increase any issue in a cumulative fashion.

I'm intrigued by the Mullen findings, accepting again the mouse model issue and how, as much as science tries, mouse models of autism are not person models of autism. I talked earlier for example about how galantamine was being touted as a possible intervention option for some people with autism (see this open trial by Nicholson and colleagues**** and this trial by Novotny which I'm still searching around for peer-reviewed results).

The primary mode of action of galantamine is with reference to its AChE-inhibiting properties, which place it not a million miles away from the actions of compounds like OPs and indeed chlorpyrifos. The difference predominantly lies in galantamine being a reversible AChE inhibitor and OPs exerting a more final irreversible effect on AChE. If one therefore assumes that the mitigating effects of CPO exposure on reelin deficient mice are potentially as a consequence of those AChE inhibiting effects and not just as the authors suggest CPO "increasing the pool of full-length reelin" by affecting reelin degrading enzymes, where does that leave us?

I'm not for one minute suggesting that OPs are, in any way, shape or form 'protective' against autism or anything else given their potentially important effects on neurodevelopment*****. But perhaps that the cholinergic system might require a little more investigation with autism in mind as per studies like this one from Ray and colleagues****** and talk of some blanket effect from pesticide exposure on the rising numbers of cases of autism is a little premature.

Finally, it also make me wonder if that graph of autism prevalence and organic food sales (shown above) which seems to be doing the rounds might actually provide something more than just a chuckle about correlation and autism, particularly if reelin is involved?


* Mullen BR. et al. Decreased Reelin expression and Organophosphate pesticide exposure alters mouse behaviour and brain morphology. ASN Neuro. January 2013.

** Michaelson JJ. et al. Whole-genome sequencing in autism identifies hot spots for de novo germline mutation. Cell. 2012; 151: 1431-1442.

*** Persico AM. et al. Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder. Mol Psychiatry. 2001; 6: 150-159.

**** Nicolson R. et al. A prospective, open-label trial of galantamine in autistic disorder. J Child Adolesc Psychopharmacol. 2006; 16: 621-629.

***** Potera C. Newly discovered mechanism for chlorpyrifos effects on neurodevelopment. Environ Health Perspect. 2012; 120: a270–a271.

****** Ray MA. et al. Neuronal nicotinic acetylcholine receptor subunits in autism: an immunohistochemical investigation in the thalamus. Neurobiol Dis. 2005; 19: 366-377.

---------- Mullen BR, Khialeeva E, Hoffman DB, Ghiani CA, & Carpenter EM (2013). Decreased Reelin Expression and Organophosphate Pesticide Exposure Alters Mouse Behavior and Brain Morphology. ASN neuro PMID: 23298182