"To examine associations between early developmental exposure to ambient pesticides and autism spectrum disorder"

The quote heading this post - "To examine associations between early developmental exposure to ambient pesticides and autism spectrum disorder" - reflects the aim of the study published by Ondine von Ehrenstein and colleagues [1]. Said aim was accomplished by examining data from "California’s main agricultural region, Central Valley, using 1998-2010 birth data from the Office of Vital Statistics" with regards to autism diagnoses (see here) and pesticide use and exposure. The results: "Findings suggest that an offspring’s risk of autism spectrum disorder increases following prenatal exposure to ambient pesticides within 2000 m of their mother’s residence during pregnancy, compared with offspring of women from the same agricultural region without such exposure." Also: "Infant exposure could further increase risks for autism spectrum disorder with comorbid intellectual disability."

The von Ehrenstein findings also come with an accompanying editorial [2] both published in the British Medical Journal (BMJ). That editorial provides a good overview of the findings and, importantly, some of their limitations. The editorial notes for example, that: "the study included only children with a diagnosis of “autistic disorder” by the California Department of Developmental Services, based on criteria described in the Diagnostic and Statistical Manual of Mental Disorders version IV-R." It cautions that the von Ehrenstein findings might not generalise to "milder forms of autism spectrum disorder." This 'lack of generalisation to milder forms' is a real reversal of what is typically seen in the peer-reviewed autism research literature (see here).

I don't want to linger too much on the von Ehrenstein study but a few points are worth noting. The question of what specific pesticides *might* influence risk of offspring autism is a complicated one. The researchers reported that "small to moderately increased risks for the disorder in offspring with prenatal exposure to the organophosphates chlorpyrifos, diazinon, and malathion, the pyrethroids permethrin and bifenthrin, as well as to glyphosate, avermectin, and methyl bromide" were observed. They (and the editorial) talk about how further research is required to "examine the joint effects of multi-exposure mixtures to more effectively protect human health." This is important in the context of other research (see here and see here) and also to avoid any big media headlines (see here) about specific preparations 'causing' autism (which has not yet been authoritatively established). Given that various different classes of pesticides have somewhat slightly different biological actions, there is a lot of work to be done on the possible biological mechanisms/targets and any synergistic effects.

Also: "children with autism spectrum disorder and co-occurring intellectual disability were examined as a separate outcome." The fact that von Ehrenstein et al observed something like a 'stronger association' between pesticide exposure and those at the "more severe end of the autism spectrum" (the description according to one media source) is another important point requiring further study. I say this in the context that 'comorbidity' might not always be the best description for symptoms and diagnoses accompanying autism (see here).

The authors conclude that their findings - with appropriate caveats - have implications. Namely: "Exposure of pregnant women and infants to ambient pesticides with a potential neurodevelopmental toxicity mode of action should be avoided as a preventive measure against autism spectrum disorder." I don't think too many people would disagree with the sentiments of 'avoiding pesticide exposure' particularly for pregnant women and those who might also be more vulnerable to their potential effects. The questions now turn to genetics and biology and the question of why...

Music to close: Hostiles on the Hill (apparently)...

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[1] von Ehrenstein OS. et al. Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study. BMJ. 2019; 364: I962.

[2] Bakian AV. & VanDerslice JA. Pesticides and autism. BMJ. 2019; 364: I1149.

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Project TENDR and chemical exposures part 2: organophosphate pesticides aren't great for child health

So, without striking too many chords on the old 'we've been here before' piano, consider this post an extension of some other discussions a while back suggesting that exposure to some classes of 'chemicals' might not be particularly great for child health (see here).

The findings reported by Irva Hertz-Picciotto and colleagues [1] continue the Project TENDR theme with their assertion that there is "compelling evidence" that prenatal exposure to organophosphate (OP) pesticides "is putting children at risk for cognitive and behavioral deficits and for neurodevelopmental disorders." Their observations have also been picked up by the lay media with some striking headlines like 'Ban entire pesticide class to protect children's health, experts say' complete with the required stock photo of crops being sprayed from the air.

Organophosphate (OP) compounds such as OP pesticides have a very mixed history. As well as being the insecticide of choice in many countries as a result of their excellent pest control profile, the organophosphate chemistry has also been utilised for less desirable purposes as per its classification as a component of nerve agents. Remember all the quite recent chatter about a nerve agent called Novichok? Well, the chemistry behind Novichok apparently has a very distinctive OP "structural backbone" [2]. That's not to say that every OP pesticide is Novichok. But rather that the activity of OPs specifically targeting the action of acetylcholinesterase (AChE) enzymes, important enzymes that are required for proper nerve function, is also an important biological action of various nerve agents. This in itself would suggest caution in the use of OPs.

The Hertz-Picciotto paper (policy forum) is pretty data heavy in terms of how much OP pesticides are used across the globe, the slew of mostly observational research studies that have looked at pesticide exposure and various neurodevelopmental variables and the concerns voiced at both high and low levels of OP pesticide exposure. They make a few recommendations: better training for health professionals on the potential risks attached to OP pesticide exposure, greater moves to switching to "nontoxic approaches to pest control" and perhaps most controversially: "Governments phase out chlorpyrifos and other OP pesticides."

The caveats? Well I might mention a few, minus any charges of me somehow 'standing up for OPs'. First, I don't think it's unreasonable to suggest that children in particular, do need to be more strongly protected against pesticides that are (chemically-speaking) not a million miles away from nerve agents. As the authors mention, there is quite a bit of evidence in the peer-reviewed literature to suggest a possible *association* between pesticide exposure and diagnoses such as autism (see here and see here) or beyond (see here). The thing is that like many other non-genetic environmental factors (e.g. air pollution) *linked* to a heightened risk of autism or other neurodevelopmental labels, it's more about environment + genetics when it comes to risk (see here) rather than environment just working on its own. We need for example, to know more about the ways and means that OPs are metabolised in the body and whether there could be some interesting biochemistry potentially linked to labels like autism (see here).

Second, some thought needs to go into the possible replacements if OP pesticides were to be banned outright. Thinking back to a post not-so-long-ago talking about DDT exposure and offspring autism (see here) I was struck by how short some memories are in terms of why such products were developed in the first place. I don't think anyone would seriously contemplate that the development of OP pesticides was anything more than to stop pests attacking crops and to maintain yields that can feed the population. These compounds were developed with good intentions. Obviously, as the research literature has grown, we have come to realise that such products are not side-effect free and more stringent controls have been put into place regarding safety. But to ban them outright is not something that can be done overnight. What do we replace them with? Do we just accept that crop yields will be lower and less food will be produced? Do we instead start thinking about other ways to make crops more resistant to the pests that blight them? That last question has already had its own 'issues'.

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[1] Hertz-Picciotto I. et al. Organophosphate exposures during pregnancy and child neurodevelopment: Recommendations for essential policy reforms. PLoS Med 15(10): e1002671.

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Ariel pesticide use and neurodevelopmental diagnoses patterns

"When compared with surrounding areas, the zip codes exposed to yearly aerial pyrethroid spraying had a higher prevalence of ASD/DD [autism spectrum disorder/childhood developmental delay]."

One does has to be a little careful in interpreting the results published by Steven Hicks and colleagues [1] (open-access available here) looking at "ASD/DD diagnoses rates in an area near our regional medical center that employs yearly aerial pyrethroid pesticide applications to combat mosquito-borne encephalitis" compared with control areas with "no state-approved aerial applications." Correlation after all, is not the same as causation. But I found the data from Hicks et al to be rather interesting and worthy of a blog entry in light of other, independent peer-reviewed data (see here).

So, looking at all children who were evaluated over a 5-year period at "one of six pediatric outpatient clinics" in New York state, researchers divided participants up depending on their zip code "into aerial-exposed and control zip codes" when it came to pyrethroid spraying. Said spraying was in relation to use of an insecticide "as a preventive tool against mosquitoes carrying eastern equine encephalitis (EEE) and West Nile virus (WNV)." The authors noted that: "The effects of this application on neurodevelopmental patterns in local children have not been investigated."

Pesticide exposure was estimated based on the amount used over a 3-year period in each zip code and reported as kilograms per square kilometre. Alongside looking at rates of "neurodevelopmental delay (ASD and DD)" as a function of zip code/exposure patterns, researchers also included various potentially modifying factors in their calculations: "regional characteristics (poverty, pesticide use, population density, and distance to medical center), subject characteristics (race and sex), and local birth characteristics (prematurity, low birthweight, and birth rates)."

When all was said and done, authors observed a significant relationship between ASD/DD and aerial pesticide exposure. They noted that: "Zip codes with aerial pyrethroid exposure were 37% more likely to have higher rates of ASD/DD."

Authors caution that "this study is observational and does not establish a causal relationship between pyrethroid exposure and ASD/DD" but also note that there needs to be a lot more experimental study done on how aerial spraying is conducted and any possible effects on the population down below. And before you say anything, yes, I know that aerial spraying is being done for a perfectly valid reason. But that's not to say it should be just given a free pass in terms of either effectiveness or safety...

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[1] Hicks SD. et al. Neurodevelopmental Delay Diagnosis Rates Are Increased in a Region with Aerial Pesticide Application. Front Pediatr. 2017 May 24;5:116.

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An excess of ADHD among children born to glyphosate appliers?

The job of pesticide applicator is one that has been discussed on this blog before (see here). Minus any scaremongering, the conclusion of that post was that under certain circumstances (e.g. a high pesticide exposure event - HPEE), the effects of that particular occupation might be pretty far-reaching for the 'cognitive' as well as physical health of the individual concerned.

Today I'm talking about other potential effects "needing confirmation by further studies" related to perhaps one of the most famous pesticides in recent times: glyphosate. The systematic review "of observational studies" by Jessica de Araujo and colleagues [1] (open-access) provides the starting material and the suggestion that whilst "exposures to GLY [glyphosate] before conception and/or during pregnancy did not increase the risk of adverse reproductive outcomes" there was perhaps more to see when it came to "an excess of risk of ADD/ADHD [attention-deficit disorder/attention-deficit hyperactivity disorder] among the offspring of GLY applicators." The de Araujo paper was a review paper and included the findings reported by Vincent Garry and colleagues [2] that: "Use of the herbicide glyphosate yielded an OR [odds ratio] of 3.6 (CI, 1.3-9.6) in the neurobehavioral category" including ADD/ADHD.

Glyphosate - N-(Phosphonomethyl)glycine or Roundup - has something of a love/hate relationship in many circles. As a herbicide (an organophosphonate), it does a pretty good job killing weeds by interfering with some important biochemistry linked to the aromatic amino acids, and has enjoyed significant commercial success for quite a few years. As with all pesticides however, there are cautions attached to its use, and this preparation seems to catch media attention on a pretty regular basis; more so when organisations such as the World Health Organisation (WHO) come out with statements like the one last year (2015).

Before going back to the de Araujo and Garry papers, I think it's worth mentioning that the idea of an 'association' between GLY and ADHD is not without some controversy. I note that at least one attempt has been made to talk about the possibility of a link between the two albeit retracted for various methodological reasons. I therefore tread carefully and note there are some important strengths and weaknesses attached to the idea that offspring ADD/ADHD might specifically be more frequently present in GLY pesticide applicators.

Weaknesses, well, Garry et al relied heavily on self-report and interviews with no detailed use of analytical measures in terms of biological load for GLY. Yes, they did survey registered pesticide applicators on the basis of their licencing and the data provided at interview was cross-referenced with other available "medical records examination" but theirs was still a study heavily reliant on recall and association. de Araujo also make the point that "the herbicide was analyzed as a dichotomous (exposed / not exposed) variable" which takes no account of variables such as "wearing protective clothes, the diet, the amount of the pesticide used" and thus, says nothing about any dose-response relationship. Strengths - the Garry paper did cover various different types of pesticides, the metabolites of some have also subsequently been linked to risk of a diagnosis of ADHD for example (see here). They also reported on quite a few other variables that might impact on risk of offspring ADHD and controlled for them. In short, an interesting association which again is: "needing confirmation by further studies."

Insofar as the possibility that there may 'associations' between glyphosate use and behavioural outcomes, some people with some knowledge of autism research might have come across some pretty stark warnings about glyphosate exposure and the quite staggering increase in cases of autism being diagnosed around the world (see here). I, myself, am not so convinced that one agent, and one agent alone, plays such an important role in autism rates but am willing to concede that there may be more research to do on the effects of exposure and offspring outcomes (see here). Indeed minus any sweeping generalisations or solely resting any 'blame' at the door of a specific preparation, science really needs to conduct some more detailed analysis on environmental components such as pesticides and behaviour and developmental outcomes (including biochemistry [3]), if anything else, just to rule out any relationship. And various lawmakers around the world might be aiding efforts to do so...

Music to close: Beyoncé plays the SoL tonight. No, I'm not going but I do like some of her music...

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[1] de Araujo JSA. et al. Glyphosate and adverse pregnancy outcomes, a systematic review of observational studies. BMC Public Health. 2016; 16: 472.

[2] Garry VF. et al. Birth defects, season of conception, and sex of children born to pesticide applicators living in the Red River Valley of Minnesota, USA. Environmental Health Perspectives. 2002;110(Suppl 3):441-449.

[3] De Felice A. et al. Prenatal exposure to the organophosphate insecticide chlorpyrifos enhances brain oxidative stress and prostaglandin E2 synthesis in a mouse model of idiopathic autism. Journal of Neuroinflammation. 2016; 13: 149.

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de Araujo, J., Delgado, I., & Paumgartten, F. (2016). Glyphosate and adverse pregnancy outcomes, a systematic review of observational studies BMC Public Health, 16 (1) DOI: 10.1186/s12889-016-3153-3

Organophosphate exposure and ADHD?

"Children with higher urinary DMP [dimethylphosphate] concentrations may have a twofold to threefold increased risk of being diagnosed with ADHD [attention-deficit hyperactivity disorder]."

So said the results presented in the paper by Yu and colleagues [1] who looking at "97 doctor-diagnosed ADHD cases and 110 non-ADHD controls who were 4-15 years of age" examined urine and blood samples for various factors including "biomarkers of OP [organophosphate] pesticide exposure." They concluded that, adjusting for creatinine, urine levels of DMP but not other dialkylphosphate (DAP) metabolites were higher in the ADHD group compared with the non-ADHD group. Further: "Organophosphate pesticide exposure may have deleterious effects on children's neurodevelopment, particularly the development of ADHD." At the same time, Yu et al also reported nothing very much to see when it came to blood lead levels (BLLs) between the groups.

This is not the first time that examination of urinary metabolites of OPs have turned up something of a potential relationship with behavioural outcomes related to ADHD. The paper by Bouchard and colleagues [2] also reported a possible connection supporting a "hypothesis that organophosphate exposure, at levels common among US children, may contribute to ADHD prevalence." There too urine was the analytical medium and dialkylphosphate concentrations the target compounds. This and other research looking at this issue have led to statements [3] to the effect that: "Children's exposures to pesticides should be limited as much as possible." I don't think many people would disagree with that sentiment.

I've talked about OPs quite a bit on this blog (see here and see here) and how various conditions/labels might be 'associated' with this class of compounds either when used as insecticides or as something rather more ominous. I've tried not to be too alarmist about the possibility of a connection with health because OPs do serve an important purpose (as an insecticide) and have probably saved quite a few lives as a result. But it is getting increasingly difficult to ignore the possibility that this and other classes of pesticides either alone or in combination with other factors, seem to be implicated in various conditions/labels and more needs to be done looking at the hows and whys. This can however be done without scaremongering.

The Yu results whilst interesting are not however without some cautions. DAP metabolites as markers for OP exposure still requires further investigations [4], not least from which specific OP they are derived from. That other factors such as exposure to second-hand tobacco smoke might also link into the presentation of specific metabolites such as DMP [5] is another consideration. Continuing the theme that combinatorial exposures might also exert an effect [6] other research illustrates how difficult it might be to pin one specific type of exposure to specific behavioural outcomes. And then also we have the added layer of complexity that is the genetics of xenobiotic metabolism with specific focus on OPs. Relationships are likely to be pretty complicated as a result.

Having said all that does not however mean that results like the ones from Yu et al can be just brushed under the carpet...

Music to close, and having watched Guardians of the Galaxy for the Nth time last evening, all I can say is the film soundtrack is kinda cool...

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[1] Yu CJ. et al. Increased risk of attention-deficit/hyperactivity disorder associated with exposure to organophosphate pesticide in Taiwanese children. Andrology. 2016 Apr 12.

[2] Bouchard MF. et al. Attention-deficit/hyperactivity disorder and urinary metabolites of organophosphate pesticides. Pediatrics. 2010 Jun;125(6):e1270-7.

[3] Roberts JR. et al. Pesticide exposure in children. Pediatrics. 2012 Dec;130(6):e1765-88.

[4] Sudakin DL. & Stone DL. Dialkyl phosphates as biomarkers of organophosphates: the current divide between epidemiology and clinical toxicology. Clin Toxicol (Phila). 2011 Nov;49(9):771-81.

[5] Jain RB. Levels of dialkylphosphate metabolites in urine among general U.S. population. Environ Toxicol Pharmacol. 2016 Feb 26;43:74-82.

[6] Osaka A. et al. Exposure characterization of three major insecticide lines in urine of young children in Japan-neonicotinoids, organophosphates, and pyrethroids. Environ Res. 2016 May;147:89-96.

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Yu CJ, Du JC, Chiou HC, Chung MY, Yang W, Chen YS, Fuh MR, Chien LC, Hwang B, & Chen ML (2016). Increased risk of attention-deficit/hyperactivity disorder associated with exposure to organophosphate pesticide in Taiwanese children. Andrology PMID: 27070915

On genes, environment, broccoli and autism (again)

Picture: Carl Warner: http://www.carlwarner.com/

I'm serving up two peer-reviewed papers for your reading delight today which draw attention to the ideas that (a) the 'causes' of autism are likely complex and as heterogeneous as the label itself, (b) gene x environment interactions affecting risk of autism are starting to get some good scientific research airtime and (c) don't 'dis the broccoli [chemical] autism connection just yet...

The first paper by Brandon Pearson and colleagues [1] (open-access) has already found some media interest as per the Guardian headline: 'Agricultural fungicides are 'bad news for neurons', study suggests'. Exposing mouse neurons - "cortical neuron-enriched cultures" - to several hundred chemicals (careful of that word) found in the modern environment, researchers concluded that several compounds "produce transcriptional changes in vitro that are similar to those seen in brain samples from humans with autism, advanced age and neurodegeneration (Alzheimer’s disease and Huntington’s disease)." That is, several types of chemicals quite commonly found in the modern environment seemed to alter gene expression in those mouse neuron enriched cultures that weren't a million miles away from that noted previously in conditions such as autism for example.

Mouse neurons, you might be thinking? Well, obviously one has to be a little cautious about extrapolating from mouse to humans (see here) but researchers did include some comparison analysis looking at "the gene expression profile of our cultures with brain cell-type-specific expression data sets and human brain gene expression data sets." The result: "cortical cultures show strong transcriptional similarities to the human brain."

Clustering chemicals based on "concordant gene expression changes", six groups emerged. Cluster 2 chemicals, containing such pesticides as rotenone, pyridaben and fenpyroximate  and also various compounds under the heading of the strobilurins seemed show some particularly interesting results insofar as they "mimicked the transcriptional changes of two post-mortem ASD [autism spectrum disorder] brain expression data sets in a bidirectional manner." The effects of this cluster of compounds also seemed to unite various conditions with autism including Alzheimer’s disease and Huntington’s disease and the "aging brain". My interest was particularly piqued by that last association in light of other research results (see here).

When it came to the 'effects' of those chemicals in terms of genetic and biological processes, researchers put forward some not unfamiliar potential roles: "These chemicals, most of which inhibit mitochondrial complex I or III, stimulated free radical production and disrupted microtubules." Words like 'oxidative stress' start to emerge as they have done in previous autism research (see here) and yet again, inflammation or inflammatory processes seem also to be indicated. Indeed, the authors also make mention of how effects such as free radical production "can be reduced by pretreating with a microtubule stabilizer, an antioxidant, or with sulforaphane." Yes indeed, sulforaphane - the chemical found in broccoli - might indeed be moving back up the autism research agenda (see here for some previous background).

There is obviously lots more work to do in this area before anyone gets too carried away. The authors note: "While usage and residue levels of cluster 2 chemicals on conventionally grown foods are increasing, in the absence of causality, it is premature to draw correlations with the increased prevalence of ASD and other brain disorders." Lessons could be learned from other blanket suggestions about 'chemicals' and autism (see here) as well as an appreciation for the concept of the the plural autisms (see here). Then there are the practicalities of whether ingesting such compounds on food or in water is the same as direct exposure to cortical neuron-enriched cultures? Or indeed, whether there may be other routes of contact? I might also suggest that further studies should focus on looking for the metabolites of such agents too [2] bearing in mind the concept of statistically significant thresholds...

If you're still here after all that, the second paper I want to talk about is that from Sarah Wong and colleagues [3] that has also received a bit of media attention. The focus this time was on a gene called p53 (see here for some background) and how issues with this gene might be 'over-represented' when it comes to autism following on from other work by some of the same authors [3]. First of all, please don't get too fixated by mention of the words 'cancer gene' when it comes to p53 given it's [protein] tumour suppressing capabilities. As I've discussed before, the risk of cancer does not seem to be elevated any more than the general population risk when it comes to autism (see here). Perhaps of greater relevance to the Wong findings is the idea that p53 has other 'activities' such as that related to oxidative stress (yes, that again) and "DNA repair, bioenergetics and mitochondrial DNA (mtDNA) copy number maintenance."

Based on data from CHARGE (beincharge!), researchers garnered blood samples from 66 children diagnosed with an autism spectrum disorder (ASD) and "race-, gender-, and age-matched typically neurodeveloping children (n = 46)" (authors words not mine). They analysed for mtDNA copy number and deletions and p53 gene copy ratios and found them to be "more common in children with AU [autism] and their fathers." The authors translate their findings as pointing to "a role for deficient DNA repair capacity not driven by paternal age." They also suggest that environment might intersect with genetics in relation to 'severity' scores of autism obtained for their cohort: "gene x environment interaction seems to play a greater role in children with autism with less severe symptoms."

Taken together the Pearson and Wong findings point to some interesting 'associations' potentially relevant to [some] autism. The idea that certain components of the modern-day environment might increase the risk of autism is nothing new but the way that Pearson et al went about studying the possible relationship is. The results from Wong et al suggesting that there might be issues with the gene 'whose role is to suppress cellular damage from environmental stressors' suggests that exposure patterns might not necessarily be where it's all at when looking at compound/chemical X or Y in relation to autism risk. I'm also inclined to direct you to some previous discussion about the caspases and autism (see here) in light of the involvement of p53 with the process of apoptosis (programmed cell death) in mind. As I've mentioned before, the biological mechanisms for how people deal with various xenobiotics needs a lot more investigation in autism research circles (see here); something that might similarly extend to genetic mechanisms too.

Oh, and just in case you think that I'm pushing the either/or of genetic and environment when it comes to autism, I'm not, as words like epigenetics spring to mind and the idea that genomic instability might, for example, have quite a few different dimensions (see here)...

To close, I'm thinking of branching out... football (soccer) pundit perhaps?

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[1] Pearson BL. et al. Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration. Nat Commun. 2016 Mar 31;7:11173.

[2] Domingues VF. et al. Pyrethroid Pesticide Metabolite in Urine and Microelements in Hair of Children Affected by Autism Spectrum Disorders: A Preliminary Investigation. Int. J. Environ. Res. Public Health 2016; 13: 388.

[3] Wong S. et al. Role of p53, Mitochondrial DNA Deletions, and Paternal Age in Autism: A Case-Control Study. Pediatrics. 2016. March 31.

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Pearson, B., Simon, J., McCoy, E., Salazar, G., Fragola, G., & Zylka, M. (2016). Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration Nature Communications, 7 DOI: 10.1038/ncomms11173




Wong, S., Napoli, E., Krakowiak, P., Tassone, F., Hertz-Picciotto, I., & Giulivi, C. (2016). Role of p53, Mitochondrial DNA Deletions, and Paternal Age in Autism: A Case-Control Study PEDIATRICS, 137 (4) DOI: 10.1542/peds.2015-1888

What can 'big data' tell us about suicide-related behaviours?

The findings reported by Yu-Wen Lin and colleagues [1] (open-access available here) examining the "characteristics and suicide methods of patients with suicide-related behaviors" and "influential factors for repeated suicide-related behaviors and death by suicide" might not make for 'great dinner-party conversation' but are nevertheless important.

Drawing on data from one of the world's premier 'big data' research sources - the Taiwanese National Health Insurance Research Database (NHIRD) - mentioned quite a few times on this blog (see here for example), researchers scanned the database for instances where people were "hospitalized with a code indicating suicide or self-inflicted injury (E950-E959) according to the International Classification of Disease, Ninth Revision, Clinical Modification" between 1997 and 2010. They then set about looking at various factors associated with this patient population (N=57,874).

With the cold, objective spectacles of science on, various important findings are discussed. Approximately 4% of those hospitalised for suicide-related behaviours had unfortunately died. Most were male and most "had died in their first suicide attempt." The most frequently cited method of suicide was self-poisoning.

Analysis by gender revealed some important trends. Males were more likely to die by suicide but females were at "significantly increased odds of repeated suicide-related behaviors when compared with men." Further: "Those who were female, had been hospitalized for suicide-related behaviors at a younger age, had a low income, had a psychiatric disorder (i.e., personality disorder, major depressive disorder, bipolar disorder, schizophrenia, alcohol-related disorder, or adjustment disorder), had a catastrophic illness, or had been hospitalized for suicide-related behaviors that involved two methods of self-inflicted injury had a higher risk of hospitalization for repeated suicide-related behaviors." And factors for males: "had been hospitalized for suicide-related behaviors at an older age, had low income, had schizophrenia, showed repeated suicide-related behaviors, had a catastrophic illness, or had adopted a single lethal method had an increased risk of death by suicide." I might also add that the experience of being hospitalised for suicide-related behaviours at a young age also increased the risk for subsequent "repeated suicide-related behaviors."

There are some important trends emerging from this and other data. Perhaps one of the most important variables was the suggestion that a psychiatric disorder seemed to be part and parcel of that risk profile, whether for suicide-related behaviours or death by suicide. I know this is not new news but does well to reiterate how effective treatment/management of psychiatric labels should remain an absolute priority. I'd also encourage greater screening and assessment [2] among populations who might be particularly vulnerable to mental health issues too (see here for example - particularly timely in light of recent media reports).

The finding that self-poisoning was the primary method of suicide-related behaviour and completed suicides also ties in with other independent data. Accepting that one cannot control every single agent that might be used for self-poisoning, I do believe there are additional measures that can be taken. So, as per the data on the use of paracetamol as a method of suicide (which is by the way, a really horrible way to die), there are ways and means to potentially reduce risk [3] particularly when overdose is an 'impulsive' decision. One might even argue that removing such medicines from the OTC bracket might also help despite the inconvenience to other users. I suppose it depends on how much value you place on life vs. inconvenience or the use of additional resources. I'd also direct readers to some important discussions on another self-poisoning method quite frequently discussed in the research literature: pesticides (see here).  As per the findings reported by Gunnell and colleagues [4], there are solutions here too: "(a) the use of pesticides most toxic to humans was restricted, (b) pesticides could be safely stored in rural communities, and (c) the accessibility and quality of care for poisoning could be improved."

As I've discussed previously on this blog, suicide (whether attempted or completed) is a very personal thing (see here) with no magical 'one-size-fits-all' formula of what to look for in terms of risk profile or indeed, how to help. That there may however be some rough-and-ready factors generally associated with cases is a start in terms of focusing on those who might need most help, including that when it comes to the engineering of social policy [5].

And just in case you need it, there is always someone to talk to (see here).

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[1] Lin YW. et al. Influential Factors for and Outcomes of Hospitalized Patients with Suicide-Related Behaviors: A National Record Study in Taiwan from 1997-2010. PLoS One. 2016 Feb 22;11(2):e0149559.

[2] Murray D. Is it time to abandon suicide risk assessment? British Journal of Psychiatry Open. 2016; 2: e1-e2.

[3] Simkin S. et al. What can be done to reduce mortality from paracetamol overdoses? A patient interview study. QJM. 2012 Jan;105(1):41-51.

[4] Gunnell D. et al. The global distribution of fatal pesticide self-poisoning: systematic review. BMC Public Health. 2007 Dec 21;7:357.

[5] Antonakakis N. & Collins A. The impact of fiscal austerity on suicide: On the empirics of a modern Greek tragedy. Social Science & Medicine. 2014; 112: 39-50.

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Lin YW, Huang HC, Lin MF, Shyu ML, Tsai PL, & Chang HJ (2016). Influential Factors for and Outcomes of Hospitalized Patients with Suicide-Related Behaviors: A National Record Study in Taiwan from 1997-2010. PloS one, 11 (2) PMID: 26900930

Toxicant exposures and Gulf War Syndrome

Of the various directions away from autism research that I tend to take on this blog, discussions based on the collected [peer-reviewed] research literature on Gulf War Syndrome will always retain a special interest (see here). Not least because here we have a group of some of our bravest men and women who went out to liberate Kuwait in the early 1990s and who came back home in an often quite appalling state and thereafter basically left to rot.

I know that might all sound a little dramatic but after having met one or two veterans down the years and seen first hand how their health and well-being has been affected following their deployment to the Persian Gulf all those years ago I'm just telling it like it is. As much due to political reasons as scientific ones, the plight of these veterans - who really only want to know what happened to them and some acknowledgement that something 'did' happen to them outside of it being wholly 'psychosomatic' - has been the source of much controversy and debate down the years. Now at last it appears that a consensus based on the available science might have been reached [1]: "the research to date supports the conclusion that veterans are suffering from a "persistent pathology due to chemical intoxication.""

The paper by Roberta White and colleagues (someone not unfamiliar to Gulf War research) carries that conclusion and is open-access for all to read. Following a lengthy review of the various exposures that faced veterans and the likelihood of them (adversely) affecting their health, the authors detailed a few 'bottom lines'.

To quote:

"Between one-fourth and one-third of deployed GW [Gulf War] veterans are affected by a disorder characterized by chronic symptoms involving multiple body systems; this condition is best identified by the term GWI [Gulf War Illness]."

Further:

"This disorder was caused by toxicant exposures, individually or in combination, that occurred in the GW theater. At present, research most clearly and consistently links pesticide and PB [pyridostigmine bromide] exposures to GWI, while exposures to low-level nerve gas agents, contaminants from oil well fires, multiple vaccinations, and combinations of these exposures cannot be ruled out."

And also:

"Further research into the mechanisms and etiology of the health problems of GW veterans is critical to developing biomarkers of exposure and illness and preventing similar problems for military personnel in future deployments; this information is also critical for developing new treatments for GWI and related neurological dysfunction."

I'm sure you'll agree that these are pretty important conclusions. That also the authors talk about the potential overlap between GWI and other states specifically related to exposure to organophosphate (pesticides) such as during pesticide application (see here) or during sheep dipping (those with so-called dippers flu) is another important element. I say this not to somehow come down too hard on organophosphate (OP) pesticides, which serve an important purpose in modern agriculture and the like, but merely to reiterate that (a) caution is needed in their handling and use, and (b) they are chemically-speaking, not a million miles away from some of the most toxic nerve agents the world has ever seen. Indeed, with all the talk about Zika virus these past weeks (see here) I'm minded to suggest that one might need some additional controls in place to ensure the safe use of OPs when controlling the insect carrier (see here).

Bundled alongside the various chemical exposures - and other events [2] such as exposure to depleted uranium - that might be linked to symptoms is the added suggestion that "multiple vaccinations" may have also played a role in the presentation of the condition for some [3]. When I say vaccinations, the data suggests that these weren't just routine vaccinations against your typical childhood diseases, but rather included those aimed at a slightly more unusual disease set such as anthrax and plague (see here). The jury is still out on the extent to which these agents (singularly or combined) might have contributed to symptoms but I'm minded also to bring in the concept of ASIA (‘autoimmune (auto-inflammatory) syndrome induced by adjuvants’) that has been mentioned with GWI in mind (see here) as potentially being relevant.

Of course, more research is indicated on many aspects identified by White et al including the idea of some overlap between GWI and the presentation of chronic fatigue syndrome (CFS) [4] being careful with how wide we cast the CFS diagnostic net [5]. Alongside, perhaps one might think that an apology or two to some of our brave veterans wouldn't also go amiss from Government and others following various comments made down the years about the nature of their illness.

And for those who still might scoff at the idea of the 'toxic' effects of war, the chemical legacy of another campaign still continues to haunt some to this day...

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[1] White RF. et al. Recent research on Gulf War illness and other health problems in veterans of the 1991 Gulf War: Effects of toxicant exposures during deployment. Cortex. 2016; 74: 449-475.

[2] McDiarmid MA. et al. Health effects of depleted uranium on exposed Gulf War veterans. Environ Res. 2000 Feb;82(2):168-80.

[3] Unwin C. et al. Health of UK servicemen who served in Persian Gulf War. Lancet. 1999 Jan 16;353(9148):169-78.

[4] Ismail K. et al. Chronic fatigue syndrome and related disorders in UK veterans of the Gulf War 1990-1991: results from a two-phase cohort study. Psychol Med. 2008 Jul;38(7):953-61.

[5] Jason LA. et al. Unintended Consequences of not Specifying Exclusionary Illnesses for Systemic Exertion Intolerance Disease. Diagnostics (Basel). 2015 Jun 23;5(2):272-86.

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White RF, Steele L, O'Callaghan JP, Sullivan K, Binns JH, Golomb BA, Bloom FE, Bunker JA, Crawford F, Graves JC, Hardie A, Klimas N, Knox M, Meggs WJ, Melling J, Philbert MA, & Grashow R (2016). Recent research on Gulf War illness and other health problems in veterans of the 1991 Gulf War: Effects of toxicant exposures during deployment. Cortex; a journal devoted to the study of the nervous system and behavior, 74, 449-75 PMID: 26493934

Organic diet and urinary pesticide concentrations

"Eating Organic Lowers Pesticide Levels in Children" went the headline reporting on the small study by Asa Bradman and colleagues [1] (open-access available here). Detailing what happened to urinary pesticides levels following trials of combinations of conventionally grown food consumption vs. organic food consumption over 16 days, researchers reported some potentially interesting findings.

Measuring 23 metabolites "reflecting potential exposure to organophosphorous (OP), pyrethroid, and other pesticides used in homes and agriculture" via everyone's favourite analytical method (LC-MS) and specifically "tandem mass spectrometry", Bradman et al observed that: "An organic diet was significantly associated with reduced urinary concentrations of nonspecific dimethyl OP insecticide metabolites and the herbicide 2,4-D in children." If I had a beef with any part of the Bradman study outside of the fairly small participant group, it would be that the reliance of urinary excretion of pesticide residues might not necessarily show the whole story, as per what data one might get from the use of other biofluids such as blood samples too or even analysis of fat biposies (recognising how invasive these can be).

These are interesting findings added to other similar research on this topic [2] looking at adults. Not only do they point to the idea that there is persistent low level exposure to pesticide residues in food but also that changes in food consumption patterns may affect such exposure events. That's not to say that food is the only way that pesticide exposure might occur, as per the findings of differences among children living in urban vs. agricultural communities (where those living in more agricultural areas generally had higher levels of some of the more frequently detected pesticide metabolites). But dietary change encompassing an organic diet did seem to lead to reductions in certain pesticide metabolite excretions irrespective of geography.

Accepting the often valuable reasons why pesticides are used in the first place, I don't think many people would argue with the idea that pesticide exposure should be limited, particularly in respect of children and their developing bodies and minds [3]. Allied to the idea that organic food might also confer other benefits in terms of nutritional quality (see here) and lower levels of fairly toxic metals such as cadmium [4], there seems to be common sense in rethinking some aspects of agriculture for certain groups. That the genetics of pesticide metabolism may also play a role [4] as per discussions about PON1 (paraoxonase/arylesterase 1), is also an important point and how childhood relates to PON1 activity among other factors [5]. Indeed, to answer the question posed in another paper [6] yes, there may indeed be some benefits from an organic diet for children...

Music: Adele - Rolling in the Deep.

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[1] Bradman A. et al. Effect of Organic Diet Intervention on Pesticide Exposures in Young Children Living in Low-Income Urban and Agricultural Communities. Environ Health Perspect. 2015 Oct;123(10):1086-93.

[2] Oates L. et al. Reduction in urinary organophosphate pesticide metabolites in adults after a week-long organic diet. Environ Res. 2014 Jul;132:105-11.

[3] Muñoz-Quezada MT. et al. Neurodevelopmental effects in children associated with exposure to organophosphate pesticides: a systematic review. Neurotoxicology. 2013 Dec;39:158-68.

[4] Barański M. et al. Higher antioxidant and lower cadmium concentrations and lower incidence of pesticide residues in organically grown crops: a systematic literature review and meta-analyses. Br J Nutr. 2014 Sep 14;112(5):794-811.

[5] Gonzalez V. et al. Cholinesterase and paraoxonase (PON1) enzyme activities in Mexican-American mothers and children from an agricultural community. J Expo Sci Environ Epidemiol. 2012 Nov;22(6):641-8.

[6] Vania A. et al. Is organic diet really necessary for children? Italian Journal of Pediatrics 2015, 41(Suppl 2):A75

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Bradman, A., Quirós-Alcalá, L., Castorina, R., Schall, R., Camacho, J., Holland, N., Barr, D., & Eskenazi, B. (2015). Effect of Organic Diet Intervention on Pesticide Exposures in Young Children Living in Low-Income Urban and Agricultural Communities Environmental Health Perspectives, 123 (10) DOI: 10.1289/ehp.1408660

On glyphosate and autism (without scaremongering)

Glyphosate use and autism rates - should I blog about it?

Well, after some deliberation I decided it was a topic worthy of an entry. There is some peer-reviewed science discussions behind it and, as per other areas of controversy on the autism research landscape, the idea that 'science is about debate' (why else does everyone keep going on about open-access and transparency) should always prevail.

I'm assuming most people have heard of the organophosphonate (that's phosphonate not phosphate) herbicide glyphosate - N-phosphonomethylglycine - over the course of its discovery and use under the trade name Roundup. First patented as a chelating agent (another area of 'discussion' with autism in mind) glyphosate has been successfully killing weeds for quite a few years by interfering with some of the chemistry of the aromatic amino acids tryptophan, tyrosine and phenylalanine via its actions on the shikimate pathway. As per many other herbicides, such formulations always require a degree of care in their use given the possibility of side-effects following accidental over-exposure. Indeed, government agencies are cottoning on to this fact (see here).

The debate on glyphosate and its potential effects on human and animal health has been a hot one in recent times. Partly overlapping with the introduction of genetically modified (GM) crops that are glyphosate-tolerant (Roundup Ready) by the company who initially brought glyphosate to the market, the safety angle of glyphosate has been scrutinised and debated. Only this year (2015), an arm of the World Health Organisation (WHO) described glyphosate (and several organophosphate pesticides I might add) as "probably carcinogenic to humans". Following such an announcement, quite a few media column inches were produced as one might expect.

Set within that context, discussions have turned to whether there may be other 'effects' following the fairly widespread use of glyphosate. Perhaps inevitably, autism, and particularly the quite phenomenal increase in cases of autism, has been suggested to be 'linked' to the use of glyphosate. One might say that in this respect, glyphosate is a victim of its own success insofar as how widely it has been and is currently used.

The paper that seems to have started the ball rolling suggesting a link between glyphosate and autism is that from Anthony Samsel and Stephanie Seneff [1]. A review paper focussing specifically on the proposed inhibitory actions of glyphosate on CYP enzymes, mention of autism in the text and particularly that "glyphosate may be the most significant environmental toxin contributing to autism" was bound to stir up debate. With added soundbites about how half of children will be born with autism in the United States by 2025 and graphs correlating autism prevalence and glyphosate use, such observations were ripe for speculation and discussion.

Further papers from Samsel & Seneff [2] have continued the theme that autism may be one of many conditions/labels where glyphosate might be implicated. Drawing on animal and plant studies implicating glyphosate use with specific depletion of manganese (Mn), a whirlwind of research studies and references have been used to link such depletions to autism (and associated aspects such as anxiety) among various other conditions. To quote: "Many diseases and conditions are currently on the rise in step with glyphosate usage in agriculture, particularly on GM crops of corn and soy. These include autism, AD [Alzheimer's disease], PD [Parkinson's disease], anxiety disorder, osteoporosis, inflammatory bowel disease, renal lithiasis, osteomalacia, cholestasis, thyroid dysfunction, and infertility. All of these conditions can be substantially explained by the dysregulation of Mn utilization in the body due to glyphosate." Just in case you thought that Samsel / Seneff are the sole research team talking about glyphosate use and autism rates, I'll also refer you to the paper by Cynthia Nevison [3] that has been previously discussed on this blog (see here).

As other commentators have noted, there are a few considerations to mention about the discussions so far on any relationship between glyphosate use and autism. That 'correlation is not the same as causation' is perhaps the most important element to the data as they currently stand given that, to my knowledge, no-one has actually published any peer-reviewed results on levels of glyphosate and/or metabolites in people with autism and/or other family members compared to asymptomatic controls for example. It's not as if such a feat is too complicated given the various means and methods already published on this topic [4].

'Correlation is not the same as causation' is one of the themes also discussed in the review paper by Miguel Faria [5] who provides an important discussion to some of the points raised by Samsel & Seneff. I don't want to head too much into this quite long commentary on the Samsel / Seneff paper (complete with author replies) but it does strike me as providing something of a counter-balance to the very hypothesis-based writings of the original authors. That glyphosate is one of a multitude of herbicides and insecticides in use is an important point made in terms of the difficulties in disentangling it from the 'chemical soup' (not to demonise) that we live our lives in these days. The only other thing that I might mention is my much-used notion about the continued pluralisation of autism (see here) and its varied comorbidity as being something to bear in mind when it comes to any discussions about aetiology.

Where next, or is there even 'a next' for looking at any possible relationship between glyphosate use and autism rates? Well, I'd like to think that autism research can learn a lesson or two about not throwing out baby and bathwater when it comes to theories about [some] autism as per what seems to have happened to something like methylmalonic acid (MMA) and autism (see here) for example. It's not beyond the realms of possibility that certain chemicals or mixtures might be linked to autism risk and/or onset as per preliminary research talk about dioxin exposure being potentially linked to [some] autism or autistic traits (see here) albeit with a lot more follow-up research required.

But such research needs to be done with care and assiduity; mindful that this is a topic that will inevitably garner significant attention (as per the editorial sentence on the original Samsel / Seneff paper: "Note added by the Publisher: This paper attracts great attention.") and knowing what can happen sometimes when science and media mix (see here).

Perhaps a little less focus on soundbites and more on cold, objective science is the best way forward in this area?

Music: Fleetwood Mac- Dreams.

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[1] Samsel A. & Seneff S. Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases. Entropy 2013. 15; 1416-1463.

[2] Samsel A. & Seneff S. Glyphosate, pathways to modern diseases III: Manganese, neurological diseases, and associated pathologies. Surgical Neurology International. 2015;6:45.

[3] Nevison CD. A comparison of temporal trends in United States autism prevalence to trends in suspected environmental factors. Environ Health. 2014 Sep 5;13:73.

[4] Yoshioka N. et al. Rapid determination of glyphosate, glufosinate, bialaphos, and their major metabolites in serum by liquid chromatography-tandem mass spectrometry using hydrophilic interaction chromatography. J Chromatogr A. 2011 Jun 10;1218(23):3675-80.

[5] Faria MA. Glyphosate, neurological diseases – and the scientific method. Surgical Neurology International. 2015;6:132. doi:10.4103/2152-7806.162550.

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Faria MA (2015). Glyphosate, neurological diseases - and the scientific method. Surgical neurology international, 6 PMID: 26322242

Temporal trends in US autism prevalence: mainly real increase

"Diagnosed autism prevalence has risen dramatically in the U.S over the last several decades 
and continued to trend upward as of birth year 2005. The increase is mainly real and has occurred mostly since the late 1980s".

"They call me Cha Cha because I'm the
best dancer at St. Bernadette's"

That was the conclusion reached in the paper by Cynthia Nevison [1] (open-access) following her analysis of temporal trends in autism diagnosis for birth years between 1970 and 2005. Based on an analysis of datasets derived from IDEA (Individuals with Disabilities Education Act) and the CDDS (California Department of Developmental Services), the author suggested that between 75-80% "of the tracked increase in autism since 1988 is due to an actual increase in the disorder rather than to changing diagnostic criteria". The question of what environmental factors might have been driving such an increase in cases is also discussed in the Nevison paper, with the author concluding "children’s exposure to most of the top ten toxic compounds has remained flat or decreased over this same time frame". That top 10 list by the way, seems to come at least partly from the Landrigan paper talked about a couple of years back (see here).

There is quite a bit of information included in the Nevison paper which I'm reluctant to write a mega-blog entry on at this time. This includes various caveats about the use of IDEA and CDDS databases and their constraints on for example, what ASDs (autism spectrum disorders) are included in the datasets. I will however summarise some of the main findings in relation to the environmental factors probed by the author bearing in mind that autism research does not appear to be her main area of scientific interest (with all due respect).

So:

• Air pollution... something which has cropped up with ever-increasing frequency in the peer-reviewed research on autism (see here and see here for example). Nevison concludes: "there is no obvious evidence to suggest that trends in estimated vehicular emissions or directly measured air pollution are consistent with the sharp temporal increase in U.S. autism". So no smoking tailpipe (exhaust) there then as per other recent research findings [2].
• Mercury in vaccines... a topic guaranteed to furrow brows and raise blood pressure in some quarters (see here and see here for example). Nevison discusses the phaseout of thimerosal (thiomersal) from paediatric vaccines used in the US concluding that "the expansion of thimerosal exposure in the late 1980s and early 1990s coincides closely with the rise in autism around that time". But... "the temporal trends in autism and thimerosal following the childhood vaccine thimerosal phaseout are incompatible". Other sources of mercury exposure get a similarly 'unlikely' mark from Nevison.
• Organophosphate (OP) pesticide exposure... an interesting area which again has been covered previously on this blog (see here and see here). Nevison points out the declining use of such pesticides in the US following "the adoption of crops genetically modified to produce Bt toxin, which repels targeted insect pests, thus reducing the need for external insecticides". Recognising that pesticides are not to be trifled with (see here) I've always been a little confused about the mechanism(s) through which OP exposure could theoretically impact on the presentation of autism. I know people have talked about PON1 and autism [3] (some autism) but I do feel as though the primary effect of OPs - acting on acetlycholinesterase -  is something in need of a lot more research with autism in mind before anyone gets too carried away. 
• There is however a caveat to the pesticides-autism conclusion by the author following some mention of "the rapidly increasing application of glyphosate, the active ingredient in the herbicide Roundup®". She continues: "it appears that glyphosate cannot be responsible for the first autism cases in the 1930s and is unlikely to have caused the late 1980s uptick, but could be interacting in recent years with other toxins to drive up the prevalence of U.S. autism". Depending on where you look, you'll get various different messages about the pros and cons of glyphosate. I remember reading a report a few years back (see here) authored by one of the researchers involved in that 'organic food might be better for you' paper recently (see here) which painted a rather disturbing picture of the product. For balance, I'm going to also refer you to the various documents provided by Monsanto (the producer of Roundup) for their response to safety concerns. When it comes to a search of PubMed with the terms 'autism and glyphosate' the current result is zero although it has been mentioned elsewhere in the peer-reviewed domain [4]. 
• Maternal obesity... I'm being quite careful here accepting the previous discussions in this area of autism research (see here). Nevison reports that: "the time trend in obesity among U.S. women correlates well to that of autism, suggesting maternal obesity may be a direct influence or a comorbid consequence of the dietary factors contributing to autism, or both". 

One needs to bear in mind that the United States was the focus on these findings and as such the conclusions may not pertain to other parts of the globe. I probably don't need to say it but one should also bear in mind the saying 'correlation is not the same as causation' too. There are also other issues which have been discounted by Nevison as being related to the autism prevalence. Lead (Pb) is one of them; something which I personally would not be so keen to disregard given the more recent evidence on even trace amounts of this stuff not being great for the developing child (see here). This on top of what has been talked about with autism in mind (see here). 

I have a few other points to make which were perhaps not readily implied in the Nevison paper: first is the assumption that autism is some kind of universal condition. What I think many people have come to realise over the past few years is that within the significant behavioural and developmental heterogeneity grouped under the label autism, also compounded by the increased frequency of various comorbid conditions, a more plural description - the autisms - might be more pertinent. What this implies is that different weightings for concepts like genetics or environment (or epigenetics!) are likely acting across risk of different types of autism. 

Second, and related to point one, is the concept of synergy across different 'causative' factors. In the same way that autism science has started to accept that there is no one gene linked to all cases of autism, so environmental examinations can't really expect there to be one environmental factor working alone pertinent to all autism. If one is to assume that various environmental factors (see here and see here for example) may be linked to autism onset, it is more likely that combinations of factors are playing a role or possibly specific environmental factors acting on specific types of autism. Take for example the early work on air pollution and genotype being potentially associated with autism risk [5] as one example.

At the risk of being too speculative, I'm also minded to bring to your attention an emerging idea which might also be relevant: transgenerational epigenetics. The idea is that what happened in previous generations might have an influence on subsequent generations without structurally altering DNA in terms of the physical language of the genome. There has been some media interest in this concept in recent times (see here). With autism in mind, we've seen hints of this idea in the peer-reviewed research literature as per discussions on how advancing grandparental age might be linked to an increased risk of autism (see here). Jill Escher also talked about past chemical exposures potentially impacting on "vulnerable fetal germline epigenetics" (see here for her presentation). The implication being that correlating current exposure patterns with current autism diagnosis prevalence might not necessarily be the best way of looking at whether (and which) environmental factors might have a bearing on autism prevalence...

The primary message from the Nevison report is that the numbers of cases of autism do appear to be on the rise in the United States, and as per other reports from geographical neighbours (see here) the debates are not yet over about the reasons for that increase. Something another study has also talked about recently [6]...

So then, Only Love Can Break Your Heart by Saint Etienne.

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[1] Nevison CD. A comparison of temporal trends in United States autism prevalence to trends in suspected environmental factors. Environmental Health 2014, 13:73

[2] Gong T. et al. Exposure to Air Pollution From Traffic and Neurodevelopmental Disorders in Swedish Twins. Twin Res Hum Genet. 2014 Sep 17:1-10.

[3] D'Amelio M. et al. Paraoxonase gene variants are associated with autism in North America, but not in Italy: possible regional specificity in gene-environment interactions. Mol Psychiatry. 2005 Nov;10(11):1006-16.

[4] Seneff S. et al. Is Encephalopathy a Mechanism to Renew Sulfate in Autism? Entropy 2013. 15; 372-406.

[5] Volk HE. et al. Autism spectrum disorder: interaction of air pollution with the MET receptor tyrosine kinase gene. Epidemiology. 2014 Jan;25(1):44-7.

[6] Dave DM. & Fernandez JM. Rising autism prevalence: real or displacing other mental disorders? Evidence from demand for auxiliary healthcare workers in California. Economic Inquiry. 2014. 25 August.

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Nevison, C. (2014). A comparison of temporal trends in United States autism prevalence to trends in suspected environmental factors Environmental Health, 13 (1) DOI: 10.1186/1476-069X-13-73