On (banned) organochlorine compounds and autism risk

'Chemicals banned decades ago linked to increased autism risk today' went the press release attached to the findings reported by Kristen Lyall and colleagues [1] (open-access).

Observing that "higher levels of some organochlorine compounds during pregnancy are associated with ASD [autism spectrum disorder] and ID [intellectual disability]" the Lyall results once again push environmental factors back into the research spotlight. Indeed, environmental factors that were banned decades ago.

Including a cohort of children diagnosed with autism (n=545), those diagnosed with ID (also known at learning disability) (n-=181) and general population (asymptomatic?) controls (n=418) researchers accessed archived biological samples taken from mothers during the second trimester of pregnancy. Using some pretty sophisticated chemical analysis methods - "gas chromatography isotope dilution high resolution mass spectrometry (GCIDHRMS)" - various chemical compounds considered as POPs (persistent organic pollutants) were assayed for. Most if not all of these compounds were banned in the 1970s because of their potential effects on health. Because of their chemical nature however (i.e. enjoying bathing in fats) they can and do still persist in the environment, particularly in the food chain.

Results: various PCBs (polychlorinated biphenyl ethers) and "persistent pesticides" were included in the chemical analysis of maternal samples. Some, but not all, were reported in samples across the different groups. After some statistical wizardry in terms of adjusting samples and the results for various factors ("children with ASD were approximately four times as likely to be male than female... have older parents, and mothers with higher education") authors concluded that a few of the metabolites looked at might be linked to autism risk; specifically: "that exposure to PCB congeners in utero may influence risk of ASD in offspring."

"Primary analyses highlighted PCB 138/158 and PCB 153 in association with ASD, though other correlated congeners also demonstrated associations above the null." PCB 138/158 also seemed to show some sort of connection to the risk of offspring ID too "suggesting the impact of exposure to this congener on neurodevelopment broadly." Conversely, none of the other organochlorine compounds seemed to show any (significant) connection to autism offspring risk. Something similar has been talked about before with this broad collection of compounds in mind under more direct analysis conditions (see here). The authors conclude that further research is required to both substantiate their findings and also ascertain some of the hows and whys of these compounds in relation to autism and ID. Importantly, they acknowledge that their list of compounds tested may not be the whole story in terms of the 'multiple chemicals' people are exposed to over a lifetime.

These are rather interesting results. Not least because the potential legacy of these compounds continues years and years after production of them had all but ceased following health concerns. That researchers also focused on maternal pregnancy blood samples again (see here) puts gestational 'exposure' front and centre when it comes to potential effects and mechanisms too. The idea that immune function could be a target effect of such compounds when it comes to offspring autism risk is also explored by the authors: "effects on the immune system is another particularly likely mechanism." This would also seem to tally with the growing evidence that maternal immune function during the nine months that made us might be an important part of aetiology for at least some autism and/or more general neurodevelopmental issues.

The story continues as it might with other compounds too [2] on this 'TENDR' area of research...

To close, Worf don't like the lute...

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[1] Lyall K. et al. Polychlorinated Biphenyl and Organochlorine Pesticide Concentrations in Maternal Mid-Pregnancy Serum Samples: Association with Autism Spectrum Disorder and Intellectual Disability. Environ Health Perspect. 2016. Aug 23.

[2] Jeddi MZ. et al. The role of phthalate esters in autism development: A systematic review. Environ Res. 2016 Aug 24;151:493-504.

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Lyall K, Croen LA, Sjödin A, Yoshida CK, Zerbo O, Kharrazi M, & Windham GC (2016). Polychlorinated Biphenyl and Organochlorine Pesticide Concentrations in Maternal Mid-Pregnancy Serum Samples: Association with Autism Spectrum Disorder and Intellectual Disability. Environmental health perspectives PMID: 27548254

"The maternal body as environment in autism science"

Although I'm not really one for deep philosophical discussions or anything related (unless linked to a specific galaxy far, far away...), I was recently interested to read the paper by Martine Lappé [1] talking about how "complex narratives of autism’s causes and social anxieties surrounding child development have helped situate autism risk in women’s bodies before and during pregnancy."

I'm as guilty as anyone for discussing the pretty constant stream of peer-reviewed research evidence suggesting that what goes on before and during the nine months that made us might have some important bearing on offspring in terms of behaviour and development. The wide range of potential variables laid at mum's pregnancy doorway with autism risk in mind have grown to overwhelming proportions in recent time, as just about every week some factor or another is said to show involvement.

Lappé suggests that such research has turned pregnancy into 'environment' when it comes to discussions about possible autism aetiology and involves "three characteristics: the molecularization of the environment, an individualization of risk, and the internalization of responsibility."  The result being that 'larger questions' have been put to one side, particularly related to the continued medicalisation of the autism label (and various other labels), alongside the idea that within the large heterogeneity of autism, pregnancy factors might not necessarily figure significantly in every single case.

I can kinda see where the author is coming from in this article, particularly how suggestions that factor X or Y during pregnancy might increase offspring autism risk does to some extent mirror the darker days of autism research in terms of 'blame'. Where once popular opinion was that autism was due to parenting issues, so now the suggestion that maternal obesity for example, might somehow increase the risk of offspring autism continues the blame-game and indeed, pushes the 'blame window' further back temporally speaking. Yes, parenting style and obesity are not one and the same thing but the common element they possess is the perception that somehow there is a choice being made; a choice to parent one way or another, to become obese or not. That idea of 'choice' moves some people's minds to the concept of blame, and onwards the blame-game once again gathers momentum. The same logic around choice can similarly hold when it comes to whether pharmaceutic A or B taken during pregnancy might elevate offspring autism risk too...

There is no easy answer to what to do about turning the maternal [pregnancy] body into 'environment' when it comes to the big question: how does autism come about? Generalising the word 'autism' to denote 'all autism' means that we don't know really know how autism comes about or whether anything can be done more generally to modify a person's risk of autism. Accepting that some people don't even wish to see the words 'modify' and 'risk' in the context of autism, I personally see such philosophical discussions in a more plural context as per all that chatter about 'the autisms' and the label(s) not necessarily existing in some sort of diagnostic vacuum (see here).

I for example, look towards the increasingly important idea that for all the different 'types' of autism out there, there may be a similar number of genetic and non-genetic factors playing some role; for some, issues during pregnancy are likely to impact on offspring autism risk more than others. The specific idea that immune function and/or 'inflammation' during critical periods of pregnancy might have offspring outcomes (see here for example) is particularly appealing, given that the whole concept of immune function is moving well outside of the realms of just infection or pathogen identification and control. Accepting also that pregnancy is characterised by a change in maternal immune function (y'know, to accommodate that foreign entity that resides inside mum's body) there is plenty of scope for such tolerance to be affected by one or more agents in quite a few ways.

Ultimately, 'the maternal body as environment in autism science' is probably here to stay. The language however of how we chose to represent and transmit information about pregnancy risk factors and autism perhaps requires some further philosophical discussions...

And speaking of philosophy, a link to a book that I once enjoyed reading.

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[1] Lappé M. The maternal body as environment in autism science. Social Studies of Science. 2016; Aug 19.

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Lappe, M. (2016). The maternal body as environment in autism science Social Studies of Science DOI: 10.1177/0306312716659372

Fatty acids and reading ability replicated

I'm a fan of scientific replication on this blog. Y'know, when one group comes out with some new marvellous research findings and another [independent] group says 'yep, we found that too'.

It is with that sentiment in mind that I'm talking about the results published by Mats Johnson and colleagues [1] who suggested that "3 months of Omega 3/6 treatment improved reading ability" following a "3-month parallel, randomized, double-blind, placebo-controlled trial" with schoolchildren aged 9-10 years old. The trial was actually a little longer than 3 months given that it also included a 3-month active treatment period for all subjects. The replication angle harks back to another study [2] that has been mentioned on this blog (see here) and that concluded: "DHA [docosahexaenoic acid] supplementation appears to offer a safe and effective way to improve reading and behavior in healthy but underperforming children from mainstream schools."

The Johnson paper, whose ClinicalTrials.gov records can be found here, utilised a gold-standard methodology when it came to testing whether a particular fatty acid formulation - "a daily dose of 558 mg EPA [eicosapentaenoic acid], 174 mg DHA, and 60 mg gamma-linolenic acid" - could improve the reading ability of mainstream schooled children. The primary outcome being measured were any changes to the LOGOS test as well as whether fatty acid intervention also impacted on attention-deficit hyperactivity disorder (ADHD) symptoms, bearing in mind those formally diagnosed with ADHD were supposed to have been excluded from the study. The behavioural side of things also coming from some history with fatty acids there too (see here).

Results: "Compared with placebo, 3 months of Omega 3/6 treatment improved reading ability – specifically the clinically relevant ‘phonologic decoding time’ and ‘visual analysis time’ – in mainstream schoolchildren. In particular, children with attention problems showed treatment benefits." The placebo by the way, was palm oil. Importantly too, side-effects described during the study were fairly rare and mild: "mainly stomach pain/diarrhea (active n = 9, placebo n = 2)." I should also mention that the participant size was over a hundred when it came to those who completed the study so these results are not to be sniffed at.

I'd like to think that these and the various other results out there on this topic will start to be taken seriously some time soon. I know that there has been a lot of hype associated with fatty acids down the years, but the science is growing ever stronger to suggest that such preparations probably do more good than harm. Health promotion messages to eat more oily fish (a good source of fatty acids) for example, are important but unfortunately as per other occasions, are unlikely to provide the same levels of such nutrients as artificial supplementation delivers. That and the fact that oily fish is probably not going to be to everyone's taste.

Insofar as the 'where next?' of this area of research, well, longer-term follow-up is perhaps an important goal to see whether positive changes to reading ability and/or potential amelioration of behavioural issues translates into more favourable academic and other outcomes as a function of fatty acid intake. Accepting that for example, ADHD and/or ADHD-type behaviours might place someone at varying degrees of disadvantage (see here for example), the onus is also on providing the best chances for a person and if that includes a daily fatty acid supplement to help in some way, I don't see too many people quibbling about it [3].

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[1] Johnson M. et al. Omega 3/6 fatty acids for reading in children: a randomized, double-blind, placebo-controlled trial in 9-year-old mainstream schoolchildren in Sweden. J Child Psychol Psychiatry. 2016 Aug 22.

[2] Richardson AJ. et al. Docosahexaenoic Acid for Reading, Cognition and Behavior in Children Aged 7–9 Years: A Randomized, Controlled Trial (The DOLAB Study). PLoS ONE. 2013; 7(9): e43909.

[3] Königs A. & Kiliaan AJ. Critical appraisal of omega-3 fatty acids in attention-deficit/hyperactivity disorder treatment. Neuropsychiatr Dis Treat. 2016 Jul 26;12:1869-82.

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Johnson M, Fransson G, Östlund S, Areskoug B, & Gillberg C (2016). Omega 3/6 fatty acids for reading in children: a randomized, double-blind, placebo-controlled trial in 9-year-old mainstream schoolchildren in Sweden. Journal of child psychology and psychiatry, and allied disciplines PMID: 27545509

Bipolar disorder in irritable bowel syndrome (IBS): real gut-brain axis stuff

"Our results support a significantly higher prevalence rate of BD [bipolar disorder] in IBS [irritable bowel syndrome] patients than in controls."

So said the results of the meta-analysis and systematic review published by Ping-Tao Tseng and colleagues [1] (open-access available here) based on the suggestion that "both IBS and BD may, at least partially, share a similar mechanism of pathophysiology" specifically with immune function in mind.

Building on previous research suggesting that (a) various psychiatric comorbidity might be over-represented in IBS (see here) and (b) that gastrointestinal (GI) inflammation and immune activation might not be unstrange bedfellows in at least some cases of BD (see here), the old gut-brain axis receives some important support from these latest findings. Bipolar disorder (BD) I should explain, is characterised by episodes of depression and mania and vice-versa.

The hows and whys: some 170,000 people diagnosed with IBS and 190,000 not-IBS controls were included from 6 studies that met the authors' criteria for inclusion. Two of the six studies originated from Taiwan and that oh-so-useful resource that is the National Health Insurance Research Database (NHIRD). In those diagnosed with IBS: "The prevalence rate of BD was significantly higher in the IBS patients than in the HCs [healthy controls] (OR = 2.48; 95% confidence interval [CI]: 2.35–2.61; P < 0.001)." The authors also suggested that they "could not find any significant association between the comorbidities of DM [diabetes mellitus]/hypertension and the prevalence rate of BD in IBS patients."

The authors provide one or two caveats regarding their results, not least that a meta-analysis is only as good as the studies it includes (see here for another example of how this might play out). They stress the observation-only link between BD and IBS in their paper "rather than any mechanistic explanation of the comorbidity of these 2 diseases." So, there is more to do in this area. Interestingly too, they also talk about what their findings might mean for the practice of prescribing antidepressants in cases of IBS. To quote: "We suggest that clinicians and researchers start to investigate the possibility of a phase-shift to manic episodes in IBS patients treated with antidepressants." Indeed.

I'm gonna conclude with two further points that might provide some avenues for further scientific investigation in this area. First is the idea that treating [some] IBS with specific probiotic formulations seems to be in the research and clinical ascendancy these days (see here). The question is what effect (if any) such treatments might have on accompanying BD symptoms? Y'know taking into account that those trillions of wee beasties that call our gut home (the gut microbiota) might be doing so much more than just digesting food and making the odd nutrient or two? At this point I might also bring to your attention the case report from Grossi and colleagues on IBS, probiotics and autism [2] that will be gracing this blog soon. This is made all the more interesting by the suggestion that bipolar disorder might not be an unstrange diagnostic bedfellow with autism (see here). Second is the potentially intersecting research talking about states such as [some] mania as perhaps being linked to bacterial infections (see here). Stay with me on this one, but is it at all possible that infection - possibly a GI-related infection - might affect both bowel and behaviour at the same time? What can we do about this? Questions, questions, questions...

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[1] Tseng PT. et al. A meta-analysis and systematic review of the comorbidity between irritable bowel syndrome and bipolar disorder. Medicine (Baltimore). 2016 Aug;95(33):e4617.

[2] Grossi E. et al. Unexpected improvement in core autism spectrum disorder symptoms after long-term treatment with probiotics. SAGE Open Medical Case Reports. 2016; 4: 2050313X16666231

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Tseng PT, Zeng BS, Chen YW, Wu MK, Wu CK, & Lin PY (2016). A meta-analysis and systematic review of the comorbidity between irritable bowel syndrome and bipolar disorder. Medicine, 95 (33) PMID: 27537599

Parental concerns about offspring autism: listen up!

"The developmental concerns expressed by parents of undiagnosed toddlers were highly consistent with the diagnosis the child later received."

So said the findings reported by Megan Richards and colleagues [1] who continue a research theme suggesting that when it comes to 'developmental concerns' about offspring behaviour, parents are generally pretty good at spotting potential red flags and professionals should perhaps take further note.

Based on data derived from "a toddler screening study" some 270 parents of autism positive screened infants and 250 autism negative screened infants were asked via a questionnaire about "their child's development, therapy received, and specialists consulted." The kinds of details collected included what sort of developmental concerns parents had about their children before any diagnostic evaluation was eventually completed.

The results suggested a few things not least that the vast majority of parents "reported concerns about their child's development." Parents, as we know from various other research sources, are generally experts in their own children. This concern also seemed to be reflected in the type(s) of intervention/therapy selected being pertinent to the types of concern parents had: "Parent concerns were associated with therapies received and specialists consulted."

Finally: "The number of concern categories was positively associated with several ASD [autism spectrum disorder] scores." This harks back to the opening sentence of this post and the idea that beyond just having concerns, quite a few parents might also have some thoughts/feelings on how 'severe' the behavioural issues displayed by their child might be.

This is important stuff. What it tells us yet again is that parents are active agents when it comes to screening their child's behaviour and clinicians and other expert groups should be further encouraged to listen to them and their concerns. I also feel it is important that such groups listen to other issues that parents might have about their child outside of just behaviour. At this point I might also introduce the findings by Little and colleagues [2] suggesting that sex/gender should also be taken into account when discussing parental concerns of offspring behaviour. The data does not however say that diagnosis should be totally removed from those in the know (similar to the problems that can arise when 'self-diagnosis' is applied at the expense of a full professional diagnostic assessment).

"Results emphasize the need for providers to elicit and take seriously parent concerns during the referral and diagnostic processes." Indeed, and one wonders whether this might extend to other symptoms/labels that seem to cluster around the diagnosis of autism?

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[1] Richards M. et al. Parents' Concerns as They Relate to Their Child's Development and Later Diagnosis of Autism Spectrum Disorder. J Dev Behav Pediatr. 2016 Aug 18.

[2] Little LM. et al. Do early caregiver concerns differ for girls with autism spectrum disorders? Autism. 2016 Aug 18. pii: 1362361316664188.

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Richards M, Mossey J, & Robins DL (2016). Parents' Concerns as They Relate to Their Child's Development and Later Diagnosis of Autism Spectrum Disorder. Journal of developmental and behavioral pediatrics : JDBP PMID: 27541581

Autism, optimal outcome and the broader autism phenotype

"Overall, OO [optimal outcome] individuals are not showing BAP [broader autism phenotype] characteristics, but may be subject to other mild ADHD [attention-deficit hyperactivity disorder]-like characteristics."

So said the findings reported by Joyce Suh and colleagues [1] who continue a research voyage based on the examination of a group of children who were very much once on the autism spectrum but no longer meet the diagnostic criteria for the label: those with so-called optimal outcome.

Including the godmother of optimal outcome (OO) research, Deborah Fein, on the authorship list, the Suh paper adds a further level of evidence that 'loss of diagnosis' might actually mean loss of the broader autism characteristics that make up the BAP description too. Looking at a small group of children classified as OO (n=22) and comparing them with a similar number of "high functioning individuals with ASD (HFA)... and typically developing (TD) peers" researchers set about comparing and contrasting the groups when it came to the BAP and also the "Big Five personality traits."

As per the opening sentence, those included in the OO grouping seemed to be free of BAP traits; indeed described as "indistinguishable from TD." Again bearing in mind the relatively small participant numbers included for study, the authors did note a few slight differences when comparing the OO group and those 'typically developing peers' in terms of their use of language and also emotional stability. There may be other avenues for further research based on these topics taking into account how OO might also provide protection against some important psychiatric comorbidity traditionally over-represented when it comes to autism (see here).

But yet again, it appears that OO does seem to denote a group of children who were most definitely on the autism spectrum but who now, for whatever reason(s), seem to be relatively symptom free including those symptoms linked to the broader autism phenotype. The sweeping generalisation that all autism is a lifelong condition takes yet another powerful peer-reviewed research hit.

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[1] Suh J. et al. Ratings of Broader Autism Phenotype and Personality Traits in Optimal Outcomes from Autism Spectrum Disorder. J Autism Dev Disord. 2016 Aug 18.

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Suh J, Orinstein A, Barton M, Chen CM, Eigsti IM, Ramirez-Esparza N, & Fein D (2016). Ratings of Broader Autism Phenotype and Personality Traits in Optimal Outcomes from Autism Spectrum Disorder. Journal of autism and developmental disorders PMID: 27538964