Maternal immune activation (MIA) and Old World monkeys

Old World monkeys detailed in the title of this post, specifically refers to a type of animal called a rhesus macaque who were the 'participants' of choice as detailed in a recent study by Destanie Rose and colleagues [1] looking at a concept called maternal immune activation (MIA).

Those who followed this blog down the years will no doubt have seen me discuss MIA before in the context of autism and/or schizophrenia (see here for example). The basic theory is that whilst in-utero and enjoying approximately nine months in a warm and comfortable environment with a reprogrammed maternal immune system to stop a mother's body from 'rejecting' a developing foetus, infections encountered by the mother at critical periods of pregnancy might themselves or through their effects on the maternal immune system, have the ability to 'affect' offspring outcomes in a variety of ways. The majority of work on the concept of MIA has been in smaller animals such as rodents, so the inclusion of rhesus macaques is an important step as it was in other work with the immune system and autism in mind (see here).

So, take 21 pregnancy rhesus macaques and give them either "three injections over 72 hours of poly I:C-LC [an immune stimulant], a double stranded RNA analog (viral mimic), or saline as a control." Said injections were given either "near the end of the first trimester or near the end of the second trimester" to see whether timing of immune stimulation might be important. Macaque offspring were subsequently born and followed for about 4 years. Blood samples were collected from offspring "at the end of their first (year 1) and fourth (year 4) years to assess dynamic cellular immune function." At the same time, the behaviours of monkey offspring were also analysed to see if there were any effects from MIA exposure.

Results: behaviour did seem to be affected by MIA exposure, particularly stereotyped behaviours, noted to be a core feature of autism. Similarly, researchers reported some important immune system 'changes' associated with MIA exposure: "elevated production of innate inflammatory cytokines including: interleukin (IL)-1β, IL-6, IL-12p40, and tumor necrosis factor (TNF)α" at 1 year of age. Immune system changes were also noted longer-term at 4-years: "the MIA exposed offspring continued to display elevated IL-1β, and there was also a pattern of an increased production of T-cell helper type (TH)-2 cytokines, IL-4 and IL-13." Although being careful not to generalise too much when it comes to immune system markers and what they mean for pro- or anti-inflammatory signals, the leaning towards the production of Th-2 cytokines is typically linked to atopy and 'the promotion of IgE and eosinophilic responses in atopy.' The authors - including some notable names from the MIND Institute - conclude by suggesting that: "Data from this study suggests long-term behavioral and immune activation was present in offspring following MIA."

Accepting that animal models of something like MIA are not necessarily the same as human MIA and its responses, this is interesting work. If one however accepts the data on something like vaccine function being modelled in animals (see here for example) is akin to what happens in people, real people, there is some added strength to the information published by Rose and other groups on how MIA may indeed be a relevant factor when it comes to immune function potentially affecting offspring behaviour and development.

This research also intersects with quite a lot of other peer-reviewed science talking about how (human) pregnancy infection does seem to be related to offspring risk for conditions such as autism (see here). That various immune-related conditions such as asthma in mothers might also 'prime' for offspring neurodevelopmental issues is another important strand of research potentially pertinent to this area (see here). And then also there is the idea of an 'inflammatory autism subtype' (see here) also previously suggested continuing the important theme of immune function and behaviour/development being linked. There are, as you can see, quite a few potentially important connections that can be made between the Rose results and other data on MIA and offspring development.

Oh, and I'll be coming to the recent paper by Zerbo and colleagues all in good time...

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[1] Rose DR. et al. Long-term altered immune responses following fetal priming in a non-human primate model of maternal immune activation. Brain Behav Immun. 2016 Nov 19. pii: S0889-1591(16)30522-0.

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Rose, D., Careaga, M., Van de Water, J., McAllister, K., Bauman, M., & Ashwood, P. (2016). Long-term altered immune responses following fetal priming in a non-human primate model of maternal immune activation Brain, Behavior, and Immunity DOI: 10.1016/j.bbi.2016.11.020

Of vaccines and monkeys

A quote to begin:

"These data indicate that administration of TCVs [thimerosal-containing vaccines] and/or the MMR [measles, mumps, rubella] vaccine to rhesus macaques does not result in neuropathological abnormalities, or aberrant behaviors, like those observed in ASD [autism spectrum disorder]."

Those were the findings reported by Bharathi Gadad and colleagues [1] (open-access available here) and their study providing "a comprehensive analysis of the influence of TCVs on the brain and behavior in a nonhuman primate model."

Giving infant rhesus macaques "the recommended pediatric vaccine schedules from the 1990s and 2008" and various combinations of vaccinations including MMR vaccine and vaccines on an "accelerated schedule" in contrast to saline (placebo) injections, authors reported no significant differences among behavioural or neuropathological parameters inspected as a function of vaccination status.

Although a little late in getting to this research, I believe this study also ties in with other recent results from some of the same authorship group [2] also suggesting that over a 5-year period of inspection, there was "no consistent evidence of neurodevelopmental deficits or aberrant behavior in vaccinated animals." Readers might also like to read an additional paper from the authors talking about the usefulness of animal models when it comes to autism research [3] among other things.

Appreciating that to mention immunisation and autism in the same sentence can stir up some significant emotions (readers may like to read Tom Insel's post on the Four Kingdoms of Autism as a background), I was drawn to blog about the Gadad paper because it is peer-reviewed science. Alongside the growing evidence base suggesting that there probably is no population-wide link between various vaccine administrations and risk of autism (see here) and the important public health message about the value of immunisation, the Gadad data represents some good longitudinal animal science.

If I had to quibble in anyway about the study, it would be that monkeys are monkeys and not humans (similarly applied to other animal models), and that the animal participant numbers were pretty small bearing in mind that said animals were eventually sacrificed for neuropathological inspection. I'd also suggest that whilst there is evidence that autism is correlated with certain brain regions (see here for example), the jury is still out on making any generalised assumptions to the very, very wide autism spectrum complete with added risk of various comorbidity. Others have also similarly mentioned that not all vaccine groups were fully studied and data presented in the current Gadad paper, so maybe there is more to come from this research project.

The use of nonhuman primates as 'subjects' in the debate about any link between vaccination and 'neurodevelopmental outcomes' has had its fair share of twists and turns down the years. Some readers might remember the peculiar case of another paper from Laura Hewitson and colleagues [4] titled: 'Delayed acquisition of neonatal reflexes in newborn primates receiving a thimerosal-containing hepatitis B vaccine: influence of gestational age and birth weight' that is listed as 'withdrawn' under another entry on PubMed [5] albeit published in another journal. On that occasion, researchers suggested that their data pointed to a possible interaction between birth weight and gestational age when it came to hepatitis B vaccination and the presentation of early reflexes in animals. Other papers from this group [6] have similarly proved controversial, insofar as the reported effects of a pediatric vaccine schedule on aspects of opioid ligand binding for example (with others challenging the results [7] and an author reply). This area seems to court controversy.

I will end however by reiterating the findings reported by Gadad et al reporting the lack of adverse effects of the pediatric vaccine schedule on some of our closest cousins in the animal world. This does not mean that continued vigilance should figure any less (even perhaps with certain groups in mind [8] as per other musings) with regards to this aspect of our pharmaceutical armoury nor that other factors around the time of vaccination are necessarily 'off the hook' [9] as potentially being important to [some] autism. But it does provide some important data pertinent to discussions on the risk/benefit ratio of immunisations and their potentially far-reaching benefits [10].

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[1] Gadad BS. et al. Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology. Proc Natl Acad Sci U S A. 2015 Sep 28. pii: 201500968.

[2] Curtis B. et al. Examination of the Safety of Pediatric Vaccine Schedules in a Non-Human Primate Model: Assessments of Neurodevelopment, Learning, and Social Behavior. Environmental Health Perspectives. 2015;123(6):579-589.

[3] Gadad BS. et al. Neuropathology and Animal Models of Autism: Genetic and Environmental Factors. Autism Research and Treatment. 2013;2013:731935.

[4] Hewitson L. et al. Delayed acquisition of neonatal reflexes in newborn primates receiving a thimerosal-containing hepatitis B vaccine: influence of gestational age and birth weight. J Toxicol Environ Health A. 2010;73(19):1298-313.

[5] Hewitson L. et al. WITHDRAWN: Delayed acquisition of neonatal reflexes in newborn primates receiving a thimerosal-containing Hepatitis B vaccine: Influence of gestational age and birth weight. Neurotoxicology. 2009 Oct 2.

[6] Hewitson L. et al. Influence of pediatric vaccines on amygdala growth and opioid ligand binding in rhesus macaque infants: A pilot study. Acta Neurobiol Exp (Wars). 2010;70(2):147-64.

[7] Novella S. & Hines T. Autism and the amygdala: commentary on Hewitson and coauthors (2010). Acta Neurobiol Exp (Wars). 2011;71(1):178-9; author reply 180-1.

[8] Poling JS. et al. Developmental Regression and Mitochondrial Dysfunction in a Child With Autism. Journal of Child Neurology. 2006;21(2):170-172.

[9] Schultz ST. et al. Acetaminophen (paracetamol) use, measles-mumps-rubella vaccination, and autistic disorder: the results of a parent survey. Autism. 2008 May;12(3):293-307.

[10] Fullerton HJ. et al. Infection, vaccination, and childhood arterial ischemic stroke. Neurology. 2015. Sept 30.

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Gadad BS, Li W, Yazdani U, Grady S, Johnson T, Hammond J, Gunn H, Curtis B, English C, Yutuc V, Ferrier C, Sackett GP, Marti CN, Young K, Hewitson L, & German DC (2015). Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology. Proceedings of the National Academy of Sciences of the United States of America PMID: 26417083

MAR autism and maternal autoimmune conditions: speculations

The term MAR autism - maternal autoantibody-related autism - whilst still a relatively new addition to the autism research vocabulary, has nevertheless already courted some controversy. This follows a decision to try and commercialise the growing research base in this area (see here) which raised a few eyebrows in various quarters.

Speculating on a dead cat bounce?  @ Wikipedia 

As I indicated on my previous post about said commercialisation, there are a few questions which perhaps need answering before this work starts down the path of becoming any sort of reliable 'autism test'. Some of these questions being particularly important if one is to learn the lessons from another proposed autism test which came across a few problems in replication recently (see here).

Away from such discussions, the notion that a proportion of mums of children with autism spectrum disorder (ASD) "have antibodies in their bloodstream that react with proteins in the brain of their babies" is potentially a very important finding. The evidence for such a process is actually becoming quite consistent (see here) following on from other investigations pointing at some role for the maternal immune system when it comes to at least some cases of autism (see here).

The paper by Lior Brimberg and colleagues* adds to the autism - maternal anti-brain antibodies story with their findings suggesting that "Mothers of an ASD child were four times more likely to harbor anti-brain antibodies than unselected women of child-bearing age (10.5 vs 2.6%)" based on the analysis of collected data from one or two quite large autism study initiatives (Simons Simplex Collection and Autism Genetic Exchange Resource). This in itself would be a worthy confirmatory research finding bearing in mind the number of plasma samples that were analysed as part of the study.

But of perhaps equal importance was the observation that "The analysis of ASD mothers with brain-reactive antibodies also revealed an increased prevalence of autoimmune diseases, especially rheumatoid arthritis and systemic lupus erythematosus". This point was covered by other commentary of this study (see here) including findings related to the detection of anti-nuclear antibodies (ANAs) (53% vs 13.4%) in autism mums with and without the anti-brain antibodies respectively.

Those who regularly visit this blog might know about my interest in all things autoimmunity with autism in mind (see here). The suggestion that the presence of brain reactive antibodies seemed to correlate with an increased frequency of maternal autoimmune conditions or their biological links represents yet another possible connection between autoimmunity and autism, at least some cases of autism.

With my speculating hat firmly in place, I wondered about a couple of things as a result of these findings. I wondered for example, whether the anti-nuclear antibodies were also present in offspring of those mums who tested positive for both brain reactive antibodies and ANAs. I note that ANAs have been previously reported in cases of autism as per the findings of Mostafa and Kitchener** who observed: "Children with autism had a significantly higher percent seropositivity of anti-nuclear antibodies (20%) than healthy children (2.5%; P < 0.01)". That and their suggestion: "Anti-nuclear antibody seropositivity was significantly higher in autistic children with a family history of autoimmunity than those without such history (36.8% and 5%, respectively; P < 0.001)" makes for some interesting connections.

Harking back to the ScienceDaily piece on the Brimberg study (see here) I was also intrigued by the suggestion that a 'leaky' blood-brain barrier may "allow the "anti-brain" antibodies to pass through to the babies' brains, possibly causing autism".

Now just before I get too carried away with this, there has been a bit of debate down the years about just when the blood-brain barrier (BBB) actually becomes effective in the foetus and infant. The more recent discussions suggest that there is a "well developed barrier mechanisms in the developing brain". This contrasts with other reports such as the study by Volodin and colleagues*** suggesting that the final establishment of the foetal BBB, under typical circumstances, is carried out in the latter stages of gestation. I'll leave readers to draw their own conclusions on which is the correct position.

This barrier however, partly physical and partly biochemical, is susceptible to 'damage' under certain circumstances as reported in an older post on this topic (see here). That alongside some of the gatekeeper molecules such as P-glycoprotein which help transport things through the BBB (see here) being potentially susceptible to 'alteration' as a function of various factors, means that BBB permeability is influenced by quite a few fluidic variables.

If one assumes that, as in the example of a potential link between maternal SSRI use during the first trimester of pregnancy and offspring autism risk (see here**** and here for my post), early stage pre-completed formation of the infant BBB is a 'risk' time for the developing foetus and its susceptibility to things like anti-brain antibodies and/or ANAs, one might get a sense of how and when such a process "possibly causing autism" may come about. I hasten to add that I'm still speculating at this point.

With leaky membranes in mind and the still-awaited peer-review publication of some conference proceedings from the lab of Paul Patterson (see here) on the suggestion of leaky gut present in their maternal immune activation offspring mouse model, I'm also wondering whether there may be another connection to be had here too. Various autoimmune conditions have been talked about with gut hyperpermeability in mind; ranging from gastrointestinal conditions such as coeliac disease (see here*****) to type 1 diabetes (see here******). It's not necessarily an all-or-nothing relationship but leaky gut and autoimmunity (with other factors such as gut bacteria also in the mix) is certainly on the scientific map.

In a similar vein to the ANA story, I'm wondering whether there may be merit in looking at whether there is any tie-up between gut permeability issues and (a) those mums where brain reactive antibodies have been reported, and (b) children of those mums with reported brain reactive antibodies and/or ANAs. Indeed, if (and it is still a very speculative 'if') there is some association to be found, whether as per the collected de Magistris work, one might envisage a role for dietary intervention to act on the permeability issue and any knock-on effects that might have with regards to autoimmune processes and presented symptoms? The other potential factor in this relationship being the link between gluten (or rather gliadin) and another barrier gatekeeper molecule called zonulin (see here******* open-access and here for a previous post) which is also deserving of some study with autism in mind.

I know that there's been speculation-a-go-go on this entry and I'm very much exceeding the remit of the paper by Brimberg and colleagues. I apologise. It's an easy thing to do when it comes to a blog, open-access, with no peer-review and full editorial control to the owner (i.e. me). I'd like to think however, that this area of immune activation and autoimmunity potentially opens up a whole range of further research questions ripe for scientific inquiry outside of just the formulation of a test for autism risk or not. In these days of autisms over autism and "autism as fractionable into different, largely independent sets of clinical features" new frontiers for autism research abound, and that's just as true for MAR autism and autoimmunity.

And for those interested in the attached picture included with this post and what a 'dead cat bounce' is, it's not as harrowing as you might think... (see here). Meow.

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* Brimberg L. et al. Brain-reactive IgG correlates with autoimmunity in mothers of a child with an autism spectrum disorder. Molecular Psychiatry. 2013; 18: 1171-1177.

** Mostafa GA. & Kitchener N. Serum anti-nuclear antibodies as a marker of autoimmunity in Egyptian autistic children. Pediatr Neurol. 2009 Feb;40(2):107-12.

*** Volodin NN. et al. Status of the blood-brain barrier in newborn infants of various gestational ages in the normal state and in pathology. Pediatriia. 1989;(3):10-4.

**** Croen LA. et al. Antidepressant use during pregnancy and childhood autism spectrum disorders. Arch Gen Psychiatry. 2011 Nov;68(11):1104-12.

***** Drago S. et al. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol. 2006 Apr;41(4):408-19.

****** Bosi E. et al. Increased intestinal permeability precedes clinical onset of type 1 diabetes. Diabetologia. 2006 Dec;49(12):2824-7.

******* Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011 Jan;91(1):151-75.

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Brimberg L, Sadiq A, Gregersen PK, & Diamond B (2013). Brain-reactive IgG correlates with autoimmunity in mothers of a child with an autism spectrum disorder. Molecular psychiatry PMID: 23958959

Maternal immune activation and monkeys continued

I sure do hope that all those fictional stories of apes turning the tables on humans don't ever come true. Indeed should you ever hear a Charlton Heston-esque character uttering 'You cut up his brain, you bloody baboon!' you might want to look to those in the field of monkey research as being the first ones with their brains on the chopping block in a sort of tit-for-tat style.

I jest of course. But the theme of monkey research runs strong in today's post as I introduce the paper by Melissa Bauman and colleagues* adding yet further evidence to the possible connection between maternal immune activation (let's call it MIA for short) and offspring behavioural development and characteristics.

For those with a close eye on autism and schizophrenia research, you'll probably already have heard of the work of Paul Patterson and colleagues (see here) and that coming out of the MIND Institute (see here) on how mothers' immune function during pregnancy might influence the risk of offspring presenting with said conditions. Indeed, with no clinical advice given or intended, the extended work looking into things like the use of suramin (see here) on offspring of mouse models with MIA in mind is also worthy of attention (note: the stress is on mouse models not human models).

For those who follow this blog, you might remember that I've already talked about some of the other work of Melissa Bauman and colleagues and the concept of maternal autoantibody-related autism (MAR). The emphasis there was on how monkeys have been introduced into MIA research and so perhaps relieving the burden on our poor Murine friends. If you happen to be a rat however, be warned... it looks like autism research is moving its eye of Sauron on to you.

The latest paper from Bauman (which also included Paul Patterson on the authorship list) differed from their MIA paper** insofar as instead of transplanting purified IgG brain reactive antibodies derived from mums of children diagnosed with an autism spectrum disorder (ASD) into monkeys, they used an artificial 'viral mimic'*** to stimulate the maternal immune system. The mimic was administered to pregnant monkeys either early or late gestation and compared with a non-mimic control group of rhesus monkeys.

As per the previous study, offspring behaviour was analysed over a 2-year period and some notable differences were reported: "MIA yields offspring with abnormal repetitive behaviors, communication, and social interactions". Readers might see a few similarities between the areas reported and the main topic of this blogsite.

This is interesting data of that there is no doubt. Allowing for the relatively small groups of animals included for study (13 experimental animals and 11 controls) and the important fact that monkeys are monkeys and not human beings with all their complexities, one might be inclined to think that MIA is certainly a field making advances.

With my own research hat on, bearing in mind MIA is most definitely not my field of expertise, I do wonder whether we might be hearing more from this group on something reported (but still awaiting peer review publication) by Prof. Patterson not so long ago: leaky gut being present in the offspring of MIA mother mice (see here). Ah yes, leaky gut (gut hyperpermeability if you will). The same leaky gut in cases of autism which has very recently been confirmed by the research tour-de-force that is Laura de Magistris and colleagues (see here). I'd be really quite interested to see if they looked at gut permeability in those MIA offspring monkeys too....

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* Bauman MD. et al. Activation of the Maternal Immune System During Pregnancy Alters Behavioral Development of Rhesus Monkey Offspring. Biol Psychiatry. 2013 Sep 4. pii: S0006-3223(13)00673-2. doi: 10.1016/j.biopsych.2013.06.025.

** Bauman MD. et al. Maternal antibodies from mothers of children with autism alter brain growth and social behavior development in the rhesus monkey. Transl Psychiatry. 2013 Jul 9;3:e278. doi: 10.1038/tp.2013.47.

*** Caskey M. et al. Synthetic double-stranded RNA induces innate immune responses similar to a live viral vaccine in humans. J Exp Med. 2011 Nov 21;208(12):2357-66. doi: 10.1084/jem.20111171.

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Bauman MD, Iosif AM, Smith SE, Bregere C, Amaral DG, & Patterson PH (2013). Activation of the Maternal Immune System During Pregnancy Alters Behavioral Development of Rhesus Monkey Offspring. Biological psychiatry PMID: 24011823

Maternal autoantibody-related (MAR) autism?

Yes you heard me right: maternal autoantibody-related autism or 'MAR autism' for short.

The term comes from some of the latest investigations published by researchers at the MIND Institute continuing an important strand of their various studies looking at the autism spectrum disorders (ASDs).

Rhesus, me? @ JM Garg / Wikipedia 

The papers in question are this one from Melissa Bauman and colleagues* (open-access) and this one from Dan Braunschweig and colleagues** (open-access) suggesting that maternal autoantibodies reactive to offspring foetal tissue might very well be an important part of quite a few cases of autism (see here for some background). An article in The Scientist covers the recent papers well so if you don't want my take, just click here and many thanks for dropping by.

You're still here. OK, thanks.

Those who actively follow this region of the autism research landscape will no doubt have already heard of similar results in transplanting purified IgG brain reactive antibodies (IgG-ASD) from mums of children with autism into pregnant mice and watching what happens to the mice offspring (see here) in terms of things like behaviour. In the Bauman study, mice were replaced with rhesus monkeys (cute picture alert) as per another occasion*** and again the development and behaviour of offspring and mother monkeys (n=8) were observed and recorded. This time around however analysis was following the application of a specific IgG mix (37 and 73kDa foetal brain autoantibodies) compared to control monkeys who received an IgG control mix from mums with no children diagnosed with autism.

Some very interesting things were observed in both mother and infants' behaviour over the 2 year period of investigation covering the main developmental periods (weaning, post-weaning, juveniles). Mums treated with IgG-ASD antibodies showed a heightened protectiveness towards their similarly exposed offspring potentially indicative of them picking up cues about their offsprings' unusual behaviour. Offspring were also more frequently taken to approaching other monkeys that were unfamiliar to them, which the authors again translated as being evidence for either not understanding the social etiquette of who and who not to approach or failing to recognise danger. Just before you sigh and click away, yes it was another study of inferring animal behaviour and superimposing it on a complex condition like autism (see here).

Allowing also for the small number of monkey participants, offspring were also tracked using neuroimaging to see whether there were any changes to brain structure or neuropathology. The authors reported that males in the IgG-ASD antibodies group seemed to show "a higher rate of brain growth" when compared to study controls added to an external control set (n=7). This alongside various other observations of the brain (see here). The net conclusion: "These outcomes are supportive of our hypothesis that the antibodies are pathogenic for one form of autism". But do bear in mind that again this was all about interpreting animal behaviour and the absolute number of 'animal participants' was small.

The second paper by Braunschweig and colleagues extended the interest in MAR by actually looking to identify the specific - exclusive - antigen(s) which were the target of the IgG antibodies. Based on an analysis of blood samples from some 250 mothers of children with autism and just shy of 150 control group mothers (with no offspring autism), researchers were able to isolate several combinations of antigens which were more reactive to the blood of mums of autistic children compared with controls. On a personal level it was nice to see mention of words like proteomics and MALDI-ToF mass spectrometry in amongst the methods.

The identified antigens were: "lactate dehydrogenase A and B, cypin (guanine deaminase), stress-induced phosphoprotein 1, collapsing response mediator proteins 1 and 2, and Y-box binding protein". They found that 23% of samples from mums with a child with autism presented with reactivity to certain combinations of these antigens compared with only 1% of control mothers. Ergo statements like "MAR autism cases could represent as much as 23 percent of all autism cases" and the subsequent chatter on developing a biomarker screen for MAR autism (of which this is the first step). Oh, and that certain antigens seemed also to correlate with specific core featues associated with autism such as stereotypic behaviours is also noteworthy.

I can't readily comment too much on the antigens linked to MAR autism. Lactate dehydrogenase (LDH) which it seems was one of the more important antigens, is for example involved in energy metabolism (see here). The authors seem to focus on its links to responding to viral infections (influenza?) or toxic exposures. I'd be interested to hear more about this as time goes by.

These are intriguing findings, of that there is no doubt and judging by some of the feedback I'm reading about the studies, this could be another important step forward in autism research (think folic acid, valproate and the elephant in the room that is glutathione). It's heartening to see that a certain Prof. Paul Patterson and his team who have also championed a role for the maternal immune system in relation to at least some offspring autism (see here) are also really interested in these findings and the potential implications of them. Indeed on the basis of the latest Patterson lab findings which I assume are going through peer-review as we speak(?), one might also start asking some wider questions about the hows and whys of maternal immune activation in relation to autism.

And finally, just in case you'd forgotten, autoantibodies outside of the maternal variety have previously been talked about with autism in mind as per the insightful work from Dr Frye (see here) who gave a great presentation at the US IACC very recently (see here).

2013 it seems is shaping up to be quite a year for autism research.

To close, Peter and Kate with some inspiring words.

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* Bauman MD. et al. Maternal antibodies from mothers of children with autism alter brain growth and social behavior development in the rhesus monkey. Translational Psychiatry. 2013. 3: e278; doi:10.1038/tp.2013.47

** Braunschweig D. et al. Autism-specific maternal autoantibodies recognize critical proteins in developing brain. Translational Psychiatry. 2013 3: e277; doi:10.1038/tp.2013.50

*** Martin LA. et al. Stereotypies and hyperactivity in rhesus monkeys exposed to IgG from mothers of children with autism. Brain Behav Immun. 2008 Aug;22(6):806-16. doi: 10.1016/j.bbi.2007.12.007.

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M D Bauman (2013). Maternal antibodies from mothers of children with autism alter brain growth and social behavior development in the rhesus monkey Translational Psychiatry DOI: 10.1038/tp.2013.47




D Braunschweig (2013). Autism-specific maternal autoantibodies recognize critical proteins in developing brain Translational Psychiatry DOI: 10.1038/tp.2013.47