Friday, 28 April 2017

Autism, pregnancy maternal immune activation and vitamin D?

Today's post is a bit of a mash-up, drawing on two articles quite recently published in the peer-reviewed science domain.

The first is by Stephanie Vuillermot and colleagues [1] (open-access) suggesting that "early dietary supplementation with vitamin D may open new avenues for a successful attenuation or even prevention of neurodevelopmental disorders following maternal inflammation during pregnancy." These findings have also received some media attention (see here for example) and continues a research theme focused on vitamin D (the sunshine vitamin/hormone) and [some] autism (see here for example).

The second paper is by Michael Lombardo and colleagues [2] (open-access) and also covers the topic of maternal immune activation (MIA) and its potential effects on offspring outcomes, concluding that: "MIA may confer increased risk for ASD [autism spectrum disorder] by dysregulating key aspects of fetal brain gene expression that are highly relevant to pathophysiology affecting ASD."

What are the connections between these papers? Well, obviously both deal with the concept of maternal immune activation (MIA) where infection, or possibly/rather 'inflammatory' responses to infection, during critical periods of pregnancy seem to be able to affect offspring developmental and other outcomes. This bearing in mind that pregnancy represents a time of 'reprogrammed immune function' such that the maternal immune system does not mount a response to the genetically dissimilar organism growing inside the body. Both papers model MIA in rodents (mice and rats respectively) given the ethics of undertaking such experimental studies in humans. Both studies concluded that (a) there is evidence that MIA is a real phenomenon and (b) bearing in mind rodents are not necessarily the same as humans (see here) (a shocker I know), MIA seems to invoke specific biochemical changes pertinent to the expression of genes *linked* to autism that are also potentially amenable to intervention.

The Vuillermot findings in particular, offer some rather intriguing prospects for further study as a function of their conclusion that: "maternal VitD co-administration blocked the emergence of the ASD-relevant deficits in social interaction, stereotyped behavior, and emotional learning and memory." I appreciate that 'blocking the emergence' of autistic behaviours is not something that everyone is going to unanimously welcome (the implication being that every single autistic trait is somehow something to be eradicated). The idea however that aspects of even something like certain stereotyped behaviours under certain conditions and with certain intensity might 'set someone up' for the presentation of truly disabling conditions such as anxiety [3] (see here too) offers a degree of support for the idea of intervention targeting such behaviours in particular circumstances.

But there is a potential research spanner in the works when it comes the idea that vitamin D might 'offset' some of the changes associated with exposure to MIA. The authors note: "VitD does not alter maternal or fetal inflammatory cytokine production." This statement was made on the basis that "prenatal administration of vitamin D had no effect on pro-inflammatory cytokine levels in dams or in fetal brains." Cytokines are those chemical messengers of the immune system. How then, you might ask? Well, back to the Lombardo paper and the possibility that vitamin D is not necessarily an 'anti-inflammatory' of choice under such circumstances but might - MIGHT - act on some of the mechanisms related to those genes expressed under MIA conditions. It's pretty well-known for example, that vitamin D does influence gene expression (see here for example) as our knowledge of the biological duties of the sunshine vitamin/hormone expand (see here). It is logical to assume that the next research step would be to see whether vitamin D administration *might* at certain times and under certain circumstances, affect the expression of those genes 'highly relevant to pathophysiology affecting ASD' under MIA conditions. This, in the context that maternal vitamin D levels during pregnancy again *might* have an important impact on the presentation of offspring autistic traits (see here).

And since we're on the topic of vitamin D and autism (yet again), how about reading a new hypothesis paper on some potentially important connections [4]?


[1] Vuillermot S. et al. Vitamin D treatment during pregnancy prevents autism-related phenotypes in a mouse model of maternal immune activation. Molecular Autism. 2017; 8: 9.

[2] Lombardo MV. et al. Maternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder. Mol Psychiatr. 2017. Mar 21.

[3] Bitsika V. & Sharpley CF. The association between parents' ratings of ASD symptoms and anxiety in a sample of high-functioning boys and adolescents with Autism Spectrum Disorder. Res Dev Disabil. 2017 Mar 1;63:38-45.

[4] Gillberg C. et al. The role of cholesterol metabolism and various steroid abnormalities in autism spectrum disorders: A hypothesis paper. Autism Res. 2017. April 12.

---------- Vuillermot, S., Luan, W., Meyer, U., & Eyles, D. (2017). Vitamin D treatment during pregnancy prevents autism-related phenotypes in a mouse model of maternal immune activation Molecular Autism, 8 (1) DOI: 10.1186/s13229-017-0125-0 Lombardo, M., Moon, H., Su, J., Palmer, T., Courchesne, E., & Pramparo, T. (2017). Maternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder Molecular Psychiatry DOI: 10.1038/mp.2017.15