Sunday, 23 October 2011

Shiver me timbers and raise the mast

Whilst Johnny Depp is the latter day face of the Pirate set, I always thought that Errol Flynn was by far the best buccaneer, particularly with his role in the 1935 classic 'Captain Blood'. And while I would love to talk more about pirates, the seven seas and the infamous skull and crossbones banner, the title of this post actually refers to another sort of mast outside of the tall, nautical-related thing, mast cells, and their potential role in some cases of autism spectrum conditions.

If you want to read quite an extensive review of mast cells then look no further than here. If you want the Mr Men version that I tend to prefer, it might go something like this: originating in bone marrow, mast cells are found in various tissues and contain several amines including histamine and serotonin alongside various cytokines. When activated by allergic and possibly non-allergic immunogloblulins as well as other compounds including some viruses, mast cells release their 'inner' contents and the party begins. Mast cells and their activation have a huge research base behind them; one of the most recent investigations centres on the engineering of molecules to out-compete allergens.

When talking about mast cells in relation to autism, one name crops up quite a lot: Theoharis Theoharides based at Tufts University. Indeed there is some pretty useful information on Dr Theoharides' Faculty website about mast cells (with lots of nice diagrams) and the various research he has been involved with. In autism, two papers about mast cells predominate this post, here* and here**. Both papers are of a more 'review' type structure rather than fizz-bang experiments but both contain some interesting details:

  • Allergy is something that had cropped up a few times in connection to autism; indeed I posted about the topic a while back. The overview of allergy research related to autism contained in both papers reviewed in this post suggests that it is a complicated picture made up of IgE-mediated allergy and other classes of immunoglobulin effects. As per usual in autism, no one-size-fits-all. 
  • I was taken aback by the suggestion that 1 in 10 children presenting with mastocytosis or 'mast cell activation syndrome' also presented with an autism spectrum condition (as compared with 1 in 100 of the general pediatric population). If this is a reproducible finding then it might be an important one bearing in mind association and causation not necessarily being the same thing.
  • Mast cell activation has been linked to lots of different things including permeability of various membranes such as the blood-brain barrier and the gut. Aside from the fact that lots of factors, different factors, are going to be involved in alterations of these complicated barriers, there are some interesting implications on how far 'upstream' mast cell activation might be in things like hyperpermeability of the gut (leaky gut). I note also that a lot of the general literature on mast cell activation and leaky gut centres on the primary role of stress. Psychology influencing biology? How about some of the behavioural or pharmacological measures to reduce stress and anxiety and any knock-on effects?

I kinda hinted that IgE might be a primary activator of mast cells but there may also be other compounds that also do a similar job in stimulating mast cells into action. So it was that when levels of the neuropeptide neurotensin (NT) potentially tied into mast cell activation, were measured in autism vs. controls. Levels of NT were elevated in the autism group. I was also interested to read that serum levels of beta-endorphin were not significantly different from controls and how that might (not) tie into some of the dietary findings in autism. Another post methinks.

The last word on any role for mast cells in autism should be 'interesting'. Interesting because a whole new world opens up on the physiological mechanism by which various stressors, biological and psychological, might be able to activate mast cells and onwards release a cascade of compounds and events tied into some pretty consistent biological ideas associated with at least some cases of autism. If mast cells are part of the complex biological picture of autism, the next question is what we do about them, indeed can we do anything about them and if so, what effect might it have on the presentation of core or peripheral behaviours associated with autism?

* Theoharides T. et al. Mast cell activation and autism. Biochemica et Biophysica Acta. 2011

** Angelidou A. et al. Brief report: "Allergic symptoms" in children with autism spectrum disorders. More than meets the eye? JADD. 2011