Tuesday, 10 May 2011

Anti-malarials and schizophrenia (and autism?)

Schizophrenia has been of some interest to me over the course of my research career. I have never (knowingly) been involved in any research to do with schizophrenia but a few things have pointed me in the direction of its symptoms and potential aetiology-pathology as a consequence of my interest in autism spectrum conditions.

A little bit of background first. Schizophrenia is a psychiatric condition primarily diagnosed on the basis of presented psychological symptoms to include hallucinations and delusions; whereby distinguishing thoughts and ideas from reality is problematic. There are quite a few misconceptions about schizophrenia related to things like the concept of a 'split personality' (based on the literal Greek translation of schizophrenia).

Many, many years ago autism was 'associated' with childhood schizophrenia (the journal, JADD used to be called the Journal of Autism and Childhood Schizophrenia). Suffice to say, autism is not childhood schizophrenia.

Schizophrenia and autism coincided in my work primarily because of the research of the late Curt Dohan and his suggestion that where gluten was rarely eaten, the prevalence of schizophrenia was also low. Indeed, my recent communication with Dr Dohan's son, Dr F. Curtis Dohan Jr (who is also interested in the connections between gluten, schizophrenia and autism!) confirmed a story that I heard many years ago, that on the day he died, Dohan Sr was reading/being read a manuscript from Dr Kalle (Tiny) Reichelt on the possible association between autism and gluten. I hope I don't reveal too much when I say that Dr Dohan apparently got to page 5 of the manuscript in question before he passed away - enough time for him to hopefully see how influential his ideas were.

The possibility of an association between schizophrenia and gluten has been rumbling on for many years. Emily Deans over at Evolutionary Psychiatry posted an excellent entry on this last year. Coeliac disease and schizophrenia? Got that. Gut hyperpermeability and schizophrenia? That too.

In more recent years, the work of Faith Dickerson and colleagues has suggested quite a few 'issues' with gluten in conditions like schizophrenia. All in all, I am inclined to say that assuming that schizophrenia is a heterogeneous condition too, there may be a sub-group of people who, like in autism, show some sensitivity to gluten through whatever process.

I digress. The title of this post concerns this paper from Dickerson and colleagues on the possible effect of an anti-malarial agent on the presentation of antibodies to gluten (gliadin) in schizophrenia. The anti-malarial agent in question was artemisinin, which by a strange twist of fate I had heard about recently from discussions with a group who have been developing assays examining yields of artemisinin for treating malaria.

The Dickerson paper is interesting for several reasons. They were examining the possible effectiveness of artemisinin as part of their studies on a possible connection between schizophrenia and Toxoplasma gondii. I did briefly touch upon these studies in a past post on PANDAS. They did not however, find any specific effect from artemisinin administration on either antibodies to T.gondii or psychiatric symptoms associated with schizophrenia. The only effect was on gliadin antibodies which were reduced in the active treatment group (significance level: p<0.005) when compared to the placebo arm of their trial.

I am quite interested in these findings. Interested that an anti-malarial compound could have such pronounced effects on the presentation of gluten antibodies (at least in this study group). Interested also in the possible mode of action, for which I have been able to find only limited data on, for example, its immuno-suppressive effects and a potential role for heme. The immuno-supressive bit could be interesting and tie into helminthic therapy (could!). It makes me wonder if such a reduction could also be achieved for other groups with other gluten-related immune-mediated conditions, such as coeliac disease for example.

Also, without wishing to offer any advice or opinion (please do not run down to your nearest anti-malarial shop and purchase), I also wonder whether such an effect would benefit that proportion of people with autism who also show raised gluten antibody levels (whether as a result of co-morbid gluten sensitivity or other by some other means) and whether or not it would affect other areas of functioning - an alternative to a gluten-free diet perhaps?

I must reiterate that all of this is speculation on my part only and should remain just that. Dickerson and colleagues noted no significant side-effects from artemisinin administration over 12-weeks but that does not necessarily mean the compound is safe. The WHO have politely asked that artemisinin monotherapy be phased out in order to combat drug resistance.

As we have seen in recent days, there is folly in extolling a non-tested intervention for autism without the appropriate safety and efficacy studies being done. I, for one, do not wish to fall into that trap.