Sunday, 6 January 2013

Gliadin antibodies in schizophrenia replicated

As per the primary message on this blog, I'm a great believer in science and the scientific method as a route to informing the public at large about lots of different issues. A recent opinion piece in Chemistry World by Prof. Steve Fuller kinda coincided with my view of science: an informer, not an instructor.

Outside of the notion of science measuring probabilities over absolutes, one of the other great pillars of the scientific method is the concept of replication: that is for a finding to be meaningful and not just a fluke or chance, one should be able to run the same experiment twice or more with a similar population and get similar results (almost) every time. A far cry from Fett's notion: ('never replicate a successful experiment').
Wheat n' chaff @ Wikipedia 

It is with replication in mind, that I'm posting today about a study by Olaoluwa Okusaga and colleagues* which looked at the presence of anti-gliadin antibodies in cases of schizophrenia building on previous work in this area such as this paper by Faith Dickerson and colleagues** and even further back, this paper by the late Curt Dohan***.

Regular readers might know that I have some interest in this area of gluten (the primary protein from wheat and other cereal crops) and schizophrenia as per entries like this one on the work of Emily Severance and colleagues and this one further extending the work from Faith Dickerson and Robert Yolken.

The history behind all this stems in the most part from Dohan and his ideas about schizophrenia and wheat which were taken up into autism research principally by a friend of mine, Dr Karl (Tiny) Reichelt. I might add that whilst the focus is on a possible effect from gluten, I'm also mindful of the research looking at casein (the protein found in dairy produce) being potentially linked to schizophrenia and related conditions too (see here).

The main points from the Okusaga paper:

  • The aim was replication, and based on a quite large target population of nearly 1000 adults diagnosed with schizophrenia compared against 1000 "healthy controls", plasma levels of anti-gliadin IgG antibodies were measured.
  • Results: the schizophrenia group were twice as likely as the control group to have elevated anti-gliadin IgG antibodies, and "the difference persisted after adjusting for potential confounders".

OK let's step back a moment and put these results into some kind of context. This was a snap-shot study and so only really gave us a picture at one point in time of the antibody status of participants. As the authors point out "replication in longitudinal studies" is required. That and the fact that much like autism, a diagnosis of schizophrenia is seemingly protective of nothing, so one cannot conclusively say that schizophrenia is the exclusive variable here over and above any other psychiatric or somatic comorbidity.

Question 1: Does this mean that some people with schizophrenia might have an issue with gluten in the same way that people with conditions such as coeliac (celiac) disease (CD) might do? Well the presence of anti-gliadin IgG antibodies is interesting but does not in itself necessarily confirm a diagnosis of CD (see this link to Coeliac UK). Whilst not ruling out CD appearing alongside some cases of schizophrenia****, I'm drawn back to the paper by Samaroo and colleagues***** (open-access) and their 'novel immune response' assertion. Perhaps even some lessons for autism research in this area bearing in mind the recent not-quite-coeliac document on gluten sensitivity.

Question 2: Does this mean that some people with schizophrenia might have an allergy to gluten? This is a possibility, bearing in mind how you define allergy based on the different isotypes of immunoglobulin. Indeed, allergy, while often used as a universal phrase to denote some kind of immune reaction to an antigen, is in its strictest sense only really relevant to something like an IgE-mediated hypersensitivity. Everything else resides in that grey area between allergy and intolerance. Although I'm no expert on allergy and intolerance, I am taken back to some related findings on complement system system activation in cases of schizophrenia which might also be relevant to this area (see here).

Final question: Where next? With no medical advice given or intended, and irrespective of the precise mechanism of how gluten comes to be related to cases of schizophrenia, one must surely start to ask the question of whether a gluten-free (GF) diet might potentially be able to resolve some of the symptoms of schizophrenia. Noting quite a few cases reports in the peer-reviewed literature on GF diets and schizophrenia, here****** for example (open-access) and this classic study from Vlissides and colleagues******* one has to wonder whether now would be a good time to instigate a large controlled trial to ascertain any potential effects alongside working on detailing those all important responder / non-responder variables which will inevitably turn up in a spectrum condition. Indeed at least one of the authors on the Okusaga paper is thinking similar thoughts...

To finish, I'm in a lazy mood today so here is some Bruno Mars to complement that feeling...


* Okusaga O. et al. Elevated gliadin antibody levels in individuals with schizophrenia. World J Biol Psychiatry. January 2013.

** Dickerson F. et al. Markers of gluten sensitivity and celiac disease in recent-onset psychosis and multi-episode schizophrenia. Biol Psychiatry 2010; 68: 100-104.

*** Dohan FC. et al. Antibodies to wheat gliadin in blood of psychiatric patients: possible role of emotional factors. Biol Psychiatry. 1972; 5: 127-137.

**** Kalaydjian AE. et al. The gluten connection: the association between schizophrenia and celiac disease. Acta Psychiatr Scand. 2006; 113: 82-90.

***** Samaroo D. et al. Novel Immune Response to Gluten in Individuals with Schizophrenia. Schizophr Res. 2010; 118: 248–255.

****** Kraft BD. & Westman EC. Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: a case report and review of the literature. Nutr Metab (Lond). 2009; 6: 10.

******* Vlissides DN. et al. A double-blind gluten-free/gluten-load controlled trial in a secure ward population. Br J Psychiatry. 1986; 148: 447-452.

---------- Okusaga O, Yolken RH, Langenberg P, Sleemi A, Kelly DL, Vaswani D, Giegling I, Hartmann AM, Konte B, Friedl M, Mohyuddin F, Groer MW, Rujescu D, & Postolache TT (2013). Elevated gliadin antibody levels in individuals with schizophrenia. The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry PMID: 23282016