Autoimmune diseases and schizophrenia

The paper by Michael Benrós and colleagues [1] talking about an "increased risk of subsequent autoimmune diseases in individuals with schizophrenia" caught my eye recently. Based on a trawl of the records of several thousands of people with "schizophrenia-like psychosis" or "individuals with autoimmune disease" derived from Danish nationwide registers (see here for some background), the authors were able to conclude that "Autoimmune diseases developed subsequently in 3.6% of people with schizophrenia, and 3.1% of people with autoimmune diseases had a family history of schizophrenia". By the way, this is not the first time that authors linked to this paper have published on this topic [2] based on similar analyses. Further coverage of this paper can also be found here.

And don't forget your lute.. @ Wikipedia 

As far as I'm aware, I've not yet covered the issue of autoimmune conditions being correlated with a diagnosis of schizophrenia on this blog. Regular readers might already know about my interest in all things autoimmunity when it comes to autism. Be it the markers of autoimmunity (see here and see here) or the seemingly wide range of conditions correlating with the appearance of autism (see here), I certainly believe that there is more to see here from a research point of view. With the schizophrenia data in mind it appears that I should perhaps be casting the research net a little wider; perhaps even talking about some closer links?

As Benrós et al note there is already some research form in the area linking schizophrenia and autoimmune conditions. Outside of the autoantibody side of things [3] and that very interesting link to anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis [4] I note some of the data available in this area to be quite nicely summarised by Davison [5] (open-access) specifically with the Chen paper [6] (open-access) in mind. Taking a few conditions noted by Chen and colleagues, I was interested to see that risk of psoriasis was elevated in cases of schizophrenia as per my interest in this skin condition with autism in mind (see here). Given my focus on / obsession with all things gluten too, the fact that a diagnosis of schizophrenia also elevated the risk of coeliac (celiac) disease similarly piqued my interest and brought back floods of memories about the late Curt Dohan and his life's work in this area (see here). In light of the not-quite-coeliac-disease-but-something-else paper on autism and gluten-related serology it also asks the question of how deep the rabbit hole might actually go?

The same questions remain about this work as they do when it comes to examining any link between autism and autoimmune conditions - whether first person or familial: What are the common denominators in terms of genes and biochemistry? Are there shared susceptibility factors evident in schizophrenia and selected autoimmune diseases including infection? But also I'm getting pretty interested in some new areas of potential overlap such as any effects from those very old HERVs (human endogenous retroviruses) and whether through expression of HERV proteins, for whatever reason(s), they are participating in a series of events heading towards autoimmunity? Well, it's not as if HERVs haven't been mentioned with schizophrenia [7] or autoimmune diseases in mind [8] but I'll wait and see how this pans out.

Fantastic Mr Fox y'say.... Will you join me? (whistle/click)

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[1] Benrós ME. et al. A Nationwide Study on the Risk of Autoimmune Diseases in Individuals With a Personal or a Family History of Schizophrenia and Related Psychosis. Am J Psychiatry 2014;171:218-226.

[2] Eaton WW. et al. Association of schizophrenia and autoimmune diseases: linkage of Danish national registers. Am J Psychiatry. 2006 Mar;163(3):521-8.

[3] Ezeoke A. et al. A systematic, quantitative review of blood autoantibodies in schizophrenia. Schizophr Res. 2013 Oct;150(1):245-51.

[4] Pollak TA. et al. Prevalence of anti-N-methyl-d-aspartate (NMDA) antibodies in patients with schizophrenia and related psychoses: a systematic review and meta-analysis. Psychol Med. 2013 Dec 13:1-13.

[5] Davison K. Autoimmunity in psychiatry. Br J Psychiatry. 2012 May;200(5):353-5.

[6] Chen SJ. et al. Prevalence of autoimmune diseases in in-patients with schizophrenia: nationwide population-based study. Br J Psychiatry. 2012 May;200(5):374-80.

[7] Frank O. et al. Human endogenous retrovirus expression profiles in samples from brains of patients with schizophrenia and bipolar disorders. J Virol. 2005 Sep;79(17):10890-901.

[8] Brodziak A. et al. The role of human endogenous retroviruses in the pathogenesis of autoimmune diseases. Med Sci Monit. 2012 Jun;18(6):RA80-8.

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Benrós ME, Pedersen MG, Rasmussen H, Eaton WW, Nordentoft M, & Mortensen PB (2013). A Nationwide Study on the Risk of Autoimmune Diseases in Individuals With a Personal or a Family History of Schizophrenia and Related Psychosis. The American journal of psychiatry PMID: 24129899