Gastrointestinal inflammation and immune activation in bipolar disorder

I want to take you back to a post I published back in April 2012 (see here) on some very interesting work coming out of the Stanley Division of Developmental Neurovirology at Johns Hopkins by Dr Emily Severance.

The Railway (Manet) @ Wikipedia 

It was concerned with the discovery that in cases of schizophrenia, measurement of anti-Saccharomyces cerevisiae antibodies (ASCA) revealed possible (probable?) signs of intestinal inflammation at greater levels than controls*.

Alongside, depending on whether onset of symptoms was recent or not and whether specific pharmacotherapy was in place or not, some interesting effects were noted in relation to mounting an immune response to foods specifically containing gluten and/or casein.

I don't mind telling you that I found these results to be absolutely fascinating; in a similar vein to some of the other work by Dr Severance and her collaborators (which includes some pretty high profile research names). As perhaps you'd imagine, I was therefore more than intrigued to read of similar findings published by Dr Severance and colleagues** this time in relation to bipolar disorder which used to be called manic depression.

The research story is quite a similar one to that noted with schizophrenia in mind: look at levels of ASCA - more typically used to differentiate between specific inflammatory bowel diseases - in quite a large group of participants, this time diagnosed with bipolar disorder (with or without recent onset of psychosis), as well as antibody responses to various other food and viral or parasitic agents. And yes, under parasite I do mean 'the gondii' and everything that has been suggested to go along with that.

The results: "Elevated ASCA conferred a 3.5–4.4-fold increased odds ratio of disease association". In other words, one marker of intestinal inflammation may very well be associated with bipolar disorder. That and: "ASCA correlated with food antibodies in both bipolar disorder groups".

I have to say that I'm not overly surprised by that last quote correlating (yes, correlating) food antibodies against gluten and/or casein with intestinal inflammation. That is, if one simplistically assumes that an inflamed gut barrier is probably going to be more porous (leaky...) than a typical non-inflammed barrier (see here***). So y'know... leaky gut, gut contents meeting immune system and antibodies being formed and that needn't just apply to antibodies to the remnants of our diet either (see here).

As for the other results reported in the Severance paper such as elevations in ASCA antibodies also being correlated with "measles and T. gondii immunoglobulin G (IgG) in the recent onset psychosis bipolar disorder group", autism research history tells me it's probably not a good idea to go too far down that path. So I won't; aside that is, from pointing out some related research from the likes of Neibuhr - that's Col. Neibuhr - and colleagues**** who talked about "antibody levels to several combinations of agents, to include casein, measles, CMV, T. gondii and vaccinia, was predictive of an 18-34% increase in the risk of developing schizophrenia".

So then, some cases of schizophrenia and now some cases of bipolar disorder seem to share some non-brain related pathology with a specific focus on inflammation*****, and particularly inflammation of that important barrier in our deepest, darkest recesses. Alongside the suggestion of similar 'issues' potentially being present in cases of autism, quite a collection of conditions are being flagged up with that gut-brain axis in mind. It brings to mind all that common ground talk when it comes to overlapping genes in various 'psychiatric' related conditions (see here) and whether from a gut physiology point of view, this might be a new element to add to the RDoC? I'm just speculatin' of course...

Issues with gut inflammation also raises some potentially important questions about what might happen when inflammatory bowel or barrier issues are treated for example, or indeed when foods potentially linked to that antibody response are removed from the diet (bearing in mind, no medical or clinical advice is given).

And then there are those trillions of bacterial passengers we all carry to consider and any potential effect from them too...

Music then to finish. How about something a little bit tranquil today... Clair de Lune by Debussy, or as being the uncultured man that I am, 'that classical music piece from Ocean's 11'. Toodle pip.

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* Severance EG. et al. Gastrointestinal inflammation and associated immune activation in schizophrenia. Schizophr Res. 2012 Jun;138(1):48-53.

** Severance EG. et al. Seroreactive marker for inflammatory bowel disease and associations with antibodies to dietary proteins in bipolar disorder. Bipolar Disord. 2013 Dec 6. doi: 10.1111/bdi.12159.

*** Hietbrink F. et al. Systemic inflammation increases intestinal permeability during experimental human endotoxemia. Shock. 2009 Oct;32(4):374-8.

**** Li Y. et al. Association between antibodies to multiple infectious and food antigens and new onset schizophrenia among US military personnel. Schizophr Res. 2013 Dec;151(1-3):36-42.

***** Berk M. et al. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med. 2013 Sep 12;11:200.

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Severance EG, Gressitt KL, Yang S, Stallings CR, Origoni AE, Vaughan C, Khushalani S, Alaedini A, Dickerson FB, & Yolken RH (2013). Seroreactive marker for inflammatory bowel disease and associations with antibodies to dietary proteins in bipolar disorder. Bipolar disorders PMID: 24313887