Sunday, 19 February 2012

Schizophrenia, coeliac disease and cerebral blood flow

Weather @ Paul Whiteley
Day: Sunday 19th February 2012. Weather: cold, bright. Mood: upbeat. Dear Diary, exactly a year since I began my blogging odyssey and I'm still enjoying the experience.

Speaking of the past, let's set the way-back machine a little further back to 1997. The UK swayed to the tune of 'Things can only get better' alongside a rare win at Eurovision. Bill Clinton also started his second term in office. An interesting paper also appeared by De Santis and colleagues* detailing some surprising findings in a case of comorbid schizophrenia and coeliac (celiac) disease. In some quarters, this single person study has taken on almost cult status. My opinion: it is interesting and I'll attempt to try and explain why.

I discuss this paper because despite being a case study, there are potentially some important facts which have never really been followed up with more rigorous study. I apologise that I can't link to a full-text of the paper so you will have to take my word for it or visit your nearest academic library to get a full-text copy.

The person at the centre of this report was a 33 year old woman admitted to hospital with weight loss and severe diarrhoea. She had a previous history of schizophrenia (diagnosed by DSM-III-R) progressively becoming more severe with accompanying "autistic disorder, social/occupational dysfunction, affective flattening and inferential thinking".

Upon admission, schizophrenia was again confirmed (by DSM-IV) alongside various other laboratory findings including low iron levels without anaemia. Coeliac disease (CD) was diagnosed on the basis of anti-endomysial antibodies and villous atrophy following jejunal biopsy. A brain SPECT scan -  (99mTc)HMPAO SPECT - was performed following some irregular activity in the fronto-temporal left hemisphere picked up on EEG. The scan showed an area of hypoperfusion in the left frontal cortex.

What this all basically means was that verifiable diagnostic accounts of schizophrenia and CD were picked up in this patient alongside some noticeable restriction in blood flow to a part of the brain thought to be involved in integrating various perceptual information and other executive functions.

Implementation of a gluten-free diet is reported to have quickly improved both physical and psychiatric symptoms "within a few days". Alongside expected gains in body weight, a repeat SPECT scan was undertaken after 6 months using as similar procedures as possible to the first scan to allow a reliable slice by slice analysis. The results were surprising in that there was a "complete normalization of the brain perfusion". The woman remained symptom-free and medication-free for at least a year at follow-up obviously maintaining her gluten-free diet.

The authors were obviously quite taken aback by these findings although I suspect not totally surprised by them. Inevitably discussions are filled with excerpts from the late Kurt Dohan and his ideas on schizophrenia and wheat intake as well as one of the modern day champions of research into the neurological effects of untreated CD, Dr Marios Hadjivassiliou. One phrase in particular stands out from the paper: ".. that schizophrenic symptoms may be the expression of organic disease, such as coeliac disease, rather than primary psychiatric illness".

I said that there were quite a few aspects of this study which have never really been followed up. Not being a neurologist or anything related, I don't know enough about SPECT scans as to be able to offer an informed opinion on their accuracy or not. Certainly with the advances that have been made in the intervening 15 years, I would imagine that technologies like fMRI might be slightly more descriptive in terms of the results produced. Scanning on just two occasions might also be subject to some bias.

Accepting that use of a gluten-free diet for schizophrenia, autism, ADHD or any other behaviourally-defined condition that you might care to mention is not exactly mainstream, I would be inclined to suggest that there is a study or two waiting to happen here. So, monitoring things like cerebral blood flow and related brain-based markers before and after use of a gluten-free diet alongside various behavioural indices. SPECT scans still mark the autism research landscape as per articles like this one. Indeed I am quite surprised that many more intervention studies in psychiatry don't look at things like cerebral blood flow when it comes to outcome measures, even as per models such as that described in this study on primates. Monitoring such parameters where schizophrenia and CD are comorbid or how about where autism and CD are comorbid? Too much perhaps..?

I don't want to get too carried away with this single-case report because for all we know, this might be a one in seven billion event. Having said that, every theory has to start somewhere, and at the moment, no-one appears to be producing contrary evidence to the report from De Santis et al.

To finish, more memories of 1997 courtesy of Hanson.

* De Santis. et al. Schizophrenic symptoms and SPECT abnormalities in a coeliac patient: regression after a gluten-free diet. Journal of Internal Medicine. 1997; 242: 421-423.