Friday, 10 May 2013

Depression or antidepressant use linked to C.diff infection?

"There's no mystical energy field that controls my destiny". So said a very sceptical Han Solo.

Regular readers might know that I'm a bit of fan of the whole gut-brain axis; indeed other kinds of axes too. I know that to some it might sound a bit daft that what goes on in our deepest, darkest bowels might actually have some important effects on the operations of the grey-pinkish matter floating around in skull central - and vice-versa -  but nonetheless it interests me. The gastrointestinal (GI) tract is not quite the mystical energy field that Captain Solo was referring to, but make no mistake, we are still very much in the infancy of looking at the connection between the two systems*.
Black dog @ Wikipedia  

I've tended to discuss/speculate on the gut-brain relationship with regards to cases of autism spectrum disorder (ASD) on this blog. In this post I'm branching out to look at the paper by Mary Rogers and colleagues** (open-access) on a potentially new dimension to the gut-brain conversation with depression and Clostridium difficile infection in mind.

The Rogers paper is open-access and has also attracted some media attention as a result (see here and here for the press release). The long-and-short of it was that based on two studies - a sort of scientific BOGOF - looking at the rates of C.diff infection (CDI) in participants with and without depression and the potential effects of antidepressant medication use and hospital-acquired CDI, some interesting correlations were noted. Note that word 'correlations'...

Primary among the findings was the suggestion that the chances of CDI were higher in those presenting with depression: "After adjusting for demographic characteristics, comorbidities and frequency of medical visits, there was a 36% increase in the odds of developing CDI for individuals with major depression compared with those without major depression" (CI: 1-06-1.74, p=0.016). Indeed when it came to the label of "emotional, nervous or psychiatric problems", the CDI risk was found to be even higher (OR: 1.47). Certainly some interesting data, made all the more credible by the fact that the total sample size numbered in the thousands.

When it came to medication use, there were some equally interesting associations (not) made. So for example, laboratory confirmed CDI (via stool testing) seemed not to correlate with the majority of medicines participants were also taking at the time of testing. The exceptions were mirtazapine (OR: 2.14) and fluoxetine (OR: 1.92) which were individually associated with an approximate doubling of CDI risk and also carrying some dose-related associations.

Authors also reported that polypharmacy - if I can use that word with less than 5 meds being taken - might also impact on CDI risk, as per the "significant interaction between mirtazapine and trazodone" where "the odds of a positive C. difficile test were 5.72 times greater" bearing in mind the small participant numbers who were prescribed these two drugs combined. As per the press on this paper: "People who have been prescribed these types of anti-depressants need to keep taking them unless otherwise advised by their physician"; a viewpoint that I can only echo at this stage.

You can perhaps see why I might be interested in this line of research. There is of course the chicken-and-egg question about which came first: microbial changes which place a person at greater risk of CDI and perhaps depression, or depression leading to changes to the gut microbiota and onwards elevated CDI risk. I'm not going to speculate too much on what came first because I dare say the clinical picture is going to be much more complicated than such a simple question. I've talked before about the possibility of a bi-directional relationship between gut bacteria and behaviour (at least in mice) and my viewpoint has changed very little in the intervening years. Bear also in mind that the hows and whys of depression (in all its forms) are likely to be numerous; perhaps even related to our earliest years****

It's interesting that the authors discuss quite a few important overlapping pieces of research in their summary of their findings related to things like the presence of bowel disease in cases of depression*** and that magical word 'inflammation'*****. To quote: "It is possible that there is a lifelong liaison between the gut microbiota and neurologic response to external stimuli" which certainly does seem to link in with at least some of the current research literature.

Alongside the tentative associations made by Rogers et al on the issue of depression and CDI, I find my mind wandering back to the question of whether such an association might be something which could be translated into therapeutic options. Y'know whether treating the CDI actually had any quantifiable impact on the presentation of depression or vice-versa. Indeed whether one of the more unusual methods suggested to help combat CDI - yep, the fecal transplant - might also impact on depression via changes to the gut microbiota as per the very preliminary reports from other conditions such as chronic fatigue syndrome (CFS)? That and possibility that gut bacteria might, just might, be in cahoots with other more barrier-related issues******, makes for some interesting suggestions for further scientific inquiry*******.

To end, y'know I prefer Constantiople over Istanbul....

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* Collins SM. & Bercik P. Gut microbiota: intestinal bacteria influence brain activity in healthy humans. Nature Reviews Gastroenterology and Hepatology. May 2013.

**  Rogers MAM. et al. Depression, antidepressant medications, and risk of Clostridium difficile
infection. BMC Medicine 2013; 11: 121.

*** Graff LA. et al. Depression and anxiety in inflammatory bowel disease: a review of comorbidity and management. Inflamm Bowel Dis. 2009; 15: 1105-1118.

**** Parboosing R. et al. Gestational influenza and bipolar disorder in adult offspring. JAMA Psychiatry. May 2013.

***** Vogelzangs N. et al. Association of depressive disorders, depression characteristics and antidepressant medication with inflammation. Transl Psychiatry. 2012; 2: e79.

****** Maes M. et al. Increased IgA and IgM responses against gut commensals in chronic depression: further evidence for increased bacterial translocation or leaky gut. J Affect Disord. 2012; 141: 55-62.

******* Hughes PA. et al. Immune activation in irritable bowel syndrome: can neuroimmune interactions explain symptoms? Am J Gastroenterol. May 2013

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ResearchBlogging.org Rogers, M., Greene, M., Young, V., Saint, S., Langa, K., Kao, J., & Aronoff, D. (2013). Depression, antidepressant medications, and risk of Clostridium difficile infection BMC Medicine, 11 (1) DOI: 10.1186/1741-7015-11-121