Sunday, October 26, 2014

Irritable bowel syndrome-mens morba in corpore morbo



The stiff-upper-lips of this world will probably always claim that irritable bowel syndrome (IBS) is "just" or "only" IBS. However, this syndrome can be highly painful and even debilitating at its most severe. It is characterised by abdominal pain and bloating, as well as constipation and/or diarrhoea. It tends to be associated with high levels of stress; childhood trauma is more prevalent in people with IBS, who have also been shown to have an altered stress response to an acute stressor in not one but two studies. IBS is also comorbid with certain stress-related disorders such as depression, although the interaction between depression and IBS can sometimes be complex-see this clip with Kurt Cobain, who suffered from both IBS and suicidal ideation for an example.

Recent research from our group (particularly Paul Kennedy, who completed his PhD in this area) has suggested that people with IBS perform more poorly on a test of memory than a healthy control group. The test (paired associates learning) involves remembering the location of abstract shapes hidden behind boxes-a bit like the kind of card game one would play as a kid. It is thought to involve activation of the hippocampus, a brain region which is also involved in the regulation of the stress response. It should be noted that although the number of errors people with IBS were making was higher than the healthy group, this was a subtle difference-but a noticeable one nonetheless.

In a just published study which I had the good fortune to get involved with, we looked at the potential neurochemical underpinnings of this change in memory performance. Specifically, we looked at whether memory performance in IBS could be changed by altering tryptophan levels. Tryptophan is an essential amino acid ("essential" because we have to derive it from our diet). It's used by the body to produce serotonin-a household name among neurochemicals thanks, among other things, to the class of antidepressants known as SSRI's (selective serotonin reuptake inhibitors). HOWEVER, most tryptophan is broken down along the less-famous kynurenine pathway, where is it catabolised into kynurenine and various other neuroactive chemicals. The enzymes in our bodies which make this happen, such as IDO and TDO, have previously been found to be altered in IBS, and there is some evidence that the chemicals produced in the kynurenine system can have a negative impact on memory. This suggests the kynurenine system could play a role in IBS-related memory attenuation.

In our study we gave people with IBS and healthy controls a drink with amino acids other than tryptophan-these compete with tryptophan at the blood-brain barrier, and consequently reduce the amount of tryptophan getting through to the brain. As a control condition, on a different testing day we gave them the same drink but with tryptophan included. We then had everyone complete a series of cognitive tasks.

What the results indicated was that people with IBS did worse than healthy controls at the memory task, similar to what had been shown before. However, this only happened when they had consumed the drink containing tryptophan. Analysis of their blood samples by Gerard Clarke indicated that the drink containing tryptophan led to higher levels of kynurenine-thus breakdown of tryptophan along the kynurenine system may explain this memory difference in IBS.

As drinking a mix of amino acids can taste unpleasant I wouldn't necessarily advise people with IBS to run to the health shops to see if they have them in. I would say that one useful step people with IBS can take is to try to keep stress at a manageable level-excessive stress is likely to lead to negative impact on your cognitive performance, particularly in the case of more complex tasks such as remembering large amounts of info. Further, although there is no cure for IBS, symptoms can be managed and minimised, and avoiding too much stress is part of this process.

***UPDATE*** For those who want to know more about the science of IBS, I forgot to mention that while  I was working on this blog post Paul Kennedy et al. published a review paper looking at irritable bowel syndrome and the microbiome (i.e. the community of microorganisms living inside us humans, and their genes). Check it out!

Kennedy, P.J., Allen, A.P., O’Neill, A., Quigley, E.M.M., Cryan, J.F., Dinan, T.G., Clarke G. (2014). Acute tryptophan depletion reduces kynurenine levels: Implications for treatment of visuospatial memory performance in irritable bowel syndrome. Psychopharmacology, doi: 10.1007/s00213-014-3767-z

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