IBS and the Ill Mind?


The high prevalence of psychiatric comorbidity in those people with irritable bowel syndrome is a reason why for so long the illness was considered psychosomatic. Now there seems to be commonalities in the causes of certain illnesses of the mind and the functional gastrointestinal disorder.

The prevalence of IBS may be as high as 10-20% in the general adult population based on the Rome II diagnostic criteria.

IBS and Psychiatric Disorders
IBS is not a psychosomatic disorder and yet there are often psychiatric complications in patients with the condition.

Typical symptoms of IBS include abdominal discomfort and pain and irregular bowel movements.

A Catchall Diagnosis for IBS
The IBS patient has been the typical difficult patient for gastroenterologists. In the past, the diagnosis has been a catchall for the functional disorder that cannot be diagnosed.

The diagnosis by exclusion traditionally inherent to IBS has added to the divided opinion about the origins of this common complaint. Many patients have ended up seeing multiple specialists in different specialties.

The fact that a psychiatric disorder is common in 70-90% of those who are treated for IBS has led to the hypothesis that there may be either in part a common aetiology or cause.

The most common psychiatric conditions are mood and anxiety disorders. There is a high prevalence of 19% in schizophrenia, 29% in major depression, and 46% in panic disorder.

The Brain Gut Axis
There is good evidence that IBS is caused by some sort of dysregulation of the brain-gut communication or axis.

Some studies have shown alteration in cortisol in a subset of IBS patients with either too much or too little being produced.

Alpha-2-adrenoceptors regulate growth hormone. Patients with IBS who are given clonidine have considerable blunted responses, which would suggest that the alpha-2-adrenoceptors are less responsive that healthy objects.

Similarly, the role of the serotonin 5HT1A receptor, which triggers the release of prolactins, has been investigated in IBS patients and controls. Patients with a functional bowel disorder exhibit exaggerated responses to 5HT1A agonism. When the 5HT1A receptor is stimulated there is exaggerated release of prolactin.

This makes a case for the noradrenaline and serotonin neurotransmitter receptor systems in IBS patients being altered. However, it does not necessarily mean that the response of these receptors is central to the pathophysiology, but patients with IBS differ in terms of their monoaminergic responses centrally when compared with healthy subjects.

Markers of Inflammation
The frequent occurrence of IBS after a bout of gastroenteritis either caused by infection or infestation with parasites has led to the proposal of a putative inflammatory cause. It is the inflammatory response to the infection rather than the infection itself that has been proposed as being central to the aetiology.

In those with IBS plus comorbid non-GI symptoms, such as fibromyalgia, CFS or atypical depression, there is significant inflammation with IL6/IL8/TNFa all very significantly increased. Toll like receptor expression is increased in the colonic mucosa and perhaps this accounts for the increased pro-inflammatory cytokine profile in patients with IBS.

Inflammatory Markers
Some research in IBS has looked at the role of inflammatory markers. In the healthy state, there is a balance between pro-inflammatory and anti-inflammatory cytokines. There has been some evidence of altered cytokine levels in IBS patients and also that circulating cytokines might play a role in brain function.

Cytokines in the plasma can impact on hypothalamic function. If cytokine serum levels are particularly high, then there can also be similar stimulation of cytokine production on the other side of the blood brain barrier.

Pro-inflammatory cytokines interleukins (IL) 6 and 8 are elevated in IBS patients. There is an increase in TNFalpha only in those patients with depression as comorbidity.

Most patients also show immune activation in the form of increased intraepithelial lymphocytes. IBS may involve some kind of infiltration of immune cells into the nervous system. In severe IBS it has been found that there is infiltration of lymphocytes into the nerve cells and fibres of the myenteric plexus.

A Role for Stress
Stress whether it be psychological stress or induced by an infectious or disease related cause can lead to activation of the HPA axis and the hyperalgesia or gut hypersensitivity typical of IBS.

The body is regulated by a series of neuroendocrine and immune processes which are in balance with one another. Generally these processes are in homeostasis but during periods of stress the balance can go awry.

Rating of Psychiatric Illness
There is evidence that some of the rating scales used to diagnose psychiatric illness in IBS patients are inaccurate.

There are a degree of false positives and false negatives using these scales.

They diagnose some people who are depressed when they are not depressed at all and fail to diagnose psychiatric illness in others who are clearly psychiatrically ill.

Using psychiatric rating measures in IBS patients may not be appropriate in all cases.

Are IBS Medications at Fault?
There is an altered serotonin metabolism in those with depression.

Tryptophan is the dietary precursor to serotonin and tryptophan metabolism may be disrupted if anti-inflammatory drugs are given.

It is seen in some hepatitis C patients who are given interferon. They become depressed due to an alteration in their tryptophan metabolism.

Using the kynurine to tryptophan ratio as a measure of tryptophan metabolism it has been found that there were far greater ratios for those who have IBS. So perhaps anti-inflammatory medications used to treat gut symptoms of IBS either trigger or exacerbate depressive symptoms.

Does Gut Flora Play a Role?
In some IBS patients, there may be an involvement of the gut microbiota in the trigger of depressive episodes. It may result in a specific inflammatory phenotype that results in increased tryptophan metabolism and changing serotonin related activities and thus making individuals more prone to depression.

So What Causes IBS?
There may be multiple causes of IBS and it may be a combination of factors that triggers the syndrome especially with IBS and psychiatric illness as a comorbidity.

The aetiology of IBS is not well understood, but there is general agreement that alterations of pain perception, gut reactivity, and dysregulation of the brain-gut axis may be important contributing factors.

Other contributing factors may include inherited vulnerability, immune dysfunction (post-infectious immune dysregulation), and prior and ongoing psychosocial stress.

Conor Caffrey is a writer on medicine and science.

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