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Wednesday, June 30, 2010

Anxiety and Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a condition characterized by the chronic experience of abdominal pain, cramping, bloating, gas, constipation, diarrhea, and/or mucous. 1 in 7 people suffer from it, but only half of those have sought treatment. And since there aren't any FDA approved treatments, a lot of people are struggling with irritable guts out there. 61% of people with IBS have anxiety disorders (1), and IBS sufferers report more stressful life events, and their bowel symptoms worsen with stress.

Anxiety itself is the result of an evolutionary adaptation to help us survive during times of extreme duress. Imagine you are hanging out with your buddies by the campfire, and a large animal suddenly joins you, looking for a meal. Your heart begins to race, your breathing picks up, your pupils dilate, blood is shunted from your digestive organs to give you more oxygen in your heart and large muscles, and your senses become acute. Steroids pump out of your adrenal glands to give you increased strength, stamina, and speed, at the cost of fatigue later on. Even your platelets can change shape to become stickier, just in case you are wounded.

Acutely, these changes can help you survive some pretty dire circumstances. But jack up the anxiety response on a chronic basis, and you end up with a classic anxiety disorder - hypervigilance, fatigue, insomnia, panic symptoms, muscle tension, gastrointestinal distress, and worry.

IBS patients have increased startle responses and increased vigilance compared to controls (2), and they have increased cortisol levels at baseline and in response to stress (3). Once again, we have two highly correlated conditions (IBS and Anxiety Disorders) with a similar pathophysiology - for both, possible disregulation of the Hypothalamic-Pituitary-Adrenal axis.

What is the HPA axis? Well, in layman's terms, it comprises three glands in the body that all send messages to each other. These glands control stress response, oversee metabolism, mineral and salt regulation, and basically a whole lot of important stuff, from blood pressure to growth to psychological states. Having that system disregulated is not good. HPA system breakdown is implicated in a dozen disorders, including PTSD, depression, fibromyalgia, and chronic fatigue.

What causes HPA axis dysfunction? Chronic stress, of course, as our body keeps trying to juice us with cortisol to help us battle a perceived threat. But another key cause of HPA axis dysfunction is inflammation. Yup, good old inflammation, the super secret cause of all diseases of civilization. Steroids like cortisol are antiinflammatory, so if our bodies perceive too much inflammation burning out of control, it will send out a wave of cortisol to quench the flames.

Whole books have been written about stress and modern life. Compared to hunter gatherers, we work too hard, play too little, exercise infrequently, hide from the sunlight, and don't sleep enough. And our modern diet, I believe, is highly inflammatory, particularly with regards to linoleic acid (4), fructose (5), and refined flour (5).

But let's step back to the brain, IBS, and anxiety for a moment and check out how they are connected more closely. Corticotropin releasing factor (CRF) is a molecule that works in both the periphery and the central nervous system, and is released in response to stress. CRF, when administered in the brain, causes anxiety and fear behaviors (at least in animals), and when administered in the body, changes the rate of gastric emptying, colonic motility, and increases gut permeability (so all the nasty things we want kept within our GI tract, such as wheat lectin, have an easier time floating through, theoretically, when we are stressed). Rats who are made more sensitive to the effects of CRF have higher rates of anxiety and more sensitivity to colon discomfort (1). For the neuroscience geeks out there - different neurochemicals and neurocharacters implicated in the whole cascade of stress to anxiety and gut issues include BDNF, the NMDA receptor, TrkB and TrkA, 5-HT, monoamine oxidase A, GABA, and the NGF receptor. Most of these activities happen within the amygdala, which is a region of the brain that is highly responsive to sex hormones (which may also explain why women have IBS about twice as often as men.)

Interestingly, sometimes antidepressants help IBS and anxiety. It might help the psychiatric symptoms, the physical symptoms, both, or neither - my definition of a toss-up.

Finally, Peter at Hyperlipid (as always) has an interesting theory about IBS and wheat opiates. Opiates (like heroin, morphine, and percocet) are well known to cause constipation while they are active, and diarrhea and overall discomfort and a lot of anxiety as they come out of your system. It would stand to reason that if someone is sensitive to wheat exorphins, the alternating exposure and withdrawal of wheat through differing meals throughout the day and week might cause alternating constipation and diarrhea, along with abdominal discomfort, the cardinal signs of IBS. Not to mention the anxiety factor. No proof other than anecdotes - but an idea to chew on.

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