The brain-gut connection

Treatments usually prescribed for mental illness are now being used for physical pain

The brain-gut connection

In the coming year, a team of researchers from Canada and the U.S. will begin a study to determine the best way to treat the worst gut problems, including severe diarrhea, gas, bloating, nausea and “chronic constipation where you have excruciating cramps [that feel] like labour pain,” says Brenda Toner, a psychologist and co-head of social equity and health research at the Centre for Mental Health and Addiction, who is leading the investigation. But they won’t be looking at antacids, laxatives or enemas. The most effective remedies may be ones normally prescribed for mental illness: antidepressants or talk therapy, or both. “What I’ve been trying to do is put the mind and the body back together,” says Toner, who heads the women’s mental health department at the University of Toronto.

This surprising study is the latest research acknowledging the connection between anxiety or depression and gastrointestinal problems. “Most of us, when we’re under stress, respond with a GI symptom,” says Toner, up to 70 per cent of people, in fact. Think about how sick to your stomach you felt before that big meeting or when you were worried about someone you love. Gut discomfort is one of the biggest reasons people miss school or work, second only to the common cold. And for people whose pain is persistent, which is typical because many GI disorders are chronic, the psychological impact can be devastating. “The brain-gut interaction is a prominent one,” says Nicholas Diamant, a gastroenterologist and professor of medicine at the University of Toronto, who is working with Toner on the study. “There are a lot of things about gut symptoms that impact patients in a mental way,” he explains, which “will not only affect their mood but also their behaviours—whether they go to work or out to socialize.”

The physical pain is real and dogged. “On bad days it feels, literally, like somebody has taken a knife and stabbed it in my lower left side and is dragging it across my stomach,” says Jeffrey Roberts, 47, who has suffered from irritable bowel syndrome since he was a teenager. The symptoms fluctuate between diarrhea, constipation, nausea and cramps. Roberts, who lives in Toronto, is also lactose intolerant and was diagnosed with Crohn’s disease on his 40th birthday. The gut discomfort has forced him to reschedule a family trip to Disney World and cancel an Italian romantic getaway with his wife.

One of the most famous victim of eviscerating GI pain was Kurt Cobain, who hauntingly foreshadowed his own death when describing how gut symptoms sent him into a downward spiral: “It had been building up for so many years that I was suicidal. You know, waking up starving, forcing myself to eat, barfing it back up . . . just crying at times, ‘Urgh, I’m in pain all the time.’ ”

On top of the physical distress, Roberts says he and others like him suffer mental and emotional symptoms. (Cobain’s proof.) Anxiety and depression begin to creep in. “You worry that people see you as a hypochondriac,” he says, “as if it’s all in my head.” Some sufferers feel hopeless, which is a common reaction to chronic pain. Even the practical aspects of living with a major gut problem—always needing to know there’s a bathroom nearby, for example—can wear people down. ‘‘I don’t know anything that is more distressing for a patient,” says Diamant, a senior scientist at Toronto Western Research Institute, “than to fill their pants full of poop at the grocery store.”

The body, of course, reacts to stress in all kinds of ways. The cardiac system may respond with a hastened heartbeat; the vascular and nervous systems may cause a migraine headache. “But the gut seems to be the one [system] that’s more sensitive,” says William Paterson, a neurogastroenterologist and research chair at Queen’s University in Kingston, Ont. The gut includes everything from the salivary glands, the pharynx and esophagus to the stomach, intestines and anus, plus organs like the liver and pancreas. It’s huge and complex. “There are more nerves in the wall of the gut than there are in the spinal cord,” says Paterson, past president of the Canadian Association of Gastroenterology. It’s so responsive that scientists often refer to the gut as the “little” or “second” brain.

One of the big questions in medical circles is what comes first: the anxiety and depression or the GI problems? At this point, it’s hard to say. “It’s chicken or the egg,” says Paterson, but he believes there’s overwhelming evidence that mental illness doesn’t cause gut disorders such as IBS, which afflicts up to 20 per cent of the Canadian population. “But if you have anxiety and depression, you’re more likely to have or be concerned about IBS symptoms,” he says. “And if you have severe IBS symptoms, it’ll affect your mental health.” Experts point out that IBS symptoms can have no negative impact on a person’s mental health, especially if they’re minor or moderate. “So some people have mild IBS and can cope,” says Toner.

A 2006 study published in the Archives of Internal Medicine showed that people with mental disorders have double the chance of having a digestive illness; 20 per cent of patients suffering from a GI disorder have anxiety, compared to eight per cent of people with a healthy gut. One of the study’s authors, Jitender Sareen, thinks the relationship is bidirectional. “The anxiety leads to more GI problems, the GI problems lead to more anxiety,” says the University of Manitoba psychiatry professor. “It becomes a kind of cycle.”

Science is slowly figuring out more about the relationship between the big and little brains. In people who experience serious IBS symptoms, some neuro-pathways may not work properly—the sensory signal may not be regulated properly, let’s say, and pain is the result. Other research, looking at how activity is transmitted from the gut to the brain, is focusing on a hormone called corticotropin-releasing factor or CRF, which Paterson says is increasingly thought to trigger abnormal gut activity during stressful situations.

High stress levels combined with a bacterial stomach infection (gastroenteritis)—say from salmonella, E. coli or C. difficile, the latter two of which plagued parts of Canada recently (remember the contaminated Harvey’s in North Bay and the hospital in Regina?)—also make people more susceptible to developing IBS, showed a 2007 New Zealand study published in Gut. In Walkerton, Ont., which experienced Canada’s worst E. coli water contamination ever, 27.5 per cent of people who reported suffering gastroenteritis got IBS.

The relationship between the mind and gut is particularly relevant—and complicated—when talking about IBS because it’s one of many “functional” disorders, just like acid reflux, chronic constipation or dyspepsia, which is characterized by persistent burning stomach pain, bloating, burping, heartburn, nausea and even vomiting. With these conditions, tests including blood work or colonoscopies often can’t detect any “organic or biochemical” abnormalities in patients, says Toner. The pain is real, but “we can’t say, ‘There’s a lesion and it’s this big and that explains the pain.’ ” Sometimes patients are told, wrongly, that there’s nothing wrong with them.

That contributes to the shame and stigma associated with gut problems. Those are evident on the IBS website Roberts has run since 1989,, which offers support and information. Although the site has 30,000 registered visitors, every month up to 200,000 unique visitors “are lurking behind the scenes because they don’t know if they have [IBS], or they don’t want their employer or spouse to know.” Gas and diarrhea aren’t considered socially appropriate talking points, says Toner, especially when it comes to females. Unfortunately, in North America women constitute between 70 and 90 per cent of IBS patients. No one knows for sure why women are diagnosed more, but a popular theory says it’s because Canadian and American women seek medical attention more often than men.

All this makes for a perfect storm that has medical professionals and scientists scrambling to find a fix. That’s where Toner’s research looking at antidepressants and a type of talk therapy called cognitive behavioural therapy (CBT) comes in. A few years ago, she and colleagues discovered that CBT was more effective in helping patients cope with moderate to severe gut problems than no talk therapy at all. CBT sees the patient work with a psychologist to identify triggers that set off the worst symptoms. Patients talk about what’s going through their mind when they are in the throes of pain or feeling overcome by anticipatory anxiety and figure out techniques to reduce symptoms such as relaxation exercises. “It’s not magical or mysterious,” says Toner. “It’s practical, and that’s why people like it.”

Toner’s research also found that a low, regular dose of the antidepressant desipramine was more helpful than a placebo pill. Now, her team is recruiting 200 women with IBS to participate in another study to determine which of the two treatments is best, or to find out if the ideal remedy would be to administer both to patients.

Diamant says that the antidepressants prescribed for pain management are usually at doses much lower than would be required to treat mental illness—a 10th or a 20th the dose sometimes. The drugs work because they affect the neuro-pathways that send and receive signals between the brain and gut. Many antidepressants have “anticholinergic” properties, which means they can alleviate diarrhea and cramps.

Roberts has benefited from both CBT and antidepressants. But he is all too aware that these treatments come with a lot of baggage. When his doctor recommended he try them, he was indignant. “I had the same reaction as a lot of people: why am I taking this? I’m not crazy.” But as he understood how the remedies worked—and when his symptoms got worse—he came around to the idea. Today he talks to people about the promise of these surprising treatments. “It really does work,” he says. “The people I worry about are the ones who are not getting treatment and are suffering needlessly.”

All this reminds Toner of a similar situation facing doctors and patients years ago, when everyone thought ulcers were caused solely by stress. Then, in a stunning discovery, researchers identified a bacteria, Helicobacter pylori, that was the culprit behind so much physical and psychological devastation. “I think that is a lesson,” she says, in particular when talking about functional disorders such as IBS, “that we’re still figuring [it] out.” Months or years from now, says Paterson, we may find out that if you really look with more sophisticated techniques there’s abnormal accumulation of certain inflammatory cells in the lining of the bowel, for example. “But just like with any other illness,” says Toner, “worry, anxiety, depressive symptoms and stress are associated.”

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