An interview with Stafford Lightman, Endocrinologist, Bristol University, England

Q:  What are the origins of the stress response?

A:  Stress is an extremely important protective mechanism for human beings, and in fact for all animals, because if you're being chased by a lion it's important to get away. In order to get away you need to give as much oxygen and as much sugar to your muscles to make them work as fast as they can, so your blood flow needs to go faster. When you're being frightened, your brain detects the danger, it sends signals down your spinal cord to your adrenal medulla to release adrenaline. The adrenaline increases the amount of sugar in your blood and increases your heart rate, and this helps your efficiency of getting away from the lion. Your brain also sends signals down to the pituitary gland, which releases another hormone which acts on the outside of the adrenal, the adrenal cortex, and that releases cortisol. Cortisol is also very important in keeping your blood sugar up, keeping your blood pressure up, and helping allow the body to have maximal exertion to get away from danger.

Q:  What happens to the body as a result of the stress response in the brain?

A:  One of the fascinating things that happens is [that] the body is being prepared only to use its really essential functions, so the muscles work well, the liver releases more sugar, for energy, but things are actually being turned off as well. Although the heart rate is going up and more blood is going round the body, parts of the body which aren't needed urgently are being turned off. The blood supply to the gut and areas like this is actually decreased, so your digestion diminishes—you don't need digestion when you're running away from a lion—obviously your sexual function is turned off, and a lot of the non-essential activities of the body just decrease so that you preserve the really essential ones to get away from the dangerous situation.

In a modern situation we don't have these same sorts of dangerous problems, but what we have are other very stressful situations. And the interesting thing, of course, is that your blood sugar goes up, your heart rate goes up and your blood pressure goes up, but you're not utilizing all of this, you're not running away, you're not having energy, so all of these hormonal responses are happening, but they're actually not being used.

Q:  When does the stress response become dangerous?

A:  The important thing about the stress response is it's adapted for short-term responses. It becomes dangerous when you get multiple stress responses, one after the other, or experience chronic stress that goes on for weeks or years. When that happens your levels of cortisol can be raised for very prolonged periods of time, and it can have lots of nasty effects on the body. It can damp down your immune system, for instance, so that you can't respond to diseases as well as you should. It can also have effects on the brain, actually decreasing the number of brain cells in certain parts of the brain and decreasing your memory. It also can affect your blood pressure, and it can affect the fats in the blood and make it more likely for you to have heart attacks and strokes. So when you have chronic stress, that's when stress becomes dangerous.

Q:  Can caring for people with chronic illnesses actually lead to illnesses in caregivers?

A:  There's been quite a lot of interest recently about what chronic stress can do to cause disease. We did a study on caregivers of patients with Alzheimer's disease…We've looked at their hormones and we find that their cortisol is indeed raised, so they have a hormonal stress response which is prolonged for a very long period of time. We've also looked at their immune function by giving them influenza vaccination, which is routinely given to elderly people, and we've found that their antibody response to the influenza vaccination is much poorer than equivalent people of the same age who aren't caring for a loved one with Alzheimer's or some other disease.

So it's clear that chronic stress does damp down the immune system. And other people have also shown that chronic stress can decrease your ability to heal wounds, so that if you've got small wounds they just don't heal as well. The body just doesn't function quite as well when you have large, high levels of cortisol circulating through it for long periods of time.

Q:  Has stress been linked to depression and other mental illnesses?

A:  It's quite clear that chronic stress is related with depression. Depression is a very major common disease in our society, and it is undoubtedly related to the chronic stress that we have in our society.

The ability of stress to cause depression as well as other problems like heart disease and high blood pressure are connected in an interesting way. [Patients who are depressed after a] heart attack are much more likely to die within the next few years than people who've had heart attacks and who aren't depressed. So again this depression, which is related to chronic stress, actually has a major effect on life expectancy.

Q:  Might there someday be a pill to reduce the effects of stress?

A:  We are involved in an intensive program to develop an anti-stress pill, and the only way we can do this really is to try and block the beginning of the pathway in the brain that causes the response to stress. And this happens at the hypothalamus, which makes a hormone called CRH. We're making a pill that blocks the effect of CRH, and therefore blocks all of the effects of stress on the body, including the effects of stress in causing an increase in cortisol. We're not designing a drug to give to everybody who's stressed. But this can be very important and hopefully should actually be an extremely useful treatment for … depression that's associated with severe stress.