British stress researcher Andrew Steptoe, a professor of psychology at University College, London, describes these experiments as probably the most elegant of all the studies of stress and infection done to date. “What you don’t usually know under everyday circumstances is exactly when people were exposed to an infectious organism,” he says. “There are bugs floating around all the time.” Thanks to those experiments, stress levels could be linked precisely to the time of infection.
While this work confirmed the association between stress and illness, it left Cohen little wiser about the mediating influence. Part of the explanation is quite likely behavioural. Stressed people smoke and drink more. They sleep badly and often take less exercise. All these things have detrimental consequences on your health. But Cohen worked on the assumption that as well as lifestyle issues there are also specific biochemical pathways linking stress and health.
One of the key molecular players in these pathways is also among the most familiar of the body’s signalling chemicals: cortisol, a steroid commonly referred to as a “stress hormone”. Produced by the adrenal gland in response to stress, the original view of cortisol was straightforward: more stress prompts your body to make more cortisol, and the higher the level of cortisol in your circulation, the worse the outlook for your health.
However, many studies have undermined this simple idea, says Professor Phil Evans, a psychologist at the University of Westminster with a long established interest in stress and cortisol. “Generally, levels of cortisol in naturalistic studies [i.e. those carried out in the real world] do not predict health outcomes strongly, or with any great consistency,” he says.
So if cortisol is involved, but not in the simplistic sense of “the more, the worse”, what is the nature of the link? Cohen’s view is that what matters more than the level of circulating cortisol is the body’s response to it. Cortisol molecules exert their effects on the body’s cells via a set of specific receptor sites: the glucocorticoid receptors, to give them their full name. When a cortisol molecule attaches itself to a receptor it triggers a chain of chemical events within the cell. Stress, says Cohen, changes the sensitivity of these receptors; they become resistant to the activating effects of cortisol.
One of cortisol’s key roles in the body is the suppression of inflammation. This is why its synthetic equivalent, hydrocortisone, is used in treating a range of inflammatory conditions, from eczema to ulcerative colitis. It’s Cohen’s contention that if the glucocorticoid receptors on the cells of the immune system fail to respond as they should to the presence of cortisol –“glucocorticoid resistance”, as it’s known – the body’s arrangements for keeping inflammation in check break down.
Inflammation in this context refers not to the sudden burst of activity you get following acute infection or injury – a protective attempt to deal with some form of harm to the body and to initiate the healing process – but to a low level elevation of chemical processes that are there all the time. “We know that stress, acutely and chronically, increases inflammation,” says Steptoe. If Cohen is right, we now know how. Stress reduces the sensitivity of the receptors (in effect chemical switches) which are supposed to control the level of inflammation in the body.
This possibility has actually been under consideration for some time. Cohen himself published some of the early work on glucocorticoid resistance. One study looked at parents of children with cancer: an extremely stressed group. “Our argument was that when you look at people who are under chronic, extreme stress you should find an increase in glucocorticoid resistance. And in comparison with matched control parents that’s exactly what we did find.” But this work didn’t set out to demonstrate any subsequent link between glucocorticoid resistance and illness in those parents.