Read more: “Infectious moods: How bugs control your mind”
Chemical messengers from the immune system can wreak emotional havoc if they cross into the brain – even in people who otherwise seem healthy
When we get sick, we often feel lethargic and lose our appetites. Our concentration suffers and we might feel anxious, depressed or anti-social. These changes are caused by signalling molecules called cytokines, which are released by immune cells in response to stress and infection.
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Although cytokines are too large to pass freely through the blood-brain barrier, recent studies have shown that they can enter through naturally occurring leaky regions and via specialised channels. They can also affect nerves that transmit signals into the brain.
There is growing evidence that cytokines associated with inflammation can cause depression. For instance, if you inject a healthy person with interferon-alpha, an antiviral drug that prompts the release of inflammatory cytokines, they will begin to show symptoms of depression ().
“Cytokines can interact with virtually every pathway relevant to depression,” says Andrew Miller of Emory University School of Medicine in Atlanta, Georgia. And the idea that inflammation induces behavioural changes makes evolutionary sense too, he says. “Cytokines are trying to shut your body down so that you can devote your resources to healing. But at the same time, a wounded animal is a target so it needs to be hyper-alert in case a predator comes onto the scene.”
Miller also recently imaged the brains of patients receiving interferon-alpha to treat hepatitis C. His team found the drug activated the dorsal anterior cingulate cortex, a brain region involved in error detection and conflict monitoring (). Similar patterns of activation have been observed in people who are highly neurotic and have obsessive compulsive behaviour. “If you get increased activity in that area of the brain, people tend to be more suspicious and perhaps interpret innocent remarks as threatening,” says Miller.
Besides infections and toxins, stress and obesity can also trigger the release of cytokines. “Obese people are two to three times more likely to be depressed, and adipose tissue is a potent source of pro-inflammatory cytokines,” says Rook.
For this reason, Rook believes that the immune system may well be affecting the behaviour and mental well-being of even apparently healthy people. “There are an awful lot of people going around with chronically raised inflammatory responses,” he says. “It seems likely that they will be suffering some effects.”
The effects of cytokines are not all bad, though. Naiomi Eisenberger at the University of California in Los Angeles and her colleagues have found that some people become more sensitive to social pain when they are injected with a bacterial toxin that also boosts inflammatory cytokines. In particular, a cytokine called IL-6 seems to boost activity in brain regions involved in empathy ().
Findings like these could lead to new treatments. A trial is underway to see whether a drug that blocks one of the key inflammatory cytokines, TNF-alpha, can alleviate depression, while other trials are investigating whether common anti-inflammatory drugs such as cox-2 inhibitors or aspirin might improve people’s response to conventional antidepressants.
