As the scientists pressed on, it became clear that this was a two-way process: not only could depression cause inflammation, but crucially, inflammation from other causes seems to be triggering depression. Some grounds for this link came from diseases that are known to send cytokines flushing through the body, like arthritis or cancer; patients often report depression before a diagnosis has even been made. “The people become depressed even before they know that they have cancer, and it ties in with the high levels of cytokines” says Michael Maes at Deakin University in Australia, who has pioneered work on the biological basis of depression.

More solid evidence comes from an ingenious experiment by Naomi Eisenberger at the University of California, Los Angeles. Her study involved injecting healthy volunteers with small fragments of the E. coli bacteria; it’s not enough to trigger food poisoning, but it nevertheless kicks the volunteer’s immune system into action, causing a release of cytokines. Although all the participants going into Eisenberger’s lab were reasonably happy and healthy, over the course of the day they began to develop many of the feelings you would normally associate with depression: their mood dipped and they were more sensitive to social slights, reporting feelings of disconnection and loneliness. And when Eisenberger asked them to play a computer game, for real cash prizes, the subjects appeared to take less pleasure in their wins than those who had not been injected with the fragment of bacteria – changes that were also reflected in scans of the brain’s reward circuits. An inability to feel pleasure, called anhedonia, is one of the most common symptoms of depression.

Evolutionary hangover

Lethargy during illness may have made sense during our evolution, says Eisenberger. “When dealing with infection, you would want to slow down, withdraw, and use your energy to recuperate instead of going out,” she says. But if, for whatever reason, the effects linger in the long-term, the results could be devastating; besides dampening your mood, inflammation can exacerbate oxidative stress in the brain. Oxidative stress, caused by toxic ‘free radicals’, could itself cause depression, since it can kill neurons, erode the brain’s long-range connections and disrupt the brain’s chemical signalling – sweeping changes that seem to come with long-term mental illness and may well contribute to the symptoms.

The upshot is that we may need to think about depression in an entirely new light – as a disease of the body as well as the mind. If so, many more things, besides life’s stresses, could put us at risk. Poor general fitness, smoking, and alcoholism are all known to increase an inflammatory response. And so, feasibly, could your diet: high fat and sugar levels – and the fatty tissue that results from it – are known to increase inflammation and oxidative stress. Conversely, certain nutrients such as omega-3 fish oils and minerals like zinc and selenium are anti-oxidants that can reduce inflammation and mop up some of the toxic chemicals, while boosting others that can help the brain to heal from damage.

Proving that this really can explain certain kinds of depression has been no mean feat, however. Although a few early studies had shown that people with depression often have a deficiency in nutrients like zinc, and that offering food supplements could improve their symptoms, the experiments were often poorly designed. “The whole area had been dogged by poor trials with small sample sizes,” says Jacka. As a result, it was difficult to know if the findings had just arisen by chance.