Anti-inflammatory drugs ‘could fight depression’

Scientists at seven UK universities are to set up a research consortium aimed at exploiting a newly discovered link between immune disorders and mental illness.

The connection raises hopes that anti-inflammatory drugs can be adapted to treat patients with depression or senile dementia.

The group – which involves researchers at Cambridge, Cardiff, Glasgow, Oxford, Southampton and Sussex and King’s College London – has been given £5m backing by the Wellcome Trust and pharmaceutical companies have also pledged support.

“Recent evidence has shown, overwhelmingly, that there is a link between depression and inflammation triggered by the body’s immune behaviour in the body,” said the consortium’s leader, neuroscientist Professor Ed Bullmore, of Cambridge University.

The exact mechanism by which the immune system triggers mood changes and affects the progress of conditions such as depression is not fully understood. Nevertheless, the signs are clear, added Bullmore.

“Obviously if you get a disease – like rheumatoid arthritis – that causes inflammation, you are likely to get depressed,” he added. “However, recent research shows the link is actually causal.” One piece of evidence is provided by studies of patients with hepatitis. They are often treated with interferon. The drug triggers an inflammatory response that drives out the hepatitis virus. The treatment is very effective – with one major drawback: 30-40% of patients become very depressed.

“These are individuals who were not depressed before they were given the drug – even though they already had hepatitis – and who had no history of depression,” added Bullmore. “Yet they became depressed as soon as they were given interferon and it triggered inflammation. This suggests strongly that the immune system talks to the brain in some way and that inflammation in the body can cause depression. It is possible that the reverse is true and that the brain somehow affects the immune system but that link requires further research.”

The link, added Bullmore, strongly suggests that it might possible to adapt current drugs that tackle inflammation so that they could help those affected by depression.

A different approach is taken by another consortium member, Professor Simon Lovestone, of Oxford University. His studies indicate that inflammation also affects the progress of Alzheimer’s disease. “We know that if you take anti-inflammatory drugs for conditions such as arthritis that reduces your risk of getting Alzheimer’s,” he said. “We also know that some of the genes that control the course of Alzheimer’s are the same as those that direct inflammatory responses in the body. The evidence connecting the two are very strong.”

However, the exact processes connecting the two conditions are not yet clear, Lovestone added. “We need to understand how inflammation affects the course of Alzheimer’s. After that, we can then look at anti-inflammatory drugs and see if they can be adapted for use in dealing with senile dementia.”

However, the timing of administration of these drugs is likely to prove a problem. Treatments will have to be given early in the development of Alzheimer’s and, at present, the onset of the condition is proving very difficult to pinpoint. Better predictive tests will therefore be needed to spot individuals who are about to succumb to dementia. Again, clues to the makeup of a person’s immune system could provide that information.

At present, the development of new drugs for treating both depression and Alzheimer’s is at a standstill. “The last range of effective new antidepressants appeared more than 20 years ago,” said Bullmore. “We badly need a new approach to the creation of new types of drugs for depression – and by exploiting our knowledge of the immune system, we might succeed.”

This point was backed by Lovestone. “Several major drug companies have suffered complete failures in clinical trials of drugs to treat Alzheimer’s. A new approach to the condition is badly needed and drugs adapted from anti-inflammatory medicines could well provide us with that.”

The cost of mental illness in the UK is huge, economically, socially and personally, added John Isaac, head of neurosciences and mental health at the Wellcome Trust.

“By looking at the immune system, which we already have an advanced understanding of, we could use that knowledge to treat mental illness.”