Depression: A revolution in treatment?

By James Gallagher, Rachael Buchanan & Andrew Luck-Baker The Inflamed Mind, BBC Radio 4

It's not very often we get to talk about a revolution in understanding and treating depression and yet now doctors are talking about "one of the strongest discoveries in psychiatry for the last 20 years".

It is based around the idea that some people are being betrayed by their fiercest protector. That their immune system is altering their brain.
The illness exacts a heavy toll on 350 million people around the world, among them Hayley Mason, from Cambridgeshire:
"My depression gets so bad that I can't leave the bed, I can't leave the bedroom, I can't go downstairs and be with my partner and his kids.
The 30-year-old added: "I can't have the TV on, I can't have noise and light, I have suicidal thoughts, I have self-harmed, I can't leave the house, I can't drive.
"And just generally I am completely confined to my own home and everything else just feels too much."
Anti-depressant drugs and psychological treatments, like cognitive behavioural therapy, help the majority of people.
But many don't respond to existing therapies and so some scientists are now exploring a new frontier - whether the immune system could be causing depression.
"I think we have to be quite radical," says Prof Ed Bullmore, the head of psychiatry at the University of Cambridge.

He's at the forefront of this new approach: "Recent history is telling us if we want to make therapeutic breakthroughs in an area which remains incredibly important in terms of disability and suffering then we've got to think differently."
The focus is on an errant immune system causing inflammation in the body and altering mood.
And Prof Bullmore argues that's something we can all relate to, if we just think back to the last time we had a cold or flu.
He said: "Depression and inflammation often go hand in hand, if you have flu, the immune system reacts to that, you become inflamed and very often people find that their mood changes too.
"Their behaviour changes, they may become less sociable, more sleepy, more withdrawn.
"They may begin to have some of the negative ways of thinking that are characteristic of depression and all of that follows an infection."
It is a subtle and yet significant shift in thinking. The argument is we don't just feel sorry for ourselves when we are sick, but that the chemicals involved in inflammation are directly affecting our mood.

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Find out more

You can listen to The Inflamed Mind documentary on BBC Radio 4 at 21:00 BST and then here on iPlayer.

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Inflammation is part of the immune system's response to danger. It is a hugely complicated process to prepare our body to fight off hostile forces.
If inflammation is too low then an infection can get out of hand. If it is too high, it causes damage.
And for some reason, about one-third of depressed patients have consistently high levels of inflammation. Hayley is one of them: "I do have raised inflammation markers, I think normal is under 0.7 and mine is 40, it's coming up regularly in blood tests."
There is now a patchwork quilt of evidence suggesting inflammation is more than something you simply find in some depressed patients, but is actually the cause of their disease. That the immune system can alter the workings of the brain.

Joint pain

To explore this revolutionary new idea in depression, we visited an arthritis clinic at Glasgow Royal Infirmary.
It is perhaps an unexpected location, but it was in clinics like this that doctors noticed something unusual.
Rheumatoid arthritis is caused by the immune system attacking the joints. And when patients were given precise anti-inflammatory drugs that calmed down specific parts of the immune response, their mood improved.
Prof Iain McInnes, a consultant rheumatologist, said: "When we give these therapies we see a fairly rapid increase in a sense of well-being, mood state improving quite remarkably often disproportionately given the amount of inflammation we can see in their joints and their skin."
It suggests the patients were not simply feeling happier as they were in less pain, but that something more profound was going on.
Prof McInnes added: "We scanned the brains of people with rheumatoid arthritis, we then gave them a very specific immune targeted therapy and then we imaged them again afterwards.
"What we are starting to see when we give anti-inflammatory medicines is quite remarkable changes in the neuro-chemical circuitry in the brain.
"The brain pathways involved in mediating depression were favourably changed in people who were given immune interventions."
One possible explanation is that inflammatory chemicals enter the brain. There they interrupt the production of serotonin - a key neurotransmitter that's linked to mood. 

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