Professor Bullmore believes the root of the problem of depression is inflammation
There hasn’t been a significant advance in the treatment for depression in nearly 40 years.
And the most commonly prescribed antidepressants, SSRIs (selective serotonin reuptake inhibitors) — once hailed as wonder drugs — do not work for a significant number. They also have a range of potential side-effects, including insomnia, sexual problems and difficulty coming off them.
But now a Cambridge University psychiatrist suggests there is a radical way to transform this gloomy picture. Professor Edward Bullmore believes the root of the problem is inflammation. In his book, The Inflamed Mind, he argues that depression is not a mental, but a physical, illness caused by inflammation — which opens up the possibility of entirely new approaches to treating it.
Inflammation is the body’s first line of defence: it occurs when the immune system’s messenger molecules (cytokines) alert white blood cell ‘shock troops’ (macrophages) to attack and destroy invaders — such as bacterial infection.
As part of the immune response, the blood vessels expand to bring more blood to the damaged area to repair it. The most obvious signs of inflammation are the redness and swelling that occur when you cut yourself, for instance.
But like any military operation, this immune response can be a doubled-edged sword; friendly fire can damage healthy cells, too. High levels of inflammation are now known to be associated with most chronic diseases, including diabetes and cancer, as well as rheumatoid arthritis, asthma and gum disease.
And as Professor Bullmore sets out in his book, it seems that inflammation is linked with depression, too. The idea is that if you treat the inflammation, the depression is alleviated.
For decades, drug treatment for depression had been largely limited to SSRI drugs that raised the amount of the brain chemical serotonin, which is known to be associated with positive feelings.
The thinking was that depressed people didn’t have enough serotonin. But if this inflammation theory is proven right, in the foreseeable future patients could be leaving their GP surgery with a much more varied package to help with low mood.
For instance, SSRIs —which do benefit some people — might be combined with anti-inflammatory drugs already on the market, even the familiar aspirin or ibuprofen found in every bathroom cabinet.
Patients with severe depression might benefit from electrical stimulation of the vagus nerve, which runs from the gut to the brain. This treatment is known to calm inflammation. Changes in diet and lifestyle could be effective, too.
There had long been hints that inflammation could play a part in depression. For instance, after being vaccinated — designed to cause an immune response — people often complain of feeling tired and lacking motivation.
It was a consultation with a woman with severe arthritis when he was a young hospital doctor in 1989 — about the time SSRIs first came on the market — that made Professor Bullmore start to think about a link between inflammation and depression.
Her swollen, painful hands made the diagnosis of arthritis obvious; but then, instead of immediately writing a prescription for an anti-inflammatory painkiller, he asked how she felt. ‘Quietly but clearly, she told me she had very low levels of energy,’ he writes. ‘Nothing gave her pleasure any more; her sleep was disturbed and she was preoccupied by pessimistic thoughts.’ All classic signs of depression.
He diagnosed not one but two disorders, though at the time he didn’t link it with inflammation.
Still, excited by what seemed to him a new finding, Bullmore told his senior physician who, unimpressed, replied: ‘Depressed? Well, you would be, wouldn’t you?’
It’s a classic problem in medicine. When two disorders come together, are they separate, or does one cause the other? Was the constant pain and difficulty moving what made her depressed or did the inflammation that damaged her joints play a part?
It was an idea that went against the conventional understanding that the immune system was blocked from acting on the brain by the blood brain barrier — effectively a filter that keeps out many of the compounds carried in the blood.
But within a few years, research showed that immune system cells and proteins could get through the blood brain barrier, and studies on animal brains revealed that these immune cells could behave like the most undisciplined militia, blasting the territory they were supposed to be protecting.
This research showed that nerve cells in the brain exposed to the immune system’s messenger cells, the cytokines, were likely to die and networks of cells became less able to learn and lay down memories. But this was different from the havoc wreaked in arthritic hands, not least because the lack of pain receptors in the brain meant it wasn’t painful.
The immune troops also made use of a form of protein called tryptophan, which is normally turned into the ‘feelgood’ chemical serotonin, to make toxic damaging compounds instead.
This could be why SSRIs don’t benefit depressed patients with high levels of inflammation — as the raw material for making serotonin isn’t available.
It’s not just illness and infection that cause inflammation. Obesity is linked with it, especially the fat stored round the middle (a source of inflammatory cytokines). Habits such as smoking, not exercising and a high sugar diet all combine to keep inflammation raised.
However, about 80 per cent of depressive episodes are connected with stress, says Professor Bullmore, citing the example of a man who starts divorce proceedings being ten times more likely to suffer depression than the general population; the risk for his wife is 20 times greater.
Such stressful events also raise the risk of conditions such as cancer and heart disease.
So the link between inflammation and depression looks very plausible. But it could have an even greater impact on medicine than improving treatments for these patients, as it questions the division between patients with physical disorders — such as heart disease — and those with mental problems such as depression and anxiety.
Physicians treat the physical disorders and psychiatrists treat the mental ones.
Inflammation is the body’s first line of defence: it occurs when the immune system’s messenger molecules (cytokines) alert white blood cell ‘shock troops’ (macrophages) to attack and destroy invaders — such as bacterial infection
But does this divide still make sense when inflammation can equally affect both types of disease?
This ‘medical apartheid’, as Professor Bullmore calls it, is very damaging to patients. Having worked as both a physician and a psychiatrist, he knows that both sides disapprove of crossing the line. When he was a doctor he was discouraged from pointing out that psychological factors, such as depression, could be making a patient’s physical condition worse and should be treated.
Later, as a psychiatrist, he was warned off suggesting a patient’s anxiety might have a physical cause — damage to the heart — rather than a psychological one, such as low self-esteem.
He describes as ‘one of the most shocking health care statistics I know’ the fact that patients with mental illness have a life expectancy at least ten years shorter than it should be.
So what does all this mean for patients? One intriguing new treatment for depression could be nerve stimulation, he suggests — specifically stimulation of the vagus nerve that runs from the gut to the brain. This helps keep automatic processes such as the heart rate stable.
It is now known that it does the same thing for inflammation. Indeed, research with rheumatoid arthritis patients has found that 20 minutes a day of vagus nerve stimulation led to a rapid, significant drop in inflammation.
‘It may prove possible to turn inflammation on and off at the flick of a switch,’ writes Professor Bullmore.
More immediately, he advises being aware of the inflammatory effects of gum disease. We should also look after our gut bacteria, which are closely involved with the immune system and directly linked with the brain. Tackling stress, obesity, lack of exercise and poor sleep should help reduce inflammation, too.
New treatments are welcome, Professor Bullmore adds, but we need to move on ‘from seeing depression as all in the mind or all in the brain to a response of the whole human self to the challenges of survival in a hostile world’.
The Inflamed Mind, by Edward Bullmore, is published by Short Books price £14.99. To order a copy for £11.24 (25 per cent discount) go to mailshop.co.uk/books or call 0844 571 0640; p&p is free on orders over £15. Offer valid until May 15, 2018.