A hypothesis of depression

At long last, a sensible hypothesis of what depression is.

This is of personal interest to myself. Recently my new doctor (straight out of the UK's NHS) suggested my debilitating symptoms were due to "depression". My response to this was she would first have to define for me what depression was, to which she said that was a rabbit-hole she didn't want to go down.

She would have been perfectly happy to prescribe SSRI's for me (long with the statins she wanted me to take, which I also refused).

Is depression a kind of allergic reaction?

A growing number of scientists are suggesting that depression is a result of inflammation caused by the body’s immune system

Could depression be a form of ‘sickness behaviour’? Photograph: Mads Perch/Getty Images

the Guardian,

4 January, 2015

Barely a week goes by without a celebrity “opening up” about their “battle with depression”. This, apparently, is a brave thing to do because, despite all efforts to get rid of the stigma around depression, it is still seen as some kind of mental and emotional weakness.

But what if was nothing of the sort? What if it was a physical illness that just happens to make people feel pretty lousy? Would that make it less of a big deal to admit to? Could it even put a final nail in the coffin of the idea that depression is all in the mind?

According to a growing number of scientists, this is exactly how we should be thinking about the condition. George Slavich, a clinical psychologist at the University of California in Los Angeles, has spent years studying depression, and has come to the conclusion that it has as much to do with the body as the mind. “I don’t even talk about it as a psychiatric condition any more,” he says. “It does involve psychology, but it also involves equal parts of biology and physical health.”

The basis of this new view is blindingly obvious once it is pointed out: everyone feels miserable when they are ill. That feeling of being too tired, bored and fed up to move off the sofa and get on with life is known among psychologists as sickness behaviour. It happens for a good reason, helping us avoid doing more damage or spreading an infection any further.

It also looks a lot like depression. So if people with depression show classic sickness behaviour and sick people feel a lot like people with depression – might there be a common cause that accounts for both?

The answer to that seems to be yes, and the best candidate so far is inflammation – a part of the immune system that acts as a burglar alarm to close wounds and call other parts of the immune system into action. A family of proteins called cytokines sets off inflammation in the body, and switches the brain into sickness mode.

Both cytokines and inflammation have been shown to rocket during depressive episodes, and – in people with bipolar – to drop off in periods of remission. Healthy people can also be temporarily put into a depressed, anxious state when given a vaccine that causes a spike in inflammation. Brain imaging studies of people injected with a typhoid vaccine found that this might be down to changes in the parts of the brain that process reward and punishment.

There are other clues, too: people with inflammatory diseases such as rheumatoid arthritis tend to suffer more than average with depression; cancer patients given a drug called interferon alpha, which boosts their inflammatory response to help fight the cancer, often become depressed as a side-effect.

As evidence like this continues to stack up, it’s not surprising that some people have shifted their attention to what might be causing the inflammation in the first place. Turhan Canli of Stony Brook University in New York thinks infections are the most likely culprit, and even goes as far as to say that we should rebrand depression as an infectious – but not contagious – disease.

Others aren’t willing to go that far, not least because infection is not the only way to set off inflammation. A diet rich in trans fats and sugar has been shown to promote inflammation, while a healthy one full of fruit, veg and oily fish helps keep it at bay. Obesity is another risk factor, probably because body fat, particularly around the belly, stores large quantities of cytokines.

Add this to the fact that stress, particularly the kind that follows social rejection or loneliness, also causes inflammation, and it starts to look as if depression is a kind of allergy to modern life – which might explain its spiralling prevalence all over the world as we increasingly eat, sloth and isolate ourselves into a state of chronic inflammation.

If that’s the case, prevention is probably the place to start. It’s not a great idea to turn off inflammation entirely, because we need it to fend off infections, says Slavich, but “lowering levels of systemic inflammation to manageable levels is a good goal to have”.

The good news is that the few clinical trials done so far have found that adding anti-inflammatory medicines to antidepressants not only improves symptoms, it also increases the proportion of people who respond to treatment, although more trials will be needed to confirm this. There is also some evidence that omega 3 and curcumin, an extract of the spice turmeric, might have similar effects. Both are available over the counter and might be worth a try, although as an add-on to any prescribed treatment – there’s definitely not enough evidence to use them as a replacement.

In between five to 10 years, says Carmine Pariante, a psychiatrist at Kings College London, there may be a blood test that can measure inflammation in people with depression so that they can be treated accordingly. Researchers have already come up with a simple finger-prick test that reliably measures inflammation markers in a single drop of blood.

And as for the stigma – could it really be killed off by shifting the blame from the mind to the body? Time will tell. This is not the first time that depression has been linked to a physical phenomenon, after all. A recent survey found that despite wider awareness of the theory that “chemical imbalances” in the brain cause depression, this has done nothing to reduce stigma; in fact, it seemed to make matters worse.

This time, though, the target is not any kind of brain or mind-based weakness but a basic feature of everyone’s body that could strike anyone down given the right – or wrong – turn of events. And if that doesn’t inspire a greater sympathy and understanding, then nothing will.

• This article was amended on 4 January 2015. It originally stated that curcumin was an extract of cumin. This has now been corrected.