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Could depression be caused by our immune system?

More and more research is pointing towards the impact that our immune system has on our likelihood to develop depression. And understanding this could have huge impacts on how we treat it. We speak to Professor Carmine Pariante, who’s been investigating this fascinating area of research for the last 20 years to find out more. 

Prefer to listen to the evidence? Download and listen to the MQ Open Mind podcast with Carmine on Podbean (Android) or iTunes (Apple).

Lucie: The impact that the immune system has on depression has been popping up in the news for some time now – can you take us back to the basics and explain exactly what you mean by inflammation and why you think this could be having an impact on depression?

Carmine: The immune system is a combination of cells circulating in our blood, accumulating in our spleen and in our lymph nodes that protect us from virus and bacterial infection. They’re what we usually call white cells that we can measure using simple blood tests.

We know that if we get infected, if we have flu or severe infection, our immune system gets activated because the cells go out there and fight the infections and try and help us survive. And we know that the immune system also gets activated during stress. 

Why does it get activated during stress?

Imagine a time when you we were living in the jungle or in a cave a million years ago. Back then, every encounter with a stressor (a factor that causes stress) would mean an encounter with a predator and a potential risk of life, risk of fight, wounding and, of course, infection 

So, it’s perfectly normal that our immune system gets activated under stress conditions – even today, when most things that cause us stress don’t involve a physical threat.

Why do you think that’s interfering with the way depression forms?

The persistent activation of the immune system that you have under the condition of chronic stress slowly changes brain function. For example, it makes cells less able to communicate between themselves because it reduces the availability of serotonin, which are messengers between cells which are good for healthy mood. Also, in general, it disrupts the birth of new brain cells. 

The problem is that stressors tend to be much more chronic in modern life – poverty, difficulty at work, difficulty in family life – these tend to be hard to change. 

Is it that our brain is not adapting to those stressful situations? 

Until our brain perceives the situation as no longer stressful it will keep activating the immune system. So, at some point there may be an element of adaptation when we no longer consider the situation stressful, and at that point, our body also changes. 

You’ve seen that there’s a correlation between inflammation and depression. What’s the evidence around this? How did you come to this conclusion?

There’s lots of evidence about this. If you measure inflammation in the blood in a depressed patient, you have higher level of this ‘inflammatory biomarker’ – in other words, there’s evidence that these immune cells are activated. Not all depressed patients have increase inflammation, probably about a third to forty per cent.

Now there’s also other evidence, for example, if you suffer from a medical disorder that has at its core the hyperactivity of the immune system, for example rheumatoid arthritis, or a condition that brings inflammation through metabolic problems like diabetes – all these conditions have an increased rate of depression. We used to think that it was because people were thinking about being ill, but we know now it’s partly mediated by the increased activity in the immune system.

And the third, perhaps even more interesting piece of evidence, is that if I give you a drug to activate your immune system, which sometimes we do to fight infection, you will get depressed.

All this evidence together is forming this picture that inflammation is linked to depression – at least in this sub-group.

Are we talking about different depressions then? If it’s only a third of patients is this a sub-type of depression? 

I see depression almost as a fever. If you put together 100 people with fever - each of them will have a different reason for having that fever. Some of them will have an infection, some of them will have an autoimmune disease. Depression is the same, it’s something we can see and we can measure in people but its activated in different ways by different people. 

This kind of inflammation-related depression is one type of depression – probably one that comes from early exposure to life adversity, or perhaps a genetic disposition to a hyperactive immune system. Perhaps an episode of depression that comes later in life after a bereavement is a different kind of depression.

Carmine Pariante and Lucie recording the podcast

It’s been described as one of ‘strongest discoveries in psychiatry for the last 20 years’. Why do you think this is considered such a breakthrough?

There are three reasons. First, it’s actually a new idea – we haven’t had a really new idea in psychiatry for at least 30 or 40 years. All the investigations and research and medication that we have developed have been an elaboration of old ideas. This is the first time we have a completely novel biological model to look at depression.

Secondly, it focuses the attention from the mind and onto the body. It’s a powerful message to explain depression as not just a disorder of the mind, or of the brain, but as a disorder of the whole body. So, I think it has a powerful anti-stigma message, bringing depression into the context of other medical health conditions. 

The third element, is that we have things we can measure in the blood, which we now know are correlated to the severity of depression and we also have drugs that affect the immune system that we’ve been using and developing for many years for use in other disorders. All of a sudden, we have a range of blood tests we can use and a range of new medication we can use, especially for those patients are not responding to antidepressants.

This is an important breakthrough, and the way we are treating depression will change in the future – perhaps even in the new future. What we don’t want though is for people who have depression to be combining their antidepressants with anti-inflammatories off-the-counter without discussing with their doctors first. We have to remember that there are side-effects for anti-inflammatories and when they’re combined with antidepressants, there can be even more side-effects.

What are the next steps for the research?

Our understanding of what’s going on in a cellular way is still quite limited. We really need to understand on a molecular level, in the microscope, what happens when an immune cell communicates to the brain cell and how that makes the brain cells ‘depressed’. 

And we’re also not sure which anti-inflammatory would be the best to treat this condition. We’re doing clinical trials at the moment to try and understand this better.

Aside from helping people who have depression, what are the knock-on effects that this research could have on society as a whole?

Pharmaceutical companies have lost interest in mental health for many years, so they’re not really investing in producing new medications. This area has attracted the attention from at least some pharmaceutical companies, between the availability for the drugs we already have and research into new drugs, I really think we will be able to produce a drug for the patients living with depression that are not responding. 

We’re still in the early stages, but I hope this gives people hope for the future.

Last updated: 27 July 2018

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