Does the immune system cause depression?

24 March 2015

Interview with

Declan Jones, Johnson and Johnson

Can the immune system cause more common complaints, like depression? We all go through spells of feeling down, but for ten percent of people the symptoms persist for weeks or months. DepressionWhat role might immune responses play in this? Kat Arney spoke with Declan Jones, the neuroscience lead at the pharmaceutical company Johnson and Johnson...

Declan - The link between the immune system and depression is not a new idea. It's been around for many years now, but it's still very exciting. There are several lines of evidence to suggest a role of the immune system in depression. First off, there's a significant increased risk of depression in patients with autoimmune diseases such as rheumatoid arthritis and psoriasis. I think some very direct evidence is that drugs which enhance the immune system such as interferon alpha which is used for the treatment of hepatitis C can cause depression-like symptoms as side effects in almost a third of patients. For me, that's very compelling data.

Kat - With cases like arthritis and things like that, is that not just because someone is in constant pain that they then become depressed?

Declan - Well, it's a good question. It's very difficult to disentangle the symptoms. We actually have a piece of work ongoing which is funded by the Medical Research Council and it's a consortium between ourselves and GlaxoSmithKline and a number of academic groups led by Ed Bullmore here in Cambridge. One of the things we're trying to do is, can we take some mood data from our immunology trials to really understand, can we distinguish the effects on mood from the effects upon say, the joint damage. At the moment, it's very hard to disentangle but there seems to be evidence that you can actually have effects on mood without actually having effects on the physical symptoms and vice versa. So for us, that's a really interesting piece that we're trying to follow up on.

Kat - So, for people where the drugs don't necessarily work for the disease you're trying to treat them for, actually, they either feel a lot more depressed or less depressed.

Declan - Less depressed, with some treatment for rheumatoid arthritis. There's been anecdotal cases by physicians and it's something that was obvious to physicians who weren't psychiatrists. It's also clear. I mean, patients with depression have elevated levels of some of the immune molecules in the blood such as cytokines IL-6, IL-1 beta and TNF-alpha.

Kat - These are all chemicals produced by white blood cells, produced by immune cells basically.

Declan - Yes, exactly and can act as messengers for the immune system to actually directly impact upon the brain function.

Kat - So, what's actually going on here? How is this alteration in the immune system causing depression or causing this very low mood?

Declan - There's increasing understanding, but it's still not entirely clear. There is some evidence to suggest that the inflammatory markers, the cytokines that I mentioned before can actually have direct effects upon - on enzymes in our brain which alter the level of neurochemicals such as serotonin, noradrenalin or dopamine. As you know, these are neurochemicals we know are associated with mood function.

Kat - They're kind of the sort of happy chemicals when your cells talk to each other in the brain, they go, "Yeah! Things are good."

Declan - That's exactly right and effects upon synaptic plasticity, actually, the way that the synapses function. And maybe, you know, neurogenesis, so production of new neurons. There's increasing evidence that immune mediators can actually have a direct effect upon brain function.

Kat - You mentioned this is not necessarily new, the idea that depression can be linked to immune function, but the idea that there is quite so much immune meddling in the brain, is this quite a new field that's opening up?

Declan - It's a field that's been active for quite a few years now, but I think the reason why we're getting excited by this is because I think there's been significant advances in the field of immunology and novel treatments for autoimmune diseases. So the excitement might be that you could take those treatments, actually use them now in depression. So, I think there's compelling evidence and there's actually converging evidence from different groups, from clinicians, from pre-clinical scientists. And what we're trying to do is say, can we actually jump on the back of the improvements in immunology?

Kat - So that's what I want to ask really. There's two prongs to this. It's the idea that maybe you could have a blood test, if someone comes to the doctor and says, "I think I'm depressed. I'm really not feeling good about life." Could you have a blood test to look for this kind of immune-related depression? And then obviously, the treatments for depression as we know are not necessarily as great as they could be so, more immune-based drugs in the future.

Declan - We're part of the consortium with the Wellcome Trust and this is led by Ed Bullmore in Cambridge and we're working with our colleagues at Lundbeck and another pharmaceutical companies and a host of excellent academic partners. But one of the pieces of work that we really want to understand is, what is the role of immune system? How can we demonstrate perhaps that there really are robust signals of immune changes in depressed patients? But also, can we distinguish between depressed patients who respond well to antidepressant drugs and those who, perhaps who don't? So, can we actually identify blood markers that would be able to help us to identify the right patients to put into a clinical trial and then as a separate piece of work, we're trying to understand what are the best molecules to test so that at the end, we may be able to do a therapeutic proof of concept trial in the right patients using the right molecule.

Kat - And the disease that I know a lot about is cancer and it's much more moving towards doing say, a genetic test on someone saying, "Okay, you have this type of tumour with this gene fault. You need X, Y, Z drug." In terms of looking at maybe someone's genome and looking at the way that their genome interacts with their immune system and affects levels of immune markers, is this the way that things might go in the future?

Declan - Potentially. I think we're a long way from that. Part of the work that we're doing in this consortium is to try and understand the genetic link, the genetic risk factors and how they may link with the immune system and depression. But I think at the moment, we're quite some distance away from that.

Kat - And very briefly, we heard from Susannah right at the beginning that she was very keen to de-stigmatise the disease that she'd had and we know that there's still a huge amount of stigma around mental illness, even very common ones like depression. Do you think more and more trying to talk about it as an illness caused by organic molecules in our body that have gone wrong? Is that going to be helpful for sufferers from this condition?

Declan - I believe so. I think the more we talk about it, the more research we do into this, I think the better this will be for patients that we may be able to choose the right therapy that might not even be drug therapy. It could be talking therapy or even nervous stimulation. But I think the more research that goes into it, the more people get involved in research and help the scientists, and I think the better that will be.

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