34th ECNP Congress Hybrid 2021
ECNP Congress programme spotlight
Plenary Lecture – Inflamed depression
Ed Bullmore

Ed Bullmore will present the Plenary Lecture “Inflamed depression” at the 34th ECNP Congress Hybrid, 2-5 October 2021, Lisbon, Portugal.

He is currently professor of psychiatry, director of the Wolfson Brain Imaging Centre, and deputy head of the School of Clinical Medicine at the University of Cambridge. From 2005 to 2019 he worked half-time for GlaxoSmithKline, as VP Experimental Medicine, latterly focusing on immuno-psychiatry, as described in his best-selling book The Inflamed Mind (2018).

From 2014 to 2020 he was head of the Department of Psychiatry at Cambridge and since 2015 he has been chief investigator on the Wellcome Trust and industry co-funded NIMA consortium for neuroimmunology of mood disorders and Alzheimer’s disease. He has been elected a Fellow of the Royal College of Physicians, the Royal College of Psychiatrists, and the Academy of Medical Sciences (AMS); he has also served as treasurer of the AMS since 2018.

Here he is interviewed by ECNP Press Officer, Tom Parkhill:

TP: How did you get here? Your previous work was on the connectome, and now you’ve changed field. How did this come about?
EB: It happened when I was working half-time for GlaxoSmithKline. I joined them half-time in 2005, while I continued to work half-time as an academic in Cambridge. The initial idea was to bring expertise in brain imaging and connectomics into drug development for psychiatry; and then around 5-6 years later GSK decided that they wanted to step back from psychiatry. That made me stop and think about what it would take to find new treatments, new therapeutics. I talked to a lot of people in the company and elsewhere, and it seemed to me that it would need quite a different approach. One thing which working with GSK gave me was an insight into the extraordinary success of immunological therapies in pretty much every other therapeutic area – cancer, CVD, and so on. And that made me take a look at the literature relating to immunology and mental health, and I thought “this looks very interesting, this might be a way forward”. So I came at this from a very therapeutically orientated perspective, and I do think that’s important to develop new drugs for mental health disorders. And while connectomics and imaging are terrifically interesting scientifically, and I really enjoyed my work in these areas, and I still do, I don’t think brain MRI or network science are sufficient in themselves to get us to new drug treatments. The immunological approach did open that possibility. We got some partnership funding from the Medical Research Council (MRC) and the Wellcome Trust, and GSK was joined by a couple of other companies – Janssen, Pfizer, and Lundbeck – and we took it from there. But you are right, it’s much less ‘pure science’ that connectomics and much more focused on the ‘applied’ question of arriving at new treatments.

You mentioned previous literature, when did the field arise?
It probably goes back to the late 1980s or early 1990s, when we see papers beginning to appear where researchers were making modern immunological measurement in psychiatric patients. Until around 15 years ago it was regarded as a quirky, marginal field, and many early researchers tell of the degree of scepticism which they met. When I was at medical school in the 1980s I was taught that the brain was immune privileged, that there was no way that peripheral immune cells, or peripheral inflammatory proteins circulating in the blood, could get into the brain. So the pioneers were very courageous, even to ask the questions in the face of quite exceptional scepticism. But the literature of the last 10 to 15 years has produced a body of evidence that the nervous system and the immune system talk to each other a lot, there are a lot of points of contact between the immune system and the brain, and therefore potentially between the immune system and the mind. A major new scientific idea is not always heralded as a breakthrough, and I think that was true of immunopsychiatry when it first emerged.

I’ve seen that 25% of arthritis patients suffer clinically significant depressive symptoms, which is a surprising statistic. As an outsider I’m always struck that conditions such as cancer or heart disease quite naturally lead to depression, and yet they are often treated as practically unrelated. This is the ‘Cartesian dualism’ you refer to in your abstract. But things seem to be changing.
There is now funding going into the field. The Wellcome Trust has been very supporting, as has the MRC and National Institute for Health Research (NIHR). And industry is now investing. When you look at how things are currently organised, how doctors are trained, there is still this strong dividing line between the brain and the body, and I don’t think that is scientifically justified. There is a lot of entrenched dualism: the idea is that the body is understandable, mechanistic; whereas the mind is supposed to be something completely different. The dualist philosophy, which has prevailed in Western medicine for 300 or 400 years now, doesn’t really allow for a meaningful connection between the body and the mind. If you look at how doctors are trained in the UK, there isn’t much crosstalk between people on different training paths. If you think about how patients are treated, the NHS (National Health Service) tends to treat either in a specialist mental health centre or an acute medical services provider; there aren’t many places in the UK where you will be seen as a patient ‘in the round’ with both mental and physical symptoms considered. And as you mentioned, 25% of patients with rheumatoid arthritis have clinically significant depressive symptoms. If you talk to charities representing these patients – or representing patients with other inflammatory disorders – it turns out that the main unmet need for many of these patients is at the psychological end of a spectrum; fatigue, low mood, what is often called ‘brain fog’, which is probably some mild cognitive impairment, are all self-reported by patients with systemic inflammation. These are the main unmet needs of many long-term medical disorders, but if you are a patient and if you go to a medical outpatient clinic, it is unlikely that anyone will discuss any of these symptoms with you, and many physicians would not regard it as part of their trained role to tackle symptoms like fatigue or low mood. So although the science is moving quite fast, and there is more investment in the field, I still think there’s a long way to go in terms of how services are provided and how medics are trained to think about the relationship between body and mind.

You’ve written a book on the topic, The Inflamed Mind. What made you write the book? It’s unusual to see scientists reaching out to the general public.
You are right, I think writing the book was motivated partly by the sense that this wasn’t quite a normal scientific area. When I was working exclusively in connectomics, I was used to having conversations with colleagues who showed a certain amount of scepticism. And that’s normal in science, being asked “did you get the sample right… have you done this…could your signal be spurious”, and so on. But when I started talking to colleagues about immunity there seemed to be a different degree of scepticism, the sense that “this can’t be right, we know that the brain is immune privileged, that the mind and the body don’t have anything to do with each other”. I thought this scepticism had its roots in basic philosophical assumptions, which were still pervasive in the medical profession, if not often explicitly discussed. I also found that when I talked to people who weren’t in the medical profession many of them looked at me as if I had rather belatedly discovered something which was obvious to everybody. Outside the medical profession, the idea that the mind and the body might have something to do with each other was common currency; inside the profession it was still almost heresy. And I thought, maybe there’s a book there which could be of interest to both professionals and general readers. I very much enjoyed writing the book, and I’ve been very heartened by the response. It’s been read by many colleagues in the medical profession, in particular many younger colleagues have said they enjoyed it and found it stimulating. I think that if it helps a new generation to re-consider how the body and mind interact, that’s as much as you can hope for.

Is Covid the elephant in the room?
Obviously I’m interested in how Covid impacts on the brain. I think the phenomenon of long Covid is interesting; this often includes psychological effects – similar to the ‘brain fog’ I mentioned earlier. To my way of thinking it’s quite plausible that a proportion of those patients with post-Covid psychological symptoms may be experiencing the effects of the immune response to SARS-CoV2 infection; yes that’s quite plausible, and there is some emerging evidence, but there is still a long way to go to confirm this. Long Covid emerged through social media, and the medical profession has been playing catch-up to understand it. We’ve had a global pandemic, which does promote an aggressive, innate immune response in many people, and we are seeing long-term psychological consequences; all of that is compatible with the idea that inflammatory mechanisms can cause mood and other disorders in psychiatry. But there’s still a lot of work to do to disentangle this.

Plenary Lecture
PL.05 Inflamed depression
Tuesday 5 October 2021

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