E98 - What can Neuroscience tell us about Mental Health? (with Dr. Camilla Nord)

Dr. Camilla Nord leads the Mental Health Neuroscience Lab at the University of Cambridge, where she holds dual positions as Programme Leader at the  Cognition and Brain Sciences Unit and Assistant Professor of Cognitive Neuroscience at the Department of Psychiatry. She also holds a Wellcome Career Development Award fellowship, and co-leads an international team of researchers via a Wellcome Mental Health Award. Dr Nord has a longstanding interest in science communication, including many public lectures and a popular science book, The Balanced Brain (Penguin, 2023), a Financial Times, Sunday Times, and Prospect 'Book of the Year'.

This episode was made possible by the Royal College of Psychiatrists Academic Faculty and the Margaret Slack Travelling Fellowship.  

Interviewed by Dr. Anya Borissova - Give feedback here - thinkingmindpodcast@gmail.com Follow us here: Twitter @thinkingmindpod Instagram @thinkingmindpodcast

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Transcript

 Hi everyone. Welcome to the podcast this week. My name is Anya and I'm a psychiatry registrar training and working in South London. I'm thrilled to be joined today by Doctor Camilla Nord, who is a neuroscientist, assistant professor of cognitive neuroscience and the lead for the Mental Health program at the Cambridge Cognition and Brain Sciences Unit. Camilla is also the author of The Balanced Brain, which we discussed today. This book and our podcast explores the many routes that exist to mental well-being. In the book, Camilla explores a huge diversity of treatments, some of which we talk about today, and reveals how these act on similar brain pathways to the small things that we do every day, like having a chocolate or speaking to a friend. Through the book and our discussion, we speak about how there are many more possibilities for recovery and resilience for mental illness than we might think. This episode was made possible by the Royal College of Psychiatrists, who awarded me a fellowship which allowed me to spend two weeks with Camilla's research group in Cambridge, thinking about how to research some of the ideas that we discussed today. This is the Thinking Mind podcast. Here you can access conversations all about psychiatry, psychology, philosophy and neuroscience, which are accessible to all. I really hope that you enjoy. Hi everyone. Welcome back to the podcast and I'm really excited to welcome Doctor Camilla Nord. Thank you so much for joining us today. Thank you for having me on. I'm so happy to be here. Um, so Camilla, you are a neuroscientist. You're leading the mental health science neuroscience lab here at Cambridge, and we're actually recording on site at the MRC Cambridge Cognition and Brain Sciences Unit. I hope I've got that in my lab. That's right. Yeah. Um, and it is kind of rainy, even though it's June. But even though it's June, we're, um. We're okay. We're putting on a brave face. Um, but. Camilla. So what I'm really hoping to talk to you about today is your fantastic book, The Balanced Brain. Uh, and also just what your research is, both at the moment and the things that you were thinking about when you were writing the book. And I guess I always like to begin by getting a sense for what is it that brought people to where they are now. And I guess I'm wondering, what is it that got you interested in researching mental health, and what is it that got you thinking that the the subdivision or the division that gets created between mental and physical health may not be quite the right way to go? Well, the answer to both in in my own trajectory is kind of one and the same. So the day that I became really interested in the biology and the neural aspects underpinning mental health was the day that I learned that a single molecule, dopamine, could cause movement dysfunction in the case of Parkinson's disease, but also symptoms that seemed to me so far away from movement, things like apathy and adonia. So this was now many years ago. But I think that idea spurred me into trying to understand what these kind of common ingredients were in our brain. And as as I've understood them, they are not something confined to a category we call mental health, but actually have broader roles, of course, in neurology and other kinds of brain health. But also, as we now know, in aspects of physical health. And the opposite is also true. Things we traditionally think of is physical health, whether that's metabolic health, inflammation have very obvious effects on our brain function, and actually perhaps more mysterious effects on our cognition and our behavior. But I'm very interested in those too. Mhm. So I mean, tell me a bit more, tell me a bit more about the things that I guess convinced you from both aspects that. That there was something there that wasn't being quite thought about yet. So I think I thought about it the other way first. I thought first how fascinating it was that functions in the brain that we didn't quite understand could imitate physical problems. And this was after my kind of a dopamine interest. But I, I was in a grand rounds where you get to sort of hear about individual patient cases and in this case actually meet patients. And it was a group of a series of patients who were experiencing functional neurological disorders, um, different types of functional movement disorders. And at the time, I wasn't even aware of this group of patients. It was a I was completely naive and ignorant in the audience. Um, and that really started one of my core interests, which is understanding how the functions of the brain can alter our experience of physical health. And I think we still don't understand it. Um, I think it's incredibly important, critically important, not just to patients who have experiences like that, although of course, them too, but also actually to all of our experience of physical health, which is, of course, kind of filtered through our brains perception of our physical health. And then the other one came a bit later. So then I went and I did a PhD, really focusing on kind of the neural basis of psychiatric disorders. That was my interest. I worked a little bit on PhD before that, but mostly on depression. In my PhD, I was very interested in kind of the brain areas and circuits that might be underpinning symptoms of depression, and how targeting them with brain stimulation could improve depression. And it was after my PhD that I thought more about the reverse direction that in fact, these symptoms that. Are we think of as mental that I maybe thought more of as neural actually sometimes are something on top of the brain. There are something external to the brain or at least part of the wider nervous system. And that was when I started doing some initial experiments on other functions in the body, for example, um, inflammation, uh, an experiment on the gut. And that's the direction that my lab has really enriched now. So that's when I later became interested in the other way around him. And I mean, in your book, you draw, uh, I think a really helpful example about pain and you sort of pull on your own experience of pain. That is not just the acute kind of pain that we get from, you know, burning our hand, but pain that continues beyond that point. And I guess I found that a really helpful way, especially for people for whom I guess because pain is an experience that so many of us have had, and then so many of us know people ourselves have had longer term experiences of pain. So I'm wondering if you could speak about if you could share that example. Yeah. So in my book, you're right. I immediately try to draw this distinction between acute immediate pain, which is often called novel perception and chronic pain. And one of the reasons for that is is neural is in the brain. They look very different and they have different causes and they have different maintenance factors in my view. Um, and because of that, I think chronic pain really needs to be considered as an entity on its own, not just by researchers, but by experiencers, people who which unfortunately is a huge proportion of the population, suffer from chronic pain. And I talk a little bit about my own experience and why I think this distinction is important. So, um, I've experienced on and off chronic pain since I was about, um, 15 because of an accident. And I was experiencing it was probably at its worst when I was in my early 20s. And so I went to see an orthopedic surgeon and, um, the orthopedic surgeon said, look, you're probably a good candidate for surgery. There's lots of osteoarthritis, but why don't we try just kind of one thing, just in case. So he sent me for, um, a steroid injection in my foot, and it had a really. I responded very well to it, um, which doesn't really tell you that much. It sort of has a local anti-inflammatory effect. But what I didn't know is that the effect of this injection wears off. It wears off in a few months, typically. Um, I've actually never returned to the level of pain that I was experiencing at that point. So my interpretation of that experience is that, in fact, I had a sort of enhanced, enhanced response to the intervention. Something you might think of as a placebo response, but that actually was directly targeting some of the maintenance factors of my chronic pain, meaning my brain had for many, many years gotten used to the experience of pain, paying attention to the source of pain, maybe thinking about the kind of implications and emotional factors related to the pain, and that had in and of itself worsened my pain. And then when I experienced what was an effective intervention, even in the short term, that actually had consequences in the longer term because of these maintenance factors. So it sounds trivial, but I actually think it's very important to make this distinction in terms of the causes of pain. Sometimes if you've been experiencing a pain a very long time, the solutions might not come from targeting that bit of the body where you're feeling the pain, but rather from targeting some function of your brain. And that might be functions like more cognitive or psychological functions that could be accessed by something like psychological therapy. Mhm. And and so in line I mean the things that you're touching on there is. You know, you you said something like you. Unbeknownst to you, the intervention was going to potentially be much shorter than it actually turned out to be. And I guess this touches on an idea that you develop in your book about our expectations, about our predictions about the world, and how important that is in our experience of our health. In all in all, its, um, in all its ways. And aside from being a cool sort of neuroscientific concept, I think, you know, you explained it so clearly in your book in a way that's really accessible. And so again, I wonder if you can speak about what why are our predictions about the world so important? What how do our expectations shape our experiences? Well, I think this comes down to one of the core messages in my book, which is the fact that it is an artificial divide that we might draw between. Causes of mental health that originate from something like your genes and causes of mental health that originate from something like the environment, because they both alter mental health by changing aspects of your brain and wider nervous system. And one of the fundamental things they change, in my view, is this role in expectation building and expectation dominance over our perceptions. This isn't just true in mental health. This is true in perception of the world where, you know, very influenced by our expectations. That's why we have what's why we're susceptible to different kinds of visual illusions. Um, it guides a lot of how we interpret the world. It makes us more efficient interpreters of the world that we rely on our expectations. But when it comes to our mental health, our expectations are critical as to whether the way we see the world is adaptive and useful and positive for us, or less useful negative, having, you know, really serious consequences for how we live our lives or somewhere in between. It's our expectations that shape or perceptions of, and therefore interactions with the world. These aren't set in stone. They're not something you can just sit down and change. These are, you know, very, very strong yet flexible beliefs that we've built over many years and that are updated by experiences, not necessarily by conscious volition. So, just to be clear, one of our strongest beliefs about the world is, you know, objects fall downward, they don't fall upward. No one's ever taught you that. You don't kind of go around thinking about it ever. And yet it is a huge and strong belief maintained by every human. So just like that, perhaps with a little more subtlety, um, are the beliefs that underpin our mental health. So they are shaped, they are shape able, but they are both very strong and not always something we are consciously aware of. Mhm. And I mean, I guess the, the thoughts that spring to my mind as you were talking there straight away just from clinical experiences, I guess the expectations that people might develop based on how they've. The types of things that they've experienced growing up and the way that that may then play out in in their expectations of how, for example, people will treat them in later life. Is that the kind of thing that you think about? Yeah, absolutely. So one of the ways that our expectations are formed are in the experience that we have throughout development. They have particularly consequential effects on expectations, but so too are the experiences we have in adulthood. It's not like we stop shaping expectations altogether. It can be experiences you've had for a long time in your own brains. Kind of interpretation and reaction to those experiences end up becoming your expectations about what will happen in that context. Um, and sometimes that's the level on which you might want to think about something therapeutically. So if you think clinically, that might be the level that a clinical psychologist might want to tackle. And sometimes that's something that you don't target directly therapeutically. If you think about some kinds of medications that are used, they might target sort of lower levels of processing, but would then which would then have knock on downstream eventual effects on these kinds of beliefs. Um, and you bring in the idea of medication and I guess one. Part of your book, and one idea that comes out of exploring what our beliefs and expectations are is the placebo effect, which is fascinating. I think there's way more conversation about it in recent years than I remember happening before, and I think that's because it's so, like confusing yet cool. And again, I guess is spoken to in your example of your experience with injection for pain, that there was something that you you were receiving a treatment, but over and above the treatment effect, something happened that couldn't just be explained by the active molecule that was in in the steroid injection. And then you hear about loads of other really cool and weird placebo effects. Like, I don't know if this was an example in your book, but one where, uh, participants were given, uh, like an allergic skin reaction. Um, and then they were given what was what they were told would be a helpful cream for that allergic reaction, but in reality was just an inert cream, something with no active ingredients. And yet the size of the wheel and the size of the allergic inflammation on people's skin diminished. Depending on whether they were told that the cream was indeed going to be helpful, or whether they were told cream is probably not going to be that helpful, but we'll give it a go anyway. Yeah, that's an amazing example. I think I didn't include that in my book, but I really wish I did. Now you, now you bring it up because that is such a perfect illustration of the observable, immediate, like very undeniable consequences, physical consequences of the placebo effect. It's why, you know, the reputation in the population is that a placebo is something bad. You wouldn't want to be susceptible to the placebo effect. Placebos are just inert sugar pills, but actually they are only biologically inert when they're outside of your body. Once they're inside of you or interacting with you in some way, they're not inert because they are working. They're functioning on your nervous system and the way that it has the capacity to change itself and kind of consequent physical things like the skin reactions you mentioned, which I guess must be somehow via inflammation. But I really can only speculate. That's absolutely fascinating. Um, yeah. So that's why I thought it was so important to talk about the placebo effect, because I think it is a, um, a very clear example of the strength of our expectations in our experiences, not just our subjective experiences, like many aspects of mental health, but even kind of visible and physical experiences. And although there's this idea that you might want to avoid the placebo effect, it's also just something that I think we all experience all the time. We just don't know it. If you take a medication and it works for you, you don't know if you're responding to it because of some ingredient in the medication. I mean, maybe you hope you are, or maybe sometimes you are, or if it's working because of the placebo effect, or if you're just getting better naturally and you always would have, you know, that's impossible to know from you as an individual. So I felt that was quite an important message to convey. And equally, the sort of other side of the coin, I wrote, um, quite a bit in my book about the nocebo effect, because I think that idea that you can have negative beliefs, for example, about side effects when you take a pill. So this is the way it comes out in clinical trials. You can see sometimes, um, side effects that people are anticipating can occur from the placebo group. You see this at the moment in the news in antidepressant discontinuation trials where you see about, um, I think it's about 15, 16% of patients discontinuing. Um, but not really. They're actually continuing on an antidepressant, but they think they're discontinuing. Sorry that I explained that to wordly, um, have side effects. And what they're experiencing there is the nocebo effect. They're anticipating withdrawal symptoms from discontinuing antidepressants, which absolutely can occur. But in their case, they're not actually discontinuing antidepressants. So they're occurring because of the strength and power of their expectations. Now it's. Scary, but it's also powerful. It's really powerful. It means that this is something that medicine can and sometimes does capitalize on, and not something we should necessarily shy away from, but something we should sort of embrace and even embrace. I think the uncertainty, this is the hardest part and things that have worked for us. You know, if you're someone for whom, uh, maybe, let's say a treatment that is not necessarily evidence based, if it's worked for you, that doesn't mean maybe this is a treatment that, nice should put in their guidelines. And this is something we should start giving to other people. It means you're very lucky that you had an effect of your expectations on your symptoms. You're very lucky indeed. Um, it's it's a really I want to come back to to what you've said, you know, that clinically, this is something that we need to grapple with and figure out what to do with, because I think on a close to daily basis, at the moment in my work, I am constantly trying to figure out what is the right. And because there's competing demands, there's sort of the, you know, ethical, moral obligations, legal obligations that we have as doctors to give people the adequate information to make a decision about whether to which and whether to take a certain treatment or not, or whether to change a treatment, which in psychiatry may mean the risk of discontinuation, discontinuation effects of one treatment before you start another treatment. So there's that information that that we we have to give and rightly so. But then there is the competing demand that this kind of research gives us, which is, I think, still gives us an, I think, an ethical obligation, you know, do no harm of of the potential harm that we could cause by. One. Underselling the potential beneficial effects of a treatment by not enhancing the placebo response as much as we could and over enhancing or, you know, giving any weight at all to just giving a nocebo response by putting too much weight on potential side effects, which exist. But, you know, like, I've never it's not like I've gone back to any of the studies of medications to look at the comparison between the negative response that people had on the active treatment versus the placebo treatment. Right. So there's how do we how do we know when was it? Help me. Yeah, I, I do actually think about this a lot because, um, I've probably fluctuated a bit on this over the years. I remember one time hearing very convincing argument from a scientist in the Oxford placebo group that maybe clinicians prescribing drugs should be more positive about their potential effects, not. Necessarily exaggerating, but not only spending time on the possible negative effects, which can sometimes take the weight of the consultation, particularly for legal reasons, as you say. Another implication that maybe is an easier one to grapple with is the idea of open label placebos. So I think this is something I would support. There's some really beautiful evidence to suggest that even when you know something is a placebo, it can have positive effects on your symptoms. And that's because, like I said about gravity, it's very difficult to change your beliefs about the world. So if I were to tell someone that this pill you're about to take is a placebo, but in every other way it looks and feels and seems like paracetamol, it may well have some effect on their pain, symptoms or whatever else you're trying to target. So I feel that there may be that might be the kind of gentlest introduction of placebo science, um, into medical practice and maybe on the other side, it's more about figuring out how to weight the balance of positives and negatives. I did actually experience this from the other side one time, where I spent days telling people about the side effects for the Covid vaccine because I was vaccinating person after person after person, and I was just every single person. I was telling them about the side effects. And lo and behold, when at the end of the first few days I got my Covid vaccine, I really experienced the side effects. Maybe that's just how my body would have responded if I hadn't been going through the negative symptoms again and again and again. Maybe it was helped by the fact that I had spent such a long time thinking about them and explaining them. So, um, yeah, I'm I'm not saying that we shouldn't discuss possible negative symptoms, but perhaps in reporting and discussing side effects, we do have to be more careful as researchers when something is apparent in the placebo group. I think this is a mistake we've made with some drugs, is to sort of make it seem like only the active ingredients of the drug could cause those effects. But I think as clinicians, you have to give patients a head up, heads up, even if they're going to experience something from nocebo, they might experience it anyway because they'll have read about it before your consultation session. So it probably is better to be as upfront as possible. But maybe think about the balance of information. Um, yeah, for sure. And, um, you know, in case anyone is concerned about my clinical work, that is that is what you do. That is what I do. But I think just in thinking about it, I'm often I do often wonder. What might be a better way, or if there is indeed a better way. Um, so it'll be really interesting to see how it goes. And, and so now I want to kind of flip us, but not, I guess, not completely flip us in thinking about psychological therapy and what your research has found in terms of the brain basis for how psychological therapies work or indeed the body basis. So I suppose this is an area where I've felt quite passionate about communicating the results of mine, many other people's research, because I think there is a supposition that in mental health there are biological treatments like drugs, and then there are psychological treatments where you can maybe deal with the mind. And actually, I am totally don't use that distinction. I don't think it's helpful at all, because the psychological treatments that we use all affect our brains. And my work in many other peoples have shown what these brain effects might be. So one fun paper that I did a few years ago showed that there are anatomically distinct areas in the brain that change from before to after various forms of psychological therapy for depression and other affective disorders. Um, and they're not quite in the same place as those that change from a course of antidepressant medication. But what they do have in common is that both of the regions that they change, one is in the sort of medial prefrontal cortex that's changed by psychological therapy, and one is in the amygdala that's changed by antidepressants. They both are part of a larger hub of networks in the brain that are involved in emotion processing. So they kind of target the same group without necessarily overlapping in their immediate anatomical basis. And I'm going to pull you back. Um, medial prefrontal cortex and amygdala give us a little bit more for our non-medical listeners, so. Or even our medical listeners. Yeah, actually, I, I sometimes shy away from these kind of one line descriptions of brain regions. But I'll say in, in the context in which we are thinking about these regions, in this study, you might think of somewhere like the amygdala as being responsible for emotion perception and sort of acute changes in response to valence good and bad information in the world, sometimes even just sort of very salient, very strong information in the world. Those are things the amygdala, um, is quite interested in. Um, and that is the region that's changed by antidepressant medication, which falls into actually quite a long and in, in my view, really important line of research, uh, from Kath Harmer and Phil Cowan about the acute effects of antidepressant medication on emotion processing and emotion perception. So I think that really, um, falls in neatly with that model. And the other reason I found the medial prefrontal cortex is has a few more roles, but one of them is in kind of awareness of emotional and bodily states. So you might think of it crudely as a slightly higher level region. Um, and that's the area that was changed by psychological therapies. Um, and, and what what for you is the importance that, of, of that finding so of the finding that. These different treatments have impact on different parts of the brain. Well, I guess there are a few things you might have thought, um, if you didn't know that one, maybe that only antidepressants, drug and antidepressant drugs affect the brain? I mean, hopefully not, but I guess that is one possibility. Um, or that they both affect the brain, but only in that they sort of make you feel better. And they do that in exactly the same way, overlapping. Um, they have exactly the same effect on the brain, uh, or that they affect the brain, but in totally different ways, in ways where you can't even really contemplate what those areas might have in common, or this finding that I've found where actually they are anatomically distinct, but they form part of a common network. Um, and, and I think that tells us that these two treatment classes both affect the brain, affect the brain in distinct ways, but affect the brain and distinct ways that could potentially be complementary or at least have downstream effects on similar aspects of processing, in particular for emotions. Mhm. And you, you touched on the processing of emotions and how it might be that a biological treatment like antidepressants from the work that's being, that's come out of lots of labs. But like you mentioned the Oxford lab in particular how antidepressants can affect our processing of emotions. What is it that's known about that at the moment or what is it that's thought about that. So in in my book, I talk a lot about this theory of how antidepressants work. And it really came out of the conundrum of why SSRI selective serotonin reuptake inhibitors, the most common class of antidepressant, immediately, nearly immediately increases levels of serotonin in the brain. But it takes so long to change mood, if ever. But it takes weeks, and that seems really discrepant that something could have an immediate effect on a neurotransmitter. And yet you sort of need weeks of that changed level of neurotransmitter for it to affect any aspect of your mood disorder. And so, to answer this question, a series of very elegant studies were done experimental medicine studies where single doses or several days of administration of antidepressants were done and found to affect acute emotion processing. This is your interpretation of emotional stimuli, like when you see a friend walking down the corridor. Um, and they blank here one day. Do you think they're angry at me? I clearly did something to piss them off. Or are they just quite busy running to a meeting? They didn't see you. So that is an example of where an emotional bias towards the negative interpretation might be more common in mood and other affective disorders, and that could be altered by a single or several doses of antidepressants, something that changes before the normal 4 to 6 week mood effect that you might expect. Um, so that's very interesting because it shows that there's a kind of cognitive mechanism happening first, potentially underpinning later mood effects, maybe even giving us an idea of who they work for and who they don't. So one suggestion from some of this work has been that maybe not everyone shows these emotional biases. Perhaps it's the people for whom these emotional biases are important contributors to their depression symptoms. They're the ones who respond quite well to antidepressants. Or maybe it's the people whose emotional biases are most susceptible to SSRIs. I think you could interpret it in either ways, but it might. It might give you a good idea. Once you know how it's working, it might give you an idea of who it's working for. And answer to restates the the the idea that's come out of this work would be that potentially if you are someone where one of the one of the things that predisposed or precipitated your depression is that you had this accumulation of potentially, uh, of experiences that might be tricky to interpret. You could sort of interpret them either way, your friend ignoring you walking down the corridor. But for whatever reason, your brain, your mind has tended to interpret them in a more negative way. You've had this buildup and build up of these negative experiences that in time have, I guess, shifted your expectations, your predictions about the world and created this more negative mood state. And if you can, if if this is something that SSRIs target, then if you can pick those people out and separate them from people for whom depressions developed in a for different reasons. Then you might have a way of sort of rejigging that balance, rejigging the balance in which they're interpreting events. Yeah. And that that might explain why it takes a few weeks, because 1 or 2 or five experiences of something not being quite as bad as you expect, it's not going to do much for a belief that is strong and entrenched and developed throughout your previous experiences, but something that you experience again and again every day for a few weeks that will be consequential enough to affect your greater sort of belief system, which might be shaping or having a strong effect in how you feel about yourself and the world around you. So that's why these kind of minute changes can kind of build up additively and shape something much bigger, like your beliefs about the world. Mhm. And, and I think, I mean, your book is called The Balanced Brain and you sort of, I guess draw on this idea of how, how our balance of interpretations of the world Can be changed, can be changed in ways that predispose us to illness. And I just thought it was a really, really beautiful idea of kind of this homeostasis that we can live in, but also that can be knocked and that the different treatments might help us to find again. I'm butchering it. No, no, that's exactly that's exactly the idea that I was inspired by. You know, sometimes it gets misinterpreted, like some people have a balanced brain and some people have an unbalanced brain. Actually, I think every brain is a balanced brain. Every brain has this system of trying to balance and rebalance itself. It's just that sometimes this same process, this balancing homeostatic process, is using the wrong information, different information, biased information to balance itself. And that's shaping how you experience the world. Um, and I think as it has been shaped so it can be reshaped. And so I really think that, you know, one of the core messages of my book is that mental health is not a fixed state. It is. Flexible and changeable. And even if one particular intervention hasn't been the thing to change what you're constructing your balance out of, actually, there may well be others. They work on different aspects of this balance, different ingredients to it, but there are many routes in which is really, I think, a point of incredible importance moving forward when we develop new mental health treatments or figure out better ways of using the ones that we have at the moment. And I mean something that I really wanted, something I guess I was really curious about as I was reading your book again on this idea of balance, I was kind of struck by some of the by some of the ways. I guess it reminded me of ideas that I I've also thought when learning about psychological therapies and the, the links, I guess, with eastern philosophies. So sort of the idea of like, you know, where you, where you point your attention to may guide, um, what kind of life you live, what you know, the ideas, for example, from cognitive behavioral therapy that our thoughts influence, our emotions, influence our behavior, and then sort of Buddhist ideas of, you know, having the right, cultivating the right kind of thought, cultivating the right kind of action. And again, this idea of balance, I'm just wondering, was that an influence to you at all, or do you think about those ideas at all? And how how do they influence you if if you do, it probably was later on in the book, especially when I wrote about, um, mindfulness based therapies or cognitive behavioral therapy, I really did. I reflected on kind of previous traditions that have come at these ideas in quite a different way, perhaps a kind of like a biological way, but still often incorporating techniques that people find very, very useful in redressing this balance and targeting it. So I, I did think about it in that respect that this can be a very, very helpful framework for some people. Um, and. And I guess another way that you explore this idea of balance, uh, which was really interesting and sort of brings us back a bit to the, to to the dopamine ideas that got you interested, um, in this in the first place, but also other neurotransmitters is kind of the balance between pleasure drives, kind of what gets us the differences between pleasure and well-being and enjoyment. You know, the difference between winning the lottery and living a happy life. Um, can you speak to some of that in terms of how, you know, pleasure and well-being aren't necessarily the same, and how wanting something good isn't is similar in some ways to enjoying that thing, but but can also be quite different. Yeah, I mean I love all those topics. So that's why I spend almost the first half of the book talking about, you know, what constructs a sense of feeling good about your life, feeling well, feeling like you're mentally healthy, you know, where do these come from? And then I sort of think as well, that gives you a framework, a better framework than maybe we have in popular culture at the moment to understand where things can go awry. Um, and that's probably where I began when I started thinking about the role of pleasure, um, in mental health. I think maybe sometimes role of pleasure is almost trivialized or ignored. I do think pleasure is very important. How can it not be when it's central to mental health symptoms like anhedonia, a lack of pleasure, or lack of desire to motivate yourself to find something pleasurable? Um, so I do think pleasure is quite central. I also think it's different sometimes. Um, a pleasurable experience can cause a very short term change in your mental health, but I think thinking about sort of wider mental health is obviously more than just a single or a couple pleasurable experiences. It has to do with sort of, perhaps an overall expectation of pleasurable experiences among other things, or maybe an overall interpretation of your past experiences as being generally better than they were. Um, worse. And so that's. Where I thought about with pleasure. I do think everybody thinks about it when they think about mental health. Um, and I so I didn't want to ignore it, but I also think it is something quite distinct. It's not something that is, um, uh, you can't sort of use it instead of mental health. I don't think you can sort of replace ideas of mental health with sort of pleasure or lack thereof. It's maybe one little component, but an interesting, really interesting brain. And I was very excited to get to talk about the neurobiology of pleasure and sort of the ways of accessing the pleasure system, including some sort of quite surprising things about our endogenous opioid system in the body. Of course, the opioid system is also targeted by opioid drugs. Um, famously. But I was just as interested in the fact that there are sort of minor stresses that can target this system. People who like skydiving, it seems to be underpinned by endogenous opioids. Um, I talk about a great study by Lowry, Newman, Maher where laughing with friends when you're watching a video seems to depend on this opioid system. So all these, you know, really quite abstract or social things have this fundamental biological underpinning. And in this case, the opioid system, which I think is so fascinating. Um, and then I guess I felt totally differently about my reasons for writing about wanting and motivation, which is that I think it is completely ignored in mental health, even though, um, within the field, it's so essential that in some studies it's essentially all all you measure. In many animal studies, for example. Um, so I think that. What I call wanting or drive. You know, the the motivation to exert a behavior for some kind of reward. This is the most important factor for mental health in some ways, because it's the the thing that stands between you and any sort of experience. Um, how those mechanisms that we speak about in terms of antidepressant medication, you can imagine they wouldn't even necessarily have the ability to work on someone who wasn't re-experiencing the world around them in some way. So actually, these sort of drive and motivational mechanisms almost presuppose any other kind of thing you might want to intervene with, or you might want to improve when it comes to mental health. So anyway, so I wrote a whole chapter really diving into where drive and motivation comes from some really dark animal studies, some really fascinating patient examples like apathy in Parkinson's disease. And then I suppose some hopes for where I think this field is going. I think motivation is a really critical topic in understanding a number of different mental health conditions. It's often an area that is not as well targeted by our current treatments. Um, and I think it's a area that we really need to understand and be able to improve in future treatments. Mhm. How? How do you think we can get there? How are you thinking about that? So I think there are a few ways. Some of it I mean, ways we've actually talked about before involve some psychological therapies that when they work, they affect these sorts of mechanisms like behavioral activation. Sometimes it's about better harnessing of neurobiology during psychological therapies. And this is something that I'm really interested in in my lab. And my future work is the use of other interventions brain stimulation, but also medication, uh, concurrently with psychological therapy or um, concurrently with sort of psychological experiments, which is what you would call clinically something like, um, go out in the world and experience this thing that you've been avoiding or that you have sort of negative preconceptions about and, and that those mechanisms as learning mechanisms, I think, can be targeted with biological interventions and have access to these really important, you know, survival dependent motivational mechanisms that can sometimes be disrupted in mental health conditions. Um, so the so the I guess the idea is that you're, you're thinking about, ah, how how can we almost unlock, like you say, these survival mechanisms, you know, something that humans have evolved to have the, uh, the drive to go out and get things or do things, but how if they get somehow bogged down through illness, how can we get at them again through a combination of psychological and. Name was. What's the better word? Biological medical therapies. Yeah, quite. And I mean, I think even in the case of, um, I know there's some really interesting research, uh, going on at the moment. There's a big Wellcome trial run by my PhD supervisor, John Roser at UCL on exercise. And I think exercise has this incredible effect on depression. Symptoms for many people are really substantial robust effect size. Um, and it may work via these kinds of motivational mechanisms. But imagine patients at the absolute extreme where it would be really quite difficult to suggest or prescribe something like an exercise intervention. So I think we need to tackle motivation from different angles depending on the person, the severity of their symptoms, the degree to which motivation is core to their symptoms and so on. Mhm. Yeah for sure. I mean again I guess thinking, thinking to my clinical experience then um how many people say yeah sure. Like I know that I would feel better if I went and hung out with my friends or if I went for the run, but I just can't. I just can't get there. And again, this touches on some of the ideas that we've been discussing. Um. Over the last couple of weeks as we've been here together, which which I won't bring in today, but, um, I guess this is probably a good place to shout out to the Royal College of Psychiatrists who have enabled me to be here with you and discussing both your book now and and these ideas in general. Um, but I guess, as I, I guess, start to bring us, um, to round things up, but I wonder to I think this touches on all of the things that you've mentioned, which is the, the end, the ending of your book where you think, where you come back to this idea that whilst there are so many different ways in which we can fall ill, there are also so many different ways in which we can get better. And like you said earlier, you know, if one thing didn't work for you, that doesn't mean that that is the only that that that is the only avenue. So I guess how how do you think about how people can personalize their road to be it well being because things are okay, but they want to continue, um, feeling well or if if things have knocked people in their mental or physical health, how can they figure out a package of things that could help them. Because it sounds like from what you've been saying, it's quite personal. Yeah, I think this is the hardest question arising from my book. And obviously, if I could answer it, then there would be millions of people around the world who would be much better, and also lots of researchers who would be out of a job because they, uh, planned to be researching this for a long time. But overall, when I when I actually think about the sort of pragmatic implications of what what my book means, I would suggest two very basic things. The first is not to give up on the basis of something that hasn't worked before. So one drug not working for you, one therapist in one psychological therapy not working for you is not predictive necessarily of the next thing that you might try. And indeed, we are improving all the time with the kinds of things that we can, um, that we can do for mental health. So I do think that's quite an important message that because there are somewhat distinct mechanisms of these different interventions, one not working for you is not a very good grounds. By which to give up. And then the second thing I would say is that when something does work for you, I think you also have to hold that truth in mind that in fact, that doesn't necessarily mean that's the solution for everyone else. This is sort of I think one thing that patients find very difficult is when someone they know has found, like the solution for their mental health and sort of keeps telling them, but what about this? And why don't you do this? And so on. And, and I think it's very, very difficult when something has been successful for us to think, well, why isn't this accepted treatment, why isn't it working for my friend and so on. But actually, you have to remember that the opposite of that is also true. If you have found a something effective to you, you've done very well. You're very, very lucky in that respect, but it doesn't necessarily tell you who else it will work for, or even whether that's an evidence based treatment in the first place. As I spoke about before. And then the third message, which is for a much smaller group of people, but this is the message that I think this needs to be the direction that mental health is going in in the near future, within the next decade. I would like to see, you know, cheap, efficient ways that we can use to predict what will work for someone because you shouldn't have to try everything in the way I'm suggesting. You shouldn't have to maintain hope after ten failed treatments, we as a community of researchers like me and clinicians like you, should have a better ability to tell what is going to work for someone. And that's, in my view, a research priority. And then something that we need policymakers to get behind and help us disseminate into practice. Mhm. And I guess to, to finish today, um, I'm, I'm going to give you a choice of questions, uh, one of which is, is there anything that I've missed that you would like to tell us about? But I always, I always know that that's a bit of a that's a question that I hate if I'm ever asked it. Um, and so I guess if not, what what are what is your in your wish list for the future? Um, be that in research questions that you want to, you know, get the funding for or in kind of policy changes that you want to see happen. What would, in your view, help build that future that you want towards better personalization? Well, as suspected, I will take the second question. Um, but but it also relates a little bit to the first, because it's something that we haven't spoken about directly, but is very important to me. And maybe one of my deepest motivations for writing the book, which is that I think we as a society need to be using evidence, scientific evidence, to inform even very difficult decisions about very personal problems like mental health. I don't think that we should be using personal experience to necessarily inform policy, although of course it can be a motivation. I don't think we should be using kind of cultural beliefs, for example, about which drugs are or aren't fine to inform drug policy. Um, something I talk about a little bit in the book. Um, and I don't think that we should be using sort of who shouts the loudest with respect to psychiatric treatments as a way to determine whether or not a treatment is safe, whether or not a treatment is effective. Um, I think we need to take this really disciplined approach to our field. And sometimes, you know, we haven't spoken directly about psychedelic treatments. But that's an interesting example where we did something really wrong for a long time in suppressing research into psychedelic drugs, which may well prove extremely useful for mental health. I would also suggest that there are sometimes globally, efforts that are pushing too far in the other direction, that are suggesting this is a kind of cure all for everyone with a mental illness, which I think is really unhelpful, probably harmful. So in both cases, I think we need to treat even exciting new treatments like psychedelics like everyone else. Wait for the evidence base. Evaluate side effects. And I think same goes for our existing treatments. We need to treat them in a fair way. That is not kind of over informed by the, you know, exactly how these debates can go. And that was probably a really a deep motivation for writing it. Mhm. So in all things balance. Quite. Yeah. Um, Camilla, thank you so much for speaking to me. Thank you for your time. Um, and I think it's, as you pointed out at the end, there are so many things in your book that we haven't touched on. I mean, luckily we've scratched the surface with psychedelics just now at the end. Um, but there is so much more, including, you know, discussions about things like ECT, which is another treatment which kind of I think has fallen prey to the issues that you describe. Um, but way more detail about the animal research underpinning some of these things. That's presented in a way that is so understandable for anyone and so fascinating. And, uh, you know, a really cool window into the weird stuff that humans have done. So hopefully, um, if this is piqued your interest, then do have a read of the full book. Um, and is there anywhere else that people can find you, follow you if they're interested in hearing more from from you and how you think about the world? Yeah. I mean, you're welcome to shoot me an email. Follow me on Twitter. Um, I'm often giving talks in different places. I'd love to meet you or hear your ideas or your questions. Yeah, do get in touch. And actually, there's a really cool talk that talks about some of the stuff that we haven't talked about today, but on the Royal Society, Royal Society, I think YouTuber institution, Royal Institution. Yeah. My bad. Sorry. Uh, but yeah. So people can check that out too. Yeah. Thank you so much. I love writing it. So thank you so much for your lovely questions. Thank you. 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