New Books in Neuroscience: Camilla Nord, "The Balanced Brain: The Science of Mental Health" (Princeton UP, 2024)

Transcript

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Hello and welcome to the new books network.

This is Melek Firat Altay.

I'm a musician and a neuroscientist.

My research focuses on deciphering the path mechanisms of neurodegenerative and neurodevelopmental disorders.

Today I will be your host and we will be talking to Camilla Nord about her new book, The Balanced Brain, The Science of Mental Health, published by the Princeton University Press.

Camilla Nord leads the mental health neuroscience lab at the University of Cambridge.

Her research has been featured in the new statesman, the Daily Mail and the British Journal of Psychiatry and on the BBC.

In the balanced brain, Nord explains how our brain constructs our sense of mental health, actively striving to maintain balance in response to our changing circumstances.

While a mentally healthy brain deals well with life's turbulence, poor mental health results when the brain struggles with disruption.

But just what is the brain trying to balance?

Nord describes the foundations of mental health in the brain, from the neurobiology of pleasure, pain and desire to the role of mediating chemicals like dopamine, serotonin and opioids.

She done pivots to interventions, revealing how antidepressants, placebo and even recreational drugs work, how psychotherapy changes brain chemistry and how the brain and body interact to make us feel physically as well as mentally healthy.

Camilla, welcome to the podcast of today.

How are you?

How's everything going?

Very well.

Great to chat with you today, tonight for my time, et cetera.

A midday for me.

So how did you get interested in mental health?

First, in cling, I had that I was really interested in mental health, came from maybe a little bit of an unexpected place, which was when I was an undergraduate, I began learning about Parkinson's disease, not a mental health condition.

But what really compelled me about Parkinson's disease, what I found so fascinating, was that the same neurodegenerative condition could cause motor difficulties, but also changes in mood and related symptoms, things like apathy or syndrome.

And I found this so fascinating how the same brain networks, maybe even the same neurotransmitter could result in such different sorts of things.

And I think at the time, you know, probably I hadn't even really thought about what the neural basis of something like mood or emotion really was.

And so it felt almost kind of incredible that there was this link.

And so that was why I began studying it.

And your book, The Balanced Brain, what was your initial motivation in writing it?

I wrote The Balanced Brain because I felt that in the public dialogue about mental health, which is big and broad and we're talking about it all the time, we get some critical things really wrong.

The first thing that I think we get wrong is we separate this idea of brain and mind, of psychological and biological.

We say, oh, they're biological explanations for depression or biological treatments for depression like drugs and psychological explanations for depression like trauma and psychological treatment but psychological therapy.

This is such an artificial division that in neuroscience, you would never even talk about it.

You would just assume that both of these factors contribute to brain changes and contribute to recovery from disorders, which is true.

So I felt that it was really important to write a book on mental health from the perspective of neuroscience with that lens on it.

And then the second aim I had, maybe a secondary but related aim, was that there is this you know, permeating idea that physical health is separate from mental health and not just separate, in fact, better than mental health, more valid, more true.

And I really wanted to fight against that idea, not just for the kind of so-called quality of mental health conditions, but actually arguing that there isn't a true distinction between physical and mental health the way you might think about that mental health processes contribute to physical health problems and vice versa.

The physical components contribute to mental health problems.

And then I guess the very final thing that really motivated me at the time, especially, because it was a couple of years ago that I first started writing this, was I felt I was bombarded with articles about single solution cures for mental illness.

And I couldn't take it anymore.

I felt that it was really important to get across the message that there are probably multiple causes, but there are almost certainly multiple solutions for every mental health condition.

And between two people, things could be totally different.

And I just think moving against the silver bullet idea and towards an idea of individualized, personalized treatment is the way that medicine is going and it's the way that we in society should be moving as well.

So let's talk about how the brain constructs mental health.

So in the balanced brain, you put great emphasis on how the mental health is closely linked to our experiences of pleasure and pain.

So how does the brain experience pleasure and pain?

I wanted to begin talking about pleasure and pain for almost opposing reasons.

Pain because you never think about it when you think about mental health, even though it's critical to mental health and pleasure because you always think about it when you think about mental health.

And I don't think that's wrong.

It's only one component of mental health.

That was why I wanted to talk about these two, I think, core aspects of mental health.

And when it comes to the brain, both are really fascinating.

So in the case of pain, I'm interested in it from the perspective of mental health because it has this bidirectional causality with mental health, meaning if you have a chronic pain condition, you're more likely to experience mental health condition like depression.

You know, you might tell me.

And but the same is true in the opposite direction.

If you have a mental health condition like depression, that actually predisposes you to experience chronic pain in the future.

And the reason for that is that there are neural risk factors changes in your brain in a variety of regions and circuits that seem to predispose, put people at risk for developing a chronic pain condition if they also have an injury or an acute pain condition.

When it comes to pleasure, the neural mix is a pleasure.

It's a little bit different and I think fascinating for different reasons.

So one of the aspects of pleasure that I talk about in the book is this idea of pleasure hotspots all around the brain in a slightly individualized map.

We'll have them.

And and these hotspots form a kind of archipelago of places in the brain that are immediately activated by pleasurable experiences.

And by that, I mean, they're not just coincidental.

They're not just related to other things that might happen at the same time as a pleasurable experience, but they seem to be at least necessary in causing that experience or unique in causing that experience sometimes.

And and I felt it was really important to kind of illustrate this immediate, this sort of very distributed, but also very personalized pleasure map that we have in our brains as a kind of first step in understanding why our mental health might be so personal.

It's actually very interesting that you mentioned Parkinson's disease because although it's a neurodegenerative disease that primarily affects the brain, one of the hypotheses that exists nowadays is that it initially is propagated from some abnormality in the gut.

So I was wondering, can we find similarities in relation to mental health and other bodily experiences?

Yeah, I think that's such a fascinating theory and of course a fascinating suggestion more broadly.

There's this contribution of organs throughout our body and peripheral nervous system and its ability to communicate these bodily signals to our brain in mental and also neurological health conditions.

So there are a few reasons why we think this might be the case.

One is something we've known for quite a while, the experience of bodily state differs across different brain health conditions.

So that means that if you were to measure it, your detection of your heartbeat, it might be different.

Maybe you have amplified detection of signals from the stomach, maybe suppressed signals from the stomach and so on.

This is called interception, the sense of the internal condition of the body.

But there are also more direct signals that are themselves disrupted to not just the brain's perception, but actually potentially in some of these conditions, the signals themselves are weaker or stronger and that actually opens up a path for possible modifications.

That is to say, if there are disruptions in the gut or elsewhere peripherally than are crucial to some mental health conditions, that could give us a new route into treating those mental health conditions.

And I did an experiment along those lines actually around the time I was writing a book where I had this idea.

The idea was maybe the reason why the emotion discussed is often in emotion science considered very distinct from other negative emotions.

For example, we habituate to fear of things don't feel as scary after we see them again and again, but it doesn't happen with disgust.

People still feel disgusted time and time again.

It doesn't really go away.

And then you see the same phenomenon clinically.

You can use clever techniques like exposure therapy, very, very effective for traumas that come out of fearful experiences, not so for traumas that come out of disgust based experiences.

It seems sticky or more intractable.

So I wondered if maybe one of the reasons that was exactly as you say this contribution of bodily signals to our emotional mental experiences.

And so I used a what's called a psychopharmacological approach, i.e.

I gave people a drug.

It was a slightly unusual study in that field in that the drug only affected the stomach.

So it didn't affect the brain.

But in affecting the stomach, that was on purpose because in affecting the stomach, I found a change in people's disgust avoidance, meaning that this was a kind of peripheral root, gut based root to weakening this intractability of disgust.

So what we're doing now is we're testing this in combination with clinical therapies like exposure therapy, with the idea that if you're targeting someone's avoidance, but you're via exposure, but you're simultaneously reducing, suppressing this peripheral signal and coming from the stomach associated with disgust.

That could make disgust a little bit more susceptible to the kind of learning processes that happen during the exposure to on learning beer.

A major part of the balanced brain also deals with means to enhance mental health.

And you discuss the use of antidepressants and the effect of classibles or psychoactive drugs.

So how do the antidepressants work actually?

So I decided to talk about antidepressants in the balanced brain.

Even though I would really say the balanced brain is for everyone.

It's not necessarily just of interest to people who have personally experienced mental health conditions.

I really intend it to be informative for all kinds of mental health experiences across the kind of healthy and less healthy side of the spectrum.

But many, many people at some point in their life will take an antidepressant.

And so I thought it was important to tell people why they work.

And we used to have slightly the wrong end of the stick about this.

A very popular theory before I was a student really when I was growing up was this theory called the serotonin deficit hypothesis, which is the idea that brains of people with depression don't have enough serotonin.

And so we should fix that by giving people serotonergic medication.

The most common class that's antidepressants does indeed do that.

Rave levels of serotonin in the brain.

This is, you can see, borrowed a little bit from diseases like Parkinson's disease, where a deficit in a neurotransmitter dopamine is genuinely treated by administering the amino acid precursor to that dopamine and neurotransmitters.

So in the case of serotonin, you can see what they were thinking.

They had a drug they knew, and they actually found this out accidentally, which I talked about in my book, and they knew it could treat depression, at least in some people.

And so they came up with a hypothesis for why that might be.

Now, today, I would say there's a lot, a lot, a lot, a lot of evidence testing this hypothesis, and the evidence is still very weak in support of the idea that people with depression have a deficit of serotonin in the brain.

I would suggest it's probably not the case, at least not in most people.

It still seems to be important to the mechanism of action of antidepressants, because if you deplete serotonin in people who've responded to drugs, well, they get depressed again.

So there's still an important role for serotonin, but I don't believe there is a deficit.

Instead, the most compelling explanation I think for why antidepressants work is that a single dose of antidepressants is not enough to change your mood, but it does change something.

It causes small changes in your perception and interpretation of the world around you.

For example, you're walking down the corridor, a colleague blanks you.

Do they hate you or are they just on the way to a meeting?

So these kind of ambiguous scenarios that actually we experience many, many, many of throughout the day.

What our brain does when encountering ambiguity is it can tend towards one side of an explanation or another.

And in depression, there's a tendency towards explaining things with the more negative explanation.

And this is the cognitive target of antidepressants.

Antidepressants seem to shift people towards a more neutral or even a more positive in some studies explanation for these events in the world around them after a couple of days, maybe after a week before they start to affect your mood.

You need many of these experiences, as you imagine, until your mood is affected.

But this is one way of quite a low level, changing the way you experience the world.

And thereby having kind of knock on effects on something as big and broad.

Fascinating.

And do you think these psychoactive drugs have potential in improving mental health conditions, or is it just a huge hoax?

And where are we wasting our time putting research into it?

You know, I've been very interested in the rise of psychedelic and psychedelic like drugs over the past decade or just over a decade.

In the beginning, boy, was everyone skeptical.

Everybody was like, wait a second, there must have been a reason.

We stopped using these a while ago.

You know, also legally, they were just enormously illegal and difficult to get a hold of and almost no labs could.

So there was really a lot of resistance from the scientific community.

I think there has been a sea change in people's kind of openness, even very traditional psychiatric and medical bodies openness to the potential utility of these drugs.

I think from a public perspective, there has been like an absolute sprint to the finish line and total enthusiasm for the clinical potential of psychedelics and mental health treatment.

And I think, you know, that excitement may be a little bit unwarranted at the moment.

I think we're in the early stages of new class of drugs that could hold potential for mental health treatment.

But I'll give you some examples of why I am, you know, very supportive of the work but more cautious than some researchers.

So one reason is that it's so difficult to do a proper trial of psychedelic drugs because in most cases, you cannot do them in a blinded way, meaning you and the patient don't know what drug you've taken.

You can do this with antidepressants and the placebo effect is very strong, as you can imagine.

The placebo effect does exist for psychedelic drugs, but you always know essentially what condition you're in.

If you've had a psychedelic, I don't think anybody would guess that they were in the placebo condition.

And that's a problem because that means from a scientific and clinical point of view, you cannot decouple the effect of the drug from the effect of expectations.

And one of the crucial themes of my book is that the effect of expectations is powerful.

It can cause transformative treatments, results on its own.

So that means that the best trials, the future trials, will need to find a way to tease those factors apart.

And then there are also kind of more niche, more nitty-gritty issues with some psychedelic research.

For example, many trials only include people who've taken psychedelics before, so it's a kind of self-selecting example who are enthusiastic about psychedelic drugs, so that could overestimate effect biases.

And trials are starting to remedy that.

Trials should use an active control condition, which would mean another drug that was somehow psychoactive, and that would help with the blinding issue.

So there are all kinds of fun, little nitty-gritty effects that the field could do better.

But I think it needs to before we have the level of enthusiasm.

And of course, it's worth mentioning side effects.

I don't think psychedelics, or I've mentioned anything, is a silver bullet.

And I think psychedelics have really neatly slipped into this category of being a potential silver bullet for mental health.

And I think that is highly unlikely, you know, really potentially impossible, because actually they work, I think, quite well for some patients, and they work actually quite poorly for others.

And maybe picking a path who those patients are should be one of the field's priorities in the next five years.

Indeed.

So we'll see how that goes.

So with the antidepressants, you mentioned that it does have an effect on us by changing our perception.

Could we also say that, for example, psychotherapy has a similar effect vice versa in the sense that psychotherapeutic experiences that we have might have physical impacts on our brains?

Yeah, I agree with that.

Absolutely.

There are measurable effects of psychological therapies.

In some of my own research, they affect neural areas, areas in the brain that are similar to but not identical to the areas affected by antidepressant drug, meaning both psychological and drug therapies alter the brain, but in slightly different ways, maybe even ways that could be complementary.

So sometimes a combination of the two therapies is actually the best approach for some patients.

So maybe they work in kind of slightly different ways.

And from a psychological point of view, I think the idea that they work in complementary ways is also supported.

So that kind of low level perceptual change that happens in depression, that's not the level that most psychological therapies like say cognitive behavioral therapy work on.

It's rather it's kind of top down approach where you're focusing on someone's general beliefs and interpretations about the world.

And then that will, you know, almost certainly have trickle down effects on things like how you interpret your day to day experiences.

But it's less about the minutiae then cumulatively building up into the whole and more about deliberately targeting maladaptive and challenging beliefs that someone might have about the world that are contributing to this.

It's been a fascinating discussion and I'm really interested in the interaction of the brain and mental health.

I'm wondering, are you working on a new project related to this topic or what's your next project?

Well, I am really in worst in my lab research at the moment.

So and I'll tell you a little bit about that because I'm hoping it may be something I can write about in a book in the future.

But at the moment I'm focusing on the experimental science.

So what we found recently, and I don't talk about this at all in the balanced brain because it is new, new, new is there is this interaction between metabolic health and mental health.

And this was already apparent in demagogical studies.

So you can look at the cross-sectional studies and diabetes and depression, for example, are highly comorbid.

But people have always thought really simplistically about that association.

Oh, I guess they're maybe like lifestyle factors that can predispose you to both or, you know, maybe we need to think about socioeconomic factors and so on.

These are relevant.

But what we're finding, which is really kind of incredibly interesting in the topic of brain effects of mental health, is that in fact some of these metabolic factors, like, for example, insulin release and how well you regulate glucose responses to glucose challenge, these are actually related to what's happening in the brain.

And so perhaps not unsurprisingly, that then changes how you process the world around you, not just food.

It's having a cognitive effect.

So your metabolism in your body seems to be related to your ability to process the world around you.

This is new work that we're doing, but it's really compelling because it suggests that there may be kind of brain and cognitive commonalities between metabolic and mental health.

Wow.

I'm looking forward to reading your next book, actually.

Camilla, thank you so much for being with us today.

Thank you so much for having me.

It was a real pleasure.

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