Instant Genius - Your brain chemistry and you, with Ginny Smith

Episode Date: June 15, 2021

Science journalist and presenter Ginny Smith tells us about the chemicals that run your brain. Once you’ve mastered the basics with Instant Genius, dive deeper with Instant Genius Extra, where you��ll find longer, richer discussions about the most exciting ideas in the world of science and technology. Only available on Apple Podcasts. Produced by the team behind BBC Science Focus Magazine. Visit our website: https://www.sciencefocus.com/ Hosted on Acast. See acast.com/privacy for more information. Learn more about your ad choices. Visit podcastchoices.com/adchoices

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I'm Dan Bennett, the editor of BBC Science Focus magazine, and in this episode I'm joined by science journalist and presenter Ginny Smith. This new book, Overloaded, dides into the mind-blown world of brain chemistry. So here's everything you really need to know about the chemicals that run your brain. I think it's a given that most people understand the brain as a sort of electrical thing, you know, nerves sending impulses around the body, brain cells firing. But something that you get across really well in your book is that just as important, or if not more important maybe is brain chemistry.

So can you just tell us what do we mean when we talk about brain chemistry and why is it important? So as you say, the individual neurons send their messages via electrical signals. Although if you wanted to be really picky, you could argue that electricity is chemistry because it's the movement of ions of charged particles. But what we tend to mean when we're talking about brain chemistry is actually what happens between the neurons. So your brain is made up of billions of neurons in this huge network, but they don't actually touch when they meet most of the time. Instead, there's a little gap which we call a synapse, and the signal has to get across the synapse. And the most common way that this happens is by

the first neuron releasing chemicals and the second neuron having receptors at its edge, which can receive those chemicals. And that can tell that second neuron what to do, whether that it should fire or that it shouldn't fire or various other things as well. So while the electrical part of the brain is really important and your brain couldn't function without it, it's the synapses that allow really quick minute by minute, second by second changes in the brain. And that's why I think they're really interesting when you're talking about human behaviour. I thought it was really interesting. Despite being a psychology graduate, I have to admit I didn't know this.

The discovery of the synapse, so this little gap that we're talking about, it was actually a very physical thing. Can you just talk about how scientists discovered it was there? So it was actually this huge row at the time. So there was this really well-established scientist called Golgi, who discovered all sorts of things. He's got an apparatus,

which is a bit of a cell named after him. And he thought that the brain was a network of connected kind of tubes through which information could flow. He didn't think there were any gaps. And that's partly because the microscopes at the time were only so good. So they could zoom in and they could see the individual cells, but they couldn't see the tiny gaps between them. And then this kind of new upstart scientist came on the scene.

Santiago Romano, Romano, oh, I always say his name wrong. I was definitely going to let you pronounce that right, that one. Santiago Raman Ikehahal, I believe it's how it's pronounced. And he was not only a scientist, he was also an artist. And actually, I think that was really important for the discovery that he made, because one of the things he was incredibly good at was making observations about the world. So he'd done a lot of anatomical sketches and stuff as a child. Then he was trying to understand the brain and looking at it under microscopes and going,

I just can't see this clearly enough to really understand what's going on. So he adapted a stain that Golgi had introduced and created this new stain. And what do I mean when I say a stain is that scientists do kind of chemical reactions which change the color of neurons so that you can see them under a microscope. But up until this point, they'd only found reactions that would change every neuron. So you got this really intricate web appearing. But the new thing about this particular stain was that it only stained, I think, about one in ten neurons, certainly only a proportion of them.

And that meant that you could actually see the individual neurons a lot more clearly. So Cahal started doing all these incredibly beautiful detailed drawings. And if you've never seen his drawings of neurons, I highly recommend Googling them because they're just stunning pieces of artwork. But he could see while doing this very clearly that there were these gaps. But Golgi never believed him.

There was this argument was raging for certainly, I think, a couple of decades. And the two of them actually won the Nobel Prize together for this kind of discovery, this reaction that was Golgis and then Kahal kind of tweaked it. And if you read their speeches at the acceptance award, it's, you know, when scientists are like shady about each other, but very polite. Yeah, Kanye and Taylor Swift. Yeah, it's sort of, it's all very polite, but there's a definite undercurrent in there. And actually, Golgi died never believing Kahal's findings. and it wasn't until electron microscopes, scanning electron microscopes were developed,

that we knew for sure that Cahal was right because they allowed us to see neurons in such high resolution that we could physically see those gaps that Cahall thought he could see from his reactions. So it's a really interesting story, I think, not just because these were two highly respected scientists who completely disagreed on a really basic fundamental of neuroscience, which is something that still happens today. But also that it was the technology that was driving our understanding and that was holding our understanding back. And it was the developments of new technologies

that allowed us to understand the brain better. And that is actually a theme that kind of kept coming up in the book that looking inside the brain is not an easy thing to do and you need the right technologies. And sometimes technologies can be a bit misleading. And it's also interesting as well because, you know, artists were so fundamental as well in anatomy and just that skill of observation was so crucial to our understanding at that time. So there's a really good example in the book that kind of, I suppose, explains the importance

and the function of chemistry and what goes on in those synapses. And that's where you explain a chemical called glutamate and one called GABA, GABA, GABA. could you just unravel that for us and explain how those work? Yeah, so glutamate is the most common chemical in synapses in the brain, but I feel like it sometimes gets left out of the story because it's sort of the workhorse of the brain. It doesn't do as much sort of the nuanced, interesting stuff as some of the chemicals will probably get on to talk about later, but your brain couldn't function without it. So glutamate is basically the go signal.

If you've got one neuron and it releases glutamate and a second neuron accepts that glutamate, receives it, the signal will be sent. So we call synapses that use glutamate excitatory synapses. We say that it excites the next cell and makes it more likely that it will send its electrical signal. And that's what most neurons in the brain do. Gabba is what we call an inhibitory neurotransmitter. So it does the opposite. If you've got a synapse that a neuron that releases Gabba into the synapse, it's going to make any neurons it connects with less likely to fire.

So glutamate is vital for almost every process that our brain does, but particularly for things like learning. When you're learning something new, you're activating neurons. And glutamate is one of the kind of vital ingredients for that. Gabba has a sort of calming effect on the brain. So it's really important for sleep. It can, has a role in sort of reducing anxiety, those sorts of things. So kind of, yeah, big scale, glutamate activates, GABA reduces activation.

And something you get across really well, which is, I suppose, a little bit of a, one of those things that's dispersed into pop culture is that, you know, if you have not enough serotonin, it's bad or if you have, you know, too much, if you've got loads of dopamine, you're happy. But actually, as you've just sort of alighted to there, these chemicals are used in, they're not just used it for one thing, they're not wasted, they're using lots of different things. And so am I right in saying that there's, for every chemical, there's lots of different uses and they're also part of systems, aren't they? Yes. So I kind of started the book thinking that for each chapter, well, each chapter I look at a kind different aspect of life. And I started writing it thinking there would be one kind of hero chemical

per chapter. And as I got further into the research, I realized that is totally not how it works. And the same chemicals were coming up in four, five, six chapters. And yet, coming up over and over again. And as you say, these chemicals don't just do one thing. And they can actually have completely different effects depending on where in the brain they're released, depending on what receptors are on the second neuron, because there can be multiple different receptors for each chemical, and the different receptors can cause the neuron to do different things. It can vary based on how long it's being released for,

what rate it's being released at. And the other thing that I think is really important and that often gets missed out is we have this idea that if it's true that being low in something is bad, then having more of it must always be good. And that's not the case when it comes to the brain. Yes, if you have low levels of a certain neurotransmitter in a certain region of the brain, that might cause problems. But that doesn't mean that for everyone boosting it is good. Having too much can also be bad. So the brain has a bit of like a Goldilocks, for each chemical in each region. So if we think of Goldilocks's porridge, say you're having a porridge with no sugar and that's not very tasty, but if you completely douse it in sugar, that's also not going to be particularly tasty. You've got to find that that middle point of it having just the right amount of each chemical

for the brain to function optimally. And you, the first, so to touch on those chapters that you talk about where you, you know, you try and look at different elements of life. I think it's really nice that you started with memory as one of the things, because it's like I say, we have in public, in pop culture, we have an idea of serotonin and other things, but we don't think of brain chemistry much when it comes to memory. So how does brain chemistry work when it comes to memory

and how we remember things? So the basic way in which you form a memory is by strengthening the connections between neurons. So each memory, each long-term memory, is stored as a network of neurons spread across the cortex, the outer layer of our brains. And when we say network, what we mean is that those neurons are very strongly connected to each other. They have strong synapses. And what we mean when we say they have strong synapses is that those synapses have changed the way they release and receive chemicals. So let's say before you start learning something, you activate this neuron, it releases a little bit of glutamate. The second receptor has a few, second neuron has a few receptors.

So after enough has been released, it's received it, and the signal gets sent. Now, if you keep activating those pairs of neurons together over and over again, both neurons start to change. So the first one actually starts making more glutamate. So when the signal comes in, more of the chemical is released. And the second neuron starts building more receptors so that it can kind of more quickly mop up what's there and send its signal on. So what happens now is that activating that second neuron is a lot easier. And you can actually kind of feel this happening particularly well when you learn a new skill. So when you first try to ride a bike or drive a car or play the piano, it's really difficult.

And you have to think about every little thing that you're doing. And it's hard work because those connections between neurons aren't very strong. But if you keep practicing it over and over again, those connections become much stronger. It's a lot easier for the signal to pass. And suddenly that skill sort of feels natural to you. And that's this strengthening which relies on changes in those chemicals. And so is that what, you know, when you hear about memory enhancing or performance-hancing drugs in the news, particularly around exam time with poor stressed out students, things like metafinil,

is that is that the process that those drugs are trying to hack their way into? What's really interesting about that is that no one knows how modafinil works. So I tried to find out. I wrote a section about these kind of cognitive enhancing drugs. And there is evidence that methanol changes a whole host of different brain transmitter levels in the brain or affects a number of systems. But no one is quite sure how it has its effect on concentration and wakefulness, which is kind of amazing. Although the further I got into the research, the more I realized how little we actually understand a lot of the mechanisms of drugs and how they affect the brain. So the evidence does seem to be that modafinil does boost alertness and concentration, even in people who are quite sleep-deprived. So there is some good evidence that medaphanal can work. Other cognitive-enhancing drugs have a lot less strong evidence for them. So the most commonly used ones,

things like Ritalin, which are amphetamines, which kind of ramp up processes in the brain cause the release of various neurotransmitters. But when I looked at the studies that had actually done kind of controlled double-blind studies on giving people these drugs and looked at performance, it seemed that they were boosting people's confidence in their own performance more than they were boosting their actual performance. So you might feel like you're being really productive and getting loads done, but actually the amount people got done was not that much better than those who weren't being given it, which I found quite interesting. So the jury's still out on whether it can help people who don't have a diagnosed condition because, of course, these drugs were introduced

for people with various different conditions. So Ritalin is an ADHD drug, and it definitely helps people with ADHD. But again, this is about that Goldilocks point. So if you are below average on whatever it's doing, then boosting it is good. If you're already at your peak performance, actually boosting levels of something might make you worse. So we get this ceiling effect that we call it, where there is a kind of an optimum point and you can't necessarily get above that, even if you find something that does help bring people up to that point. But I think it's also really important to kind of mention the risks with these kinds of things, that we have short-term safety data.

We know that they are safe for adults to take in the short term. There aren't studies following people who take them for 20 years, because you can't do that kind of study. And there are also very few studies on young people who don't have a diagnosed condition taking them. And we know that our brain kind of fights back against whatever you do to it. So we become coffee, for example. The first time you drink coffee, it gives you a huge burst of energy. Over time, your brain adapts to it and it doesn't have that same effect.

So the same might happen for these drugs. We don't know. and actually what happens with coffee is that over time you need it to get back up to your baseline. So there's a chance that if you took these drugs for a long time and then stopped them, you might be worse off than you were to start with. And we also don't know what they might do to a developing brain. And our brains don't stop developing until our mid-20s. So I would be very hesitant to take them.

And particularly I'm concerned about their use in universities in people whose brains are still developing because we just don't have the data to know how that might affect them. Absolutely. I was about to say that, you know, that effect you were talking about is probably very, feel very familiar to anyone who drinks a lot of coffee and feels the effect wear off. And you do eventually get to a point where actually the caffeine can make you feel more tired simply because once it leaves your body, you're actually at a lower kind of energy level you were than before you started drinking it.

So I suppose an area where we're arguably a bit more sort of familiar with the effect of neurotransmitters and brain chemistry is depression and serotonin. Antidepressants are kind of widely known about what's the role of serotonin there? Because I think often there's an idea that low serotonin equals I am unhappy. But you clear that up in the book. I think clear that up is a bit perhaps an overstatement. I was actually really surprised to discover that the low serotonin hypothesis is not something that came from directly looking at serotonin levels in the brain. And partly that's because it's actually really difficult to test chemical levels in someone's brain. The brain is separated from the bloodstream by the blood-brain barrier.

So a lot of neurotransmitters stay in one or the other. there are some that can pass through. So it's not easy to do a test on someone who comes in with depression and say whether they have low serotonin. The hypothesis actually came kind of the other way round to the way you might think. It came from the drugs. So drugs were discovered that either lowered or boosted serotonin levels and clinicians noticed that these had an impact on people's mood. So they hypothesized that if by giving you a drug that boosts your serotonin, I make you feel better when you're depressed, that must mean that you were depressed because your serotonin levels were low. That isn't necessarily the case. I mean, if you came in with a broken leg and I gave you morphine, your pain would feel better. But that doesn't mean your pain was caused by a lack of morphine. It was caused by a broken leg. So the kind of the logic there,

it's missing a step in a way. And there have now been lots of studies that have been trying to unpick it. And it turns out the relationship, there does seem to be a relationship between serotonin and depression in at least a proportion of people. But it might not be quite as direct as they thought. And one of the things that kind of gave us this hint that it wasn't quite that simple was that SSRIs, which are selective serotonin re-uptake inhibitors, boosts the levels of serotonin in the synapses really quickly because they block off the machinery that recycles left over serotonin, basically. So as soon as it's released, there's more of it hanging around in the synapse

because nothing's sucking it back up like it normally does. But people who feel better on SSRIs often don't feel better for about six weeks after they've been taking them. So why would there be such a long delay if they were low in serotonin? within a few hours, there should be more serotonin. So that kind of gave us a hint that there might be something more complicated going on. And there are now a whole bunch of different theories as to what that more complicated thing might be, some of which I go into in the book.

But the answer is we still don't know for sure what causes depression chemically, molecularly in the brain. And I think it might have multiple causes. And it might be that in some people, it is low serotonin, but it might be that in others, there's a different mechanism behind it. And we know that not everyone responds to SSRIs. So it might be that that's because some people, that's not their problem. And actually a different drug would work better for them.

And then just lastly, addiction is something I just wanted to touch on, because again, it's something that I suppose is quite common in pop culture and people quite familiar with. It's sort of the, I suppose, the consequence of, you know, it's the other side of this story of brain chemistry, so when brain chemistry goes a bit wrong. So in terms of neurons and synapses, could you just describe what happens chemically when we become addicted to,

I mean, take a substance of your choice? Because, again, it's different depending on what the addiction is. Yes, that was what I was going to say. So there are a few different things that can drive addiction. one of them we think is this tolerance that we kind of talked about a little bit with caffeine. So, for example, with opioids, things like heroin, once you start taking them, your brain downregulates the receptors for those chemicals that it causes the release of. And then when you stop taking it, you're not naturally producing as much of that chemical as you should be and you don't have as many receptors. So you get all these horrible side effects.

and that drives people to keep taking it. A lot of drugs that can be abused do cause the release of dopamine in the brain. And this is why people think of dopamine as sort of the addiction chemical. Again, it's a bit more complicated than that, but dopamine is all about motivation. So it drives you towards a goal. And in a healthy person, your dopamine might drive you towards food when you're hungry and water when you're thirsty and getting a promotion at work and lots of different things and it can vary. But if you take a drug like cocaine that causes a huge amount of dopamine to be released,

your brain thinks that you've just done something that's really good for your survival, like drinking when you're thirsty. But because those levels of dopamine are so much bigger than you would ever get naturally, you can get this kind of spiral forming where your own motivation your only drive is to seek out more of this drug. And that we think is one of the things that drives addiction. But again, it's very complicated and it's not just one chemical system that we think is implicated in addiction. We talk about systems in the brain a lot now. And this has kind of moved on from 10 years ago when neuroscientists were talking about areas of the brain. It's now all about systems. But one of the really important systems for a

of different areas is our prefrontal regions which kind of exert control over some of the areas further back. So this is important for mood regulation because your prefrontal region can control your limbic system, which is involved in emotions. But it is also important for drives and motivation and addiction because your prefrontal region can exert control over the kind of the bit of your brain that goes, oh, give me that. I want that thing. So if you're you've ever said no to a second piece of cake, that's probably your prefrontal region going, calm down, there'll be cake another time, we don't have to eat it all now because our kind of ancient evolutionary systems are telling us to eat all the cake right now because we don't know

when we might see cake again because cake is a really rare thing in evolutionary terms. So we also think that this system goes a bit wrong in addiction and it might be something about the drugs themselves that damage the prefrontal region or it might be. be a kind of more diluted process that over time happens. But it seems that addicts have less active prefrontal courtes, so they're less able to inhibit these drives as well. So it kind of escalates the problem. And that's one of the reasons drug addiction can be so hard to get over. And that's one of the great things about your book, I think, because as a science journalist and as a psychology grad, you often have lots of conversations with people who, you know, ask about

serotonin or dopamine. And it's, you know, I kind of want to show them this book to say, no, look, it's all about systems, not just one linear thing. You can never, if someone comes at you saying, you can do this one thing and it will change your brain in this way. You should always be a bit cynical. Yeah. And it was such a luxury having a whole book that meant that I could actually go into the idea that, well, there's this theory and then there's this competing theory, but actually we could look at it this way. Because when you're writing articles, you just don't have the words to do that. So while I do kind of want people to take things with a pinch of salt when they read them in the media, I don't actually blame the journalists

because I've been there as well and you've only got 200 words and you have to simplify these things. But yeah, that was one of the really nice things about the book to have the space to go into a bit more nuance. And so just lastly now, I just, you touched on this earlier that part of this is a story about technology, about how we have opened up new ways to see the brain and understand what's going in there, because obviously experimenting with brain chemistry could be quite tricky, probably quite harmful. So I just wanted to get a taste of how much do we have left to discover and what's on the horizon

in this area of study. think there is a huge amount left to discover. As I say, we've kind of recently moved from this idea of regions of the brain, which basically arose because fMRI was invented, which allowed scientists to put people in a brain scanner, see where the blood was flowing when they were doing certain things and say, okay, this area is more active. But the original fMRI machines weren't very high resolution, so you got these kind of blurry blobs. Now we're realizing with higher resolution ones. Okay, so there's this big blurry blob here, but then there's a smaller one here and a smaller one here. So actually this is a system, a network. I think as we get higher and higher

resolution scanners and things, we'll be able to see those networks in more detail. And the human connectome project that's going on at the moment is aiming to map every connection in a human brain, which is a huge project. And I think that's really exciting, as well as the images that they're producing are absolutely beautiful, just showing the intricacies of those networks in the brain. But I think that's a really exciting area. I think one of the areas that I'm kind of hopeful for in a, it might really help people in the future is the kind of area of targeted and potentially also personalised medicine. So we talked about depression a little bit earlier, and I mentioned this idea that different people might have different causes of the same symptom, depression.

But at the moment, we have no way of telling them apart other than doing trial and error with different drugs until we find one that works for them. And that can take months, which is awful if you've got really bad depression. You don't want to be spending months trying different drugs, which might make you feel worse rather than better. So the idea that we might be able to develop tests that could tell you, what the underlying cause was. And there are some in development. So there's been some research into a blood test for inflammation because it seems like inflammation can lead to depression. And people who had high levels of inflammation were less likely to respond to certain drugs. So that's really exciting. There was also a brain scanning study that showed differences in brain

activation after just one dose of SSRIs in people who would go on to respond to that SSRIs. so they weren't feeling better yet, but their brains looked different. Now, these aren't in clinical use yet, but they could be, and that could really help people. So the idea of kind of being able to personalise your mental health treatment based on your brain. But then the other half of that is targeting because drugs at the moment, they affect chemical levels all throughout the brain and often the body as well, which is why they can often have nasty side effects. So if we could find a way to just affect the neurotransmitter levels in one region of the brain, the region where those levels were wrong, let's say, or had gone out of whack,

then we might be able to give people lower doses of drugs, and they also wouldn't have such systematic side effects. And there's loads of really exciting research going on in that. it's really difficult to get drugs into the brain in the first place because of the blood brain barrier. So then how you direct them to a part of the brain. And there's all sorts of wacky ideas from nanotechnology and magnets and ultrasound and all sorts of cool things going on. So I think we're a little way away at the moment. But I'm hopeful that in the future that those two things together might make a huge difference in mental health treatment.

That was Ginny Smith there, revealing how brain chemicals influence our lives. If you want to hear Ginny and I dig a little deeper into the science of brain chemistry, check out Instant Genius Extra, a subscription podcast available on Apple's podcast app. There, we talk about the people who feel no pain, what brain chemistry has to do with hunger, and whether brain-enhancing drugs might one day be commonplace. And of course, the best way to discover more about the inner workings of the brain is to check out Ginny's book, Overloaded, how every aspect of your life is influenced by brain chemicals. Thanks for listening. The Instant Genius podcast is brought to you by the team behind BBC Science Focus magazine, which you can find on sale in supermarkets and newsagents now. Alternatively, do come find us online at ScienceFocus.com.

See you next time. This podcast is sponsored by Name, Audio and Focal. The texture and emotional depth of music can be lost through digital sources or poor signal. Name Audio believes you can have digital precision with analogue warmth. Alongside French acoustic specialist focal, Name creates high-end audio systems, combining innovation with craftsmanship, so you can listen to music, just as the artist intended. Discover more at Name Audio.com.

In a place like Los Angeles, people don't stop being who they are. Writers, thinkers, creators, people with stories still unfolding. That spirit lives on at Kingsley Manor, a community shaped by individuality, creativity, and lives well-lived. So when the conversation turns to what's next, it isn't about stepping away. It's about continuing the story. Explore your options at kingsley Manor.org, a nonprofit month-to-month senior community within the Front Forch family.