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Narrator: Thanks for joining me for Life Solved, from the ºÚÁϳԹÏ. In this series, we're bringing you conversations with brilliant researchers and scientists about the world-changing work they're doing. Whether it's in science, the environment, security or society, work at ºÚÁϳԹÏis decoding how our world works and combining ideas to find the bigger picture.

Narrator: Today, our guest is challenging the idea that our emotions and mental experiences are somehow separate to our bodies.

Jerome Swinny: What we now understand is that things like mental illnesses have physical constructs.

Narrator: Professor Jerome Swinny explores how the physical development of our brains is shaped by our life experiences.

Jerome Swinny: The mind is just the last frontier. You know, we've made such huge strides with so many diseases, things like epilepsy, which are kind of neurological. So things that, so brain function that are similar, uniform across, individuals like the way we walk, you know, things like that. But I think when it comes to the mind that is so individual, you know, the way you think, the way you see the world. And if the way you see it is in a way that could be detrimental to you, that's a very unique disease.

Narrator: In this episode, we're finding out why the key to our mental health might lie in the way our brains respond physically to the world and our experiences. Kate Daniell found out more over a coffee.

Narrator: Professor Jerome Swinny has been curious about how our bodies connect with our experiences ever since he was a child.

Jerome Swinny: I've always just wanted to know how things work and the body. And so I think it must have been 10 or 12 and I knew I'd be doing this. Precisely what I'm doing right now.

Narrator: Jerome works at the School of Pharmacy and Biomedical Sciences here at Portsmouth.

Jerome Swinny: What I'd like to know is I would like to understand the fundamental biology of our nervous system. How does our nervous system work? So this includes all aspects of our nervous system. So the brain as well as the parts that are in the rest of the body.

Narrator: We've already heard how researchers are uncovering the secrets of our own biology to help develop therapies and drugs. Since he came to Portsmouth, Jerome's been focussed on learning more about how stress impacts our systems.

Jerome Swinny: Stress is linked to everything cardiovascular and not just the brain. It's linked to the immune system, metabolic system. So it's a huge impact in terms of, you know, medical priorities. If you want to modify the disease, you need to know what caused it.

Narrator: Last year in England, the NHS planned to spend £12.2 billion on mental health. In spite of the huge impact of our minds on our wellbeing, it's only in recent years that we've begun to accept a more joined-up view of how this can affect all aspects of our experience, from our emotions to our physical health, thoughts and motor skills. Jerome told Kate about the big role our nervous systems play in connecting all these vital body processes.

Jerome Swinny: I'm particularly interested in how stress or life experience impacts on the nervous system and how the changes in the nervous system drive our behaviour or our thinking so that this then allows us to deal with all of life's challenges. So we know that stress is a really fundamental, it's something that we experience throughout our lives, from the time you are born to the time we die. And nature or evolution has recognised this. So there are certain biological processes that help us to deal with this ever-changing environment. And this is essentially the stress response within our body. So the nervous system is the overall regulator of the stress response. So obviously stress has a huge impact on how the nervous system works, but it can delegate some of these responsibilities to other body organs as well. So and this will manifest in how we behave, but also in diseases as well. So, for example, we know that stress affects the brain, you know how we think, but also certain diseases. But it also affects different parts of your body, for example, when you're nervous, like giving this interview, you might feel a knot in your stomach. That is your stress response in your gastrointestinal tract because it says, well, right now we probably need to shut down this intestine is false. So we stop all kind of motility. And that is the knot in the stomach that you feel. And then, later on, you know, when you realise, well, this is not a life-threatening situation, it will relax.

Jerome Swinny: I mean, public speaking is recognised as the worst stress. Throughout. You can speak to the most accomplished speakers and they will say before they get on, they are nervous, you know. And obvious to a certain degree. And everybody will recognise that kind of feeling in the tummy. And this is exacerbated if you speak to people who suffer from anxiety, you know, the stresses, the respect of anxiety. And there will invariably have GI, I mean, severe GI disorders like inflammatory bowel disease or irritable bowel disease, irritable bowel syndrome.

Jerome Swinny: So that's basically the overarching thing. I'd like to know how stress impacts on the functioning of the nervous system. How the nervous system then reacts to elicit certain behaviours. And then, and I guess the fascination arises from if you look at certain people. Some people can deal with anything life throws at them. They can just take anything, any kind of stressor. And then there's some people that, you know, just crumble at the first kind of, you know, challenge that they face. And the question is why? We all have the same basic machinery. So we have the same kind of cells. We have the same proteins that are there to mediate the stress response. But for some people, it's adaptive. We experience the stressor, we overcome it so the next time we can deal with it in a better way, so we adapt to our changing. And some people it's maladaptive, it results in a disease.

Narrator: Unless you live a charmed life, it's unlikely you'll pass through it without experiencing stress to a greater or lesser degree. But what Jerome seems to be saying is that different levels of stress might affect our functions to different extents.

Narrator: We've all felt a knot in our stomach at a tense moment. But could this theory suggest that people living with gastrointestinal disorders might have a clearer link back to the way our bodies physically process external events?

Jerome Swinny: So the beauty is that what we now understand is that things like mental illnesses have physical constructs.

Jerome Swinny: During my PhD, I was fascinated. So I was working the part of the brain called the cerebellum. So the cerebellum is one of those parts of the brain, if you lose it, you're not going to die. You just going to walk funny because it's a part of the brain that helps us to learn certain motor acts. So it's part of the brain that's important for motor learning. So when you learn to ride a bike that is the cerebellum. It helps you to adapt your motor function in terms of change.

Kate Daniell: Yes.

Jerome Swinny: So when you learn to ride a bike [what] cerebellum is doing is it's checking what you're doing internally so what muscles are you saying contract? It's checking the external environment to make sure that they're contracting in a way that it is appropriate. So, for example, if you're cycling on a windy day, you need to cycle differently to on a day that it's not windy because you'll be constantly adapting and that's what the cerebellum is doing.

Jerome Swinny: The fascinating thing is there is the stress hormone. So the stress hormone called corticotropin-releasing hormone, that is the initiator of the stress response. So corticotropin-releasing hormone. So it's the nervous system and the hormone system. But the strange thing is this part of the brain that is involved in motor learning has the highest amounts of CRH. It's not really a part of the brain that's involved in kind of emotional disorder, the stress induced disorders. So I thought, what on earth is it doing here? And it's developed mentally regulated so you get a lot of it early on. So what we did for the PhD was basically, characterise what it is doing. And in a nutshell, we are able to show that the stress hormone is responsible for the development of the neurones. So it makes them grow out.

Narrator: From observing high levels of the corticotropin hormone in the cerebellum, Jerome was just a step from this to asking how anxiety and depression symptoms, historically stigmatised as non-physical, might also have a clear connection to the way our brains and bodies develop and cope with life's ups and downs.

Jerome Swinny: So it changes the structure of the brain. And from then on, there's this body of work that has grown to show how stress and life experience changes the structure of the brain. So small amounts of stress that is adaptive makes them grow up, you form more sinuses, some more communication, more memories can be formed. Whereas, chronic severe stress, the stress that induces the mental illnesses, it actually makes neurones shrink. So there is less chances to connect with one another, the less chances for synapses to form, so there's less chances for memory. Smaller neurones are just unhealthy neurones and eventually they die. It is about trying to deal with life's challenges and how the functioning of our nervous system helps us to do that. So what are the proteins and what are the cells within our brain that helps us to deal with these emotional challenges mainly? And what goes wrong that results in us becoming susceptible to some of the stress-induced diseases like depression and anxiety?

Narrator: Jerome has also contributed to cutting edge work that's exploring these vital connections in certain diseases.

Jerome Swinny: There's been another large body of work saying so you can now image your brain of somebody who's depressed and it looks completely different to somebody who's healthy.

Jerome Swinny: My focus has been on early life stress. So the early life environment and the interaction between the parents. Well, with mice, its mother's. But it's the maternal interaction.

Kate Daniell: Yeah.

Jerome Swinny: And basically, if we can... we manipulated it so we can get the mother to be a bit more loving and all you do is just separate them for 15 minutes from the pups and you put them back. She's so anxious she just smothers them with love. And when they grow up, they are so calm, they are so placid. Whereas if you impair that maternal barrier and the mice, the young mice are exposed to stress very early in life, now that evolutionary does not happen. That is the role of the parents because of stress hormones are generally bad for you. So you don't want that to be happening at a really early stage of your brain development. So that is where parental care comes in. It dampens the stress response.

Narrator: From anxious mice mothers to complex human lives, the idea of being able to find a tangible physical pathway between stress, anxiety and depression and our early life experiences is tantalising. However, Jerome thinks drug treatments based on these clean-cut ideas are a long way off, if ever within reach.

Jerome Swinny: Eventually, we are see going... now the larger picture. We want to know, we are driven by trying to understand science. But at the end of the day, it should be for the betterment of animals and mankind because I use animals, of course. And I think it can work in both ways. If you can talk about it and find the origin, hopefully, that might inform the drug therapy later on.

Narrator: Instead, he explained how we can apply these ideas to change real lives immediately using tools we already have.

Jerome Swinny: The mind is just the last frontier. You know, we've made such huge strides with so many diseases, things like epilepsy, which are kind of neurological. So brain function that are similar/uniform across individuals, like the way we walk, you know, things like that. But I think when it comes to the mind that is so individual. The way you think, the way you see the world and if the way you see it is in a way that could be detrimental to you. That's a very unique disease. So to find a, you know, I think we're a long way away from that. That is why I still think counselling is probably will outweigh anything that we'll be able to produce medically.

Jerome Swinny: We know that we are finding such fundamental genetic cellular changes as a result of this that would at least enlighten how we talk to these individuals. Even if you don't have a drug to offer them, we can at least say, well, we know. Because very often people don't. A lot of the concern or the anxiety comes from not knowing what is going on.

Kate Daniell: Yes.

Jerome Swinny: So if you can at least play into them, well, tell us about your life. Oh, this happened. Well, you know, we know that this causes it. You know, so in terms of what you're going through, we know exactly why it's happening. So let's, now that we know that, let's see how we can get you better. That kind of thing. It's important because we need to remove the stigma attached to this degree. Nobody would say if you have a cancer and you have a tumour, oh just deal with it. Whereas, you know, if you have depression, it is a physical construct now rather than it's just all in the mind.

Jerome Swinny: So what is emerging is essentially it's probably going to be more personalised medicine. So up to now, let's take something like depression.

Kate Daniell: Yes.

Jerome Swinny: Generally, people will be diagnosed because they have the classical symptoms and they are guidelines to say if you have this, then you are depressed. And then you will get a class of drugs that is an antidepressant and everybody gets them. The problem is, is that while you might have the same symptomology, you might have got to that point from completely different origin. We should not underestimate the value of just talking and trying to get a perspective or contextualising. So I think that goes hand-in-hand with the pharmacotherapy. I'm a scientist, a basic biomedical scientist, so drug therapy is something that is tangible for me and I see it as a tangible option. But I don't think this has to go hand-in-hand with, you know, some kind of psychotherapy or counselling, because very often, especially in terms of stress, it's a lot about how you perceive it.

Narrator: Thanks to Jerome for talking to us. As human beings, we cross borders and frontiers in terms of place and space, but it seems there are still many unmapped mysteries within our own internal landscapes. If you'd like to find out more about Jerome at his work, you can get all the detail on our research portal at port.ac.uk/research.

Narrator: Thanks for listening to this episode of Life Solved. We'll be back with more world-changing research.

Sarah Fouch: Are we increasing antimicrobial resistance within our normal gastrointestinal flora? Is it removing bacteria or is it helping them to overcome the effects of that antibiotic?

Narrator: Our new magazine, Solve, follows ºÚÁÏ³Ô¹Ï research when it's put into practice. It's full of news and stories on our world-changing advances and the changes these are making to lives and futures across the world. Go to port.ac.uk/solve. And please tell us what you think via social media using the hashtag life solved. Or maybe just share the big idea with a friend. I'm John Worsey. Thanks for listening.