Stress and Future Therapeutic Approaches

Welcome to Zoe Science and Nutrition, where world leading scientists explain how their research can improve your health It doesn't always begin with an obvious illness Sometimes it starts with a feeling that something simply isn't right You wake up exhausted after a full night's sleep Small problems suddenly feel overwhelming patience runs thin Motivation disappears Maybe you stop calling friends back The world feels heavier. as though your brain is struggling to keep up with life around it. Most of us would blame stress, burnout aging or modern life itself. But scientists are beginning to uncover another possibility inflammation inside the body may directly influence how we feel, think and function For years. I thought finding things difficult was just part of being an adult A normal response to building a company, supporting a family and carrying responsibilities I was raised to believe that emotions were private Hardness was weakness and that the mind and body lived in entirely separate worlds So like many people I became very good at appearing fine on the outside or feeling flat and exhausted on the inside. But over the last few years, I've started to question that story What if the way we feel is deeply connected to our physical health? to stress, sleep, diet, inflammation the immune system itself What if some of the feelings we associate with modern life? are actually being shaped by biology inside the brain oday I' joined by Ed Bilmore. Professor of psyiatry at Kingingss Coege Lond and a leading voice in brain research Ed's work challenges how we think about the relationship between the body and the brain suuggesting that inflammation may directly influence mood, motivation, behavior And the way that we experience the world around us More controversial His theory is rapidly moving from the fringe to mainstream sucks From the biology of inflammation to the idea of a brain on fire And finally to what we can do about it This conversation explores how inflammation may shape how we feel and what this means for life in the modern world Ed, thank you so much for joining me today Pleas to be here, Jonathan So we have a tradition here at Zoe where we always start with a quick fire round of questions designed to be very hard for professors because we have some strict rules. You can say yes Or no, or if you have to, you can have a sentence. Are you willing to give it a go? Of course. All right. Can my brain be affected if another part of my body is inflamed? Yes A I more likely to experience depression if my body has inflammation. Yes are more people than ever visiting their doctor with mental health issues like anxiety, depression and stress? Yes is someone's risk of depression mostly due to their genes Yes and no. If you have inflammation in your body, can you always tell? Did we evolve to sometimes feel depressed? P fininally, What's the biggest myth that you often hear about depression all in the mind I was brought up with a very traditional British attitude towards emotions I was supposed to have a stiff upper lip Stay calm and carry on and absolutely no matter what, never talk about my emotions And I suspect there's quite a lot of listeners who are probably brought up in that same way And I've realized over the last sort three or four years that this hasn't always been helping me as well as doing this podcast and the CO a startup It's immensely stressful And I find that trying to be a good husband and father is also really hard And I think I have built this way of behaving over the last decadade to pretend that everything is fine on the outside Wh often on the inside, I'm feeling very low, you know, sometimes really empty, you know, struggling to sort of keep going And I understand that there are like millions of people who like me, you, affected by low mood or anxiety or depression. know, sometimes they might call it stress And that many people continue to feel that even talking about that is a stigma likes something that shouldn't do. And you've spent many years researching mood and mental health in the brain. What is mental health? and maybe how does that tie into some of what I've been talking about I think, you know, when we were brought up and actually still There's a very strong traditional view that mental health, physical health are completely pulls apart Mind and body have got nothing to do with each other. It's perfectly okay to go with your to your GP with a cough or a broken arm or some kind of physical claimed It's perceived quite differently or has been to fess up to some of the issues that you've just mentioned Anxiety, depression other mental health symptoms have you know, traditionally been shrouded in secrecy shame stigma And I think that's partly because they've been regarded as completely separate from physical health. And one of the things that has intrigued me over the last and fifteen years particularly is that the evidence is all pointing in a different direction. If you look at it scientifically and forget what you were taught growing up or what views you inherited from your parents, If you just looked at the scientific literature now, you would not come to the conclusion that physical and mental health were completely separate. There's all sorts of evidence indicating that they are linked and particularly through the immune system. and that accounts for the connections between bodily inflammation and let's say, increased risk of depression that we touched on earlier So The scientific landscape has shifted. But a lot of people's The habitual ways of thinking about these things haven't yet changed. so many of us might say, oh, you know, I feel really stressed or I feel, you know, really anxious. probablyrobably far a few of us would say I feel ress or at least with like the sort of sense of a clinical depression, I feel a little bit depressed, but it might be so different. Can you help us understand what that is and like how common this is? particularly like that phrase, actually mental health. I don't like the idea that we can think about health as entirely of the mind. or entirely of the body mind and body goes back a long, long way. I mean You know, you can find traces of it in the Bible. It comes through the Western philosophical tradition with desescardes. It gets embedded into the way that we think about scientific medicine and it's carried on in the medical tradition ever since So that's an ancient idea. It's got very, very deep roots And the way the medical profession has been organized since at least kind of at the turn of the nineteenth twentieth century is to split out the doctors that look after the mind from the doctors that look after the body. I'm a psychiatrist. So I'm trained in the specialization of the mind So the disorders that we would talka about and primarily treat thingsings like psychotic disorders So that would be Um fight severe mental illness with symptoms of delusions, losing touch with reality, hallucinations, seeing things or hearing things that aren't really there can come in a variety of different forms. Schizophrenia is one, bipolar disorder is another. And then there's depression which can range from mildly off color or blue all the way through to severe hopelessness, a sort of nihilistic sense that really nothing is worth doing or maybe even that nothing is really real. Depression can merge into psychosis at the sort of extreme end. Adiction Obsessive compulsive disorder. And then there are a whole other group of disorders For example, attention deficit, hyperactivity disorder, ADHD that are sometimes categorized as neurodevelopmental rather than mental illness, but they contribute to a lot of problems for people, not just in childhood and adolescence, but into early adult life So there's a whole catalogue of psychiatric disorders. I mean, the American Psychiatric Association publishes periodically, a manual, a diagnostic manual called DSM which has been increasing in size ever since the nineteen fifties, when the first edition was published, it's become a thicker and thicker volume as if we're discovering more and more different psychiatric disorders. And are we discovering more and more psychiatric disorders? orr are we just getting better at recognizing? I think we're putting more and more labels on things behaviours and experiences have we discovered new diseases in the same way that let's say goingoing back a hundred years, there was a kind of flurry of activity with people discovering all sorts of new infectious diseases or what caused infectious diseases, cholera, tuberoculosis, syphilis, and so on You know, there was a period in the history of medicine where there was a real surge of new discoveries about diseases most of what we're talking about in psychiatry doesn't really stack up as a disease. It's more like a sort of descriptive Syndrome if you wanted to have a formal diagnosis of depression, let's say, or bipolar disorder or schizhrenia That would mean basically walking through a checklist of symptoms. And if you tick off the right combination of symptoms, you end up in a particular diagnostic category unlike the way that disease is diagnosed in the rest of medicine In psychiatry, it's just enough to have the right list of symptoms for a particular diagnosis. It's not historically been important to understand the cause, the root cause. And I think that is the direction that we have to see things move in future, scientifically. And I think as we get closer to understanding the causes of depression or anxiety, we'll discover that actually you can be depressed for many different reasons And sometimes there's going to be a significant genetic contribution, sometometimes there'll be environmental factors playing into it sometometimes it's going to be a combination and really the future of Psychiatry, I would say, is going to take a much more causal approach to understanding what's going on And the treatments that we offer people are going to be much more focused on what we think is the root cause of their symptoms rather than as we currently do, offering a sort of one size fits all treatment. Anybody that comes to their GP and says a few things about how they're feeling low during the day or they're having difficulty sleeping or a little bit of anxiety, that will usually be enough to trigger a prescription of an antidepressant drug which is offered to patients more or less across the board without any deep understanding of what might have caused the symptoms in any particular case. So sort of like you're treating the symptoms. I think about this, you know, like I've got a cut of my arm, but you put plaster on it to deal with a cup. But if there's something underneath that's actually causing this to keep happening you're not really treating the underlying cause of this is that am I understanding that right If you're anything like me then at three or four o'clock in the afternoon brain starts thinking about only one thing. a snap And for years I followed a very simple routine I feel tad and hungry. It' stop work G go to nearby shop and buy the nearest snack bar that promised to give me energy And if it seemed to have some nuts or raisins in it or had any health claims on the wrapper then I had the added bonus that I was eating something healthy Now if you're a regular listener to this podcast, you've probably been on the same health journey that I've been on And you'll know that those snack bars are jammed full of added sugar and artificial additives. So they spiked my blood sugar through the roof every time I ate them And sure enough I ended up hungry again a few hours later as my blood sugar crashed So imagine my surprise when Zoe's chief scientist, Professor Sarah Berry came to me a year ago and said that the Zoe science team had completed a massive study of our data It revealed that ninety five percent of us snack every single day. and that those snacks make up a hidden fourth meal that accounts for twenty five percent of our daily calories. However What it shock Sarah with something else Her data showed that forty percent of people who eat a healthy lunch gone to eat a poor quality afternoon snack In other words, they're working really hard to eat healthy during their main meals and then their snacks were sabotaging their gut health I was definitely in that category. The good news Sarah told me she thought we could solve this. and create a snack that was actually good for your gut health while also tasting delicious Obviously, I said let's do it And then I waited. And I waited. But finally, after a year of work with Zoe's gut healthsciatist Sarah came back with a Zoe Gut Health bar Turning that snacking blind spot into a win for your gut I find that it's delicious and satisfying to eat while also containing a huge diversity of plants all carefully selected by Sarah and her team It preserves the cell matrix of the plants. which we talk about so often on this podcast And it's designed to feed your gut microbes It's got seven grams of plant protein a huge eight grams of fiber twelve to thirteen plants in each bar, depending on the flavor My favorite is of course the seventy percent dark chocolate bar But my co founder Tim Spector prefers the raspberry gojubererry flavor Phaps I'm bias But I think our Gut health bar is delicious And I love the fact that it takes time to chew instead of being hyper palatable and stuff full of artificial additives And I think it's time to stop giving in snacks that don't serve your health And if you feel the same way, why not head to Zoe d. com slash snackbx and try for yourself That Zoe. com slash snack bar g. Well, thank you If you had, let's say malaria in the nineteenth century You would have been diagnosed as fever fever maybe You're feeling hot, you go and see your GP. He tells you you've got fever and then treats the fever And there are treatments that will lower the temperature of the body in the short term they're not treating the cause breakthrough infectious disease was recognizing a lot of people can have fever But There might be a lot of difference between people in terms of why they've got fever. What is the germ? What is the root cause And once you understand the root cause, then you can offer a treatment that tackles the cause, which is how we got to antibiotics and vaccines. and why infectious disease, at least for many of us in the West, is much less of a problem than it was historically But in psychiatry, we're still more or less in the space of treating fever rather than treating specific bacterial infections How can you really be effective in terms of treatment or prevention if you don't understand what's causing the problem in the first place And then if you think about, you know, let's say depression What are the causes of depression? If you look at the current Sn camp trick manual that I was talking about earlier and you read the criteria for a diagnosis of depression You can have all sorts of symptoms. You can sleep too much, you can sleep too little, you can put on weight, you can gain weight, you can be hyperactive, you can be slow in your behavior. All of those are symptoms of depression So you can see just by that checklist that you're going to end up with a very heterogeneous group of people you might have quite different experiences of illness, but they're all lumped under the same diagnosis. The only exclusion criterion is that you can't have a diagnosis of major depressive disorder if there's a physical bodily cause for it or if there's any kind of, you know, background physical illness. So if I had rheumatoid arthritis, for example, which is you know a bodily inflammatory disorder pain in my joints And I went to my GP and said, my general practitioner, primary care physician and said I've got the pain, I've got these arthritic joints and I'm feeling depressed At the moment, people would say, well, that's coorbid depression. That's some kind like you're feeling depressed perhaps because you realize that you've got this systemic autoimmune Cm It might get worse over time Maybe you've seen other people with rheumatoid arthritis who' become progressively disabled. You know that and you're predicting them gloomy future for yourself, and that's why you're feeling depressed as well as having the joint pain. That's the traditional web dealing with it to separate the mental symptoms of depression and fatigue and brain fog which are extremely common among people with all sorts of bodily inflammatory disorders from the physical problem and the physical treatment I'm just struck by this conversation. you said that in medical profession, we sort of split doctors very early in their career between doctors of the body and doctors of the brain, whichich is a really funny thing to do when the brain is part of the body. And we split the doctors into doctors of the mind, doctors of the brain and doctors of various other bits of the body I would say administratively convenient for the medical profession to organize itself in that way but it doesn't really address the reality of illness. because I think anybody who's been through any kind of illness episode. I mean, it couldn't not necessarily severe will know that their experiences of Seamless, mental and physical symptoms usually I mean, in my book, The Inflamed Mind, I talk about my experience with perioddontitis, right Gum disease and going to a dentist with pain in my jaw and feeling quite low and The dentist did a root canal treatment. fiddle the that in the sort of infected by the removed tooth And I went home and felt Re quite blumb and My first thought about that was along traditional lines You know, I had a problem in my mouth This tooth had been infected and I've gone and got treatment for it And I was feeling depressed because that experience had made me realize quite literally that I was getting long in the tooth. It had given me a sort of foresight of my own mortality. And that's why I was gloomy. And then I thought, well, no, actually Maybe it's not that. Maybe the infection in my mouth and the dentist fiddling about there and kind of aggravating the local inflammation has triggered a release of proteins called cytokines, which are like you can think of as inflammatory hormones from my tooth circulating through the body. getting into my brain and biasing the way I think about things into a more depressive perspective. That's an experience of illness where you've got a local problem in your body, in this case, mud tooth, and you've got a psychological reflection of that feeleing depressed And usually we say those are two separate things you're saying, actually, this inflammation in your tooth and then indeed the dentist sort of treating it, you know, we all know when we go to the dentist if they do anything like that, it's painful at the time, right. You're actually saying that is triggering a set of chemicals and the cerkines as part of that that actually cause your mood to change for you to feel lower mood, maybe even depressed as a direct result of this physical thing. I think one key thing that you know It's worth just emphasizing at the outset is the immune system is a whole body. system you know, so Even if you've got inflammation, tooth or in your thumb. Even if you can kind of point to the bit of your body that feels most inflamed or looks most inflamed isn't the limit of the body' inflammatory response almost always when you've got a local hotspot of inflammation You're going to have a systemic response as part of it. So you will have increased levels of these hormones, cytokines, which you stimulate immune cells in other parts of the body, they will be increased concentration in people with local inflammation. you know the levels of immune cells, the white blood cells in the circulation will also change as a result of local inflammation. So I think that's one thing that is important for people to understand it is that Inflammation is almost always systemic. It almost always involves the whole body to some degree I think that's fascinating. and I think it links back as you said to your book, The inflamed Mind, which talks a lot about these links between sort of the inflammation that you have in your body and your mind and particularly depression there If I'm thinking about this, I'm thinking that my dad is nearly eighty and he still thinks that being tired is mental weakness that should be overcome and has like no relationship. That's anything you can do He'd be like, Ed, this is nonsense. If you just have the right mental attitude, you could ignore all of this. like this is completely separate whatever the cause of fatigue or depression, mean I think it is important often to kind of with that as Um ly as you can which I suppose would be in line with your dad's advice I think we should also just give ourselves a break and recognize that if people are coping with persistent fatigue struggling to think clearly about things feeling quite gloomy or tearful at times It's not just that they lack moral fiber or that they should pull up their socks or you know, all of their you know, sort of more traditional ways of kind of encouraging people to sort of just power through these symptoms They will have physical causes You already mentioned the fact that the sort of inlammation is happening and it's a sort of whole body thing. Could you just explain in very simple terms what is inflammation? And you know you gave us an example of your sawtooth, but why in general is it ing in the body Inflammation really is the first line of the immune system defense against attack. As soon as you're born you are exposed to what is actually quite a hostile environment biologically. There are all sorts of germs, bacteria viruses other sorts of risks that you're exposed to as a very young child And you need to be defended against that and it's the immune system provides that defense. and particularly, there's a part of the immune system. It's called the innate immune system Meaning that it's kind of fully wired, it's fully programmed at birth. You're born with this and it's the innate immune systems response to the infections that you first encounter as a child causes inflammation innate immune system, that innate responsivility to being attacked from outside often by a germ of some kind is hugely important But also, inflammation can cause disease, It's a bit of a double edge sword sometometimes the immune system can get a bit carried away, you might say it can misidentify parts of the body. as if they were infectious agents. This is the story for autoimmune disease For example, arthritis many other kinds of joint disease. good example of an autoimmune disease where the immune system has mistakenly identified some part of the body as if it was a hostile agent and has started attacking the body which causes persistent inflammation And so persistent inflammation means rather than like I've had a cut, something happens, my immune system evolves and it swells and then it treats it. It sort of continues ongoing, you know even though in fact, my cut is healed over and I don't need it anymore. Exactly. If I had an infected cut in my hand, as you say, it would get inflamed So it would get swollen, it would go red, it would feel tender is all indicating that the immune system is piling into that area and trying to kind of kill off the bacteria that are causing the wound to be infected And if the immune system is successful and it can kill off the bacteria and eliminate the problem, then the inflammation fades away. And you think, great, the immune systems all good. But if the immune system mistakenly identifies some particular protein in your as a problem and starts attacking your joints It's never really going to go away because the immune system can't kind of eliminate your joints in the same way that it could kill off the bacteria that are causing the infection in your hand, there's never going to be a decisive victory for the immune system once it starts attacking the body itself. Could you help link that to the brain now? My information seems to come up over and over again on these podcasts is fascinating. It's never really been linked to sort of the brain and your mood and things like that. So what happens? How does something that's going on in my joint or my arteries or whatever lead to something happening in my brain When I was at medical school which was in the nineteen eighties One of the things we were taught, as a matter of fact, is that the brain is somehow protected from the immune system The jargon for it was the brain is immune privileged. It sort of sits outside the immune system And that was supposed to be because it was protected by this thing called a blood brain barrier Sounds like a handy thing to have. What does it do To be honest, it doesn't really exist. But what we were taught at medical school is that there was something like a berlin wall around the brain that meant that blood cells and proteins that were circulating in the bloodstream couldn't get across the blood brain barrier and into the brain So Let's go back to the example of rheumatoid arthiitis The idea that somebody with rheumatoid arthritis and all sorts of inflammatory activity going on in the body and circulating the blood But that could have anything to do with mood. That was kind of ruled out straightway. because How could it have an effect on mood if it didn't have an effect on the brain, and it couldn't have an effect on the brain because of the blood brain barrier That was what we were taught. and actually I think that is still current teaching in a lot of medical schools. The brain is sort of sealed off from the rest of the body or at least from the rest of the immune system. And it's not true? No, it's not true. So you know, I was talking about cytokines, these kind like inflammatory hormones that are triggered whereever you have a local inflammation anywhere in the body those proteins We used to think couldn't get across the bladbin barrier, but now we know that they can by various different routes In fact, the white blood cells, the cells of the immune system can also get across the blood brain barrier So this whole idea that none of the like your blood can't get into your brain, and none of the components of the blood can get into your brain, which I have deffinitely been told. Yeah yeah. this just isn't true. It's not like a wide open door nor is it a Berlin Mall? It's a filtered tootal Protein cells can get in. and That is very likely how somebody with a physical disease like arthritis, again and those kind of oren circulating the blood The circulation carries those inflammatory horments to the brain and they can get into the brain. and trigger changes in neuronal activity in nerve cell and the activity of the nerve cells in the brain. So I've got this infammation. It's created these hormones you called cytokines.. They are in fact slipping through the Berlin wall, you know late at night or you know, under the barbed wire or whatever, getting into my brain How does that then cause me to be depressed or anxious or whatever We think of the brain as important in perceiving the outside world in a vision hearing smell and so on picking up sickles from outside. But there' also parts of the brain that are specialized at kind of tuning in into the bodily environment They're called intraceceptive systems in the brain. So they're focused on perception of the internal state of the body rather than the external state of the world around us and those systems are quite responsive to inflammatory changes in the body generally You're going to ask me, how does that cause mood changes how does a conscious sense of gloominess about the world around us, how does that arise from the activity of nerve cells But what we can see quite clearly from let's say brain imaging studies is that if you change the inflammatory state of the body, you will change the functional activity of the brain in the brain circuits or brain networks that we know are important for mood and for mood disorders You're saying the science is really quite clear now that if I have this raised inflammation in the rest of my body It sends hormones into my brain and those literally lead to changes in parts of my brain that are directly related to my mood. Exactly And the other thing I would say is that if you look at animals and you make animals inflamed that's experimentally been much used in China of this in detail If you make an animal inflamed, it changes its behavior I can't tell you it's feeling gloomy about the future But if you look at the way it's behaving, a mouse that becomes inflamed will be less exploratory. It'll be less mobile It'll be less interactive with other mise there's a whole sort of suite of behavioral changes that you can trigger in animals with inflammation that look a lot like some of the things that we experience as humans and call depression thing to remember about the immune system is basically it's only job is to try bus alive And if It helps us to stay alive. even after we've been infected or injured or suffered some kind of cause of inflammation, if it helps us, to survive to change our behaviour. U change our sleeping patterns, change the amount that we eat, perhaps change the extent which that we interact with you know, our family or the wider social group that we're part of if those changes help us survive then they will be selected b natural selection, there will have evolved as part of the immune system's repertoire of response to help the animal or the human get through the trauma or injury of which might otherwise be life threatening So Ed, I'm listening to this And the other thing I'm thinking about is it feels like there's been this explosion of rates of mental health issues over the last few decades. And anxiety is one of those things that people report enormous increases Is there like a big increase in these issues of mental health over the last twenty or so years? And then how do we understand this? Because you're saying there's this mechanism that like your body is inflamed, this leads to these mental health issues So does that mean that also that the inflammation has been rising? What's actually going on from your perspective We are facing what looks like a wave of increased incidents and severity of mental health problems some people would say that's just because the current generations is of it p. Or maybe instead of kind of ulling this up and trying to cope with it. peopleeople are more vocal about him. and open about it or maybe that Pactitioners are getting a little bit more liberal in making these diagnoses. And Ed, what about sort of anxiety and depression? Be I definitely feel like we're all just a lot more anxious than we were when I was growing up Well, we're definitely talking more about it, perhaps not as startling as some of the other areas that I already mentioned. But I think yes, there is certainly increasing demand for services If I go back to this idea you're sharing that theseese mental health issues have been driven by inflation in my body Puming that means that we're having more inflammation, more of this long term inflammation in our body in our ancestors used to have What's causing this brain infammation One dinner important nuance here is that there's a difference between having a syndrome and having a disease. At the moment, we're talking about depression as a syndrome. And I would think that Over time, what we will discover is that there are a number of different pathways to becoming depressed in the same way that there are a number of different infections that can cause fever some of those people with depression are going to have an important inflammatory or immune component I think it's probably about thirty percent or of people with severe depression have got a significant inflammatory component to it. And then there are all those other people that have got inflammatory disease in the body, like rheumatoid arthritis who will have depressive symptoms that we can't currently diagnose as a major depressive disorder because of the curious diagnostic system that we've inherited in psychiatry If you go to your primary care physician and you say I'm feeling low gloomy about the future, I'm not sleeping very well and the other symptoms of depression Within a few minutes, they will have prescribed and it's present and or a course of cognitive behavioral therapy and you'll be out the door and back on the street as it were. It doesn't happen very often is people takeaking a moment to think, okay, So you've got these depressive symptoms, Are there relevant inflammatory or other physical problems that we should be thinking about as a sort of three hundred sixty degree approach to investigation and treatment of your issues. GPs don't routinely screen for inflammation when they're consulted by people with depressive symptoms. And could we talk about those now? And I think some of these you mentioned in the book And the first one to me is a huge surprise Oesity No obesity, the more inflammation if you do epidemiological research or large scale population research There's a lot of evidence for a pretty robust association between obesity and depression People with depression are more likely to be obese. People with obesity are more likely to be depressed. We've known that for ages The way that we've usually interpreted it, the way we've traditionally interpreted it is to say Maybe people with obesity are depressed because they don't like the way they look or they feel ashamed about their appearance. So that's a kind of psychological sort of overlay on the physical problem of obesity the new The concept is just that this very robust association between a boosting depression is driven by a causal process, you know, the accumulation of fat tissue and the immune cells in the fat. causes release of these inflammatory hormones which chang the way the brain operates in a way that makes people feel Depressed That actually switch to me almost naturally I think onto the second one the microbiome. Yeah. Lots of people are listening to this podcast obviously arezZoe members and have used it and sort of adjusted their diet and one of the things that people tend to be most surprised by and I was most surprised by is the way in which your mood can shift, like your energy and things like this very fast, like much sooner than you then see in like some of maybe some of the blood work that might take three or longer months How does that tie into this story you're talking about? and is there any role for the microbiomome in here? Do we know? Oh yeah, definitely. I think what I was taught at medical school is what everybody was taught at medical school and what everybody is still taught at medical school to a large extent. And that matters because that fixes the medical mindset And what we were taught about diet and mood was nothing. And what we have seen progressively since then is people becoming aware that inside our We have are large and complex collection of bacteria, some of which are potentially dangerous And if you change the composition of the microbiome, You are going to elicit an immune response in the gunt You know, if you look where in the body, The immune system is concentrated a lot of it is in the gut and that makes perfect sense because the gut is arguably are M vulnerable frontier And it has to be vulnerable by design because the gut is intended to kind of extract nutrients out of what we eat gut wall is permeable if you change the composition of the microbiome. and uh, you know hostile bacteria become more abundant, there is going to be an immune response So do you by the fact that we have worse microbiomes in the past could be something that helps to explain the fact that mental health is worse. And the other way around that if we had better microbiomes, that could potentially reduce U these symptoms of mental health I think so in some people. Okay, againgain, I'm not I don't want to kind of like imagine there's a panacea and that everybody needs to have you know, fecal transplants or some kind of radical treatment for the microbiome and that's going to make impression go away, but there will be cases where You can see that there is a change in the microbiome and that there will be dietary or other interventions that can shift things into a healthier direction and that should trigger less of an immune response in the gut give a better sense of mental health, but probably also better brain health as well. Amazing. Let me move on to the next one and I feel that it was triggered by your little story at the beginning decay. Hmm. Yeah That seems like it can't be very important. Oh, it's very important The mouth, the teeth, the gums or obviously the province of dentists. Dentists and doctors hardly talk to each other Doctors very rarely look inside a patient's mouth My mouth is part of my body How have we got used to the idea that, you know, I go and see a doctor then in my general practice clinic. for a bodily symptom and I go and see a completely different find a practitioner when I got a problem in my mouth and they don't talk to each other. You know my dental records are invisible to my medical practitioner and vice versa to a large extent. A problem that a lot of people have, particularly adults is gum disease You know, which is a low grade infection which can cause inflammation that's quite you difficult to eradicate in the mouth Inflammation is systemic I've got a local inflammation In my wisdom tooth here is going to be causing release of cytochines is going to be, you know, I would be able to tect that. a source of inflamation and a blood test And that is I think can contribute to brain and mind problems. And so Ed, is there a real link between like people with gum disease having higher levels of depression and things like this Yes, and also I should say I'm not percent or how solid this evidence is, but I've always thought it's very interesting and it needs to be further investigated The links between dental inflammation and brain aging and whether Gum disease is contributory to risk of dementia Sounds slightly outlandish when you first think about it And we've talked mostly about the psychiatric disorders of let's say children, adolescents and adults. But I think we need to also think hard about the role of inflammation in brain aging. and how inflammation of the brain can accelerate dimmentia And there is a clear link between raised gum disease and more risk of dementia. There is an epidemiological association. ye What about menopause and post menopause that is some evidence that going through menopause changes. the inflammatory state People have talked about menopause being a risk for inflammation. and certainly going through the menopause is offtten a crisis or can be a crisis in mental health for some women I would say this is another area where We've traditionally sort of not taking a very integrated approach to understanding what's going on So a woman who is feeling depressed around the time of menopause. or afterenopause might often be told, well You know, that's You're just reflecting on your loss of reproductivity I think there are important endocrine and immune changes around the time of menopause that we should be thinking about as contributory to the mental health symptoms that arise then One of the things I'm really interested by is the way in which you say the traditional way that doctors thought about this is almost let me explain this away. L something's happened like you've put on lots of weight or you're going through menopause or you're sick or whatever. therefore, it's logical that you would feel depressed about things. therefore that explains it. Yeah Whereas it feels like you're saying, well, in all of those cases, you can see there are these really big changes in hormones in your body. Your inflammation levels are really high. And actually that could be the cause. And therefore, if you were to be able to treat the underlying inflammation, but not change the rest of it, then actually suddenly those mental health situation might fall away without the change in situation that you're sort of claiming is the logical argument. Right, whichich is a pretty radically different way of thinking about this It is from the point of view of the medical profession. Yeah You know, I think from the point of view of most patients, it's not that radical. I think if you talk to a lot of people who are going through the menopause or who are obese or have arthrites If you actually talk to people about they're experiencing As I said earlier, they will usually have a kind of more or less seamless experience of both physical and mental symptoms. The idea that the bodily illness can have something to do with the brain I mean How on earth has that come to seem like a radical idea? You know Really? I just don't understand it I come on to aging now Yeah, which also was a big surprise to me. We tend to get more inflamed as we get older. brains as we grow older, they lose processing capacity, basically, they lose nerve cells Cgnitive capacity falls off as you get older, working memory. So there are these normal background changes in the brain And there is also a tendency over time for the immune system to become more inflamed as people grow older. you' saying Aing in general leads to brain changes and increases the risk of things like dementia and Alzheimer's and things like that.. If I have a high degree of inflammation in my body, then actually that's going to accelerate the rate at which those changes happen and therefore increases my risk of Alzheimer's and things like this? Yes. I mean, that's broadly correct. But I think it's not so much that inflammation causes Alzheimer's disease so much as inflammation could accelerate the rate of progression of Alzheimer's disease. Should I think about it a bit like I might have a genetic risk of heart disease If I eat terrible diet and you know sort of bacon for breakfast every morning, I've got a really high chance of it. If I eat really well and I'm exercising and all these sorts of things, then actually I might you know be fine and live to be ninety five. Yes That's roughly right Obviously there's a major focus on trying to find new treatments for let's just focus on Alzheimer's disease. And you know causes dementia as well ment that is currently out there Pretty minimal But when you actually look at the brains of people with Alzheimer's disease, what you can see is that these amyloid deposits No these abnormal proteins that are kind of like the diagnostic hallmark of Alzheimer's disease They are recognized by the immune system as if they were hostile or alien agents so they trigger an immune response, an inflammatory response in the brain And if you can damp that down, You can protect the nerve cells and you can slow down the rate of nerve cell loss and therefore slow down the rate of cognitive impairment that ultimately ends in a state of dementia. So if we could reduce this inflammation and the effect of this inflammation on your brain, then we could really slow down the rate at which you develop dementia, Alzheimer's whver Yes Yes what are the lifestyle factors that are most important for affecting brain inflammation that we could So physical exercise, particularly if it's sustained, is anti inflammatory and it has beneficial effects on mood if you look at trials and large scale observational evidence It's pretty clear that there is an association between physical activity, physical fitness and levels of Mental health It's also pretty clear that there is an association between Physical fitness and inflammation People have done randomized trials of physical training, physical fitness, and have demonstrated moderately effective shifts in mood, equivalent to what you'd see with antidepressant drugs My doctor could prescribe me exercise or antidepressants and they have about the same level of impact Yeah, they do. It's always important just to bear in mind that a lot of the evidence we're talking about is kind of like aggregated over thousands of people But if I was struggling with symptoms of depression and anxiety, that is one thing I would definitely do What is beneficial seems to be from the data that we see at the moment is a sort of sustained regime of physical health maintenance and that't ne I don't think that necessarily needs to be kind of like going to the gym and doing something extreme It just needs to be making sure that you kind of stay active every day. So could walking every day, like couldn't that count as exercise or does it have toly It count. Yeah. I just count my steps every day and just make sure that I'm doing ten thousand or thereabouts. What about diet pretty good association between so called Mediterranean diet and both inflammation and depression. does also some associations between processed foods and both inflammation and depression I'm guessing the Mediterran diet is good, but the utra processed food not so good. I think what's interesting about those three prorocessed food phhysical fitness, mobility and rainian d is that There's a lot of data accumulated particularly of the last five years or so. to show that in all three of those cases There's an association with both inflammation and Mental health symptoms I mean, the most parsimonious explanation for that is that there is a causal relationship between diet the state of the microbiome inflammatory response And that's why dietary changes can shift mood. I'd like to take a second to tell you a story about me For a lot of my life I've given the impression that I'm totally fine on the outside But on the inside I felt overwhelmed by anxiety or sometimes so low that I don't know how to keep going I found immense relief from talking about this and from the realization that my body has a huge influence on my mind and that the right habits of diet, activity, sleep and exercise can make a huge difference to how I feel If you know anyone who's under a lot of stress, maybe worries about anxiety or maybe even talks about feeling depressed Why not share this episode with them? You never know They might find it as helpful as I have One thing we haven't really touched on at all is stress in our lives. So, you know, we talked about many other factors, some of which, you know, a number of which we can change, some we can't How much does that matter? what can we do to improve things. People think of stress, particularly social stress as if it was only by the mind. But what We can see you can see this in animals. and for example, if you stress an animal, llicits. an immune response And this goes back to what the immune system is there for. The immune system is there to keep us alive under hostile conditions. and those hostile conditions could be a bacterial infection or it could be some kind of psychosocial stress perhaps particularly in the first few years of life You know, one of the One of the things that we really know in psychiatry and we've known this for a long, long time is that if you're exposed to stress as a child that has very long term adverse consequences or often has very long term adverse consequences for your mental health in decades to come Why is that You know, I think a really interesting idea that needs further investigation is that if you're exposed to stress and I'm talking things like abuse, neglect reme poverty loss of a parent in the first few years of life. Those are major to the survival of that child. They elicit an immune response and the immune system has a memory. We haven't really talked about that. but I mean, that's why vaccination works You know, you can you can expose the immune system. to a stress and it will remember that decades and I suspect that how the immune system responds to stress how the immune system remembers the stress it was exposed to as a child I think is going to be really important for us If you were advising a patient, actionable advice, things that you could choose to do, you know, whether that's talking therapy on one side and all the stuff that people in wellness are so keen on about meditation and yoga, what would you say across those sorts of things? If you'd ask me fifteen also years ago What do I think about benefits of yoga for mental health, I would have thought that was a bit woooo Now, I think ' much more liberal in what I can imagine could really work new ideas that have come out of the science of the immune system, the brain and the mind. Over the last ten, fifteen years, they do allow us to think quite differently about what might work and why. The interventions you're talking about Lifestyle, changes, activity, diet, yoga, meditation. There's not really much downside to any of that I don't see any reason why you wouldn't want to give it a go. and certainly for the exercise and dietary things, I think there's pretty good evidence that if it's effective, it might be through the immune system. What does the science say about talking therapy Well, they're moderately effective on average Let's say callording to beavioral therapy, which is a sort of default for mild to moderate depression and anxiety. There is an effect that has been evidenced in trials. Psychotherapy lookooks like it works some people One final question So if someone is listening to this podcast and really resonated with them. Maybe they've been feeling consistently low or emotionally flat or like really anxious Where would you suggest they start The official answer to that is they should start by consulting there prrimary care physician or general practitioner People really shouldn't feel shy or ashamed seek medical attention And this is easier said than done Ted to get into a conversation with The award primary care physician about your mental health symptoms as part of your broader physical health So in other words, try get the medical profession to think more about you as an individual with both mental and physical symptoms rather than allowing the medical profession to compartmentalize you into different kinds of problems that need different specialist input And thank you so much I would like to do a quick summing up and just correct me if I get anything wrong, please The thing that I go to first of all is this amazing idea that when I have inflammation elsewhere in my body, it actually changes the part of my brain that controls my mood And you describe that there are these hormones like these cytokines that might be caused by this inflammation somewhere else and actually those get through into my brain. And so this idea that my mind and my body are two completely separate things just isn't true there has been a surge of mental health issues over the last few years And that one of the reasons why somehow we don't talk about this in the same conversation as we talk about maybe you know, the ultra processed food or the obesity epidemic and the rest of it is that the medical profession is broken up. People think about the body, people who think about the mind, and people who think about the mouth. And they're like three completely separate groups that never talk to each other. And you sort of said, it's sort of mad. That's not the way the body is. It's just an accident of history I was really struck that there are a number of like sort of factors that can drive depression and mental health that I wouldn't have thought about. So you for example, describe, you living with obesity, that just leads to much higher levels of inflammation in your body. That leads to higher depression talked about the microbiome, like the evidence is earlier, but again, seems like lots of reasons with so much of the immune system being focused on managing the microbiome to think this is directly linking through to mood Gum disease. You said like if you have higher levels of gum disease, that is actually linked to higher levels of dementia and Alzheimer's. there's like this direct link between sort of this inflammation around your teeth and like this terrible brain disease perenopause and menopause. You said that often changes levels of inflammation and it's a time of li many mood issues for a lot of women. And again, you could jump to it's something that's all in the mind, but actually very often it could be to do with you know something that we know we've done a lot of menopause related studies at Zoe, these huge changes in your metabolism and all of these sorts of things. And last but not least, you know, aging Naturally your brain changes As you're aging, your risk of dementia goes up, if you have this higher inflammation, then this can sort of accelerate your rate. So if you're aging and you've got a higher inflammation, this is a really big risk for them get Alzheimer's But the good news is You're not all stuck with whatever sort of your genes gave you. There's things you can do. You started with exercise. You said, like the evidence for this improving mental health is really strong And you don't have to be like pounding away in the gym Even just walking every day, like doing more movement can have a real impact, but it's something you want to do regularly. that the evidence for a good diet, you talked about a Mediterranean diet, which is very similar to what we talk about a lot across the show can improve mood and your hypothesis is probably the microbiome is essential. part of what shapes this for the reasons we've talked about. And similarly, we're just starting to see ultra processed food is bad We know to ultra processed food in increases inflammation. So I think that also helps to explain depressing that this is about seventy percent of our diet across the Western world now. And last but not least, we talked a little bit about stress and yoga and meditation And so you said fifteen years ago, you would have thought it was wishful thinking, woo woo, a bit mad. But you're starting to think that it might be possible that things like yoga meditation could really impact your mood for the reasons that we think about the mind and the body are in fact one thing. That's right That's a very good summary Hosting this podcast means I get to quiz world leading scientists every week