Dr Brendan Stubbs: People with mental health conditions such as schizophrenia or major depression or bipolar disorder are dying on average up to 15 to 20 years earlier than people in the general population who don't have those conditions.
Dr Rupy: Welcome to the Doctor's Kitchen podcast with me, Dr Rupy. Today's guest is Dr Brendan Stubbs. He's head of physiotherapy at the South London and Maudsley NHS Foundation Trust and a clinical lecturer at the Institute of Psychiatry, Psychology and Neuroscience, King's College London. Brendan's research focuses on physical activity and mental health and the mind-body interface. Brendan and his team have published over 400 academic papers and in 2016 he was identified in the journal Nature, which is sort of like one of the biggest journals you can imagine, almost like the Oscars of all journals, as one of the most productive scientists across all disciplines in the world. He's published a book called Exercise Based Interventions for Mental Illness. I'll put the link to that in the show notes. I highly recommend you get it, particularly if you're a health professional. And the links to all the academic papers that we talk about are referenced in the show notes at thedoctorskitchen.com. And don't forget my new book, Eat to Beat Illness, is out now on Amazon and in all good book stores where I talk about the principles of healthy eating and how I apply these to how it can improve our brain, skin function, heart health, stress, amongst other medical specialities. And I introduce Lifestyle 360, which is a journey through what additional activities can complement your health and wellbeing. Plus, obviously, there are over 80 new delicious recipes that you can try right now in your kitchen. Go out and get it. The link to it is in the show notes. But for now, onto the podcast. Brendan, welcome to the show.
Dr Brendan Stubbs: Thank you so much for inviting me. I'm delighted to be here.
Dr Rupy: I'm so happy for you to get and I think honestly, I was looking at your bio a couple of days ago and you're probably the most published person that I've had on the show thus far. Literally hundreds of papers.
Dr Brendan Stubbs: Well, it's all the result of teamwork. I've got some fantastic colleagues I work with locally and also internationally who've been really supportive and encouraging in terms of helping us develop the evidence base. So really the reflection of the number of publications is just as a result of working with wonderful, collaborate and collegiate colleagues.
Dr Rupy: And talking of collegiate colleagues, you've written a book, Evidence-Based Interventions for Mental Illness that you've kindly given me today. I'm very touched by this by the way.
Dr Brendan Stubbs: It's a pleasure.
Dr Rupy: Honestly, this is an incredible resource. I was looking through it, I was going to get it this week as well and you pulled up with it today for today's recordings, but it's it's just it's so vast. You've essentially, well I'll let you describe actually. You've done this with Simon Rosenbaum, right?
Dr Brendan Stubbs: Yes, so this is a book I've co-edited with Simon Rosenbaum and he's an exercise physiologist in Sydney. And essentially we've been on a journey which we'll go through over the course of the podcast, really trying to get to the the nuts and bolts of the evidence of physical activity to promote mental health and also to be used as a strategy to manage various mental health conditions. So we've done lots and lots of research and published academic papers, but really not many people, even clinicians or the general public are not going to have time to read 20, 30, 40 or more papers. So what we wanted to do is work with many of our other experts to condense the evidence base into practical tips for personal trainers, allied health professions, doctors, nurses or anyone interested in the area to say within all of these different mental health conditions, what are these mental health conditions? Why may exercise be useful for this mental health condition? What does the actual evidence say? Because it's important that we built this on evidence and what can we do to implement the evidence for exercise in these individual conditions? And we brought it together all in a book.
Dr Rupy: And talking about all the individual conditions, you've ticked off so many of them. I mean we're ranging from everything from depression to anxiety, schizophrenia, alcohol issues, addiction, eating disorders. I mean, this is like my psychiatry placement in a book here, but all to do with exercise. It's so exciting.
Dr Brendan Stubbs: Absolutely. We're really pleased to have it going out so people can have access to it and pull it up off the shelf and say, what can I do for this particular person? And and really give people an additional option because you know, currently within psychiatry, it's a really important part is is medication and that's really important for people's journey. Also psychological therapy is really, really important. But also give people that added arm that exercise can be a really important adjunctive or complementary treatment for people with lots of different mental health conditions as is sort of evidenced by the the underpinning science.
Dr Rupy: And you've done so much research. It's not all to do with mental health actually. I was looking through some of your publications and it spans everything from I think you looked at cannabis and suicide, you looked at osteoarthritis and inflammation, inflammatory diets, it's just it like you said, it's teamwork definitely. But that's a very, very impressive mate.
Dr Brendan Stubbs: Thank you. It really is the result of of teamwork and forming good collaborations with people. But my my main sort of real interests are looking at physical activity for the promotion of mental health because most of what we talk about, although it's changing recently, has been how physical activity and exercise can make us look different or physically changes, but I'm really interested in how it makes us feel different and how it may help prevent the onset of mental health conditions or be used as a treatment. The other sort of main arm of the research that I'm really interested in is is how the mind and the body connect together.
Dr Rupy: Interesting.
Dr Brendan Stubbs: And how the the body can affect the mind and the risk of mental health conditions and vice versa. And the other arm is is really healthy ageing and trajectories and what influences how we we age over the course of the lifespan. And I suppose a cross-cutting theme of the research which we've done to date is looking at something called meta-research. And that's looking at all of the research that's been published on a particular area to try and give us more definitive answers. I'm sure perhaps we've all read a newspaper story about a particular exercise or a particular drug. One week it works, the next week it doesn't, the next week it does and it gets very confusing. And what meta-research does is look at all of the published data, has a look how good is the research and brings it together to try and come up with a more definitive and overall answer to say, does a particular intervention work? So we use those particular techniques to answer lots of research questions.
Dr Rupy: And I've noticed that actually, you pointed me in the direction of something you recently had published, I think it was in February 2019 about the effects of dietary improvement on the symptoms of depression and anxiety. And it was like a huge, huge study looking at 45,000 patients.
Dr Brendan Stubbs: 45,000 people. Yes, so again, massive teamwork and we worked with some really, really renowned experts on that particular project. So Professor Felice Jacka is a co-senior author on that and she did the SMILES study which is absolutely fantastic. So that's the the first randomised control trial looking at a nutritional Mediterranean style dietary intervention to try and improve depressive symptoms in people with major depressive disorder. So we worked with her and other people to look at all of the evidence base to say what happens when you try and improve people's diet and you compare it to control conditions or treatment as usual and do you get changes in people's symptoms of depression? So we included people with depressive symptoms and also major depression. And what we found is really exciting and encouraging is that you can get improvements in depressive symptoms when you have improvements in people's diet, particularly following a Mediterranean style diet. And we found some really interesting results within the subgroup analysis. So interestingly, we found that with there were beneficial effects in in in females but not males. We're not quite sure why that is. And another really interesting finding from that is that studies which also focused a nutritional intervention on weight loss also had larger effect sizes in reducing people's depressive symptoms.
Dr Rupy: Interesting.
Dr Brendan Stubbs: And we know that depression and and and overweight and obesity are commonly co-morbid or or can affect each other. So that's very interesting and also very exciting that in addition to usual care, trying to improve your diet and focusing particularly on a Mediterranean or a natural style diet, you can get improvement in in in symptoms.
Dr Rupy: Is there a way of teasing out whether it was overall BMI or waist to hip ratio or whether there was any assessment of the visceral fat and if that was more associated with depressive symptoms or depression?
Dr Brendan Stubbs: We couldn't go down into that granular detail, but it was just changes in body mass index. So we don't know if it was changes in visceral visceral fat or changes in in in muscular tissue. But it's it's really interesting.
Dr Rupy: Are there any hypotheses as to why we see a greater effect with women in these sorts of studies?
Dr Brendan Stubbs: No, we're not sure. We're not sure particularly why that is. And the the field's really emerging and exciting. So this has been all looking at trials, so interventions, but there's been some observational data where we look at people over time and look at how their diet may influence the risk of developing depression. And what what has been demonstrated again with meta-analysis of observational data is that people who eat a more traditional Western diet, so you know, higher in sugars and more refined carbs and and saturated fats are more likely to go on to develop depression compared to people who eat the less inflammatory diet. So the inflammatory hypothesis is one of the mechanisms through which may increase the risk of developing depression, but also the Mediterranean style diet is also quite anti-inflammatory. So that may be one of the mechanisms which reduces the depressive symptoms for people with with depressive symptoms and major depression.
Dr Rupy: I have so many questions about this.
Dr Brendan Stubbs: Sorry, that was a bit of a waffle.
Dr Rupy: No, no, no, of course, that's absolutely fine. Because I'm fascinated by this theory of inflammation almost underpinning a lot of different chronic lifestyle related diseases that we're seeing in the Western world or creeping up into developing countries as well as they adopt a more Western diet or Western lifestyles as well. There was a book, I'm sure you've come across by Professor Edward Bullmore that's talking about the inflamed mind and and I I absolutely love the perspective on that and how we've had a dualistic theory of of of thinking about mind and body as separate and now we're actually becoming more receptive to the idea of inflammation actually affecting the brain which was previously thought to be immunoprivileged. And also the inflammation component and how that is directly related to or causal for depression. Is there are we getting any closer to a biomarker that could essentially that we as as frontline practitioners could use in the diagnosis of mental health issues, particularly depression, and medications as well? Or lifestyle changes as I'm sure we'll talk about with exercise.
Dr Brendan Stubbs: Yeah, sure. I don't think we're at that stage yet. Most of the evidence around inflammatory changes is cross-sectional and there is some prospective data. So I don't think we're particularly at that stage yet. But as you you know, many of these inflammatory changes also occur as a result of many other factors as well. So it's quite difficult to disentangle is there a causal pathway. There has been some really nice Mendelian randomization studies and this is a really fancy genetic type of study where you look at causal pathways between an exposure, say in this instance an inflammatory cytokine and chemokine and an outcome in this instance depression. And there is suggestion that some of these inflammatory cytokines, particularly C-reactive protein, may be causally associated with higher depressive symptoms and major depression.
Dr Rupy: So I think like what I find fascinating is we can measure a lot of these different chemokines, IL-6, interleukins and all the different and TNF alpha in laboratory sessions, but we can't do that in frontline medicine at the moment to essentially give people an understanding of what may be related to their symptoms.
Dr Brendan Stubbs: Yeah, quite. And it's you know, some of those tests are as you know, particularly expensive and you can't be routinely going around taking people's TNF or or C-reactive protein as well. So hopefully some of the evidence which we'll go over the course of this talking about lifestyle being a marker of people's wellbeing and also risk of depressive symptoms could be a good indicator.
Dr Rupy: Because looking at some of the patients that I see on a day-to-day basis, I can understand where they're getting inflammation from, whether it be the another condition that they're suffering alongside depression that's causing an inflammatory output, whether it's their social situation, whether it's lack of of movement and sedentariness, which we know is associated with higher levels of inflammation. It's it's quite amazing like, you know, that we haven't developed something or something's not on the horizon to essentially test that hypothesis that I form in my sort of clinic when I'm looking at someone and how we can actually treat them using lifestyle other sort of pharmacological therapies.
Dr Brendan Stubbs: Yeah, hopefully that will be a good next stage and then we could ultimately develop personalized interventions on the front line for people based on their presentation. I think that'd be amazing. Particularly if we could go down the non-pharmacological route and looking at lifestyle as an approach for those particular people.
Dr Rupy: So we were connected by Romy, who's a good friend of mine, who's a psychiatrist, training psychiatrist. And she connected us on email. She was like, you guys definitely need to speak to each other. I'm fascinated as to what you were chatting to the trainees about because I reckon they were completely blind to the idea of exercise being therapeutic and all the other and the science base behind this because this isn't a natural part of their training, right?
Dr Brendan Stubbs: No, absolutely not. As as you know and you've championed, lifestyle medicine has has not been routine part of general medical training for a start, but particularly within psychiatry, it's it's adopted very much this dualistic treatment approach where medication or psychotherapy is the frontline treatment approach for people. And there's really good evidence base for for both of those approaches in a range of mental health conditions as well. And clearly it's important. So very much I'm a person of of invitation. I was kindly invited to go and talk to the psychiatry higher trainees about the evidence base for exercise and various mental health conditions. And I just
Dr Rupy: Where do you even start?
Dr Brendan Stubbs: Well, well, I well, we're very concerned in mental health services particularly at the moment around the scandal of premature mortality where people with mental health conditions are dying, you know, it's a human rights disgrace really that this is happening to this portion of society. So what I'll often do is when I'm talking to medical doctors or or psychiatry trainees is I'll put up some of the hardcore evidence looking at physical activity and exercise as an actual treatment for cardiovascular disease and also preventing mortality. There's a particular paper within the BMJ in 2013 which I love to put up. And it was a paper by Naci and Professor Ioannidis, who's the you know, the awesome professor at Stanford University. And essentially what they did was this head-to-head comparison in the general population of huge numbers compared physical activity versus common pharmacological interventions for cardiovascular disease mortality, such as statins, beta blockers, ACE inhibitors and and various medication classes. And essentially what they found for cardiovascular mortality is exercise and physical activity was broadly as effective as these common pharmacological interventions. So it often is a very good weighty study to put up. Obviously, medics like the BMJ, it's commonly read, it's got a lot of kudos with it. So I often use that as a particular hook to get people interested. I could keep going on and on about the evidence base.
Dr Rupy: You mentioned two different things there, physical activity and exercise. Is there a distinction between those two in the literature and how do we define what is exercise and what is physical activity?
Dr Brendan Stubbs: There is. So there's a really famous definition from the 1980s which and essentially physical activity is defined as any bodily movement that increases energy expenditure. So that literally is any bodily movement. So that could be just going to pick your hand up, pick up a cup of tea, going to do the washing, going up and down the stairs, just general moving. And and that's really important for all of us. But exercise is a a subset of physical activity where you have a specific intention to improve your fitness. And often exercise is a higher intensity than physical activity, although physical activity can be vigorous. And when we're talking about physical activity and exercise, we talk about how how difficult it is based on the energy expenditure. So we talk about light physical activity, which is typically lower levels of activity such as very light walking or doing some housework or chores. And then we have moderate physical activity, which could also be classified as exercise. And that could be brisk walking where perhaps where you're getting slightly short of breath when you're doing something or having a gentle jog or perhaps playing badminton at a not very high level. And then we have vigorous physical activity, which is at the other end where you're really panting to get your breath when you're doing a particular exercise. So it could be sprinting or doing something else quite vigorous. So that is a distinction between physical activity and exercise and the different categories of it. And most guidelines such as the government guidelines here or also international guidelines have really focused on trying to get people to do more moderate and vigorous physical activity. So currently here it is recommended that you do 150 minutes of moderate physical activity over the course of the week or 75 minutes of vigorous. It could be in in chunks over the course of a week. And we've really neglected the importance of light physical activity as well, that incidental sort of light walking, just moving around because there's really good evidence for physical and also mental health benefits that this is also important for a range of different outcomes as well.
Dr Rupy: I remember from my psychiatry rotations when I was training as a general practitioner and actually when I was a junior doctor as well, I was rotating in psychiatry, it seems like the healthcare professionals in psychiatry are not as as aware as they perhaps should be about the different issues that we were talking about there causing health inequalities, cardiovascular disease, diabetes and how they can better prep themselves and actually inspire their patients to do better and actually improve their sort of outcomes. Has that changed now? Because I remember on the mental health wards when I was working in Brighton, there was a dedicated smoking room to help essentially allow their patients to, you know, still smoke because it was thought of well, allow them to do it because otherwise it it can worsen the psychiatric outcomes. What's your opinion on that? And does that still happen?
Dr Brendan Stubbs: So things have massively changed. So when I first came on mental health wards, it was in sort of 2003 and people would say, what the heck have we got a physiotherapist on a mental health ward for at that particular time? And and times have changed and improved. And at that time we had smoking wards and if someone was going to be taken out for a walk, it would be very much let's go out for a walk and a smoke. And some of the staff would smoke with the patients as well. Thankfully, particularly around smoking, perhaps before we move into the lifestyle, things have changed massively. So my own trust, the South London and Maudsley, went smoke-free a couple of years ago. And they did lots of consultations with people using services and also staff. And there was a lot of anxiety, particularly from healthcare staff that there was going to be major issues and patients were going to get very violent and aggressive. But some colleagues published a paper in the Lancet Psychiatry, did with a time series analysis looking at all of the incidents of aggression for all of the time before the smoking ban and all of the time afterwards. And what they actually found once the smoking ban was implemented over this two-year period was violence reduced significantly by about 30% compared to the earlier part. And one of the hypotheses particularly related to that is that if you're not able to smoke on the ward and you're continuing to sort of facilitate smoking breaks, you're continually taking people in and out of sort of nicotine withdrawal. So people are getting more anxious and and agitated. So that could be one of the mechanisms. But also it frees up staff time to do more meaningful activities, perhaps, you know, taking people out for a a walk or doing something more therapeutic as well.
Dr Rupy: That's a really good way of looking at it actually. I never really thought about it because I remember that sticking in my head as a as a lowly sort of GP trainee, trying to trying to figure out like, why why are we not promoting smoking cessation? Obviously, there were it it becomes very obvious to a healthcare worker as to why we wouldn't have done that. But now looking at the data, that doesn't seem it for me, it didn't seem extensive. It didn't seem that something that would improve violent violent episodes.
Dr Brendan Stubbs: Yeah, it's it's an amazing result. I mean, you would have hoped for at least really at the data that it wouldn't have had any change, but to actually see a reduction is quite remarkable. And it's looking across big data and big numbers. So it's it's believable real life data of what actually happened. And another one of the misconceptions around smoking cessation for people with mental health conditions is that people are not interested in wanting to quit smoking or not able to and are not offered help to stop smoking. But there's really robust data from randomized control trials which is very good evidence showing that people can stop smoking. And going back to some of the points I made earlier about people dying, you know, like 20 years earlier with these common mental health conditions. You know, it's absolutely tragic. So we must do everything we can to improve the lifestyle for these particular people as well. And and it's a frightening statistic from the United States, again, nationally representative data showing that one in every third cigarette is smoked by someone with a mental health condition. So it just goes to show how common it is in mental health conditions.
Dr Rupy: And I think that that really is a a good way of describing just how much health inequality there is with those suffering with mental health conditions, particularly those with severe mental health issues, schizophrenia, depression, severe depression, because I think it's the last thing that we think of when we when we're looking at a patient, we're like, well, first let's treat the psychiatric issue because that seems to be most pressing and then we'll think about the other issues that can potentially improve their lifestyle and their risk of other lifestyle related diseases. And I think that's the wrong way of looking at it. We have to look at them more as a general patient that we're trying to improve a whole bunch of outcomes because that does have an impact on their mental health issues, right?
Dr Brendan Stubbs: Absolutely. And what I would really like to do as a piece of research going forwards is when people first come into services, particularly young people, is if at that point of crisis, obviously we can help stabilize people's mental health, but at that time, we really get in a robust evidence-based lifestyle intervention package then to support them to, you know, improve their focus on their diet and also increase their physical activity and having some of those interventions which can really improve their mental health and physical health because some of the medications which are often used, and again, I'm not going to knock the medications because they do work and they're really important for people. But like all medications have unwanted side effects, but some of the most common side effects are weight gain and also increased risk of other cardio metabolic issues and diabetes. So if at that particular moment, we can also really throw the kitchen sink at people to do this non-stigmatizing intervention of exercise and you know, lifestyle could be a real opportunity to prevent some of the downstream issues of the the weight gain and the low moods that may come as a result of it.
Dr Rupy: What sort of ways and methods have you introduced to the psychiatric trainees, the psychiatry trainees, with regards to improving their ability to motivate their patients to increase physical activity and maybe even do structured exercise?
Dr Brendan Stubbs: So it's been relatively simple pieces of advice. Equipping people very much with the knowledge about the evidence base has been an important first part to get people on side. But then it's been very much reinforcing the message that just encouraging people to do small changes can make a really important difference. Many people with long-term mental health conditions, particularly if they've been in services for a while, are inactive and not doing much. But it carries a lot of kudos if their sort of leading doctor or their doctor makes recommendations about being more active. So just having those encouraging conversations can be really, really important. So I just reinforce that message that just getting off the bus a stop earlier or just, you know, going for a walk on your lunch break or just once a day, just doing five minutes and that can be really, really important to get changes in people's mental health and physical health. And once people become more active, then they can move along that physical activity continuum and increase the intensity and the amount which they can do. So it's really empowering people with the knowledge and also the the sort of support to be able to do that.
Dr Rupy: We talked a little bit about the mechanism by which physical activity and exercise can improve mental health outcomes. It being an anti-inflammatory essentially, that's comparable to some of the drugs actually from some of the research that I've seen. Are there any other hypotheses or actually mechanistic reasons as to why we see improvements in mental health across the spectrum as is evidence in your book for, yeah, for for mental health issues?
Dr Brendan Stubbs: So there's a number of different hypotheses which we're working on at the moment. The anti-inflammatory hypothesis is is a is a common one. We're still learning in the field, but one of the other areas which is really exciting is looking at the area of the brain called the hippocampus, which is responsible for, you know, our feelings and consolidating memories from the short to the longer term. And if we look in lots of different mental health conditions such as depression or schizophrenia or even some cognitive issues such as mild cognitive impairment, we see a decrease in volume in the hippocampus. But this area is also really responsive to aerobic and potentially resistance exercise as well. So there's some, we did a paper in Neuroimage published in 2018 looking at all of the interventions for aerobic exercise over 12 to 16 weeks and do we get changes in the hippocampus across clinical and non-clinical populations? And we found that over this relatively short period of time, you can get improvements in hippocampal volume.
Dr Rupy: Increases in hippocampal volume.
Dr Brendan Stubbs: Increases in hippocampal volume, which is really, really powerful. But there was a really, really nice study conducted earlier this year and the the first author's gone from me at the moment, but it was conducted in in Japan. And it wasn't actually in people with a mental health condition, but what they did do was they they randomized these people in their early 20s to light physical activity where they just did some very, very gentle cycling and the other group just sat still. And they did a functional magnetic resonance imaging scan. So they're having a live picture of what's happening within people's brains. And after just 10 minutes of light physical activity, this really important area of the brain for how we feel and also our memories and which is decreased in many mental health conditions, they found there was this rapid firing up in terms of connectivity within the hippocampus and increase in blood flow. So although we've shown over a 12 to 16 week, you can get improvements in the volume, just doing 10 minutes, you can get real life, real-time changes in this essential emotion processing area of the brain as well and from light physical activity as well. So
Dr Rupy: That's incredible. Are there particular mental health conditions that respond better to those sort of even milder, mild increases in physical activity compared to others?
Dr Brendan Stubbs: So most of the evidence today has been looking at anxiety and stress disorders and also major depression and schizophrenia. And if you look in say depression for instance, there's there's really good evidence now that from randomized control trials, so we're comparing it to no intervention and we can causally say is the treatment that's making an improvement in outcomes. You can get improvements in people's depressive symptoms, which is absolutely incredible. So we've got really convincing evidence that exercise, aerobic and also resistance exercise can reduce people's symptoms. And the NICE guidelines which guide clinical care in the UK and carry a lot of clout are going to be changed later this year. And very much in line with the evidence around the treatment of depression, there's going to be a recommendation that as a frontline treatment for mild to moderate depression, exercise is offered as a frontline treatment, which is really exciting to see that recognition.
Dr Rupy: Is that going to be alongside treatment therapy or is it as a first step?
Dr Brendan Stubbs: Either. So it could be a first step recommendation or alongside treatment.
Dr Rupy: I can imagine it almost being a package like going along to park run or walking groups or like a whole bunch of other activities that are available to the locality of a general practice, a general practitioner. I find that there's a lot of variants up and down the country as to what is actually available to patients. And it also depends on how enthusiastic the doctor is about the evidence base or if they're even aware as well.
Dr Brendan Stubbs: Absolutely. And the individual sort of knowledge and confidence as a as a clinician to make recommendations has such a a powerful impact on whether you're likely to pass that information onto your colleague. And I I find that when I talk to healthcare professionals or medical doctors, that there is a real increased sort of thirst for knowledge. But some of the evidence is is is still not being filtered, particularly on the ground floor. Of course, you get some really interested and very forward thinking and and colleagues who will really push that. But generally because people are so busy, it's very difficult even if you are immersed in the area of the literature like we are to keep on top of it all of the time.
Dr Rupy: Yeah, totally.
Dr Brendan Stubbs: That's why, you know, podcasts like this are so important to get the evidence out.
Dr Rupy: Yeah. Well, we'll actually talk about tips for general practitioners and other healthcare practitioners at the end of the podcast just to sort of give people an understanding of like what how and why this is so important to to bring up with with everyone, I think, in a preventative manner as well as in a therapeutic manner. We talked a little bit about the anti-inflammatory effects and the changes in hippocampal volume. Are there any other sort of hypotheses as to why this might actually be having benefits on mental health issues?
Dr Brendan Stubbs: Yeah, so I don't want to be too reductionist about it. We're very much learning at the moment. You know, I spend quite a lot of time looking at the literature and we're we're not we don't have a definitive solution yet. And in reality, it's probably very complex and multifactorial. There's many factors which contribute to it. So clearly there's some psychosocial mechanisms which contribute, you know, perhaps increase in confidence in in your body, increase self-efficacy. And just feeling better about yourself and that's really important that contributes to people's mental health and wellbeing also as well. And there's also emerging evidence around sort of the endocannabinoid system, although we're not there yet, whether we can say if that definitively contributes to protection of mental health. But one of the areas which has floated around for a very, very long time is endorphins. And is it endorphins that really account for this feel good and anti-depressant effect? But we actually don't think that's the mechanism through which exercise makes people feel good because if you look at some of the physiological data, endorphins can't cross the blood-brain barrier very easily. So it's probably not related to endorphin release and many of these other factors.
Dr Rupy: Interesting, because that's like a commonly held belief I think amongst a lot of practitioners that you exercise, you increase endorphins, it makes you, you know, feel good and happy hormones and all the rest of it.
Dr Brendan Stubbs: Yeah, but the science is actually really, really shaky and there's some robust physiological data showing that endorphins have a, you know, great deal of difficulty permeating the blood-brain barrier. So it's it's not likely to be that. But, you know, unfortunately some of these hypotheses can stay entrenched for many, many years afterwards. I mean, it's kind of like the old antidepressant sort of effect that you address this chemical imbalance, you're you're depleted in serotonin and we give you these antidepressants and they replenish and improve your serotonin levels. And again, that's that's that's not how we believe antidepressants work.
Dr Rupy: We as human beings have a tendency to think about things in a very binary fashion, but unfortunately our our physiology just doesn't work like that. I'm fascinated by the number of different pathways like a single drug can impact and almost, you know, the covariance amongst all these different factors when you go to park run, for example, not only are you exercising, but like you said, you're part of a community that can again have an impact on your psychosocial factors, feeling of self-worth, feeling of community, a sense of purpose, that sort of things. So there's so many different things that you can't really count for and factor into scientific research.
Dr Brendan Stubbs: Absolutely. And we can only do our best in that. I mean, as humans, we're we're amazing what we do. I mean, we're incredibly complex and we don't understand many of the underpinning mechanisms which can contribute to it. And all we can do is try and adjust in what we do in statistical models for all of these other factors. But no human research really, particularly when you're looking at lifestyle is perfect. There's always going to be unmeasured factors and and unknown unknowns which can contribute to it. And I suppose when you're developing interventions and you're looking at a randomized control trial, so theoretically speaking, the only difference if you do a robust randomized control trial between the people getting the intervention and the control should be your actual intervention. If you do a good randomized control trial, everything else, so psychosocial mechanisms, contact, circumstances should if you use big numbers even out across both groups. But of course, it's it's research is imperfect because we're as people we're so complex.
Dr Rupy: Yeah, it's definitely and it's very hard to randomize certain lifestyle factors as well.
Dr Brendan Stubbs: Very, very, very difficult. And you find something really interesting within the physical activity literature generally. So there's a really nice interesting meta-analysis generally which looked at what happens to the physical activity levels of people in control groups. So they sign up to an exercise intervention study and then you get randomized to the exercise or the control group. So you know you're signing up to an exercise study. You would have been given an information sheet and told about the benefits of the study, why exercise is going to be good for you. And then you get assigned into the control group. And then what they find consistently is that people in the control group all of a sudden start becoming more active as well because they're enrolled in this study telling about the benefits of an active lifestyle. So it's very difficult to control for those things.
Dr Rupy: Yeah, it is. Yeah, yeah. So it's sort of sort of healthy behaviors that as soon as you heighten in people's awareness, they're like, okay, I might start moving a little bit more. You become a little bit more consciously aware and stuff.
Dr Brendan Stubbs: I find it's almost one of the ways in which I like to motivate people when I see them, you know, instead of saying you should exercise 150 minutes per week, which I find for a lot of people is largely unhelpful because it sounds very, it sounds very overwhelming, I think, for for a lot of people.
Dr Rupy: Fully agree. Yeah. 150 minutes is a lot. And there's been many weeks when I've not met 150 minutes of moderate physical activity. But the American guidelines recently came out at the back end of last year and they've they've actually shifted the goalposts in line with some of the research which is demonstrating that 150 minutes should be the lower threshold but aiming to get up to 300. But they've added a really, really important caveat to that because recognizing that so many people do not meet 150 minutes, particularly those with chronic physical or mental health conditions. And just really emphasize that if you are, these are aspirational targets and if you're not meeting those, just getting started and making small changes, just a couple of minutes a day can have a real important impact on your physical and mental health as well. Because these targets are not meant to put people off from being active because it's it'd be easy. I mean, many of the people that I work with would look at the and say, I'm I'm never going to do that. I'm just not going to get started. But that is not the purpose of guidelines. So that's been reflected recently within the American guidelines as well.
Dr Rupy: I like this concept of physical activity and improvements in that because there's so many different movement hacks that I talk to people about, like standing desks, for example, moving around every hour or putting a timer on your phone so you actually get away from your screen, as well as things like using the stairs or I I don't use the stairs when I use the underground, but I do walk up the escalators. I think that's kind of like my compromise for it.
Dr Brendan Stubbs: Yeah, those small little snacks throughout the day are just so, so important as well. Yeah, just taking those small changes.
Dr Rupy: I'm fascinated by the evolutionary advantage of or disadvantage of having depression. Like, why does this actually happen? There's so much beauty in our design, like how our cells work and how we take in macronutrients and then convert them into energy and stuff. Why does depression happen and why do we and I'm putting a massive question to you at the moment. I'm going really deep here, but why does this happen? Why are we seeing record levels of it? And I I know this is a complicated question and and answer as well because there's so many different factors that will contribute as to whether one person has depression or not. And our traditional treatment is just you give a pill for an ill and there's there's one diagnosis and there's one answer. But this there has to be a reason as to why we are seeing record amounts and what has happened and what we've done to our environment that can be contributing to it.
Dr Brendan Stubbs: Sure. So let me start by
Dr Rupy: Big question.
Dr Brendan Stubbs: Yeah, no pressure. Okay. So let me let me start by saying, you know, depression is extremely complex. You know, there are there are really there's a number of important genetic factors which contribute and increase people's risk of developing depression as well. So we can't ignore genetic predisposition for some people. But there's a number of important environmental risk factors which predispose people's risk of developing depression earlier. I mentioned earlier Professor John Ioannidis at Stanford University and he has developed a particular technique to understand how good is all of the evidence on a particular topic. So if you look in the literature, for instance, at what may contribute as environmental risk factors for depression, there will be lots of meta-analyses that have looked at individual exposure such as, you know, social status, whether a relationship breaks up, whether sex makes a difference. And he's developed this method called an umbrella review where you quantitatively reappraise all of the evidence for risk factors for a particular condition. So we worked with Professor Ioannidis and published a paper last year to look at every meta-analysis that had ever been looked at to say what are the environmental risk factors which contribute to depression. And you do a number of statistical tests and you essentially classify the evidence into four different grades through some statistical tests. And if I go into detail, I will send everybody to sleep, but I'm happy to send people the paper. But essentially you come up with is the evidence convincing, highly highly suggestive, suggestive or not significant. So you look for biases within the data, is there enough cases and samples. And essentially out of 134 pooled meta-analyses, so people had pulled data 134 times from lots of different environmental exposures, we only actually found five environmental risk factors with convincing evidence which contributes to the risk of people developing depression.
Dr Rupy: Okay.
Dr Brendan Stubbs: So those risk factors with convincing evidence were obesity, having four or five metabolic risk factors, sexual dysfunction, trauma during the childhood, and also relationship issues if I remember correctly. So a lot of the evidence is really not up to scratch about what is actually contributing environmentally to the onset of depression. This is looking at big data population level. So that's not to say that other factors don't contribute. Clearly it can for individual people. So hopefully in a rather sort of long-winded way, I've I've emphasized that depression is complex, it's genetic, there are environmental risk factors which come together to increase people's risk. Getting on to your other point about why are we seeing this increase in surge and high levels of depression. Again, I think it's it's complex, but we're we're much more open now as as a as a population and and as a community, we're being much more open to talk about our own mental health and you know, there's been some great role models within the media of people talking about struggling with their mental health and it previously we've, you know, very much had a sort of, you know, don't sort of talk about it, you know, don't sort of disclose it. But now there's been a real shift in awareness for high profile people coming out and talking about it. And also amongst healthcare professionals as well. People are much more aware about it. So I think it's a combination of increased awareness, people's increased willingness to go and seek help and increasing information that there are treatments that we can do to help you.
Dr Rupy: Actually, there's a colleague of mine who's on the on the clinical entrepreneurship program as well and he talks very openly about mental health issues within medical staff, particularly those in the front line. He's a pediatrician and you know, the concept of having to deal with psychological trauma of being in an emergency scenario where you're at a cardio arrest situation and then you're expected to just go to work straight after that and then go to work the next day and the day after that, having had that traumatic incident. For most people in general sort of like non-medical environments, that would be harrowing and they'd have to take weeks off work. But being a medical practitioner, you need to get used to that. So there has to be some sort of way in which we allow for that sort of that that normal response to a stressful scenario like that to to essentially process it ourselves. And at the moment, we don't we don't have that. And I think that's a really important point amongst medical practitioners to be very open about the fact that we we we do have issues and it is we have to process them ourselves.
Dr Brendan Stubbs: Of course. And you know, it's so so important because life can be hard for for us all at certain times and particularly when you witness difficult situations like you will do in hospital environments. I mean, generally when people come and see us as healthcare professionals or particularly in emergency departments, things are not going particularly well for people. So it's you know, it's it's quite obvious that we're going to see difficult situations and people in great distress. So to not be affected by that and be surrounded by that, you know, you'd be you'd be superhuman or you you wouldn't be human. Of course, it's natural that we're going to be affected by people's distress and people's loss and bereavement. And it's so important to be open and honest and you know, have good role models who can you know, talk openly about how they're dealing with things as well.
Dr Rupy: What what was sort of your fascination for the field? Because you've dedicated 15 years of your clinical life to this now and you're super published as we as we mentioned. What's like your driving force for this? Why are you so fascinated with mental health?
Dr Brendan Stubbs: I just find it such a fascinating area for so many reasons. I just really feel a passion for people with mental health diagnoses and coming in as a as a physiotherapist with physical healthcare training, I was immediately in mental health services able to spot those inequalities and the the high levels of of of lifestyle sort of behaviors which weren't particularly positive. And I just really came in and started to try and do understand what the evidence base was for what I was trying to do as a clinician and just sort of thought, gosh, you know, there's really not much evidence at this particular time. And I just thought, gosh, you know, maybe I should try and do something about it and went on a long journey to try and to become better at research and contribute in in that way. And I just feel it's it's an enormous privilege to be part of people's lives and stories and working with with those in mental health services. So my Thursdays is a clinical day for me and I work in a secure hospital in South London. And it's just such a privilege to be part of those people's lives and to to help them on an individual basis. And and a lot of the other things is the the scandal of premature mortality. I mean, people with severe mental illnesses are dying 20 years before people without, you know, that's an absolute disgrace and it's largely due to preventable physical healthcare conditions. We can do something about it. So just trying to jump up and down and make some evidence to try and do something about it is really what drives me.
Dr Rupy: It's very humbling to be in a position where you can help people at their most vulnerable states. And do you think you going in as a physiotherapist and actually spending a lot more time individually with patients, even though a lot of psychiatrists actually do have the the privilege of spending a lot more time with them. Do you think that gave you a different perspective and it was actually a lot more obvious to to you the health inequalities that you saw and now are trying to do something about?
Dr Brendan Stubbs: Yeah, it was immediately obvious to me because naturally as you'd want, mental healthcare teams are really, really good at looking and focusing on looking at people's mental health and managing their mental health symptoms. Coming in as a physio with a, you know, an overwhelming focus on physical health and lifestyle, I was immediately able to see some of these issues that people are having, you know, people having like pain or, you know, being really overweight and seeing how I could contribute to that. And now going forwards, I think it's a real advantage, particularly with the evidence base, but I also find that because I really go in and often help people's physical health, some of the patients or service users I work with, you know, really enjoy that time out from sort of the core mental health team and come and see me and perhaps go and see people in the gym and have that time to talk out of the context of sort of core mental health team, although I am part of it, but being a sort of physio, I can, you know, sort of slip under the radar a little bit and build up a good rapport with people and it's it's just such a privilege to to go in and do it.
Dr Rupy: Do you think their guard kind of slips down because you're spending a little bit more time, you're talking about something a little bit different outside that sort of like medical medicalization of what they're used to with the doctors and and nurses and stuff?
Dr Brendan Stubbs: Yeah, I do. I think it really does go down. I mean, most of my clinical work at the moment is in a secure hospital. Just also to sort of say that data has shown again and again and again from robust data that people with mental health conditions are much, much more likely to be victims than to be perpetrators or engage in any sort of crime. But some people do end up in in in the criminal justice system. So instead of languishing there and not having their mental health treated and being and being really unwell, they come into a secure hospital and that's where the focus of my clinical work is at the moment. So many of those people I work with have have been in, you know, prison for a very long period of time or mental health services have difficulty building up trust with people. And I often find that sort of being in a in a physio and looking at people's sort of muscles and bones and fitness, they really like that. You know, they don't see that I'm coming in to sort of come and assess their mental health and I can really build up a good rapport with people and it's it's just such a privilege to to go in and do it.
Dr Rupy: If you could redesign, not maybe you don't want to redesign, but if you could design the perfect sort of like mental health environment for those who are in a mental health institute or in those in the community, how would you do, how would you go about doing that? And where would you put perhaps a little bit more focus? I pretty much know what you're going to say, but just for those listening at home.
Dr Brendan Stubbs: So, early intervention is key. So when people are presenting with their first mental health crisis, clearly they need to have their mental health assessed. In an ideal world with unlimited funds, what I would like to do at that particular time is also have like an adjacent, you know, gym or other fitness health studio which is also has like kitchens. So immediately when people come in for their first treatment and perhaps when they're they're sort of stabilized or they're well, they can come in and we can really engage people in exercise and also, you know, nutritional interventions as well. But that should be very much a follow on because we don't want people to stay in mental health services, we want people to get well and go out in the future. So help support people once they are stabilized to go into the community to live, you know, healthy lives longer term. That would be a sort of real dream when first comes into contact and we can really help boost people's self-esteem and prevent some of the other issues which can arise when medications are perhaps first prescribed and people get weight gain and so on and so forth.
Dr Rupy: So I know your legacy is going to be kitchens and gyms in institutions that are helping people A with their acute interventions, but B helping them again go back into the community and live normal happy lives.
Dr Brendan Stubbs: Absolutely. Because, you know, if you go into like a new gym or something like even myself, if I go into like a new gym and it's busy, you know, it can be quite anxiety provoking if you don't know where the equipment is or where stuff is. So I think, you know, enabling people when they first present to have positive experiences around making lifestyle choices, but then also in a, you know, buddying up with people and going into like local community and supporting them to make links and have positive first experiences would be so important for people because we don't want people to be put off to engage. And of course, gym's not for everyone. It could be going to park run, it could be going for a walk, it could be trying out a local yoga class. But just really helping people make that smooth transition would be really powerful.
Dr Rupy: And you said at the start that you're interested in mind-body interventions and stuff. Are there any particular ones that that shout out to you or perhaps have a bit of an evidence base than others?
Dr Brendan Stubbs: Yeah, so interested in yoga. So there's good evidence around yoga as a particular mind-body intervention for various mental health conditions going forwards. There's also some evidence around Pilates can help as a as a mind-body intervention. But they're the main ones I'm interested in at the moment.
Dr Rupy: I had a colleague of mine, Dr. Claire, come in and we're talking about yoga and the evidence base behind that. It's quite fascinating just how many different health issues that yoga can be helpful for. I practice yoga myself. I go to the odd class, but I tend to do it on my own because I don't like looking at the teacher all the time and cricking my neck and figuring out which position is the best to to be doing or whether I'm doing it right at all. But that's super interesting. So
Dr Brendan Stubbs: One thing I didn't mention was about like why exercise helps with depression.
Dr Rupy: Okay.
Dr Brendan Stubbs: So we we we did a randomized control trial with some colleagues in Germany and again, we we looked at aerobic exercise supervised over 12 to 14 weeks. And we wanted to try and understand what are the neurobiological underpinnings of that. And we found that there was a change within this substance called BDNF or brain-derived neurotrophic factor, which is very important to stimulate brain cell regeneration in in key areas. And we found quite an exciting increase in BDNF and that could be one of the mechanisms which is related to the antidepressant effect of exercise and also really influential into the hippocampus.
Dr Rupy: That's really interesting because I've read a lot about that with regards to Alzheimer's and cognitive decline and how that might be having a positive effect on symptoms and slowing, I know there's nothing that really definitively reverses Alzheimer's at this point, even though there have been some anecdotes in the literature, but certainly helping with symptoms and slowing the progression of a quite a harrowing disease.
Dr Brendan Stubbs: Yeah. Yeah, so yeah, the evidence around sort of exercise as an intervention for dementia is there has been some promising smaller randomized control trials which have been published previously showing that it may help slow the decline compared to treatment as usual. And there's been a number of pooled meta-analyses that have looked at that particular data. But there was a big study done led out of the University of Oxford by Professor Sally Lamb called the DAPA study. And it was published in the British Medical Journal in in 2018. And essentially what they did was a real high intensity supervised exercise intervention, a really robust, credible study and they compared it to treatment as usual and recruited a large number of people over 300 people with dementia from memory. And they actually found that exercise didn't have a beneficial impact on people's cognition. So because this is a particularly large trial, larger than anything that had ever been published before, we're we're sort of a bit more less optimistic about the potential for exercise for slowing cognitive decline. However, adding that caveat, there are many other benefits from being active for people with depression such as working on helping people improve their mobility, preventing falls and all of the other things as well.
Dr Rupy: Especially if you consider depression and mental health illness is actually one of the commonest causes that we see for sick days and people not going returning back to work. You know, there's so many other benefits of exercise that you want to factor in. It's not all about the parameters within a particular experiment.
Dr Brendan Stubbs: We we published a meta-analysis last year looking at people's physical activity levels in the general population. We looked at over 260,000 people across the world. And we looked at how active they were and what was their risk of developing depression like in the future on average seven and a half years later. And we found that people who were most active compared to those who were least active were around 15% less likely to develop depression in the future. That was evident when we adjusted for other factors that may contribute such as people's body mass index, chronic conditions, people's age and sex. It was evident in children, in adults and older adults. But the most potent effect was when people met 150 minutes of moderate physical activity over the course of the week and there was around a 30% reduced risk of developing depression in the future. And that was evident across all geographical continents. So we're looking at population data here. Now this is observational data, so we're just observing people over time and we can look at the direction because people are free from depression at baseline and we're looking at follow up, do they get depression? But it's still observational data and we can't make causal inferences from observational data. But there's very, very recent, literally within the last month been a very exciting study, again, a Mendelian randomization study, which is a real fancy genetic type study looking at gene environment interactions to say is there a causal pathway between physical activity and major depression? And essentially they found in over 300,000 people, there is a causal pathway between being more active and protecting against the emergence of depression. But also there's a number of small randomized control trials which have also backed this up. So there's been two randomized control trials where instead of the intervention being something helpful like let's give people a drug or give people exercise, the intervention for people in their early 20s with no mental or physical health condition was sit still, do not move, be more sedentary and the control group carried on as usual. And what they found is this enforced sedentary behavior in these healthy young, you know, people in their 20s.
Dr Rupy: They made them sit down.
Dr Brendan Stubbs: They made them sit down. That was the intervention. They enforced sedentary behavior.
Dr Rupy: Wow.
Dr Brendan Stubbs: And what they found was over a four week period, those in the intervention group who became more sedentary started to have low mood and become depressed. So we've got the observational data from our meta-analysis showing an increased risk of depression from being inactive. We've got this genetic Mendelian randomization data now showing there is a causal pathway. We've got some randomized control trial data showing if you enforce sedentary behavior, there is a causal pathway. And one of the studies published in the British Journal of Psychiatry looked at the mechanisms for that and they found it was related to changes into interleukin six as well. So that's probably one of the mechanisms which goes again to the inflammatory hypothesis. I don't want to be too reductionist about it again, there's many other factors which contribute. But it just goes to show at a population level just how important being active can help us to maintain a positive mental health.
Dr Rupy: Wow, what an episode with Dr Brendan Stubbs. He really is an absolute fountain of knowledge. He was sat across me without any notes and just pouring out study after study just at the top of his head. He really is an incredible academic and a clinician and I'm so excited that he is pioneering the research looking at exercise-based interventions for mental health illness. And coincidentally, exercise-based interventions for mental illness is the title of his book that I highly recommend health practitioners in particular get. One thing to reiterate from our conversation with Brendan and something that he agrees with is that it would be naive and reductionist to think that we can reverse all of our symptoms of depression or other mental health issues with just one intervention alone, be that diet or movement or pharmaceutical. And in many cases, patients require more than a collection of foods or an exercise regime to treat something as complicated as mental health issues. So it's not simply a case of a neurochemical imbalance that needs boosting and it's really, really important to keep sight of that. Making sure that you get the right help and interventions from your doctor and other health professionals is key. And psychotherapy as well as exercise, as well as diet, as well as pharmaceutical interventions on occasion can all have an important role. We talked about inflammation, we talked about diets, we talked about movement and just increasing physical activity rather than just focusing on specific exercise regimes can all have benefits to our overall wellbeing and in particular our mood. These are all topics that I talk about in my new book, Eat to Beat Illness, in the section on mood where I talk about nutritional science, but also lifestyle features that can improve and preserve our brains, our cognition, as well as our psychological wellbeing. The links to all the academic references are on the show notes at thedoctorskitchen.com. You can find Brendan at Brendan Stubbs on Twitter and Brendan.Stubbs on Instagram. Plus, the links to all his research is actually on thedoctorskitchen.com as well. He has a research gate profile, the links to all of his 400 plus academic references. It is really a library of information that he's created. Make sure you give this podcast a five-star rating if you enjoyed it. It really does help other people who can find the information useful, find it. And subscribe to thedoctorskitchen.com on the website. I'm trying to put out newsletters every two weeks to give you top tips on how to improve your wellbeing. See you next time.
