Presidential Lecture Awardee: Holistic conceptualization of patients with chronic illness | Congress 2025

At the Department of Basic and Clinical Neuroscience Institute of Psychiatry, Psychology and Neuroscience at King's College London, and he also happens to be the winner of the Stan Fahn Award lecture during the MDS International Congress in Hawaii this year, 2025. And today we're gonna talk about what he's been musing about with regard to interface disorders, neurology, psychiatry and all that goes along with that.

So thank you so much for joining us and welcome.

Prof. Mark Edwards: Thanks very much. Thanks for having me.

Dr. Sara Schaefer: And of course, congratulations on [00:01:00] your award.

Prof. Mark Edwards: I'm extremely honored and grateful and still in a little bit of shock to be honest. But yeah, it's a great honor to me to receive that award from the MDS.

Dr. Sara Schaefer: Well deserved. You have been on our podcast a couple of times talking about various things and you spoke in our June 2024 hot topic episode about the breakdown between pathology and phenotypes. So how one pathology or one genotype can lead to multiple phenotypes and how one phenotype may be explained by multiple pathologies.

And then of course Mark Hallett pointed out in that episode that there's the black box of physiology in between, some of which we understand and some of which we do not. As much as we would like things to be clean, straight lines, they're usually not, is basically the long and short of it. So how does this line of thinking affect your approach to your patients and your work?

Prof. Mark Edwards: Well, I think it's part of, really just a general recognition of complexity and I think [00:02:00] in order to do anything, you have to try and get rid of some of the complexity. 'cause otherwise a problem is just too big. But I think sometimes that results in forgetting about the fact that actually you did do a lot of simplifying in order to answer the very narrow question that you've then tried to answer.

And that ends up producing problems, I think, in the way that we might interpret research results. Or we might think about treatments for specific patients, test treatments, then try and implement them and can result in a bit of frustration I suppose. In a clean, very controlled situation you can get something to happen and then when you put it into a more real world situation, it doesn't work like that.

And I suppose one approach to that is to say we need to do the experiment again. We need to think more. But some of it is just that the way that things have been set up sets you up to fail a little bit in that way.

Dr. Sara Schaefer: [00:03:00] Definitely. So you're talking about science, right? Thinking about science and how we always want things to be nice and clean and crisp and wrapped up in a little bow, and we wanna get rid of any confounder that we possibly can and exclude any patient that might make things a little bit more complicated.

It sounds like you think that scientific inquiry might be approached a little bit differently.

Prof. Mark Edwards: Yeah I think it's not an either or because I think there's a big, there is a benefit for really trying to simplify and define things and to control things very carefully. It's just you have to keep remembering that you've done that when you then try and extrapolate the results, and I think that's the thing that goes wrong.

One can see it all the way through medicine in clinical trials, definitely not the first person to say this that, randomized clinical trials are a fantastic tool, but they are done in a very well-defined, very controlled population. And so it's not surprising, therefore, [00:04:00] that when you try and put that into practice.

In real life, sometimes the results just can't be replicated or you get other results. We've seen that recently in, Alzheimer's disease trials where the makeup of the populations in the trials, and this is quite common, tend to be from a higher socioeconomic group, they tend to have less ethnic diversity and so on.

And so then you end up with results, which can't be applied to a larger population. And I think that's also the case in more basic scientific research. Particularly when you're involving patients, because we're defining patients often in a phenotype way.

So if we say we're gonna do a study in people with cervical dystonia, we get those people because we know what they look like basically. And then maybe we get some results, which are a bit difficult to interpret. Maybe at a group level there's no effect of the intervention or the thing we're testing.

But actually it might be interesting to look beyond that [00:05:00] and to see maybe there's individual clusters of patients within that and because maybe actually they've got a different underlying mechanism for their cervical dystonia compared to the next person, even though we lump them all together. 

Dr. Sara Schaefer: I think ataxia is a really good example of that. You know, the older studies took all comers with ataxia some including genetic ataxias and maybe you throw some MSA-C in there and see what happens with these medications. And then interpreting the results is so difficult and that now that we're getting down into actual genetic diagnoses like SCA27B for example, we're finding that these smaller subsets of patients do respond really well to certain things whereas other ataxia patients don't.

Is that kind of what you're saying?

Prof. Mark Edwards: Exactly right. But at the same time, there's complexity there as well because it depends what you're trying to do in the end. If you've got an intervention which is [00:06:00] working at a low mechanistic level then it's really important to do that clustering and to maybe get more isolated groups, which have a particular mechanism.

But there must also be a higher level where all of these patients converge on a higher mechanism that's producing the things that we can probably see in clinical practice, or maybe a small number of mechanisms. And one example of that might be the use of deep brain stimulation surgery to treat tremor. Where effectively, more or less, whatever kind of disease it is that's causing the tremor, you can put a lead in part of the thalamus and you can get a response.

So that's telling you that there must be this higher level of mechanism for the movement problem, which is active across multiple diseases. So that gets to this point that we need to investigate at multiple levels, but keep thinking about what we can achieve best at one level [00:07:00] versus another.

Dr. Sara Schaefer: You make me also think about, Parkinsonism. And in my mind, sometimes I split people up into presynaptic Parkinsonism versus post-synaptic Parkinsonism. And those post-synaptic patients may respond to different medications like dopamine agonists, for example, more than levodopa. If it's from some sort of subcortical insult, for example, it sounds like that might be another example do you think?

Prof. Mark Edwards: There is a value in understanding the mechanisms that are really close to the production of abnormal movement, the actual production of abnormal movement. So if you think about a complex degenerative disease there's lots of changes that are happening in the nervous system or in the brain, for example, which may not be mechanistically connected to the production of abnormal movement. They're just part of the disease process. And when you [00:08:00] do an investigation, you do some sort of study on the brain, you are picking up those things. You may be picking up things which are actually mechanistically related to the movement problem itself, and it'd be nice to be able to separate them out a bit because you could do something maybe quite specific if you knew exactly what was the mechanism of the movement problem itself, and that might be common across multiple underlying diseases. So it's this idea of having a kind of multi-layer look at things rather than just saying, oh, we're gonna investigate, I'll say cervical dystonia again. And you just grab a group of patients with cervical dystonia, do some tests on them, and assume that everything that you found is mechanistically related to the production of abnormal movement itself.

'cause it probably isn't.

Dr. Sara Schaefer: It sounds like you're a splitter, not a lumper.

Prof. Mark Edwards: I 'm [00:09:00] both. So I think it just comes down to saying what is the purpose that you're trying to achieve, and what is the level that you're investigating? And that allows you to shift between these different perspectives. And I think it's that, that gives you more insights.

One could see that in the, this whole debate around the biological definition of Parkinson's disease, for example. And the recognition that within this thing we call Parkinson's disease, there are probably multiple, there are multiple disease processes. So there is a clear rationale for splitting in that way.

But there's also a clear rationale, I think, for lumping together, not just from clinical services, but actually from a development of novel treatments point of view. Because if you can understand that higher level of how is this particular time of abnormal movement being produced, you could do stuff about that regardless of whether you change anything about the disease at all.

So it's got that real therapeutic potential, which we can see [00:10:00] is, you know, manifesting in things like deep simulation, for example.

Dr. Sara Schaefer: I'm gonna switch gears a little bit here to to one of your favorite topics, FND or functional neurological disorders, which talk about complexity. That would be the common thread here. It's such an interesting case study when one thinks about how neurology and psychiatry divorced 150 years ago or whenever it was and how we think of things in terms of this dichotomy between the two.

It's one or it's the other. What is your exploration into FND taught you about the way the medical community approaches FND and other amorphous disorders. We could throw in chronic fatigue syndrome, fibromyalgia, dysautonomia, hypermobility disorders, these amorphous disorders that are not well understood.

What are your thoughts on that? 

Prof. Mark Edwards: Wow. It's a big topic and one that I've thought about a lot. I think first of all, just f [00:11:00] undamentally, I cannot see how one can be a successful clinician or researcher in the neurosciences without having an interest in psychiatric and psychological and psychosocial levels of behavior and function because it's all in the brain.

And if you've got a brain problem, it's likely to affect all of those dimensions. I think that, good clinicians have always recognized that and have that holistic approach, but unfortunately that's rarely facilitated within our clinical services. And it's rarely facilitated within research where things tend to be split up into different things.

I think one of the issues there is it's really hard to measure and therefore to value the complex interventions or [00:12:00] complex management that people with disorders that cross over this barrier between neurology and psychiatry need. And that's most of our patients in neurology, particularly movement disorders.

Because the other stuff, which is not the sort of hard, measurable, objective stuff, feels very soft and it's quite hard to characterize in the way that we got used to characterizing our interventions and so on from a neurological point of view. So it's therefore very easy to say it doesn't really matter or that it should be quite cheap or it's easy.

In fact, I think that's the hardest aspect of medicine really. And I suppose my overall feeling is that this comes down in the end to complexity. So when you ramp up the complexity that's where health services start to fall apart, and that's where health professionals get under increasing stress and strain.

And that's when patients and families get a [00:13:00] bad deal. And that's magnified or, incredibly obvious in FND. So one of the main reasons why people with FND often get quite a bad deal is because of that complexity. But actually that's true for multiple patients. And particularly within movement disorders, we regularly see people with high complexity.

And I think if the listeners think of people where things have gone badly wrong, it's usually because of this complex relationship between neurological and psychological and psychosocial factors. That's brought me to this place in the end, I think making things better, so understanding FND more, making better services, that's a good thing in its own right.

I strongly believe that if we could really get that right for people with FND, then that would help everybody with chronic complex illnesses because the things that you need to do to get it right for people with FND are the [00:14:00] things that would benefit people with other conditions.

Dr. Sara Schaefer: Yeah, with any chronic illness, your psychosocial dynamics impact your physical self and vice versa. So that needs to be recognized and addressed.

Prof. Mark Edwards: Absolutely. I think that something that's been made clear to me in seeing people with functional neurological disorder where there's often this question about voluntary and involuntary, and how much is the person participating, helping the person understand their own illness and so on.

This loss of sense of agency that appears to be there in functional neurological disorder, and how do you give it back? That's taken me into this space that I wasn't in before, which is really fundamentally about rehabilitation. So a rehabilitation approach to medicine, and understanding that you then see that how actually modern medicine takes that away, takes that agency away, often from people who are ill generally. [00:15:00] And giving that back or facilitating that in the person and within their family unit is a massively important part of successful management, people with neurological conditions. And so you could see that in the, for example, in the use of exercise as a treatment for Parkinson's disease and how, if you instill from the very beginning that somebody's got this really frightening diagnosis.

But look, there's something that you can do, you can put into place that can help with this. And that's your responsibility. But I'm gonna help support you with that. That's a massively beneficial thing then this sort of passive situation of being told, oh, you've got Parkinson's disease, it's incurable.

I'm gonna give you some medicine. I'll see you in six months. It makes a massive difference. So I'm really enthusiastic about this rehabilitation model of management of neurological conditions and that, that comes across really strongly in management of people with functional neurological disorder.

Dr. Sara Schaefer: Absolutely, [00:16:00] and I agree with you that it is just so paramount to the treatment of patients with Parkinson's and other neurodegenerative or chronic conditions. I've definitely found that in my own practice. 

Prof. Mark Edwards: I was gonna say that also one thing about that idea of shifting to that rehabilitative model of medical practice where the person you're giving the person themselves agency is it does require the health professional, the doctor or the other health professional, to have a degree of humility.

'cause you're effectively giving up some control. You're saying, actually some of this is for you and you are gonna help me understand how best to treat your illness. That's not easy. And you also see it in the sort of relationship between doctors and allied health professionals and psychologists as well, where in order to work in that multidisciplinary way, again, you have to give up [00:17:00] control. I think that sometimes things that are called multidisciplinary are really not, they're people working in silos in their own very strictly controlled bit of work. But true sort of interdisciplinary care does involve this, which has to involve the patient as well, does involve this reduction in your own control as a health professional.

And that's not easy. But I think it, when it works, it works really well.

Dr. Sara Schaefer: Not easy for all us type A personalities.

So you're talking about multidisciplinary and interdisciplinary care, which is so important and I mentioned the divorce of psychiatry and neurology that happened way back with Sigmund Freud and ultimately resulted in split specialties, split departments, split lines of research. Do you think that this institutional dynamic needs to change, and especially as we start having the [00:18:00] ability to less expensively and only in experimental settings and more in clinical settings. See what's physiologically happening on the psychiatric and psych neuro overlap, functional side of things. How do you see the future as it relates to the care of patients with these diseases?

Some of which we may right now be able to explain well physiologically and some of which we can't. Do you think that neurology and psychiatry are gonna ultimately come back together?

Prof. Mark Edwards: I really hope so. I think it's quite hard to do that. And I think there are reasons for specialization. Management of severe mental illness like schizophrenia, that demand some specialization. But even in that example, if you look at people with schizophrenia, they die on average 15 to 20 years earlier than they should. Not predominantly from suicide, but from treatable physical health problems like chronic airways disease, diabetes, heart [00:19:00] disease, cancer. Human beings demand an integrated healthcare system, and we have to do something to make it better than it is at the moment, because by splitting off into smaller and smaller bits, particularly this big divide between physical and mental health, we do people a massive disservice.

That also requires, though, some change within the way that the sort of discourse happens within the public as well. Because it is not just health professionals who are dualistic, it's everybody. And you can hear it all the time. For example, there was a recent paper published that was looking at genetic markers in people with chronic fatigue syndrome and the reporting on the news was largely, CFS is now shown to be a real condition because it's been found to have these genetic biomarkers. So that is a pervasive view out there. When you start to break it down, it's completely illogical.

And the people [00:20:00] saying those things are really intelligent people, but there's just a blinkered way of thinking about what's real or not real. I think there's a danger of going the other way in functional neurological disorder and psychiatric disorders to say that, oh, now we found some brain biomarkers, or there's this brain network dysfunction.

That means that's the best way to talk about this problem. That's stupid as well because we know that people who develop functional neurological disorder have about six times the risk of having past traumatic experiences. Doesn't mean everyone has, but it's there. People with functional neurological disorder often their symptoms are made worse by psychosocial stressors, and they often are in complex psychosocial situations and there's high comorbidity with mental illness. So if you treat it just like a sort of brain network disorder, then you don't get any of that either. But again, I think it's about trying to understand that all of the disorders we're talking about are [00:21:00] basically in this same space. If we understand that, then we understand that all of the people in this space need an integrated kind of approach to clinical services and to scientific research.

And so it takes a little bit of the sting out of the making FND some kind of weird or bizarre thing. It's actually just really very much the same as lots of other things as well. And we should just have the same general approach to that. Just be normal.

Dr. Sara Schaefer: This has been a really interesting and enlightening conversation. Thank you so much for sharing your thoughts, and I really look forward to your lecture in October.

Prof. Mark Edwards: Thank you very much. It's a pleasure. [00:22:00]