When Psychiatry Meets the Immune System with Dr. Tom Pollak

And then there's this sort of. This recent emergence of this other strain which is saying, well, no, no, quite the opposite. Psychiatry is not medical enough. It's not, you know, we are psychologizing these people too much. There's no way that the psychological formulation of my problems could have any kind of truth at all. And in fact, the answer is some sort of biological factor. And usually it's only one. Right. And of course, a lot of the work that our group does shows that the. There is this hugely dynamic interaction between the biology and the psychology. And in fact, then they're not. They're not separate things.

Hello, I'm Dr. Farah White.

And I'm Dr. Grant Brenner.

We're psychiatrists and therapists in private practice in New York. We started this podcast in 2019 to draw attention to a phenomenon called the Doorknob Comment. Doorknob comments are important things we all say from time to time, just as we're leaving the office, sometimes literally, hand on the doorknob.

Doorknob comments happen not only during therapy, but also in everyday life. The point is that sometimes we aren't sure how to express the deeply meaningful things we're feeling, thinking and expressing, experiencing. Maybe we're afraid to bring certain things out into the open or are on the fence about wanting to discuss them. Sometimes we know we've got something we're unsure about sharing and are keeping it to ourselves. And sometimes we surprise ourselves by what comes out. Today on Doorknob Comments, we're delighted to welcome Dr. Thomas A. Pollock. Dr. Pollack is a reader in immunopsychiatry at the Institute of Psychiatry, Psychology and Neuroscience at King's College London and a general adult psychiatrist at South London and Maudsley NHS Foundation Trust. His specialist clinical interest is in neuropsychiatry, and Tom has more recently been applying his considerable talents to address emerging psychopathologies of the technologically extended mind, sometimes referred to as AI psychosis. Tom's research focuses on neuropsychiatry, psychotic disorders, encephalitis, neuroimmunology and immunopsychiatry. And he's a consultant neuropsychiatrist with a special interest in autoimmune encephalitis. He leads an immunopsychiatry research group at King's College London oriented towards understanding the role of autoimmunity and infection in psychiatric disorders. His recent piece in Brain Journal, why Inflammatory Reductionism Is a Threat to Psychiatry, explores the emergence of a new worldview which attempts to explain all manner of ills as the result of inflammation or immune dysfunction. He argues that while this view is rooted in science, it neglects the true complexity of most health conditions and risks undermining the more holistic concepts of illness favored by psychiatry. Tom is co investigator and clinical lead for the Wellcome Trust funded Immune Mechanisms of Antipsychotic Treatment Response Study. He has a developing research interest in the neuroscience, phenomenology, neuropsychiatry, benefits and adverse effects of meditation and other contemplative practices. Sounds like you're very busy. Welcome to Doorknob. Comments, Tom thank you.

Thank you. It's a very extensive introduction. I, I appreciate it. It's all accurate.

Very good. So, you know, we thought our focus today could be on helping people understand the concept of autoimmune disease as it relates to psychiatry and psychosis. Though you have many other things we may touch upon. I think there is a lot of misinformation about this and it's always the case in psychiatry that whatever is most present in the news cycle, you'll see people coming in and kind of wondering about that specific thing. As well trained clinicians, we know we want to approach the patient as a whole person, though, and not get channeled in too quickly. So that's what we would like to start with today. Could, could you tell us a little bit about how you see the state of the art when it comes to this concern?

Yeah, thank you. I mean, I've been sort of interested in the immune system and mental illness in the mind for sort of been working it for around 15 years or so now. And I. And they've been sort of two discernible hype cycles that have been kind of right the way through. It's like, it's like my Birkenstocks.

I've.

I've had them for about the same amount of time. They've been fashionable at least twice in that. In that period. But I think we're. I think we're in a second time actually a second sort of period where for various reasons there's a lot more interest in the immune basis of psychiatric illness, psychosis in particular. There's a wonderful article last year in the New Yorker which really helped sort of shine a lot of attention on it again by Rachel Leviev, who writes so, so beautifully about, about mental health and in a really nuanced way, and it's actually that kind of nuanced approach that I think is missing a lot of the time. I, I went into neuropsychiatry rather than going into psychiatry. So It's a. It's a branch of psychiatry. But I knew from the start that there were at least two languages that I wanted to. To be able to speak. And sort of the, the. The immunology bit came along for the ride eventually, and some other sort of languages as well. And, and that took a lot. I mean, it took a lot of. It took a lot of learning. It took a lot of. A lot of study. And I think it's. It allows a perspective that I feel really passionate about, which is in mental health in general, in psychiatry in particular, we are so often sucked towards one kind of reductionism or another. I don't think historically any of these reductionisms have ever ended well. And I found myself super passionate about the immune system and the brain, engaging in research in it. And then I suppose it was about five years in that I realized that the enthusiasm that I was obviously exuding was obviously felt by a lot of other people. And then I started to sort of see things in clinical practice that suggested that maybe the enthusiasm was. Was getting ahead of the evidence. And so I've tried since then to sort of take a little bit more of a more. A more measured or cautious stance. I'm not sure everyone would agree, but I think the nice thing about these kind of opportunities is to be able to dispel some of the myths around actually what is the relationship between the immune system and the brain? What is the relationship between the immune system and psychosis? So I'm. Yeah, it's a. It's a pleasure to be able to do that.

Yeah.

I am curious. I don't know if you're able to talk about it. What were the things that you were seeing where you thought people were getting ahead? Was it really making treatment decisions guided by the idea of an autoimmune process?

Yeah. So, I mean, to put it in context a little bit, I mean, these ideas that the. That sort of psychiatric illness might be immune in nature have gone back a long way. You know, there are some amazing stories from the 1950s about people who were convinced it was all to do with infections in the teeth or in the gut. And, you know, they would. They would remove the teeth of all their patients with schizophrenia if that didn't work. They do a colectomy, they cut out large portions of their colon. And of course, you know, that. That lots of patients didn't. Didn't do very well after that. And these people have been rightly sort of. And rejected. The current wave of enthusiasm, I suppose, came about in sort of mid 2000s with this discovery of this very exciting new neurological disorder called anti NMDA receptor autoimmune encephalitis. It's a subtype of autoimmune encephalitis. Right.

So just to pause a little bit for listeners who may not know the medical lingo. So encephalitis or encephalitis is an inflammation of parts of the brain. And NMDA receptors are an important receptor class that is involved with learning and glutamate receptors. And if we have antibodies to these very, very common NMDA receptors in the brain, it can seriously affect psychiatric and neuropsychiatric illness, Correct?

That's exactly right. The encephalitis is an ITIs. It means inflammation. And traditionally encephalitis was understood mainly to occur from infection of the brain. But this sort of immune mediated encephalitis is in the last decades really taken a bit more of a kind of center stage. Although the two, the two are related and autoimmune encephalitis is. It's an all kind of autoimmune disease. So the body creates antibodies and another, other parts of the immune response against its own proteins for various reasons. We could go into and among those are proteins in the brain. So you have a bunch of antibodies that are being produced by the body. They circulate into the central nervous system and then they attack these NMDA receptor receptors, which is, as you say, a really important protein in the brain that is responsible for. It's totally ubiquitous, it's all over the brain. It's, it's responsible for sort of memory, learning, emotion. And we know from other bits of medicine that if you mess with the NMDA receptors, you get really interesting results. So we have a couple of drugs, things like ketamine or PCP that are NMDA receptor antagonists. And so if you take these either because you're having fun in a club or you've gone a bit too wild on some sort of therapy or something like that, you can develop sort of dissociation, you can develop a sense of unreality. Sometimes if you take too much a kind of catatonic type sort of psychomotor presentation, some people will have hallucinations and some people will kick into a sort of delusional state. Which sounds a bit familiar, right? I mean, these are many of the kind of cardinal symptoms of psychosis of a psychotic disorder like schizophrenia. In parallel, there's this now decades old strain of research showing that schizophrenia is likely to be caused by, by dysfunction of the NMDA receptor alongside the other problems with dopamine that we kind of all know about. So what we're seeing in this newly discovered form of encephalitis is yet another way of getting those NMDA receptors to not do their job properly. It's not caused by neurodevelopment or genetic problem or environmental, as appears to be the problem in schizophrenia. It's not caused by ingesting a substance immediately. It's caused by a sort of internally produced agent, as it were, which stops those NMDA receptors functioning. So there's this kind of similarity between the symptoms of acute intoxication with ketamine or PCP schizophrenia and on the other hand, NMDA receptor antibody encephalitis, which is why when these people come down with it, and typically they are of the same sort of age range and demographics as people who experience the first episode of psychosis. Very often they are initially thought to have a first episode of psychosis. And so they get seen by mental health services, they get assessed by psychiatrists. Often they get detained against their will in a psychiatric setting. And that can be for a long time. And in some cases, the disorder makes itself known because after the initial psychotic period, there's the development of seizures, of autonomic instability. So blood pressure and heart rate are all over the place. The catatonia looks a little bit, you know, more intense than what you might see in sort of normal psychiatric presentations. And so in the majority of cases, you know, they get spotted eventually, but sometimes it can be quite a long period of time. And part of what motivated our work was to ask the question, well, okay, there are these really obvious cases where even a psychiatrist who really wasn't paying much attention would be able to say, okay, something is not quite right here. Let's send them to the neurologist for a checkup. We were interested in the cases that might appear more subtly and how big is the base of that iceberg, as it were? Which turned out to be a very difficult question. Question to answer. But I.

There's no simple test for this, right? And we're talking about like a psychiatric presentation that's analogous just for listeners to, like rheumatoid arthritis. There's auto antibodies and rheumatoid arthritis that attack the joints. In this case, it's attacking some protein in the brain. The. The more common one being anti NMDA receptors.

Yes, yeah, exactly. And so, I mean, it's an amazing story of medicine to how they found these antibodies. And it was clear that a new disease subtype had been found. Right? And these antibodies were often, I mean, they were found in the csf, the spinal fluid of these patients, but the tests in these neurological patients would be done with blood. And so when we had this idea that maybe there were psychiatric patients who also had this disorder, but when undiagnosed, the initial feeling was, let's just do blood tests, see if we can find these antibodies. And if they have those antibodies, then we just call up our friendly neurologist, get them to give them some immunotherapy, and we've changed the course of this person's life. As with everything in the history of psychiatry, and particularly when it comes to these kind of new biological approaches, it turns out that it's not that simple, because it turns out that the antibodies that we have in our blood, in our periphery aren't necessarily a good guide to what's going on in the brain. And in fact, one of us three, for example, may well have those antibodies in our periphery, but it's not getting to our brain and it's not causing us to become infected. Catholic.

It's like not a good test. It's not a good. What we want are biomarkers, right, that are sensitive and specific, meaning that if you have them, you have the disease. If you don't, you don't. But it's very gray.

That's exactly right. And we actually do have a really, really good biomarker of this disorder, and it is this antibody. But we need to find it in the csf, in the spinal fluid. Now, you're both psychiatrists, and I think you both worked in sort of public psychiatry at one point or another, right? And it's not easy on a busy psychiatric ward, particularly if you're in a kind of inner city setting or a resource poor area where the ward is full of very, very ill, often chaotically behaving people. You're not going to be able to do a full neurological examination and an MRI and an EEG and a lumbar puncture on every patient who's presenting acutely with psychosis. So that is, is the problem really.

It's pragmatically very difficult. And yeah, Farah, you look like you want to say something. I did general surgery for two years and I'm remembering all the lumbar punctures. And doing a lumbar puncture on someone who's acutely agitated is not so easy and could be dangerous. But Farrah, what were you going to say?

So I was just going to say that, that, you know, we do have a process here that involves for sort of first time psychotic symptoms, that involves a lot of imaging and blood tests. But right now it does not a lumbar puncture. And I think it's because there's so many like logistical and ethical issues to try to get that work up.

Some of it is like cultural too. If someone comes in and they're like not feeling well as a psychiatrist in New York anyway, if I say get an mri, that's hard enough to do. And then if you say, well, you need to get a lumbar puncture, what does that mean? Well, you know, someone is going to do a procedure, they're going to take this very long needle, they're going to insert it in into your back, they're going to withdraw fluid. It's a little bit like when you get anesthesia for an epidural giving birth. It's a very safe procedure. Usually you need neuroimaging first because there's a risk that if you do a lumbar puncture you can cause serious problems. Is called a herniation. If the intracranial pressure is high, it's a tough cell, as they say.

You would think that and I think you're right. But I sometimes wonder, I guess to put it a bit more psychotherapeutically, where the resistance is coming from here. And actually all the studies that have looked at the acceptability and take up of the offer of a lumbar puncture when it's systematically offered to people with the first episodes of psychosis, the take up is in the 70 to 80% region.

In an inpatient setting, I assume, right?

No, in an outpatient setting.

Outpatient. Interesting.

In a mixed setting, actually.

Interesting.

There have been a few different studies looking at this. I mean we, we have an ongoing study where this is exactly what we're doing. It's the early days yet, but we're quietly hopeful that we'll get a reasonable acceptance rate. But what we don't get is frequently the clinicians and the nursing staff agreeing that this is a good idea. And often there's a lot of reasons that come up for why it's difficult, why it can't be done on this site. I don't know what the situation is in the States, but if you're a mental health nurse in the uk, you have had a totally different training scheme to if you're working in a general hospital looking after physical health conditions. And so for quite good reason, the nursing staff might not feel comfortable looking after people that have complex Kind of physical health needs, who might need drips, who might, you know, will need lumbar punctures. And so I mean I sometimes say, you know, these dualisms pill and actually, you know, there's so many ways where I think, I think that is true that the kind of knockdown effect of these artificial separations we have have real clinical impact on our patients.

Right, right. Psychiatry is less medicalized. I have to say I don't have that many folks. But when I recommend imaging, even though I, I believe that I am not anxious or sending the wrong messages, it's still very hard to get people to do it. I find the same thing comes up with things like I, I treat people with transcranial magnetic stimulation and I don't have much of a problem getting people to get an MRI to do neuro navigated tms. And the recommendation, and I think you're also alluding to the training really needs to happen so that the rest of the staff is on board. I'm curious what your experience has been Farah, because you know, without getting into too much detail, you see a lot more people with a presentation like this. And it's relatively unusual for someone with psychosis to have tom those other symptoms you mentioned, like having had an illness beforehand or having seizures or blood pressure changes that are indicative of more traditional biological process. But Farah, I'm curious how you find it and what you would want listeners to understand as to why it's important to sort of follow these recommendations.

Well, when I was in residency we had someone, a journalist, Susanna Callahan, who wrote a book about her experience with anti NMDA receptor encephalitis. And she gave a grand rounds and it was really interesting. And I think my work treating women in their 20s, 30s, 40s has really well prepared me in some way to transition into looking at sort of inflammatory factors as, as part of treatment. So we're seeing a lot of things from like a post Covid pots type picture where people are just not really feeling great and anything that we can do right to bring down that inflammation is a good thing. I feel really lucky because most of my patients are very motivated and they want to get better so they will do things that are not super convenient towards that goal. But usually when people come to my practice, they have already gone through the process of being stabilized, usually, not always. And so sometimes I do wonder like did we miss the moment for that sort of workup and then do we need to wait until we get to a place where they're motivated to figure out more about the cause of some of their symptoms.

Yeah, I mean, I think it's so interesting the way that this plays out in different contexts. So one of the reasons that we ended up deciding that we had to write a bunch of very specific clinical criteria and guidelines aimed at psychiatrists for how to recognize these conditions, because some great guidelines existed for neurologists, but they existed on the assumption that all these investigations had already been done, which, as I think we said, it's very difficult. And it was precisely. What you're saying is that people come at different stages, but also in, in the settings that I work, you know, we have a very demographically diverse population and we were beginning to see signs that there are clinical biases that are at work, that certain segments of the population are far less likely to be systematically investigated for secondary causes of psychosis. And these, you can exactly imagine what these, what these factors are. They're ethnic, they relate to a whole bunch of different sort of socio. Demographic variables. So one of the main motivations for us as well was if we have some guidelines out there, then at least we can try and apply them across the board. Because, yeah, we have a lot of sort of well resourced, well to do families who come in, they've read Susanna's book and I've met Susanna many, many times and I think she's done an amazing job at sort of getting over the, you know, just educating people about this. But there are plenty of people out there who haven't read the book because they don't read those kind of books, et cetera. And who. It's quite possible that when these symptoms come on, it would, it just would not occur to sort of them or their, or their family that this is an issue. I mean, incidentally, if you. I think Susanna writes around about this very beautifully. But if you see the way that, for example, in the film the, the different characters are portrayed, you have the, the psychiatrist who's making this kind of slightly bumbling diagnosis of. She sees her ones are, you got schizoaffective disorder and it's. Alcohol's got something to do with it. And, and then, you know, it doesn't paint a very flattering portrait of a psychiatrist. Right. And then of course she doesn't get any better. She takes the antipsychotics or whatever. And then a few weeks later she, she has the catatonia or the seizures, I can't remember quite which one it is. She gets admitted to what is strongly suggested to be a kind of proper hospital. And you know, and Then comes the, the, the doctor in the white coat who, who, you know, gets her to draw the clock face and, and, and in a sort of Dr. House style, you know, makes the deduction and everything gets sorted. And while that may well have been a good representation of how things were, I think what it also does is it, it underlies a kind of caricature about the different worldviews and approaches of psychiatry versus neurology. And that's, it kind of hurts a little bit as a, as a neuropsychiatrist.

To see that, no doubt it is Sherlock House. I mean, you know, you mentioned, you mentioned in your article in In Brain why inflammatory reductionism is a threat to psychiatry and the rest of the, of medicine. You know, some of these problems and you know, it is, there is always an element of truth to the caricatures. Right. So it is often the case that community based psychiatrists who are stressed out and overworked don't do a fastidious job and can't and it often pains them. And if someone comes in, they treat symptomatically and it's very hard to do a proper job. It's also the case that sometimes at proper hospitals, people get the same kind of care that's not so great, you know, depending where you are. I've certainly seen that. So you, you talk about in, in this article kind of the pendulum swinging the, the other way back. So we, I want to come back to your work and what are the, what are the actual diagnostic criteria that, that both psychiatry and, and, and laypeople listening to our podcast can really learn from you? And so you talk about kind of. Well, first there was this increase in awareness and that's very helpful because maybe we catch people we would have missed who really deserve to recognize certainly if they have obvious symptoms, that they need a different workup. But now you're talking about what, what is called monocaus taxophilia. Like everyone, as Farah was saying, is coming in saying, hey, I have an immune problem. And there's plenty of that with depression too. The, you know, the inflammation. And of course there's a very understandable human wish to find one thing that kind of fixes everything. So could you talk a little bit about the way the pendulum has swung in the other direction and what you're seeing and particularly what, what listeners really should be thinking about when they're thinking about their own best well being or their family members?

Yeah. Thank you. It's such a question that's really close to my heart and I think I wrote that article maybe two or three years ago, and since then things have only got worse, to be honest. And I think what we started seeing in clinic eventually would be often families coming in with a loved one who. Sometimes it was psychosis, more often it was something along the anxiety or depressive kind of spectrum or a kind of complicated sort of what we might call a kind of interface type presentation or what other people might refer to as sort of psychosomatic with a bunch of sort of different somatic symptoms, kind of ill defined. And occasionally there might be a story of a preceding infection or something like that. As, as it turns out, if you ask systematically to almost any psychiatric patient, there's often that, that sort of story there, which I think is interesting. But you would have families coming in. Sometimes they'd have Brain on Fire by Susannah Cahalan, sometimes they'd have articles that I'd written sort of in their hand saying, you know, I think that my loved one's brain is on fire. Can they have immunotherapy? And my concern, and this was happening sort of during COVID was that giving people immunotherapy in the context of, at the time of sort of pandemic illness is not, not a great idea.

So, not, not a great idea because it might make them more susceptible to.

Infection, susceptible to, to infection. And it, it became more and more common and it became clear that at the sort of level of the public understanding the idea of inflammation and the immune system turning on itself and these kind of notions, which are all good scientific notions, had a kind of sway and, and it was resulting in people being diagnosed on the basis of inadequate evidence with sort of inflammatory disorders and in turn being treated with often extremely potent and powerful immunosuppressive medications, often in, by sort of clinicians at the fringes of sort of mainstream medicine. Now in the uk, that is a very easy demarcation to make. I become aware that in the States it's, it's, there is a difference in regulation, has profound effects on the way that this plays out, right? So I've had at least 10 and probably close to 15 patients who've been to the States to get immunotherapy, whether it's intravenous immunoglobulins, rituximab, sometimes therapies that don't even really count as immunotherapy, like sort of ozone therapy or hyperbaric oxygen, you know, these sorts of things, often at huge personal cost. You know, people are remortgaging houses and the like. Right. For treatments that have no evidence base or no significant evidence base. Right.

It's hugely, let's just, I'll be blunt, it's hugely unethical and it's easier to happen in probably in the US than in the uk. Because of the nhs though I think you have private consultants, it's a lot harder to access, you know, sort of whatever you want.

Right, that, that's right, that's right. And I, and it, it's had some really tragic consequences in the families I've met because of course, in the vast majority of these cases they don't respond. And in the more upsetting cases, then that's the opportunity for the clinician involved to say, well, you need to be on these things long term. And that has its own sort of set of consequences, financial and kind of health related consequences. But where's this coming from is the thing that interested me. And this all came up for me at a time where skepticism around vaccines was sort of exploding over the world, particularly in communities that you wouldn't have expected, sort of wellness communities and the like, which you would have thought would be interested in staying well throughout a pandemic, as an example, where that turned out not to be the case. And you know, things that things have gone even further with, you know, some sort of high, high profile government appointees, you know, who.

Yeah, we're all thinking the same thing, which is kind of narrative. Ethylene blue. Right.

Well, amongst other things. Right. And so, you know, where does that come from? And I think that word you mentioned, monoclosal tax, ophilia. And it is a word that's coined a little humorously, but it's the search for a single silver bullet that explains everything. That's never going to be the case in psychiatry except for a few kind of rare causes. But more than that, it's based on two other things. One I think is a failure to understand what inflammation even is. And it's wild that inflammation, which is the body's way of getting rid of infections, it's our body's defense system. I remember in the 1980s growing up and watching kind of early morning cartoons where you had the white blood cells weari hats, you know, sort of going off defending you these days, that's not how, how people think about things. This kind of martial metaphor, this warlike metaphor has kind of mutated into inflammation being this damaging fire that if you don't put out is going to kind of burn, burn the house down. Now that, that may be true, but Actually inflammation is far more complex than that. For a start, the idea of there being high inflammation and low inflammation is an utter myth that you know, there is that it just isn't the correct way of thinking about things. The immune system has many different arms. It interacts extremely reciprocally and, and, and it's not just causing trouble. It's often part of the, it's one of the way ways that the body is actually, body actually regulates tissues and, and, and responds to other sort of non infectious challenges as well.

Like it's a balance. Inflammation is. No, it's not black and white. Right. There's this tremendous oversimplification. It's somewhat understandable for human psychology because you really do have to be very smart and dedicated to understand the complexities. And you know, you talk about the difficulty tolerating ambiguity. Right?

Yeah. I mean I think again, I think people have often say to me it, it's nuanced and it, it's difficult to, to understand the complexity. That's true. But actually you can go back a few thousand years and find early kind of models of medicine in Chinese medicine, for example, Indian medicine, where the notion isn't one of if it's too high, make it low, if it's too low, make it high. It's actually one of dynamic balance. And there's this notion of harmony which actually I think is far closer to the way that the body actually works. So I think that inflammation is deeply relevant to psychiatry and deeply relevant to almost all the presentations in medicine in the same way that for example genetics is or life experiences. But it's never, or at least not in most situations going to be the only cause. And I would just say the other sort of, I'm sad to say that the other maybe motivating sort of stream of thought that I think sometimes leads to this is a kind of anti psychiatry. And you know, I guess when we were all training we knew what anti psychiatry was. It was people who'd read R.D. lang and Sats and there was this notion that psychiatrists are the thought police. We're pathologizing normal sadness. We're psychologizing or medicalizing things that don't need to be medicalized. Those people still exist and their criticisms are nuanced and sometimes true. And then there's this recent emergence of this other strain which is saying well no, quite the opposite, psychiatry is not medical enough. It's not, you know, we are psychologizing these people too much. There's no way that the psychological formulation of my problems could have Any kind of truth at all. And in fact the answer is some sort of biological factor. And usually it's only one. Right. And of course, a lot of the work that our group does shows that there is this hugely dynamic interaction between the biology and the psychology. And in fact they're not separate things. I mean, I mean, just yesterday a beautiful study looking at, I think from Israel, showing that the antibody response to a vaccine can be modulated by essentially neurofeedback by changing the sort of the psychological, the reward based response to stimuli. So these things are so dynamic. And it's only when we realize that dividing things into sort of inflammatory versus psychological or biological versus something else, it's just a non. Starter.

Yeah, I mean, this is very much, you know, I think that is a false dichotomy in a sense between psychology, neurobiological. I'm very much a fan of dynamic systems theories. I like Glenn Sachs's work on causal diagnostic modeling using Markov dynamics, which is very congruent with Carl Friston's work. You know, a psychological process must have a correlate with what's happening in the brain. And as someone who does interventional psychiatry, I've seen, you know, remarkable changes in people who have been making progress in therapy. And I've seen some less remarkable changes, but it really shifts the way their whole physiology and brain functions. And you know, you also see that in things like dissociative identity disorder, where people have different physiological presentations because of their brain state. I would imagine that that math and artificial intelligence holds a lot of promise for creating models that account for the complexity and can also identify what are the multiple causal factors so that we're not overwhelmed by what researchers sometimes call the curse of dimensionality. There's so many different factors. You have to have like a lower, a more simple but not too simple model that actually allows you to get stuff done. But with respect to time, we have about 10 more minutes. I want to sort of call Farah in and see because I would love to just talk for hours, how we can kind of come back. I don't want to digress into AI psychosis and your specialization. We won't have time. But what sort of. What do you think, Farah? What, what do you think listeners want to know? What, what would you want to know as a psychiatrist?

Well, I think that this really highlights an issue that I come up against every single day, which is that I feel like my work with patients is really siloed off from whatever other work they're doing. From whatever hormones they're taking, from whatever their primary care document says, whatever their, you know, acupuncturist is doing. And I think that that really limits the success.

Whatever they're. So I would jump in and say whatever they're doing it also whatever they're telling them.

Right, right.

Which is often anti psychiatry.

Certainly. I guess that part, when I hear the sort of anti psychiatry, I just think, and Tom Grant knows this, that, you know, my family has been in this business for a long time and I have embraced the fact that there is a dark history. And as a result, I practice in what I think is the most open minded way. Like that's always my goal is to say, well, I don't think so, but maybe. And let's see. And there's so little that we can actually say for certain. So just getting comfortable with that ambiguity.

I completely agree. We do have a dark history in the field that we need to own. I'm also talking about, you know, someone who might say, you shouldn't take that abilify, it's bad for you. And then the person crashes into depression or psychosis a week later.

Right. And I think my job would be a lot easier if I didn't have to have those discussions. But I've just accepted it as part of my day to day. That's what distinguished me from like a vending machine. Right. And I think we all want to be good clinicians and use our, use our minds, but how is that dangerous? Right. And I think about the siloing. Yeah, the siloing. I think about when I work with, let's say a new mom and the opportunity cost of being depressed, not bonding with their newborn. I mean these days we get like a couple of chances at that. And so to not be able to be present or to not feel like oneself in that moment, like that's something that people regret. Right. So that's where I come from. And when I'm thinking about how to treat someone.

Yeah, I think, I think that that's beautiful and I think that's how we, how we ought to approach our patients. I mean, I think there's a way to, to, to hold these different ways of seeing at the same time and do that with your patients. It's, it's actually, you know, for all that I've been saying about the kind of the, the sort of culture wars aspect of it, it's actually when, when you're face to face with an individual patient and you can really kind of talk about things, I think it's It's a lot less difficult than that sometimes that, you know, just coming to, you know, thinking about inflammation. I mean, what this discourse has done is it's highlighted the importance of staying well, of avoiding things that are going to be bad for your body, essentially. And that's a good thing, right? You know, if it's getting people exercising that, that, that's great. And I think there's a way to sort of encourage that while at the same time not allowing that way of thinking to foreclose other sort of ways of working. And, you know, one of the major projects that we're working on at the moment is the immune mechanisms of antipsychotic treatment studies. So, you know, we have now ample evidence that antipsychotics modulate the immune response. And if you think of something like clozapine, which is the most effective antipsychotic that we have, it is a profound immunosuppressant that is comparable in some respects to something like rituximab. You know, in some patients, it can produce a reduction in antibody production and a reduction in some white cell subsets that is essentially like an immunosuppressant.

So very important work. Antidepressants also change the expression of a variety of inflammatory meteors. Of course, if we didn't have inflammation, we'd probably all get sick and die.

Exactly that. Exactly that. And actually, the thing that our group is looking at is this idea that it's not about the high versus low information, it's about the shape of the response. So we have some data that should be published soon showing that people who, when they have a challenge, whether it's a life event or an actual sort of more biological challenge, they mount a kind of brisk immune response and then recover quickly. Appears to be psychologically and in some other areas, the most healthy thing. People who don't respond at all, who have low inflammation, they do worse. People who respond and stay at high inflammation, they do worse as well. And that makes sense, right? We are. We are regulatory systems who are designed to rebound when we get out of joint. The whole point of having a homeostatic sort of body is that we come back to where we were. And, and again, it's that dynamic systems kind of thinking grant, which I think is really important. And there are, I think there are some ways that we can talk to our patients which, which get that over in a way that doesn't sort of throw, you know, too much.

It's not hard to follow. I do that all the time. We do it in disaster response, we developed a systems oriented model. It's like stress regulation, you know, shutting down versus being overactive. Exactly. We need to have that conceptual framework that that's how we think about things and then we can deal with ambiguity and complexity. Again, I wish we had more time. I want to ask you, to the point though, what is your recommendation to patients who have a clinical presentation like this and what should they be having in their back pocket when they go to talk to their doctors? What is your best advice for patients?

Yeah, so I've realized that probably it's important that I do this because otherwise I'm saying a lot about what isn't this problem. So I, you know, we, we have a number of sort of papers specifically addressing this, including our autoimmune psychosis criteria. But really one of the major things is in, in the vast majority of what we call primary psychiatric illness, it doesn't come on overnight. Right. Most people have what's called a prodrome, or they start to get sort of, you know, worse over weeks, months, even years. If you're doing well one day and then the next day you're in a terrible, terrible sort of state psychiatrically, whether it's psychosis, whether it's other sort of symptoms as well, that very acute onset might be a red flag. There are other red flags. Confusion, suddenly not knowing where you are, what the date is, who you're talking to. That's not meant to happen in sort of primary psychiatric illness either. If you happen to also at the same time have a major immune, an illness that's likely to affect your immune system in some way, whether it's cancer or an autoimmune disease like lupus or something like that. Well, of course, then it's reasonable to say, well, hey, what's the relationship between this disorder and what I'm experiencing at the moment? If you develop neurological symptoms, whether that's, you know, sort of jerks or difficulties moving or forgetting to an extent that again, we wouldn't really see in most psychiatric disorders, apart from the, you know, the dementias, then these are all sort of so called red flags. But the point is that none of these red flags is absolute. You can't see the presence of one of these and say, oh, hey, this person has an immune problem. And the problem is, and we saw this recently in a UK newspaper saying, you know, do you get brain fog? Do you feel, you feel anxious, you tired all the time. These are symptoms of, of autoimmune encephalitis. And well, yeah, the brain Fog is such that some people aren't able to speak, they're tired all the time, is sleeping 23 hours a day. And so, you know, the idea that there are symptoms that are present in this disorder but get sort of so diluted in the kind of retelling that people can read and say, well, hey, that's me. And you know, that's not even to mention what happens if you go on TikTok or Instagram or something. And I think that's where, that's where there's a responsibility and where these things are so unregulated because people are going to be looking at these things and thinking, hey, that is me. And what that also does is they turn away from the treatments. That may well be exactly what they need. You know, whether that is a psychiatric treatment or a psychological treatment or, or some other area of medicine that needs to be inputting here.

You know, the same type of messaging that you described that's kind of vague, non specific, could be almost anything, is also used by people who market alternative medicine things. Do you have brain fog? Are you tired? I'll use the same example. Take methylene blue, because I saw it on Twitter, and it does real harm. You know, these are not innocuous treatments. They can do real harm and they prevent people, as you're saying, from getting proper care. So I hope listeners will take what Dr. Pollack is saying to heart that when, when you are concerned about something, please, you know, go to your doctors, do the research, read his work. There are ways to be more specific, but also keep an open mind that it's very hard to make these diagnoses properly and you really deserve to have a good evaluation and to Farah's point, a multidisciplinary evaluation. You know, it's very hard to do what I do when people consult for tms because I really believe the TMS interacts with the psychotherapy over a much longer term than has been studied. You know, as a psychoanalyst who does interventional psychiatry, I have my team operationalize it so that we try to book a team meeting at the same time as the consult, often with the therapist and the outside psychiatrist. And that's very hard to do unless you have the luxury of working in a hospital based setting and you have weekly case conferences. So, you know, let, let us help you in the ways that we know how to. And the other thing is, right, there's been an erosion of trust in the professions that we need to kind of win back.

Yeah, yeah, 100%. And we're we're equally. You know, we are. For a while now. We've been in these sort of bubbles, these echo chambers, where we kind of can't really agree about what our sort of methods of. Of confirming, you know, a diagnosis or, in fact, many, many other things. And that's a real problem. There's a problem of knowledge, and one that's only going to get worse with AI and the like. And actually, that was something that I was so aware of when I started working with immunologists and neurologists, because I found that we talk about a patient, and then I'd hear the neurologist talk about it. I thought, is this the same patient that we're talking about? You're talking about. About an expressive dysphasia? I'm pretty sure I thought I was seeing formal thought disorder. You know, what. What is this? And so. So we did something which I think doesn't happen very often. We now see every single patient who comes to our clinic sees the neurologist and me, the neuropsychiatrist, at the same time.

We're in a room at the same time.

And, you know, people talk about, you know, finding the elephant in the dark. Well, if you've got two people at the same time saying, is this a leg? Is this a trunk? It makes a little. A little easier. And it's remarkable, I think, how that dynamic where in real time, you can say, yeah, you know what? This is really atypical for psychiatry. We really need to investigate this person, or for the neurologist to point out that person's got a tremor or they've got slight facial weakness or something that perhaps I wasn't about to notice if I was on my own, that's amazing. And I think we need more of that.

That's brilliant. And I think for the patient and to have the communication skills between the psychiatrist and the neurologist, that the patient can hear that dialogue and internalized, that there's a real thought process going on is also very valuable. Farrah, would you like to read us out? Yeah.

So, Tom, thank you so much. This was really awesome to hear about your work, and I hope that you'll come back and join us later on. But in the meantime, where can people.

Find you so they. They can find me? On my King's College College London webpage, I also have a substack where I talk about much more speculative matters, but also a lot that pertains to this.

Kind of thing and media, too. You have some pieces on movies in the media. And that would be another conversation for another time, but definitely check out Tom's substack. It's really smart and entertaining.

I'm gonna go subscribe and we'll link to it as well.

So thank you very much.

It's been a real pleasure. Thank you.

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