S3 E21: My Eclectic Conversation with Fulvio D'Acquisto, PhD: From Carl Rogers to Immuno-Moodulin

What if sudden OCD, tics, and food restriction after an infection aren’t “all in the head,” but start with immune cells carrying a biochemical message to the brain? We sit down with Dr. Fulvio d'Acquisto—immunologist, psychotherapist, and founder of affective immunology—to trace the language between emotions, living conditions, and the immune system, and why that conversation can erupt into neuropsychiatric symptoms in PANDAS and PANS.

Fulvio introduces Immuno-moodulin (iMood), a small protein produced by T cells, found in higher levels in people with OCD and elevated in PANDAS/PANS. He explains how iMood behaves like an intrinsically disordered protein: it can cluster in blood, cross into the brain, and temporarily disrupt neural communication—then disassemble as triggers fade. That dynamic process mirrors real life: flares during infections, relief during remission, and stubborn persistence in complex cases. We unpack why peripheral therapies—antibiotics, IVIG, and plasmapheresis—can reshape central symptoms, and why response varies based on disease staging rather than a one-size-fits-all pathway.

We also explore the bigger map: proteomics that can distinguish PANDAS from controls with striking accuracy, autoimmune conditions that cluster with specific psychiatric diagnoses, and a cautionary tale where “schizophrenia” resolved after immune therapy revealed underlying lupus. Along the way, Fulvio reframes inflammation as a repair system gone repetitive, not an enemy to be extinguished at all costs. And beyond the lab, we talk belonging—how shared meals, genuine dialogue, and community aren’t soft add-ons but active inputs that steady immunity and help people reclaim identity, empathy, and meaning.

If you’re curious about immune-brain crosstalk, novel protein targets, and why conversation can be medicine, this deep dive offers science you can hold and stories you’ll remember. Subscribe, share with someone who needs hope, and leave a review to help more families and clinicians find this work.

Disclaimer: The views and opinions expressed in this program are those of the speakers and do not necessarily reflect the views or positions of any entities they represent.

Credits: Music by Kingsley Durant from his "Convertible" album

To learn more about PANDAS and PANS and The Alex Manfull Fund, visit our website: TheAlexManfullFund.org

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Transcript

Opening, Mission, And Guest Intro

Susan Manfull, PhD 0:07

Untangling PANDAS and PANS is a podcast about two little known medical disorders characterized by the sudden and dramatic onset of symptoms such as obsessions and compulsions, vocal or motor ticks, and restricted eating behaviors, and a whole host of other symptoms following a strip or other bacterial or viral infection. I have the privilege of interviewing some of the top researchers and clinicians in this rapidly growing area, known by various names such as immune-mediated neuropsychiatric disorders, infection-associated neural immune disorders, and other immune encephalitis, or simply pandas and pants. My name is Dr. Susan Manthell. I am a social psychologist, the executive director of the Alex Mantel Fund, and the mother of Alex Manthov, who died at 26 years old due to pandas. A disorder my husband and I knew next to nothing about. Certainly not that our daughter could die from it.

William Manfull 1:18

This is episode 21 of Untangling Pandas and Pans, recorded January 22nd, 2026.

Cooking, Conversation, And Healing Spaces

Susan Manfull, PhD 1:27

Welcome to Untangling Pandas and Pans, a monthly podcast in which we talk about infection-associated immune-mediated neuropsychiatric disorders. I am very fortunate to have as my guest today Dr. Fulvio De Quisto. He's an immunologist and a psychotherapist, and he is particularly interested in how emotion, personality, living conditions, and lifestyle influence the immune system at the cellular and molecular level. He is founder of effective immunology, an area of scientific and translational research focused on establishing a better understanding and appreciation of the immunological basis of mental disorders and the emotional side of immune disorders. His academic path began with a PhD in natural substances and pharmacological action at the University of Naples, Federico II, in Italy. And that was followed by a postdoc at the Department of Immunobiology in Yale, where he focused his work on cellular and molecular immunology. At William Harvey Research Institute, he accepted his first position as a senior lecturer in immunopharmacology. Somewhere along the line, he received a master's degree in transpersonal psychotherapy, and a project that examined the dreams of patients with autoimmune disorders was completed. Later, he went on to Queen Mary University of London and the University of Roehampton. He currently teaches and conducts his research at the University of Teramo in Italy and returns to London on the weekends. Dr. DeCisto and his teams at Queen Mary University of London and the University of Roehampton recently discovered a very important protein produced by T lymphocytes. It connects the immune system and mental health. It's called immunomodulin, eye mood for short. It's found in the immune cells as opposed to the brain. People with OCD have up to six times more eye mood in their immune cells compared to healthy individuals. There is a potential for treatments that target the immune system rather than typical treatments that target the brain chemistry. Other psychiatric and neuroimmune disorders have been found to have elevated eye mood levels, including pandas and pans. Aside from his passion for the emotional and immunological systems, he is especially interested in the work of Carl Rogers and Carl Jung. A little known fact about Dr. Tequisto is that he is a self-described INPJ, according to the Myers-Briggs type indicator, a personality assessment based on Carl Jung's theory of personality. Therefore, he said that he is reluctant to refer to himself as the founder of effective immunology. He prefers instead to be called its number one fan. I encourage you to look up the different personality types according to Jung and see how well it matches Dr. Tequisto's personality. Let's go ahead and get started. I have with me today Fulvio DeCuisto, and I'm very excited to talk with him. You're cooking, and we're having a chat, okay? Because I know you like to cook, and I know you like convivial kinds of atmospheres and just talking. And so do I, and so does the Alex Manfell Fund. You may know that we have an expression, dialogue saves lives. And we feel very strongly about that. We feel that we will move forward when people talk to one another. And that's why we set up our symposia, for example, so that physicians and researchers and counselors and whoever is attending our symposium has this opportunity. And we found that as a result of that, people who did not know one another before the symposium are now working together. And I think that's really important. All right. So I'm very attracted to your work for a lot of different reasons. And speaking personally, which I'll go in and out of in this talk, what you're interested in is much of what got me interested in psychology. Read a lot of the same books. And like, for example, Carl Rogers, very drawn to him. And when I was teaching, I always talked about Carl Rogers' work in therapy and what he would consider sort of a foundational relationship with unconditional positive regard and empathy and genuineness and the ability to express those things. And early on, I and through graduate school, I was also very interested in Carl Jung. I mean, who is interested in Carl Jung, and I used uh his Myers-Briggs typology assessment during some of the work I did with businesses. And I also read Herman Hasse. So uh much maybe never.

Fulvio d'Acquisto 7:52

Yeah.

Susan Manfull, PhD 7:53

And I now, though, I'm very interested, was sort of thrown into this field of um the immune system and how it relates to well, infection and the immune system and psychiatric disorders, and of course, in particular, pandas and pans. I also I'll just tell you this too, that in my daughter Alex's last few years, I went into her apartment one day, and uh this was a few years before she died. But what should I see was on her nightstand were books like Man's Searching for Meaning, Man's Search for Himself. She asked me about Herman Husa and which books I would recommend. So I think she was beginning to wonder who she was, and I'll get into that a little bit later. You commented on wanting to focus some of your work more on how happiness makes you feel good as opposed to the opposite, because in psychiatry there is so much uh focus on on feeling bad. I I mean talking about uh mental illness. But it would be great if we did have more focus on happiness and what brings purpose and meaning and well-being in life, instead of or in addition to, I'll say, what makes you feel sad, depressed, and generally unhappy. So I'm drawn to your work for a number of different reasons, and more recently, your your research.

Defining Affective Immunology

Fulvio d'Acquisto 9:46

What can I say? I mean, I wish this podcast or chat lasts forever. I mean, we really have so much to talk about. I mean, um, obviously, I met you in one of your wonderfully organized meetings, and uh, that was really um an excellent experience for me to meet people like yourself and many other uh like-minded people that come to the Alex Mantle meeting every year. And let me start. I want to address the cooking part, uh which is quite interesting. So, as you might know, I also have a double degree, so I have a master in psychotherapy and I practice as a psychotherapist. And one of my placements was for a wonderful association of a charity in London called uh Maitree. And this is a respite for suicidal people. So very interesting model. You you can kind of um enroll in this, you spend four nights and five days, and during these four nights and five days, you have rotational uh volunteer, and usually they're also psychotherapists in training. And you know, the the guests they end up talking over and over and over about their narrative and the story, and so at the end of the staying, they kind of change their mind. So it's a very interesting model that really fits with your idea that you know talking about it works really well. Guess what? You know, I did a couple of my ministroni and a couple of other pasta that I know how to do it. I just won the place for lunchtime. My shift has always been for lunchtime, and um, when we were at the table, you know, you get like five guests and a couple of others volunteer. I always found the guests will talk more if they were eating, you know, there is the pleasure of the food, and okay, I'm I'm showing off here a bit. But also, there is the I think the idea that you've been fed that kind of foster a welcoming space for you to open up and say things that you want to say or share it with other people. So I absolutely believe in what you're saying and uh in aspect, you know, the the convivial, eating together, and also the talking definitely is one one of the main things that I think are very, very important. So thank you for that. I'm so happy that I say that. I always wanted to kind of um thank you know all the people that I met there, and this might be an opportunity for me. Thank you. I guess my uh yeah, it's it's an obsession really. Even uh I think three days ago, uh whenever I have you know some sort of uh I feel unsettled, I just put some video on Jung and immediately I come down and I even went to see his house, Switzerland, then I found out it was closed, and I threw myself into the lake because I really want to see it. I have so many things to talk about, but you know, I'll I'll try to be not too much Italian kind of going everywhere, chaotic, um, explosive.

Susan Manfull, PhD 13:26

Uh well no, that's that's what we're here to do, and there is so much you can say on uh coming to the table and and getting together with people, and I'll just provide one other anecdote. My husband and I give tours in Provence. I know you know we love Provence, can go there frequently, but sometimes we bring along a group of people, never more than eight, just enough to fit around the table. And sometimes when those people arrive, because very often they don't know one another, and we wonder at the end of the first day, whoa, are they gonna like one another and talk and have a good time? And one of the things we do to bring them together is every night we go to the long table and we have a very nice meal and wine from Provence. And I think that that is uh an amazingly successful way of bringing people together. And uh I think the sort of milieu therapy, I think that you're describing in the in the group where you do some of the cooking. I just think that's great.

Fulvio d'Acquisto 14:44

So in my public engagement or patient engagement activity, I used a system which had been taught to me by people in humanities called the long table. And that comes from a book of an American going back to France because the mother has died and she inherited the house, and she goes there to sell the house, and every night has one person coming to the table, and then this table becomes bigger and bigger and bigger, and at the end she doesn't sell it anymore and moves to France. So again, um, quite interesting. There is even a movie, and in my public engagement, you know, we we try and do not have the expert and then the audience, but we have this long table, and everyone comes to the table, the experts and uh the audience, and we facilitate discussion that way to be all the same in the same place.

Immune-Brain Communication And Sickness Behavior

Susan Manfull, PhD 15:47

That's so interesting. I have to give one more example and then we'll get going on the real subject, I suppose. But this is setting the stage for our conversation, really. In the elementary school where Alex went to school, and I think that that's generally true here in the States, they're discouraged from talking at lunch. And in fact, if they talk too much, the the lights are blinked, and I suppose the response by the lunch monitors is elevated if it gets really loud. And Alex actually found that very distasteful and had her own little protest for that when she first started going to this elementary school, which was great. Otherwise, I love the elementary school. When she went to school in France, in the equivalent of an elementary school here, they all talked. They were encouraged to talk. And she loved that, initially found it, wow, this is really, really strange. We can talk, and I don't have to whisper. But I think as a society, we're we're losing the fine art of conversation. And I'd like to see that changed beginning at the elementary school for the reasons that we're we're talking about. All right, let's get started. Let's start with your idea that you refer to it as effective immunology, I believe, or that's the broad term. So, what is the link as you see it between emotional states and living conditions and the immune system and inflammation?

OCD As Adaptive Signal Turned Maladaptive

Fulvio d'Acquisto 17:35

So, very good question again. Thank you for asking that. When I uh teach immunology, you know, as I always say, when man was just starting life, you know, they had dinosaurs, they were chasing them, and they developed the brain as a way to uh fight these very big animals and kind of preserve themselves. So, in a way, the brain is the uh introduct of sensing the danger outside and trying to have a strategy to avoid death, if you like. But then I move on to a slide where I show lots of other dangers like viruses, bacteria, uh, all sorts of things that we actually do not see. You know, we we didn't see COVID. We we haven't seen bacteria in the air, but we will never uh do that. So, how does the body deal with that type of danger? And so, based on that, yeah, I kind of introduced the idea of the immune system as a sensor of the external reality. So the immune system is the eyes for something that is very small, very tiny, that you need to be alerted from. Now, of course, you know, if you drive in the same car, the brain and the immune system cannot just go everyone on his own accord. You know, they need to be communicating with each other, and that's the idea. So another clear example that I do, you know, when mice get infected by a certain type of pathogen, there's some very nice scientific video that they show that they actually get closer to a cat, so a predator animal or a cat uh that is leaping, so to speak. And that is a way through which an infection push a mouse to do something that is not natural, but is natural for the bacteria or for the pathogen. They want the passage from the mouse to the cat and then the cat and so on. So there is these things about the sickness behaviour, all this uh sort of evidence that whenever we have an immune dysfunction, somehow the brain has to be in sync with that. So, you know, you're fighting an infection that takes a lot of energy, you know, the whole immune system is sucking up. The energy, but yet you know you want to go party party and uh you know dance all night, you can't do that, so then you feel miserable and sad, and you just wanna stay home and you know drink chicken broth. So the way the two systems are connected to me is a positive, and you know, I'm interested in what you're saying about positive. I think this interaction is an interaction that is positive to begin with, as in the goal is the same, the trying to uh save the human body, so to speak. In affective immunology, I'm particularly focusing on the idea that we are like this sort of a very fluid biological system. So, easy example, water. You know, water takes the shape of the container, doesn't have a shape itself. If you try to hammer water, you can do that, but then it goes back to normal. So there is this plasticity that is very unique to the immune system, and I would argue the brain. Now, with that in mind, I think that whatever we do, this conversation right now, I'm sure is doing something to our immune system. An hour of laughing or an hour of crying, anything that is very tiny and small in time, or you know, in sort of uh transient, if you like, has a mirror effect on the immune system. So if you want to mobilize your immune cells in the body, you know, you just do five flights of stairs in a rush. The body feels like, what the hell is going on here? Why are you rushing? You know, is that a dinosaur chasing or something like that? And so immediately you get a flash of uh neutrophils, you know, these innate cells that are there for the infection. So as soon as we experience something, the immune system has to match it up. So to get ready, and you know, possibly also other systems they work that way. But I think there is a very sort of tight connection between what we experience and the response of the immune system. Response being kind of adjusting the player in the blood or the type of mediators, and so on and so forth. So I'm interested in this small tiny transient event, the sum of which dictate the immune system training. While these days, you know, most of the psychoneuroimmunology people, what they tend to do is like, okay, uh, two weeks of meditation, two weeks of uh, you know, keto diet, and uh so that there's this sort of banking idea that you need to accumulate, you need almost to violate um your own previous setup to then see the effect of this new thing. I don't think it works that way. I think that there is a this very tight connection between the two. And so we should be mindful of balancing on a daily basis, you know, the positive and the negative, rather than thinking about okay, I need to do three hours meditation a day for 20 days to then see an effect that's not the way it works. And also in experimental animal, that doesn't work because there is habituation. So I want to know what is the language between these two people. I want to know how you know what I see with my eyes, what I experience with my uh mouth, you know, lips kissing someone, how at the level of biology of you know cells and everything, how that is translated. I want to know what are the the tools, if you like, whereby these things are happening, and so that is my specific effect, you know, kind of focus. So affects uh, you know, like emotion is something that's a beginning at the end, so it's a pick. It affects you, you know. That's the the reason why I choose affective immunology rather than emotional immunology. They would have been the same, but for me, affecting emotion are different in balance, and affects means that it leaves you with something is stored, you know, in the immune system. So yeah, without going into negative uh divorce or being raped, that has immediately on the immune system an effect. So there is a very quick way to kind of rearrange everything, and I want to know how that works, and I want to know that works, you know, mainly in a positive way, as in you know, it's interesting you brought up you know the um the positive. I don't know if you know Nancy McWilliams. She's in US, she's um big in psychoanalysis, she did uh the DSM5 of psychoanalysis. Uh, I love her, uh, absolutely amazing person and uh psychologist. And you know, she recently laid out you know the 10 rules of emotional wellness. So, what do we need to do to keep ourselves healthy? Because you know, a state of health is not lack of disease, it's something that you foster it, you know, it's an active process, being healthy and balanced rather than healthy, probably. It's something that you fuel, you know, you you do things to keep that way. And you know, she has many of the things that we briefly talk about, like sociality, uh, intentionality, very, very interesting point. And all of them I can see how they will be linked to the immune system in many ways. With my heart as a psychotherapist, and let's take a look at OCD. You know, to me, OCD triple inverted comma is healthy. What do I mean by that? I'm in my house. I actually did that, and I imagine that there is a bunch of mice or you know est or of any sort that are outside the house, they're trying to get in, and one manages to get in. So a mouse is in my house, I'm trying to chase it and trying to kill it, or trying to well kill it, no, but you know, trap it and get him out, and I'm all stressed because you know maybe he will go this way, this way, this way, this way. Now, I'm totally focused on finding the mouse. I haven't got the energy to deal with more. Now, if you take that aspect of OCD, you have to be hyper-vigilant that not other mice are coming in. Interesting. So think that symbol makes perfect sense. You know, you don't want to get infected more, and therefore you create a reality whereby I'm not touching that, or you know, you start to have very intrusive thoughts about what would happen. The whole idea is that mate, as they say in English in England, I'm busy in doing this. Can you just stop doing something else? And the other point that is very important to me, somehow the brain is stupid. What do I mean by that? You look at the horror movie, you know, you jump on your chair, or you look at a love movie and you start to cry. None of that is happening to you.

Susan Manfull, PhD 28:23

Interesting.

Fulvio d'Acquisto 28:26

But then you act it out. So if you go strip, you can't find it. Is it time to get other infection going on? So, in that sense, OCD is triple quadruple inverted, comma, uh, healthy, and probably it is healthy, you know, probably we all are OCD, but then at some point, and I'll come to that, there is no mouse. You just set the trauma of the mouse in your head, and you hear something, and you think it's a mouse, so the immune system gets activated without even an infection, and the behavior changes, and that is the psychiatric condition. So, you know, the what seems to be healthy to begin with, then it moves on to be distorted, and therefore, you know, that becomes a problem.

Susan Manfull, PhD 29:29

And so there's a limited number of people for whom that happens. And why does it happen to some people and not to others?

Fulvio d'Acquisto 29:45

Yeah, so within uh, you know, that that cohort of OCD people, why some of them have an infection and some they don't. That would be the question marked or you know, kind of um strip positive and strip negative.

Susan Manfull, PhD 30:05

Um it's really in some cases, normal cases of um of um level C Then it's related to your immune system in the case in with some people, okay. Some in the research in um in affective immunology, some people call it psychonomal immunomology or immune psychometry, there's there's several different names for it. You identified something called immunomodulin.

Fulvio d'Acquisto 30:48

Yeah, modulating modulation, yeah.

Susan Manfull, PhD 30:51

Can you tell me about that research?

The Serendipity Of Immunomodulin

Fulvio d'Acquisto 30:56

Yeah, yeah, yeah. So that was a discovery by serendipity, if you want. You know, I was studying mice that are prone to autoimmune diseases. So I was studying another protein that makes mice prone to develop autoimmune inflammation. And the PhD that I had at that time, which is quite fun, used to come to me and say, Oh, those mice are just crazy, they are crazy like you. They're just the same craziness that you have, they have it. So I don't know what you've done to them, you know, kind of thing. And I I probably was curious about finding more about myself, I don't know. Uh and I went to see this mice, you know. I went to see the mice, and uh, if you go to even the paper that we published, you can see this uh open cage. You know, we don't do anything, we just open the cage of the mice, and they are frantically kind of digging the sawdust, they're very scuty, they are very kind of agitated, and I haven't done anything to them, you know. Kind of I just opened the cage, and so that was very strange because they had this very um anomalous behavior when they came in contact with someone, so to speak. The female line, we had the male and the female line. The female line, I couldn't get it to uh to you know make more mice, they were cannibals. Uh so as soon as they delivered the baby, they eat them up, and so that is a sign of uh post-neonatal depression. And then again, if you go to the speedious, you also see that when I put like four females together, there was a bossy uh sister. Uh, they um did heterogrooming that means you know removing the fur from the other sister, so there was a sort of dominance, it was all sorts of very strange behavior. And to get that line going, um, I had to administer some antipsychotic at that time. So basically, this mice that I generated by changing only the immune system, specifically T cell, they had this very strange behavioral phenotype, and that was something completely unexpected to me. And when we then did the sort of uh classical basic science experiment where we took those T cells and we put it in a normal mouse, and we saw that the disease was coming up in there in the hosted mouse, we realized that they might produce something that would uh influence the behavior of the mice, and that's how we ended up discovering this very small protein that is secreted by T lymphocytes. And uh, when you just give the combined protein to mice, uh mice show sign of one side or uh kind of repetitive anxious behavior. So it started with serendipity, but then uh kind of it developed in something that it made sense to me, especially you know when you look at uh certain type of patients, you know, these are not fixed statistics, but you know, one in four uh multiple sclerosis patients commits suicide. They commit suicide when they're actually well, as in they can walk and they can do their things. So you can fix the body, but then you get this compensation, and the mind becomes super alerted, and you know, you go in psychiatric condition. That to me again makes sense because okay, you fix your neurons and you're now able to do the movement that you can normally do. You don't want to go rock climbing, so the psychiatric aspect, if you like, has a protective meaning in a very generic triple inverted comma way. So it's another distorted way to balance the two. And also when you look at this patient with autoimmunity, when you look back in their records, let's say 10 years before, they hadn't psychotic condition. They were diagnosed with some sort of either depression or anxiety or uh borderline. So when you put the puzzle all together, you know, I come to life, I live a normal life, and then something goes wrong. Could be my family, could be the environment that I live, something goes wrong. That to me kind of creates an immune response, and like you know, like you had an infection. So the trauma becomes similar to an infection. Then the body says, Okay, this is not a place to stay. Let's move, let's move, let's move, let's do something. So it blocks your behavior, and so you get depression and all of that, because you need to change something, you need to move out, you need to do something else. People keep in that loop. Okay, you're not listening to me, you're not listening to me. You know what? I'm blocking your body now, and that's where you get autoimmunity. It's a romanticized way, uh, for me, you know. Obviously, do I have a hundred papers that support exactly this hypothesis? No. Do I have bits and basis? Yes, we do. You know, when you talk to the rheumatologist, you always ask, do you do you ask about your patient about you know psychiatric condition, psychological condition? No, no, no, we didn't do that. You talk to the psychiatrist, do you know how many neurophemes did they get? Do you know if they had an infection? No, no, no, we didn't do that. But when you find someone that looks at the whole thing, then you get the 3.1 line, more or less.

Susan Manfull, PhD 37:14

So you're trying to further understand that connection. I I just to read, I think, the first line from one of your papers on immune mood healing. You ruminate them patients suffering from no immune diseases more susceptible to mental disorders, yet the existence of specific salelium or molecular mechanisms behind the comorbidity of these pathologies is far from being fully elucidated. I mean, that is really a huge question in this field, isn't it?

Inflammation Reframed As Repair

Fulvio d'Acquisto 37:59

Yeah, and uh I think what I'm about to say next will attract the hatred or not of millions of people, and I'm willing to take the risk because I'm 55, I just uh want to be me for the next 10 years, and actually I do believe in what I say. So I am well, yeah, I'm quite an expert in inflammation. I always worked on inflammation. I teach inflammation not just in my course, also to other universities tomorrow, for instance, I'll do a lecture on inflammation. When we study inflammation, we say it's a physiological response to a damage. Inflammation, it's a physiological response. Without inflammation, we wouldn't be alive. You hurt yourself, you have dead skin, you have dead cells, who's gonna take them out of the immune system. How to inflammation? Your wound there is inflammation there to repair and to attack the bacteria there. The job of an inflammatory necrosis is to maintain homeostasis in the body, that means a balanced state. Full stop. I mean, there is no way anyone can change that and say that inflammation is bad.

Susan Manfull, PhD 39:36

As you said, balance is such a key word.

Fulvio d'Acquisto 39:40

Yeah. So inflammation becomes bad when it is repetitive or it becomes chronic for no reason. So the body is looking for the streptococcus infection. Streptococcus infection is not there, chronic inflammation. Obviously it's not gonna go anywhere. So going back to my metaphor, you can picture me spending one day, two days, a week running around the house trying to find something that is not there. What's the outcome of that is that one, I get exhausted, two, I don't solve the problem, right? So for me in psychiatry, the height and level of inflammation is accumulation in the brain or something that should be cleaned of all these neurodegenerate diseases. So you have something in the brain, that cells and neuronals and that whatever you want to call it, something needs to be clean in the body, in the brain in particular. So the brain obviously has to call the immune cells to come there. So there has to be an inflammatory process that then drives the immune cells there. They go there. We have now wonderful signs from Jonathan Kickness. Immune cells go in and out the brain all the time to clean up. That's the job. The job is to go there and clean up. However, if you haven't got immune cells because you're stressed and you're immunosuppressed, all you have is the sirens you know to recruit the medical people, but no one is coming. So it's a complete to me misunderstanding of the role of inflammation in psychiatry. The inflammatory process is not always there as we know. Even in depression, it's 50% more or less. In those cases, is the body trying to push the immune cells to go there, but there is very little immune cells available. And so it's like a constant alarm that doesn't get you anywhere. If inflammation was truly, truly the driver of psychiatry, well, I mean, glucocorticoids fantastic. Neurofen. Plenty of the anti-inflammatory. I mean, if there is one overcrowded stack of drugs is anti-inflammatory drugs, we got at least 40 types. We know where we know how it works. I guess what people with OCD until you know when you go to blog that I love to listen to the patient rather than the scientist, they say, ooh, take a low dose of ibuprofen or neurophen. It makes you kind of positive boot. So clearly there is something there that is being I'm not saying obviously I'm not God far from it, but I think we've taken away the basic biology. I challenge everyone to take a book of pathology in medical school and biomedical science and read to me inflammation is a pathology. It is not. Inflammation is a physiological response of vascularized tissue. It happens in plants, it happens in drosophila, it happens in all sorts of animals. They have a vascular system, so a system of communication. Where there is communication, there might be a mistake, you need something that fixes. You have a house, your pipe gets broken, you get the plumber. The air conditioned system doesn't work, the electricity doesn't work. All those things are immune cells in inflammatory process. They are a fixer. We need EU from the Greek good inflammation. We need that. In fact, I mean when you are stressed, what do you do? You may not surprise you haven't got self in your body. Maybe you haven't got the soldier. Your alarm bell doesn't go anywhere. Well of course you're getting blamed. How do you fix it? Stop. Go back to it.

Why Treatments Differ And Staging Disease

Susan Manfull, PhD 45:01

So what are your thoughts about why for some people one inflammation uh soldier, so to speak, is effective in one person, and yet for another person, well, one one person takes advil in their their their will, another person needs steroids, another person needs uh IVIG. What are your thoughts about the underlying mechanisms to explain that? I mean, honestly, let me preface that by saying, of course, we don't have all the answers there, but do you have any thoughts on that?

Fulvio d'Acquisto 45:41

Well, I mean, let's start from something, you know, the intense code that I found pans and pandas, even in a from scientific point of view, because he helps me so much consolidating lots of questions that like this one that you have. Yeah, we we do know that plasmapheresis works in pants and pandas, right? So plasma pheresis, you remove anything soluble, allegedly, and you just leave the cells from the blood. So clearly there is something soluble that is produced that does something. But it is a fact, you know, that if you remove the plasma, the patient gets better. So that's number one. Now, the plasma must contain something that then causes Tanz and Bandas manifestation. Now that as we've seen, and again, I can never be grateful enough uh for giving me the opportunity to come to one of your meetings. I learned so much, you know, from obviously I knew Jennifer Frankovich and you know all these other uh kind of pillars of the field, but it's different when you see them all together. And you know, you get this picture of well, it's not just OCT, and then there is a bit of uh rheumatoid arthritis, and then there is the dysgraphia, and then there is this and this and that. So the way I picture in my mind is that um the disease is like a book. So there is a narrative going on, there is this a process with stages, stage one, two, three, four, five. The drugs just act at different points. Now, if you like enough to go with the right drug at the right stage, it works. If it doesn't, then obviously you either too late or too early. And that, for instance, in my case, works wonderfully. When you think about emot, imode immunomodulin, think about the domino, right? So your one domino knocks down, becomes two, two becomes four, four becomes eight. So it's a protein that kind of aggregates like dominions. So it depends on where you are, you can interrupt that chain of reaction. Because then when you have aggregated imod, that's the time we think it goes to the brain. When it goes to the brain, then it deposits in hydrils like amyloid and cynuclein. So there are different stages, not like what we think. You know, there is a receptor and the ligand, and I just block the receptor or the ligand. That's a like a love story that focuses on a case. There's the whole love story. There's the flirting, the meeting, you know, the sex or the fight. And you know, the drugs are just acting at different points. We don't know what these points are, maybe. That's the reason why some works and some not, because we we're just trying our luck and see which one works.

Susan Manfull, PhD 48:53

Yeah, if only we had more personalized medicine so we could see at what stage the individual was more research to do.

Fulvio d'Acquisto 49:04

And also, when we had the meeting, you know, we were talking about the auto antibodies in Panzer Pandas, and you know, they were never the same. They were all over the place because that is a personalized response. So there was no correlation in this is not my work, but you know what I mean? For me, that made a lot of sense. It's just uh you know, like you know, the experience of a glass of wine for you is different from me, and this is the same thing. There are steps in progression, it's not just two points, one line, and then the breakage of the line.

Proteomics, Autoimmunity, And Psychiatric Links

Susan Manfull, PhD 49:46

Mm-hmm. It's much more complicated. There's a researcher, Dr. Lauren Breithop, who was at Harvard Mass General, and we've supported her work. Uh she does proteomics, in which she looks for proteins in patients with pandas, with OCD, with ARFID, and with different disorders, and she's really just started to analyze that data. She's found she on the basis of certain protein profile, she's able to distinguish pandas from quote-unquote healthy patients with 91% accuracy. That's pretty remarkable. So, but that doesn't answer, as what what we're talking about, doesn't answer what treatment would be best, but it does show that we can distinguish the two groups. And in fact, she and Kyle Williams have applied for a patent for this. So there's some movement forward, but all the questions are not answered. I think the other interesting observation, and you're right about this too, I think, is it's known that autoimmune disease is um closely related to certain psychiatric disorders, in fact, quite a few of them. But um why is it that they're related to more to some psychiatric disorders than to others? Like um the relationship between psoriasis and OCD is is pretty strong. And that that's a subject I'm I'm really interested in. And Kyle Williams from Mass General in Harvard is doing some research on that subject, and he hasn't uh finished the paper yet, but he completed an extensive study of the association of obsessive-compulsive disorder with multiple uh autoimmune conditions. And he looked at over a million medical records at Mass General, and so he's looked at OCD and bipolar disorder and schizophrenia and depression and autism. And the autoimmune conditions, I think there's probably 20 of them that are listed here: children's, autoimmune thyroid disorders, alopecia, ariana, Addison's butulus disorder, psoriasis, psoriatic arthritis, Crohn's disease, all sorts of colitis lupus, and more. And this is just preliminary but he found that OCD show disproportionately high prevalence of inflammatory battle disease and dermatological autoimmune conditions, such as psoriasis, and with IL-17 being the connection there. And in contrast, he found diabetes, rheumatoid arthritis, demyelating disease, and myasthenia gravis were more prevalent in mood and psychotic disorders. So I find that really interesting that with certain psychiatric disorders, certain uh autoimmune conditions are more likely to be uh identified. And it kind of goes back again, supporting the role of, well, this is sort of obvious, but the role of the immune system. Right? Would you agree?

Fulvio d'Acquisto 53:45

Yeah, yeah, yeah. And again, I'm gonna give you this is so liberating today. I'm saying everything that I want to say. Um we'll go into the very hocus focus part of me.

Susan Manfull, PhD 54:01

Oh, good. I like the hocus-focus part. I like it.

Fulvio d'Acquisto 54:05

Very, very philosophical, so to speak. So the way Symptom and Symbol famous book in America. Uh I don't remember the author, but it's called Symptoms and Symbols.

Susan Manfull, PhD 54:17

Oh, okay.

Fulvio d'Acquisto 54:19

The symptoms are symbolic of a certain psychological state or processes. Uh-huh. So I have OCD, and um, I'm 100% I'm talking as immune system and OCD, and I'm sure that there is some sort of infection that I don't know what it is, and I'm trying to find it and trying to find it. So we need to make sure that we don't add more steak, you know, to the barbecue. Let's put on some very disgusting kind of something that pushes people away. So psoriasis in that sense, you know, it's a visual thing.

Susan Manfull, PhD 55:02

Mm-hmm.

Fulvio d'Acquisto 55:03

Absolutely. I'm always trying to kind of have a look at that. It's a distorted nature, but it's nature. So what is this body trying to achieve? Theoretically, those should lead to a better survival if this is a strategy for survival, and there's a distorted one. So it is a distorted one. One thinks that you know there is an infection that is in there, and then because he can't find it, it puts these things out to block the person from doing other things or being approached by other people.

Susan Manfull, PhD 55:45

That's very interesting.

Fulvio d'Acquisto 55:48

I try and reason it, if you like. Um that would be the link uh for me between um the two. And the other more scientific way, I think, when you go to depression, there is more reduced number of immune cells in the blood. Like, you know, you're just immunosuppressed by the stress, while you know, in OCD and all these other conditions, there is not much of that going on. The cells are there, but they are all over the place, they are doing something which is uncontrolled.

Susan Manfull, PhD 56:31

Yeah, that's really interesting. So much of it, I think, has to do with making sure it's uh a correct psychiatric diagnosis, and whether our understanding is sufficient yet, and like in terms of psychosis, what are we talking about? And and there's multiple types of schizophrenia. In fact, every DSM I think has a different number of the different types. And maybe taking a closer look at the diagnosis and whether or not they're accurate and what autoimmune conditions they're associated with might be valuable. And I guess what's making me think that is a case that I found myself re-referring to quite a bit. Uh, and that was a an article from The New Yorker about a woman that was diagnosed with schizophrenia. Her name was Mary. Did you read that article?

Fulvio d'Acquisto 57:34

No, um, but I heard of it, yeah.

Susan Manfull, PhD 57:37

Okay, I found it really fascinating. For listeners who are not familiar with it, it was a woman who in her 40s is diagnosed with schizophrenia. And it's a very unusual age to be diagnosed with schizophrenia. Most of the time, it's in the late teens or likely the early 20s to early 30s. And she lived for 20 years, being pretty treatment resistant. I mean, she was in and out of hospitals on multiple different psychiatric drugs and just not responsive in general. So you can imagine what happened to her life in 20 years. Her family, although her daughters were very supportive, they did not get to enjoy the richness of what those relationships should have been. And as I said, she was on so many drugs with many side effects and in and out of hospitals. And about 20 years after she was diagnosed, that is again meeting the criteria for schizophrenia, she developed uh cancer, lymphoma. And as a result of that, took rituximab, the immune-modulating or immune-pressing drug that's often used to treat pandas and pans, and she suddenly lost all of her symptoms of schizophrenia and was no longer able to diagnose her as having schizophrenia. So 20 years ago, I understand why they didn't test for other medical conditions, but had they, perhaps they would have identified the autoimmune condition, which was lupus, and treated her differently. I uh I guess I bring that up because we need to know so much more about what autoimmune conditions, well what medical conditions in particular autoimmune conditions need to be tested when we see a psychiatric disorder uh presenting itself.

Symptoms As Symbols And Psoriasis-OCD

Fulvio d'Acquisto 59:50

So I have two points to make on that, which are very relevant. And I'll pick up lupus. So lupus is in autoimmune diseases where you have auto antibody against. DNA. Circulating DNA in the body. This is a very generic and very approximate definition of the disease. I'm about to publish a study where I simulated fear in mice. So basically I spose the mice to a predator order like fox urine. You know, you spose the mice to foxurine, they have a fear response. And then I induce an inflammatory process. What you see is that again the immune cells in this case they explode. So the one they've been subjected to fear, the neutrophil, they actually overreact, and by doing that they expel all the inner material, including DNA. It is over the last ten years that we've done a connection between neutrophils and lupus. So you know, you can see how you just need to be going through a war having sort of social fear and fear. Your immune system might have blasted all this DNA out. That didn't make sense. Generational antipode. Yeah, yeah, yeah.

Susan Manfull, PhD 1:01:26

Uh-huh.

Fulvio d'Acquisto 1:01:27

It's interesting that when I look at FIA, even at the level of the immune system, you know, the neutrophils should be very slow to react and then do their things. When I took the mice to have a fearful um condition, they just go ballistic and they it's almost like killing themselves, though. They don't even have the time to do their job, they just explode.

Susan Manfull, PhD 1:01:50

Wow.

Fulvio d'Acquisto 1:01:50

And so tells you so much about you know that one hour window, two-hour window of a cotton piece of cotton with fox urine in it. So you can see the idea of the effect, you know, those little things that you think they do nothing, but they do. They actually do. And if that is repeated, then that's how you get autoimmunity and auto-antibody by resposing to the same antigen or the same protein that it shouldn't be there. So repeated exposure causes autoimmunity as well. The provocative side of uh going back to pants and all of that, you know, uh here we go the Nobel Prize for medicine in the palating words. My approach will be very simple. All the OCD tourette, uh, pants and pandas, they should have bone marrow transplantation. Like, you know, wipe off their immune system completely. You know, when you have cancer, you you remove all your immune cells from the body, and then you transplant with the bone marrow so you the the precursor of immune cells uh of your sister or parents, you know. So you basically uh delete from the body all the wrong immune cells, and in that case, in cancer is cancerous cells. So immunotherapy, bone marrow transplantation, and then see if disease is still there. Because the you know the crazy T cell will not be there. In the case of depression, all you need to do, triple invested coma, is to pump more immune cells in the body. IL7, GMCSF. When you look at this cytokine, what they do in the body, you know, they they stimulate T cell production or they stimulate neutrophil production, so you make more immune cells, and then guess what? They all have a behavioral effect.

Susan Manfull, PhD 1:04:03

Wow. So I um see an immediate practical problem, of course, but if we only could do that.

Fulvio d'Acquisto 1:04:11

But we know why this is not happening, right?

Susan Manfull, PhD 1:04:15

Yes, exactly. Insurance companies, cost, which is just so disheartening. But you're saying to have a a drug like rituxamab or plasma phoresis.

Fulvio d'Acquisto 1:04:30

Yeah, it really depletes certain cells. I'm talking about wiping off completely. When you have bone marrow transplant tissue, you basically uh you wipe off completely your immune system and doesn't exist anymore, and then you receive progenitor cells which are in the bone marrow. Those are the cells that then give you immune cells. So you replace the patient immune system with uh in the immune system or someone in your family that is compatible.

Susan Manfull, PhD 1:05:02

Really interesting. That's really interesting. So just so I understand, I mean, would you have something like plasmapheresis first or just go right to uh bone marrow transplant?

Fulvio d'Acquisto 1:05:13

Yeah, I think bone marrow transplantation would be, you know, wiping because at the end the plasma is just a container of what these immune cells have produced, right?

Susan Manfull, PhD 1:05:23

Wow.

Fulvio d'Acquisto 1:05:23

So if you wipe them off because they are producing an unregulated amount of whatever is causing the disease, then you replace with proper, not sensitized uh immune cells, then is anyone doing that? Absolutely not.

Susan Manfull, PhD 1:05:44

Yeah, yeah.

Fulvio d'Acquisto 1:05:46

Fair enough. I've been saying this for over the last five years.

Susan Manfull, PhD 1:05:49

Uh-huh.

Fulvio d'Acquisto 1:05:50

Uh here and there in some reviews, they start to popping up.

Susan Manfull, PhD 1:05:55

Talking about having a bone marrow, the value of having a bone marrow transplant.

Fulvio d'Acquisto 1:05:59

Oh, yeah, it's a thing of depression and inflammation is not really connected. So, but you know, there are the holder of the truth. And until it comes from them, everything else is you know what has to come to certain people. Yeah. Other people are crazy.

Misdiagnosis, Rituximab, And Lupus Lessons

Susan Manfull, PhD 1:06:24

Sort of harkens back to Similvice's problems in the end of the 19th century, yeah. Um, and then he had proof if you looked at his data. Doctors who washed their hands with his chlorinated substance and then delivered babies and a reduction in uh the mortality, but there wasn't an explanation by the doctors in Panor, so to speak. And in that case, that was in Viennin, and then uh Dr. Stimmelweiss was from Hungary, and um maybe he didn't carry the same gravitomas as the other doctors. It's very interesting. Okay, I just have a couple more questions. I want to I want I just want to ask you if you can tell us a little bit about what you're what kind of research you're doing with brain tissue.

How Fear Primes Immunity Toward Autoimmunity

Fulvio d'Acquisto 1:07:25

Yeah. So as I mentioned to you, immunomodulin is this sort of um uh imagining. I don't know if you ever seen those toys with uh magnets, you know, you you have like little sticks of magnets, and then you have other sticks, and then uh if you put them close to each other, they kind of ta-ta-ta-ta-ta-tago. So that's IMUD or immunomodulin becoming pathogenic. So is the conversion from a single molecule to a cluster of molecules, and then it becomes a fabrible. And this process is pretty much what happened in Alzheimer's and Parkinson. So there is a class of protein, and IMUD is one of them. So then you know you have nuclein, alpha C nuclein in Parkinson or beta-malloid in uh Alzheimer's, so they share certain behavior, they are called intrinsically disordered protein, which means basically they are very flexible, they are very unstable in the structure. And on top of that, they tend to aggregate. So in Parkinson and Alzheimer's, this protein they aggregate first and then they form fibroults. Fibro in the brain then goes cell debt, and then obviously neural damage and the symptoms there we know. Where are these protein to begin with? In blood. So, like, guess what? Serotonin is like 100 times more present in blood than in the brain. Let's not go there. IMUD is in the blood, and then an infarction can happen, or something or traumatic can happen, and then IMUD basically becomes aggregated. Once it becomes aggregated, it becomes um lipophilic. That means they can cross a lipid bilayer, the brain. And then once it gets to the brain, this bubble of aggregated amount, uh, for reasons that we don't know yet, uh, becomes possibly a fibril or a bigger bubble. The presence of this bigger bubble or fibrill will impact the way neurons talk to each other. I don't know if you ever use one of those foams, you know, when you have a hole in the in the wall and you want to fill it in, and you have that kind of polystyrene expansion thing. That's that's Simon, you know, it's basically like polymerize uh gung in the brain that stops you know the two neurons talking to each other. The beauty of it, once that is done, is that it's not always there, you can also disassemble and come back in blood. Why is that important? Because that would display acute phase relapse. Yeah, remission relapse, so you get high disease during the infection. Infection activate these cells, these produce more IMUD, more immod becomes gunk, gunk in the brain becomes these sort of things they obstruct neural connection, then infection goes away, eye mode goes down in the blood, the one from the brain goes back into circulation. So that will give you this waves of psychiatric manifestation. Now, I've been lucky enough through you, once again, that I had the chance to opportunity to have access to the brain of a patient from Pants and Pandas and some control. And we can see these bubbles of IMUD in many of these sections. I haven't got the full picture yet, but I can clearly see that there are some brain tissue that have this bubble of IMUD and some others they don't. So the brain is like you know the endpoint of a run, you know, kind of when you when you're running, when you're doing a marathon, that's the finish line. So the finish line is the bubble. If I see bubble, that means that it's pathogenic. And so I need the brain of patient to show that there is a correlation between the formation of these bubbles and the disease. Oh my gosh. Yeah, yeah, I wouldn't need you know the three things. I would need the blood. But what is very uh, you know, you were talking about proteomic and with 90% confidence. In these other diseases like Alzheimer and Parkinson, where you have two other proteins that have similar behavior to IMUD, so they they have disordered in the form of this bubble and thing. They are right now antibody, they are administered in vivo in patient. They block the this process of polymerization, they stop the change like you stop the domino. They are working. Yeah, oh my four drugs from Eli Lilly, you know, they are currently test when you take the plasma of those patients and you trying to reproduce the bubble formation, you can do that in vitro. That test is diagnostic with the power of 95% accuracy.

Susan Manfull, PhD 1:13:25

Wow, that's huge strides in understanding the uh ideology of some of the symptoms and um and the treatment.

Fulvio d'Acquisto 1:13:38

Yeah, yeah, so it's a good sign for immune psychiatry in that sense. Because then this neurodegenerative disorder, they've been treated in the periphery. Peripherically, in blood, not in the brain. You know, the antibody are in blood. When you administer IVIG, they stay the majority of it in blood, and that's how they work. So they clearly block something that is circulating in the body. Antibody cannot go into the brain that easily.

Susan Manfull, PhD 1:14:11

Okay.

Fulvio d'Acquisto 1:14:12

But it stays in the blood forever. The key aspect, I think, is that you have this sensor molecule in the body, right? And you have a certain level, you have a healthy level. Then something goes wrong, an infection. You overcharge the system, and that overcharge causes this sort of chain reaction that then goes to your brain and does something.

Susan Manfull, PhD 1:14:38

Interesting.

Fulvio d'Acquisto 1:14:39

So again, it's a very homeostatic system, right? It's a very sort of uh plastic, movable things that you see also in OCD, you know, and you know, definition of pans and pandas is wax and waning.

Susan Manfull, PhD 1:14:56

Is the presence of the eye mood and the the clusters of that is do you feel that that's related to flares that have come on? And flares that and and not present or not as present when the flares remit. Yeah.

Fulvio d'Acquisto 1:15:16

Yeah, I think when you see the symptoms, all the iMod, the gunked IMOT is in the brain. Then when the symptom goes down, it's going back into circulation. Because the trigger is gone. For some other people, you might stay there forever and therefore the symptoms never go.

Susan Manfull, PhD 1:15:36

So in the limited sample that you had of brain tissue, you were able to see the eye mood evidence of that.

Fulvio d'Acquisto 1:15:45

Yeah, which you know, I I I kept saying to you, you know, when I did the first data. So Susan, I need to show you slightly dumb up and down, but you can get time and things and uh uh power, uh power, I must admit, you know, uh is slowing me down. But uh, you know, I'm definitely getting there.

Susan Manfull, PhD 1:16:08

So wow, that gives us a lot to think about. We um well, I encourage you to request more tissue from the brain bank to further understand that. That's really amazing. Maybe that should have been our headline.

Fulvio d'Acquisto 1:16:25

Um but also, you know, just let's forget about emos for a moment. Let's, you know, look really at the idea that antibiotic works, IBA works. So these are all things that are peripheral. When I say peripheral, I mean blood, not in the brain necessarily. Plasmapheresis work. So clearly, and then that's the other thing. I went with fantastic meeting organized by Andre Laguliari Messine about pants and pandas, everyone was there. And then it turns out that many people do plasmapheresis. And guess what? Where is this plasma going? Thrown away. Why we haven't got the bio bunk for the plasma or the plasmapheresis?

Bold Ideas: Bone Marrow Reset For Neuroimmune

Susan Manfull, PhD 1:17:15

Wow, well, why now I'm gonna be asking that question. Why is that just such an oversight? Um all right, and I think I um had better ask you my last question. And it's going back to something that we talked about at the very beginning. Just this idea of not only learning more of them, just generally speaking, what makes you similar to promised or feeling as if there isn't a purpose for you versus what makes you feel good and um have a purpose and meaning in life. And I just want to say, and maybe you can just comment on the minute. I told you the minute when I went in Alice's apartment just in a few years before she didn't mind that she had those books on her nightstand of finding purpose, finding meaning. There was another one she had afraid to tell you whom I am because if I tell you whom you might not like me. So within when I tell you that in one of my conversations with analytics, you probably know that she initially had a fairly mild case and then was highly functioning. Um finished Princeton when I went to work in towns on Wall Street and one of her managers that I still speak with who she worked for Morgan's family, said that she remains the best analyst that he's ever worked with. So she was functioning very well. But she said to me one day on the phone, and I don't remember what prompted it, but she said, you know, Mom, I'm not the same person that I was at 12 South Street. 12 South Street is where we live and where she grew up. And I talked to a neurologist about them, and he said that when someone makes a statement like that, then it really reinforces his belief that the person has a neurological disorder. And so I have that in mind, and then I have in mind the patients who do get better. And I'm picturing one young woman in my mind right now who'd not been well for a little while, and she went the psychiatric route to begin with, and then finally when she was. Was treated for the infection-associated neuroimmune disorder that she had. She got amazingly better. She's doing remarkably well. And I venture to say that she feels more herself. She's told her parents that she feels more herself and that she's beginning to reclaim some of her confidence that she had before and her sense of self. I guess when I read that you were very interested in that idea of what makes us feel happy and having a purpose and what have you, that that needs more study. And I look at what my daughter said and what this young person who's on the other side said, I do think that's really important work. Like what happened to her, aside from the obvious fact that she's is not suffering from these symptoms, but I think it goes beyond just not suffering from the symptoms. What do you have any thoughts on that?

Fulvio d'Acquisto 1:21:10

So these are again, uh these are very, very, very strong beliefs that I have and which I never share, but you know, I feel so connected with you on that. And if I were to write a book about the last hundred years, I think uh this is the century of the disease of belonging. The core of everything that we are having health-wise is a crisis of belonging. And you know, to try and do in my little word something about it. There is a colleague of mine, a psychotherapist, Emanuele Roberti. We wanted to launch something called salotto. Salotto is you know in Italian means you know, living room, or you know, is where the Italians used to entertain you know artists and poets. And uh in Italian we say when you say sta facendo salotto, she's doing salotto, it means that you're having a chat with like-minded people, you know, you're having a stimulating conversation. So we decided to do that, to the salotto podcast or something, and then they said, Well, that was the first thing that we want to explore. I say, No, let's go for belonging, belonging is very important to me. Search in social media. People are trying to belong to someone else. Loneliness crisis. I'm not the same person that you met, is the lack of space or reality to belong to another group of people because we are all scattered. So before there was an enforced belonging before social media, so to speak, or you you kind of worked with what you had and you make an effort, and probably it was similar. Now we are so scattered that it's very difficult to belong to someone and then to to a group of people to just be something, or just be yourself. And uh, when we there was Manuela's son, and uh we made some interviews uh with uh scientific people and psychological people, you know, expert in those fields, and then we asked Manuela's son and said, you know, what's belonging to you? And uh he's 12 years old. He said, You are mine, you belong to me. And that caught us by surprise because you know, we thought, you know, football team or something. So that is another key point, you know, the son and the mother, the son and the parents, it's a model of belonging, it's the initial exposure to belonging. And then if that is not followed up by an equal model where you leave the home and then you have an equally accepting or not uh environment, then there is a crisis and you don't know who you are, and you start to question who you really are. You know, I'm not the same as anymore. I haven't got you know, it's like going back to the water example, it's a water without container. And the container is made by belonging to something. Look at Netflix, you know, Netflix series, you know, the record, world record, you know, there are the people they uh challenge themselves in eating uh the hottest chili, the one they have competition for the hair. That is another evidence of well, actually I want to belong somewhere. And then you find an excuse to connect. And that's the problem. That is the problem. So if we fix belonging, I'm quite confident that many and fair enough, you know, if you isolate yourself and you stay by yourself and then kind of thing, uh uh immunologically you become weaker. The hygiene hypothesis, you know, don't touch that, don't clean everything. So being clean is equal, you're a good person. You belong to the environment, those bacteria are not there to kill you, they belong to your life. You got 20 kilos of bacteria in your guts. So at the bottom of it is really a societal issue that just gets manifested in such a powerful and damaging way.

Aggregating Proteins And Brain “Gunk”

Susan Manfull, PhD 1:26:07

So a couple things. One, as I mentioned at the beginning, I've been a long time fan of uh Carl Rogers. So we made a concerted effort to raise Alex with those qualities in her environment. And she did have a very good sense of self, a very healthy view of herself. And I wonder what there is beyond some of the things that you just talked about where you end up isolating yourself because of the condition, or because you believe there's some stigma attached to it, or what have you. What is it about this condition and and other ones that test your empathy? I felt she began to lose her ability to empathize at times, and she didn't have as much unconditional positive regard for other people. So I think uh I mean, I'd love to see that investigated. And then the things that you're talking about, at the risk of being political, I'll just say that in this country at this time, there are uh it is the antithesis of Carl Rogers. And I I I'm frightened about what that environment will do to young people who are growing up.

Fulvio d'Acquisto 1:27:37

If I want to console myself, I look at the introduction becoming a person of Carl Rogers. It was a big challenge for him to find his place in the world of psychology and to have such a revolutionary idea. And you know, that was the America of the sky is the limit. That was the dreamland. But would you compare his time to our time? Clearly not.

Susan Manfull, PhD 1:28:05

Okay. Well, I think we have a lot more to talk about, and this is a good way to end our conversation for now. We all need to take the time out of our increasingly crazy busy lives to focus on taking care of ourselves, and maybe as you write, you know, get a massage every once in a while, or listen to music that moves us in some way, or art doodling.

Fulvio d'Acquisto 1:28:41

But look at what you and your husband are doing. You are giving us a platform to belong. Can you see that?

Susan Manfull, PhD 1:28:53

Thank you.

Fulvio d'Acquisto 1:28:55

You know, what that has done to all of us. And look how enthusiastic we are about doing this.

Susan Manfull, PhD 1:29:06

I guess we all do feel like we're a part of this.

Fulvio d'Acquisto 1:29:10

Yeah, exactly. And that that makes you know that even the research lab, you know, it becomes an inspiration, becomes something exciting, something that gives you meaning. Yeah. Because you know, you don't have the right people to talk about it, you know. You can be happy about you and your discovery, but about the people in the journey with you. You know, again, America always led. Remember when I was in the US for my postdoc, you know, there was an association, I can't remember now, the Anne Fuller. I think uh rheumatoid arthritis charity. Once you get the fellowship, the first thing you need to do, you need to go out for a dinner, gala dinner, where you sit in you, and then at the table there are all the donors, you know, all the family of people with the rheumatoid arthritis. That is the way to do it. That is the way to do it. You know, from very early on, I was just 26 or something. You know, that's where you need to understand that those plastic tubes that you do in the lab, they mean something. They have an impact.

unknown 1:30:19

Absolutely.

Fulvio d'Acquisto 1:30:20

Yeah, of course. I mean, I'm not saying the research should be all like this, you know. You can also do very basic research just for the fun of the science, but there is an element of meaning and belonging that they should be included in the in the journey, but not probably just in science.

Susan Manfull, PhD 1:30:36

Well, and maybe the basic researchers need a little more support to meet who it is they're doing this work for that might not be translated right this moment, but when you put it all together, it can be very meaningful. And let's hope it doesn't take 17 years to do to go from the the bench to the bed. All right, Fulvio, thank you so much. What an interesting conversation. And I look forward to to more of them, but thank you very much.

Fulvio d'Acquisto 1:31:13

And thank you, Susan, and you know, your family to allow me to be part of the family.

Susan Manfull, PhD 1:31:20

Absolutely. We'll have to come to the table together. All right, thank you, Fulvio. Bye.

Fulvio d'Acquisto 1:31:26

All right, bye-bye, bye.

William Manfull 1:31:29

This concludes episode 21 of Untangling Pandas and Pans. Thank you for listening. For more information about pandas and pans and the Alex Manful Fund, please visit the AlexManfulfund.org. The content in this podcast is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare provider with any questions you may have regarding a medical condition.