From Our Neurons to Yours

What is psychosis? Navigating an altered reality | Jacob Ballon & Shannon Pagdon

• Wu Tsai Neurosciences Institute at Stanford University, Nicholas Weiler, Jacob Ballon, Shannon Pagdon • Season 7 • Episode 14

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Imagine if you couldn't distinguish between dreams and reality. If you couldn't tell whether what you were seeing or hearing was really there in front of you. What if you discovered you couldn't trust your own perceptions? 

Psychosis is something three out of every a hundred people will experience at some point in their lifetimes. But what exactly is it, and is it something people can learn to live with?

Today we're fortunate to have on the show Dr. Jacob Ballon, the founding co-director of Stanford Medicine's Inspire Clinic, and Shannon Pagdon, a doctoral student, peer counselor, and advocate for those living with psychosis.

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Nicholas Weiler (00:10):

This is From our Neurons to Yours, a podcast from the Wu Tsai Neurosciences Institute at Stanford University, bringing you to the frontiers of brain science.

(00:24):

Imagine if you couldn't distinguish between dreams and reality. If you couldn't tell whether what you were seeing or hearing was really there in front of you. What if you discovered you couldn't trust your own perceptions? As we have learned many times on this show, our brains are constantly working under the hood, blending our internal model of the world with external sensory data in order to help us make sense of our surroundings. We depend on that process to go smoothly for our perceptions to shape our beliefs and our decisions. Most of us take this for granted, but what happens when it doesn't work the way we expect it to when we experience what today's guests call non-consensus reality? In medical terms psychosis, this is something three out of every a hundred people will experience at some point in their lifetimes. Now, there are a lot of myths and misunderstandings about what it means to experience psychosis. The term psychotic is a very loaded one in our discourse, and we've come a long way in terms of understanding what psychosis is and in terms of treatment options for disorders like schizophrenia.

(01:35):

Today we're fortunate to have on the show Dr. Jacob Ballon, the founding co-director of Stanford Medicine's Inspire Clinic. This clinic has become a model for spearheading a different, perhaps more humane, approach to treating people with psychosis focused on recovery and patients' lived experience. We're also joined in this conversation by Shannon Pagdon, who is diagnosed with schizophrenia as a teenager and still lives with psychosis today. Shannon previously worked with Ballon as a research coordinator at the Inspire Clinic, and she's currently a PhD candidate at the University of Pittsburgh. I started this conversation by asking Shannon to tell me about the first time she had a psychotic episode.

Shannon Pagdon (02:17):

Yeah, so when psychosis first started for me, it was around 16, 17 years old. I was in high school. I distinctly remember actually my first visual hallucination experience because I was walking back from a class up to my locker, and I remember just very vividly seeing this image of a grape with wings right in front of my face and noticing that none of the people around me were responding to that or noticing it in the same way that I was. From then, it really turned into a lot of more classical psychosis experiences. I started to constantly experience voices and visual hallucinations. I became really paranoid and started to have a lot of extreme beliefs and thoughts about the world and voices being transmitted into my head or feeling like I was a video game character and my actions weren't my own, things like that. I had a lot of nightmares and essentially, I just could not tell the difference at all between reality and dreaming or what was real and what wasn't real.

(03:31):

I did finish my senior year of high school, but with a lot of help from the school at that point. I still have a lot of those experiences on an ongoing basis, but they're much more manageable and I've certainly developed a lot of coping skills. 17 feels recent, but it's less recent, increasingly over time.

Nicholas Weiler (03:50):

For someone who has not experienced that sort of waking dream, it may be hard to understand. You see a grape with wings. What is the experience of whether you believe your own mind or not?

Shannon Pagdon (04:03):

It's actually something I still struggle with a lot. I tend to assume that what I'm seeing is not real or not happening until I get confirmation from people around me or something in the world around me. I actually use my dog a lot for that. She's very grounding as far as walking into a space, seeing something, and then she's very friendly, so if she tends to react or not react, it gives me a good indication of whether that thing is there. But to be honest, I don't, at this point, remember very well what it's like to not navigate the world that way.

Nicholas Weiler (04:41):

I guess in a way that's very scientific, right, but definitely I imagine that can be a little bit exhausting. Can you tell us a little bit about what was your journey from getting those symptoms to getting a diagnosis and how was that helpful for you?

Shannon Pagdon (04:55):

Yeah, so I grew up in a relatively rural area of northern California, so getting the diagnosis was a little bit tricky. There weren't a lot of treatment options in the area, and this was also pre-specialized psychosis services in Northern California. I ended up going to a private therapist and a private psychiatrist. It took about a year from when I first started experiencing psychosis to getting the diagnosis. It was right after I turned 18 that I ended up getting the official diagnosis of schizophrenia, and then before that it was labeled as psychosis, not otherwise specified.

Nicholas Weiler (05:37):

Well, Jake, I'd love to bring you in here and help connect the experience that Shannon is sharing with us to what you see in patients more broadly at the Stanford Clinics. How unique is each case and how difficult is it to get to a specific diagnosis?

Jacob Ballon (05:54):

Yeah, thanks. It is one of those things that every case is absolutely unique. So Shannon is the only person I know of who's seen a flying grape, but the idea that needing to check on what's happening in your space and trying to call into that into question, that's not unique. There are themes that certainly exist amongst folks, and that's what I'm looking for often is what's the pattern?

(06:15):

But I want to call back actually to one part from earlier, which is the idea that I actually think everybody has experienced some measure of psychosis because to me, psychosis exists on a spectrum. There is the psychosis that leads to a diagnosis that's associated with distress, with changes in behavior, perhaps with social withdrawal or confusion, but that there's also the psychosis that is how many times did I walk into my baby's room thinking that they were crying only to realize that I must've just been hearing something? Or how many times after you've watched a scary movie, are you just a little bit more jumpy than you were before? Or you thought you saw a bug, that there's bed bugs in the area, all of a sudden you're feeling things crawling on your skin. So the idea that our minds play tricks on us at times, that's not necessarily pathological and it's not necessarily problematic, but it is on that spectrum to psychosis.

(07:10):

Where it gets to be challenging and different is in that part you pointed out, which is at what point can you no longer trust your own thoughts as having been correct or your own senses as having been accurate? And that's a really hard thing for people to come to grips with often because if you can't trust that what you hear is what is actually happening, or that what you think is true is really true, some of the things you do think in fact are true, but how do you differentiate those can be really hard. And the experience of being told that what you think is true is not true, also can be very devaluing and can lead people to also want to withdraw because they're just not sure that people are going to understand them and that they're not going to get rejected for what they think all the time.

(07:53):

So when I look at the theme for people, I am looking for where are the areas of distress? Where are the areas of behavioral change that is making it difficult for them to experience the things they want to experience to hit the goals that they're looking for? And that's where we start a diagnosis conversation.

Nicholas Weiler (08:11):

What is the difference between psychosis and schizophrenia?

Jacob Ballon (08:16):

That's a great question. So psychosis is a symptom, ultimately, and psychosis, they often use a term "break from reality". I'm not sure I love that term, but I think it gets across the idea that there are these non-consensus reality experiences that people might have. It could be a thought, it could be a behavior, it could be a sensation. Most commonly it's an auditory hallucination, something that people are hearing that's just not there to anybody else. But it could also be a sense of being watched or followed. And so those are all part of what we call positive symptoms that are maybe the most classic symptoms in a psychotic disorder, but they're all examples of psychosis.

(08:57):

When I talk about schizophrenia, now I'm including not just these positive symptoms, these things that exist in excess of the real background experience, but I'm also talking about things like cognitive challenges that can happen for people, which can be difficulty with working memory, difficulty with reaction time, executive functioning. I'm also talking about things like negative symptoms, which is difficulty with motivation, struggling with things like hygiene and social connection.

Nicholas Weiler (09:26):

And when you say positive and negative symptoms, that can be a little bit confusing because it sounds like good and bad. It actually means things that are happening that don't happen to people without the disorder and things that are not happening that would usually happen for people without the disorder.

Jacob Ballon (09:41):

Right, exactly. So it's things that are in excess or in deficit. So in excess would be hearing something that's not there, your mind is working overtime, so to speak. In deficit is lacking motivation, not wanting to get up, get dressed, be social with people, and that ties into a lot of other aspects to what it's like to experience psychosis and to experience schizophrenia. And I will say that sometimes I may use the terms interchangeably because to me, I spend a lot of time with people who do have schizophrenia, and psychosis is the leading cause of what brings them to see me. But if I'm being really specific, I would not use the terms interchangeably. I would say that psychosis can exist in a number of different circumstances. You can have psychosis after having experienced trauma. You can have psychosis as part of a mood disorder, whether it's associated with mania or depression. You can have psychosis as the end stage of a very significant anxiety disorder.

(10:38):

But one of the things that separates psychosis from other symptoms is this inability to talk yourself out of the thing that you're experiencing or a lack of real cognitive flexibility around what it is you're experiencing. It becomes real. The thought or the experience becomes as real as the sky is blue. That's where it becomes challenging. That said, even when there's that level of conviction on things, sometimes there's still an openness to alternate explanations, and that's what we can often use as a gateway to being able to work with people in treatment.

Nicholas Weiler (11:09):

Well, I'd love to do a quick lightning round. I'm going to say some things that people might think about psychosis. You tell me if they're right or wrong and how they're wrong. We'll try to keep this quick.

Jacob Ballon (11:22):

Yeah.

Nicholas Weiler (11:23):

People with psychosis are psychopaths.

Jacob Ballon (11:26):

So that's a challenge of using language because in fact, psychosis and psychopathy sound alike, but are notably different. Psychopathy refers to what is now often referred to as antisocial personality disorder or essentially a state where people lack remorse. They will do things to other people without any sense of concern as long as it serves their interests. People with schizophrenia or who experience psychosis, that's just not their experience.

Nicholas Weiler (11:53):

Next one, similar. People with psychosis have split personalities.

Shannon Pagdon (11:58):

This is one I get a lot, actually. I think it is a confusion of the meaning of the term schizophrenia, which translates into split mind. That often gets confused with what is dissociative identity disorder. I think it also is in part the idea of seeing somebody maybe talking to themselves if they're hearing voices or experiencing non-consensus reality that sometimes gets misconstrued as dissociative identity disorder. But Jake, I'm not sure if you wanted to add to that at all.

Jacob Ballon (12:31):

I would say that with multiple personality or dissociative identity disorder, when you see and talk to people who experience that, it can have a similar feeling to things related to psychosis. How could you be in one state and then completely be amnestic to it, and be in another state and not be able to understand where you were and not be able to explain it as well? This was just a thing that happens to me. Again, there can be a lot of very strong conviction as to what the experience was like. That said, psychosis can be related to trauma, but dissociative identity is almost exclusively going to be related to people who've experienced trauma and is, in essence, a reaction to that. Thus, it really is a separate category. So there can be some overlap, but definitely one is not the same as the other.

Nicholas Weiler (13:19):

Here's another one for you, Jake. People with psychosis are dangerous.

Jacob Ballon (13:23):

Right, so that's a challenge of the media. So there are people who experience hallucinations and delusions and act upon them in violent ways. We see that with postpartum psychosis when there's been tragedies around infanticide and things like that. We see that sometimes when there's a mass shooting and the media is quick to jump on and say, well, this person has schizophrenia. But if you look at overall experience of people with schizophrenia, the vast majority, just like the vast majority of any population, are not violent. And in particular, people with psychosis are much more likely to be the victims of a violent crime than they are to be the perpetrator. So while it makes for sensational media coverage and headlines and feeds the narrative of what people already have as assumptions, the reality of it is that people who experience psychosis are much more likely to be withdrawn than they are to be outwardly violent.

(14:16):

It's also the case that who we see on the street can sometimes shade this same kind of narrative. So when you see somebody in San Francisco talking to themselves and shouting, that feeds a narrative of that person is probably also violent. Now in reality, that person probably is not necessarily even aware of your presence and would just keep walking past you. But when you have a preconceived idea that this is a violent person or person for whom violence is likely, it shades that image that you might have of that person and how you might think of helping them, as well.

Nicholas Weiler (14:46):

Well, that leads to my next myth for us to bust, and I'm going to address this to you, Shannon. And I hesitated about how to frame this one. I'm going to frame it the way I think people think it, which I know is problematic. The myth is people with psychosis are crazy, meaning constantly hallucinating or delusional, just not with us, always out there.

Shannon Pagdon (15:06):

I would say this is definitely another big one, and I've also heard it framed as people with psychosis don't recover. I would definitely say that, that is wholly inaccurate. Certainly early intervention into services is a huge way to support people getting into care early. There are so many ways that one would navigate their experiences. I alluded to this earlier, but I still very actively have "symptoms of psychosis", and it's something that I've found different ways to navigate in my life, and a lot of the people that I know with psychosis, everybody has different ways of navigating those experiences, as well.

(15:50):

But part of it to me is an issue of openness because there is so much lack of conversation around psychosis. We get in our heads this idea of people don't recover because people aren't open about recovery or having psychosis, when I meet people all the time who are graduate students or professors and have these experiences, but just don't disclose them.

Nicholas Weiler (16:13):

Interesting.

Shannon Pagdon (16:13):

And so that is a lot more common than we think it is. And Jake was saying the media coverage, I think it is the media coverage. That's the much more extreme end of things, but that doesn't tend to be the reality of most people's situations.

Nicholas Weiler (16:28):

Right. And we're naturally going to notice more if someone is not doing well.

Shannon Pagdon (16:33):

Exactly.

Nicholas Weiler (16:34):

Than if someone is doing well.

Jacob Ballon (16:35):

And let me add, I think the medical and psychiatric community are not immune from these biases, as well, which is actually, it's easy for those of us who spend a lot of time in this area and do a lot of advocacy in this area to lose track of. But in fact, the way that people often enter treatment reflects these biases when they see people who don't have a recovery oriented mindset as the first point of contact, and they maybe are still told that what they have is something that they never will recover from. It's like a cancer diagnosis or something that can be almost like life ending. But I have medical students and residents who work with me in my clinic, and one of the things that every student or trainee who rotates with me leaves with is this tremendous sense of what is the wide-ranging experience that people can have.

(17:22):

And so I will have patients in my clinic, some of whom are engineers at large companies, are high ranking in all different areas of work, including in the university or elsewhere. I also have people in my clinic who are struggling, who have constant symptoms, who are really unable to live independently, who maybe are in and out of the hospital at times and who are doing their best, but they're up against something that is a big challenge. And there's such a wide range. But our earliest training experiences for psychiatrists are on the inpatient unit and even medical school, often, it's in the inpatient unit. So our healthcare workers first and sometimes only experience of seeing somebody actively with psychosis is, in the most extreme circumstances, when they're having the hardest times when for one reason or another, things have gotten worse for them. And so that in and of itself sets a bias frame from the get go.

(18:14):

And so I love to have trainees come in and see me in the outpatient clinic where I work so that they can see what does it look like for recovery and how do we have those conversations with people about recovery and about setting goals and about aligning our treatment with their goals in order to not sell them short and not feed that narrative, which they may have within themselves. We call it internalized stigma of, I have this diagnosis, therefore I can't get married, I can't graduate from high school or college, this is my lot in life. We don't want people to walk around with that internal monologue, nor do we want to be the external reason why they might think that. And so it's actually one of the reasons why we call our clinic the Inspire Clinic. We both want to draw inspiration from our patients, but also want to make sure that people walk out the door with a sense that they can be inspired to do the things that they really do want to do in life and largely are going to be capable of.

Shannon Pagdon (19:07):

Just to briefly add to that, that was certainly true to my own experience of getting the diagnosis and being told you won't be in a relationship or get married, you'll be on this medication forever, et cetera. And I think that it really contributes largely when people don't have access to more specialized support to the internalized stigma. And also just briefly to Jake's point around training, I think that that's true across disciplines because certainly in social work there's a lot of perpetuating of just not teaching people anything about psychosis. And so something I think a lot about is I don't think I would feel comfortable if I didn't have any kind of extra support around supporting individuals who are hearing voices or experiencing, again, non-consensus reality because you're not really taught how to do that. And despite it not requiring an enormous amount of specialized services, there is a level that you want to be aware of different experiences with psychosis that I don't think we tend to teach people, and I think it exacerbates a lot of the fear that people have around working with individuals who are experiencing psychosis. So just to add that briefly.

Nicholas Weiler (20:16):

That's really helpful. Shannon, I've noticed you use this term consensus-based reality. I really like this term that you use. I think listeners can probably deduce what you mean, but maybe we shouldn't make assumptions. Can you tell me a little bit more about that? Why do you use that term?

Shannon Pagdon (20:31):

I really love the term consensus reality or non-consensus reality. So I was mentioning before about assuming that everything I'm experiencing in the world is not real until it's confirmed that it is real. I conceptualize my experiences as us all existing in consensus reality and this access to this extra reality. And for me, they just overlap. But it's a term I really resonate with because it's broader. The idea of consensus reality is a lot broader than some other terms.

Jacob Ballon (21:06):

One of the things that is interesting, and one of the reasons I like that term is when people experience hallucinations, they are generally indistinguishable from, let's say, if they're hearing a voice from voices around them. And you can demonstrate that by putting people in MRI scanners and seeing auditory cortex light up when people push a button saying that they're hearing voices. So the idea that it is anything other than their reality is selling them short, but it's not the consensus reality and the sounds that they are hearing and the meaning they're putting to that is not something that anybody else is going to be able to share with them. And so that's why I like that term non-consensus reality because it really does reflect that this is real to that person. It's just not real in the way that things we can agree upon are real, are real.

Nicholas Weiler (21:51):

So I want to get into a little bit more of what psychosis is and what is actually going on in the brain. What do we understand about how the brain falls into this state of not being able to distinguish reality from invention or from the individual's perceiving things that may or may not be real? It's, as you mentioned, Shannon, can feel like a waking dream at times. Jacob, what do we know about the brain systems that are involved? What's different in the brain when someone is experiencing psychosis?

Jacob Ballon (22:22):

Well, I think to start with, I would say there are almost certainly numerous different possible pathways in the brain that could lead to an end result of psychosis. And it's actually one of the things that makes the study of schizophrenia and the development of new medications in particular very challenging because there is the conventional and longstanding dopamine hypothesis, for example, which is to say that a state of excess dopamine can cause things like hallucinations. And there are different dopamine tracks in the brain. And as dopamine goes through certain tracks, like the mesolimbic track is a pathway that is associated with excitement and things. And when there's excess dopamine in that pathway, you're likely to hear hallucinations. And you can validate that by giving somebody an amphetamine or something and that can cause certain psychotic experiences by flooding dopamine. That is insufficient, though I will say all of our medicines up until very recently in one way, shape, or form, blocked or modulated the dopamine D-II receptor, and in doing so, turn down the volume on psychotic experiences for many people.

Nicholas Weiler (23:31):

So I think you're going to say that that doesn't explain all of it.

Jacob Ballon (23:33):

I doesn't.

Nicholas Weiler (23:33):

But I wonder if we could... I want to make sure that we understand that hypothesis first and then we can say where is it lacking? We've talked before on the show about dopamine. We try not to call it a pleasure chemical anymore, but it sometimes gets called a reward chemical. I've recently heard it called a learning signal, which feels valuable. And I think the important thing that you just said is dopamine is not one thing in the brain. There are multiple different pathways that use dopamine as a signal and do different things. It's involved in movement, and when we lose dopamine neurons, people get Parkinson's disease, which involves difficulty moving, but it also, as you said, involves signaling in this mesolimbic area which signals, what did you call it, interest and excitement about things?

Jacob Ballon (24:15):

Well, just in terms of limbic pathways generally being often associated with excitement and interest,

Nicholas Weiler (24:21):

Has the theory been that there seems to be too much sensitivity to dopamine in this particular pathway? You mentioned D-II receptors, and so maybe the brain is learning that things are important that would not normally be important. Is that how people have framed it?

Jacob Ballon (24:36):

Yeah. Well, and actually the framework is often more as an inability to filter out what is important from what's not important. A salience model that if you can't filter out what is truly important in a moment and everything in your environment takes on equal importance.

(24:56):

Imagine you and I are sitting at a coffee shop, sitting outside and we're having a conversation. Ordinarily, you and I would focus on the conversation but we pay no mind to what airplane just flew overhead or what color shirt the last three people were wearing or that a Waymo just happened to go by, and what are those cameras on top of the Waymo really recording? But if all of those suddenly take on equal weight, our brain's heuristics are going to somehow need to put those into a coherent narrative. Well, suddenly now there's meaning, perhaps, behind this otherwise coincidental thing that was in the background that was unimportant. And if you're living in a state of this aberrant salience all of the time, that your brain is constantly making sense of the world in a way that is including too much data and too much irrelevant data. And as such, ultimately, many people then leave with this thought that, well, all of this stuff at some point must, in some way, relate to me because the one constant in the narrative is your presence and your experience.

(25:58):

And so now, suddenly these things all have some relation to why am I always there when three white cars go by in a row, one has to make meaning of what comes up, and that meaning is based on a false sense of facts. And so I often like to remind people that, again, that people with schizophrenia often make very reasonable decisions, but with unreasonable facts. And so if you think that there's all of these different things in the environment that are related to you, you're probably going to withdraw from the environment, to some extent, in order to maintain your sense of safety. But again, that's probably because of this aberrant salience.

(26:35):

So that certainly is a very common experience, which is, I can't filter out what's going. They can't always articulate that way, but this idea that they're being watched or followed, that there's messages to them from things like the television or the internet or that people are talking about them who they've never met or know about them, even though they've never met, that somehow everybody knows about what's going on. That is all, to me, related to this aberrant salience. But what this part does leave out is the other aspects that we were talking about largely including the negative symptoms, for example, are not necessarily fully addressed through this part of the model.

Nicholas Weiler (27:15):

And so would that be something that's more specific to schizophrenia? Do you think that the dopamine hypothesis is a good model for psychosis specifically?

Jacob Ballon (27:22):

I think dopamine model can be used for psychosis, and certainly in drug development it's often used as a marker, especially in animal studies. It's a necessary first step. If you give mice amphetamines and then you give them medicine, does their behavior normalize or not? It's often a marker. But the challenge is as we get more and more specific in our targets with medication, then the likelihood that this is actually the right measure becomes less and less and the need for better biomarkers and new biomarkers has increased. So the newest medicine now is a muscarinic agonist.

Nicholas Weiler (27:55):

Which is a totally different brain system.

Jacob Ballon (27:57):

Totally different, although not completely out of, it's in the same playground as dopamine, because in fact, the muscarinic receptors are in the same pathway with dopamine, and so there's certainly crosstalk back and forth there. It's not completely orthogonal idea, but then there's also people for whom these medicines don't work. And so if the dopamine hypothesis really explained everything, we wouldn't have 30 to 50% of people for whom the medicines are either insufficient or ineffective. What that highlights is that there are also in large part, likely to be inflammatory or immune factors that could be causing things we don't fully understand the relation of trauma to, how does that relate to downstream changes? We know also that there are numerous genes that all can confer small amounts of risk for schizophrenia, but there isn't, say, a true genetic signature that we can say, "Well, this genotype for the D-II receptor causes schizophrenia or for dopamine transport causes schizophrenia."

(28:58):

There's not that one big gene causing a major effect. It's lots of small genes and we can put together a risk score, but we can't get to a hundred percent, and we don't necessarily know all of the impacts that trauma might have on genetic signaling and changes genetically. So there are a lot of things that are still left to be determined, and when we look at where is the future of treatments that are more of these biological treatments like a medication or something like TMS or other things more circuit based, the more our neuroscience gets specific on the possibilities, the more we realize our clinical phenotyping, our ability to discern who has what type of condition that leads to their psychosis, you realize how much fuzzier we really are with things.

(29:44):

And so right now, there's a lot of emphasis on trying to figure out, well, are there ways to use large data models or other things to be able to start understanding a bit more about what are the folks who don't respond to medications experiencing or how is it that they got there? What makes them unique? Is it that they don't have the same dopamine dysfunction, or maybe they do, but they also have a glutamate challenge. There's been a lot of work on NMDA systems.

Nicholas Weiler (30:11):

So there are a lot of different systems and figuring out the balance for an individual person, this is another thing that comes up quite a bit when thinking a lot about precision psychiatry, precision neurology. We need to know exactly which systems are leading to your particular symptoms. It's not going to be the same for everyone. I often like to think about the brain as having a set of common failure modes because we have these different specialized systems and there can be many different paths into a state where this particular system is not working for you.

Jacob Ballon (30:45):

The thing I would just say real quick is that when it comes to voices or hallucinations, a lot of people find companionship through their voices. They find that it gives them a sense of meaning and purpose in their life. They often can be a source of humor. Even for people who don't like their voices, there's still often some aspect of positive voice on the shoulder or something about them that's looking out for them in the world, keeping them safe. And so when we give medication, we have to be very mindful that if that is diminishing everything, it may be diminishing the part that is scary or upsetting or distressing, but it may also take away that companionship. And if people have negative symptoms and have withdrawn from friends, this might be their main source of companionship, and that in and of itself can be problematic.

(31:32):

So when we think about giving medication, we have to think about what's really happening for that person if we do diminish things or if we had a magic wand or a TMS wand or something that could instantly take away symptoms, it wouldn't be so simple as just doing that. And it's one of the reasons why it's important to think about treatment of schizophrenia is not simply the reduction of symptoms, but it is the movement towards recovery.

Shannon Pagdon (31:58):

Related to that, Jake, I just would say to that point, not assuming distress is really important, just really asking the person to understand what parts of their experiences are distressing, because I know a lot of folks who have, generally, it's much more common to have a mix of both. And generally when we hear about an experience like voice hearing, there's a lot of assumption that it's distressing, whereas that's so deeply personal, just about as personal as psychosis itself.

Nicholas Weiler (32:28):

Right, checking in with people, how are you doing? What's a problem for you? What's working? What's not working? Well, speaking of that, you've been gathering these remarkable compendia of first-person narratives from people who experienced psychosis. I think you've got three of these collections going now. Do I have that right? Four? Three collections?

Shannon Pagdon (32:50):

Working on the four, but we currently have three.

Nicholas Weiler (32:52):

So what's your objective here? What are you trying to learn or to teach maybe by bringing these experiences together?

Shannon Pagdon (32:59):

So Rethink Psychosis came about a number of years ago because I have had a lot of experiences in my life that don't map onto traditional diagnostic criteria perfectly. Specifically, I have experienced a lot of things that I describe as alterations of time and space where you're touching something and it feels different or you're looking at somebody's face and it starts to alter. I had, at the time, I created Psychosis Outside the Box with a mentor of mine. We had just found this enormous lack of information and resources on experiences like that. And so we wanted to create these anonymous, unedited narratives for individuals. And then also, specifically, we ask about strategies and how people manage those experiences for themselves. So we have the classical psychosis outside the box, which asks about those experiences as well as visions, and then we also have one on negative symptoms, and then we're working on two more related to paranoia and delusions and cognition, as well.

Nicholas Weiler (34:13):

Just in preparation for this conversation, started flipping through those, and it was really eye-opening and humanizing. These are people, they're not just symptoms. I hope that it is able to give people more empathy, more understanding, and also people who experience psychosis to see, oh, I'm not so strange. What are one or two things that stick out to you? A story or an example from these first-person narratives?

Shannon Pagdon (34:39):

I pulled one out I wanted to read actually, on Felt Presence, briefly.

Nicholas Weiler (34:43):

Please.

Shannon Pagdon (34:44):

And I'll just say for myself, I have gotten a lot of meaning and personal support by going through because it's an active project. We continue to ask for these narratives from folks, and when I go through and update it, I do get a lot of just personal sense of, oh, yay, I'm not alone in this. And other people experience this, too, so I definitely have found that for myself.

(35:08):

And this person talking about their experience of felt presence says, "Pretty much anything and everything that my clinicians describe as hallucinations or delusions feel, to me, like they have invisible presences that I can see. For example, people who are maybe chasing me or voices I might be hearing. They're all, in various ways, out there in the world, but not as literal visible figures or people I can reach out to and touch, but also very different to just imagining something in one's head. They have a ephemeral reality."

Nicholas Weiler (35:42):

Like ghosts almost.

Shannon Pagdon (35:44):

Yeah. And if we have time, I can read one more.

Jacob Ballon (35:45):

Read it.

Nicholas Weiler (35:45):

Let's do one more.

Shannon Pagdon (35:50):

Okay, we'll do one more. So this person is describing their experiences of alterations of space and time. So they say, "Pretty much all of this: Falling through or into objects, solid things seeming like they're liquid or permeable, space becoming kind of fluid. I also get really paranoid about people being able to access all the thoughts in my head or the emails I'm writing. I just lose any sense that the obvious boundaries, physical and electric, are still there. I try to tell myself that they are, that empirically they must be, but it doesn't stop my experience from being an experience of all that having dissolved. This is easily the hardest thing I have to deal with, and when I get really stressed out, it overwhelms me, having lost all boundaries, having no boundaries around my thoughts or my mind that I can control."

Jacob Ballon (36:35):

Wow.

Nicholas Weiler (36:36):

Well, that certainly does sound challenging. It must take incredible fortitude for people to find a way to move forward, and so I think that's where I'd like to end, which is we've talked about how you can live a life with schizophrenia. You're going in and getting your doctoral degree, and many people are able to find a productive path forward. Jacob, what is the prognosis right now or what is the approach for people who are diagnosed with schizophrenia or who are dealing with psychosis?

Jacob Ballon (37:08):

This is a great question. So first off, let's make no mistake, Shannon Pagdon is a superstar in so many different ways, but Shannon is representative of this new era where we really do think about people being able to experience the full range of the human experience.

(37:26):

That said, when a person first is coming into my office, it can be a challenging and certainly is a very scary time for their friends and family. I like to frame the conversation to start with by saying, "If you have psychosis or if schizophrenia is the diagnosis, this is something we need to really respect. It really does require some treatment and commitment to work on." That said, I also refuse to let people surrender to that. That has to be the opening frame, which is we can't ignore this. We can't pretend this never happened much like you can't pretend that you don't have diabetes, if you have diabetes. Things will happen if you let it go, but you don't have to surrender your life to it.

(38:04):

I will say that I don't start articles any longer with the classic first sentence that you sometimes see, which is, "Schizophrenia is the most debilitating illness in psychiatry." That used to start every article about schizophrenia. I refuse to let that be the opening for any article that I write, and the reason for that is that we have a number of different treatments and a number of different strategies we can use with people. We know that engagement is crucial, and so the idea that coming and seeing a psychiatrist is the only way to enter treatment. We don't subscribe to that any longer.

(38:35):

So we have built through what's called the Coordinated Specialty Care Model. Now, at Inspire Clinic recently launched as our Inspire 360 program, a number of different potential entry points and connections. Peer specialists are crucial to be able to translate that lived experience and that fear into hope in a way that is digestible and not from the old guys sitting in a chair with diplomas on the wall. We have people who focus on supported employment and education, making sure that we're keeping people engaged in school and work, and trying to really recognize that the negative symptoms and the cognitive symptoms really actually drive prognosis, and that the more that we can keep people engaged in their world, the more likely they're not going to fall as far off of their trajectory and be able to stay engaged with their friends, engaged with their community, and engaged with their occupational goals that they would before.

(39:28):

From a medication perspective, every medication from Thorazine that was released in the mid-fifties, until very recently, has been focused on dopamine. There have been a number of different medication trials of other mechanisms, most notably in the glutamate and glycine space that haven't worked, but we did have the first medicine that made it over the line for treatment of schizophrenia is Xanomeline and Trospium combination, which is no longer a purely dopamine drug, as I mentioned before, but focuses on acetylcholine and muscarinic receptors. I mentioned that because it means that there may be different routes now and different medicines we can try, one might work better for somebody than another.

(40:07):

I get approached all the time with people who have new putative mechanisms that they think might be helpful, and they're wondering, can we develop a medicine? Can we do a phase one trial? What can we do to start a process in inflammation or other pathways related to psychosis that will help us with coming up with new ways to reach people that we haven't been able to before? There are things like TMS and deep TMS, which is Transcranial Magnetic Stimulation that allows for either the turning up or turning down of different brain circuits that we think are related to psychosis, so that perhaps irrespective of the route by which a person has that circuit turned up or turned down in a way that is unhelpful for them, we might be able to help modulate that and make it so that they're not experiencing the ongoing hallucinations, perhaps, or they are experiencing a little bit more interest in what's going on around them, or they're more cognitively attached to what is happening in their surroundings and therefore, more interested in things.

(41:07):

So even in the 15 years that I have been working in this space, the narrative around what we expect from people, the way that we include people in the decision making for their treatment has changed 180 degrees. We know that we work with people best when we are led by their specific goals. When we all can share a common North Star, this is what we're working towards, this is why we're even here in the first place. When we can do that, then we can start to say, okay, well, I have these set of tactics I want to try to suggest to you, and they may take it or leave it. They may not want to take medication, they may want to take medication, but when we meet people at the right place at the right time, that's where we really do see magic happen.

(41:50):

We see college graduations, weddings, we see all of the things that we would like to. We just recently celebrated a graduation party for a number of different people who graduated high school and college within our clinic. It was unbelievable to see the list of accomplishments, and people are not accomplishments. But when you think about the messaging that Shannon got when she was first diagnosed, and the messaging that I delivered to people at that same time, which was, look, this is where you are right now, it's medication for life or nothing. That is just not how we handle it anymore. We didn't even get into discussion of the non-medication treatments around cognitive behavioral therapy for psychosis, compassion-focused therapy, and the numerous different therapy modalities that we know can pay tremendous dividends to people as they go through the world and learn how to come up with a different narrative for their experiences that is less distressing and allows them to flourish.

(42:44):

There's just a whole wealth of possibility for people. Now, that doesn't mean it's not hard. That doesn't mean that everybody succeeds, but it means that we always feel like at the beginning when we're working with people, that we have a lot to offer evidence-based treatments that can really set people in the right direction.

Nicholas Weiler (43:00):

That's beautiful, Jake. Thank you for bringing up the therapeutic side, cognitive behavioral therapy. That was something that I did want to ask about, and we'll definitely put a link to the Inspire 360 multi-prong wraparound care model in the show notes.

(43:16):

Shannon, is there anything else you'd want to add as we wrap up here?

Shannon Pagdon (43:19):

What Jake said was so powerful. I would just briefly add that sometimes what supports people can feel a little bit counterintuitive. I know for myself, I was applying for disability when I was working minimum wage jobs, and then getting into slightly higher paid work was when I realized I could work because it was much more flexible and open and distracting. So I think just being open to where people are and what they want.

(43:50):

Also related to what Jake was talking about earlier with the shifting and how people are getting their information, it's really difficult because a lot of folks when they're first diagnosed with schizophrenia will go and Google the diagnosis, which is, I know, what I did. And I think that that ends up reinforcing a lot of the more tragic or less hopeful narratives around schizophrenia. And so having access to providers and services that are more up-to-date on recovery and what folks' lives could look like, I think is just a really important part of the healing process, because it can be very depressing to just be told your life is over at 17 years old. And so I think to the best of our abilities increasingly shifting that narrative, and hopefully, in turn, Google will end up matching that. But until then, I think just being out there and being able to debug some of the myths like we were talking about earlier.

Nicholas Weiler (44:51):

Shannon Pagdon, Jacob Ballon, thank you so much for joining us on From Our Neurons to Yours. This has been very illuminating.

Shannon Pagdon (44:59):

Thank you.

Jacob Ballon (44:59):

Thank you so much. It's been a pleasure.

Nicholas Weiler (45:02):

Thanks again so much to today's guests, Shannon Pagdon and Jacob Ballon. Jacob is an Associate Professor of Psychiatry and Behavioral Sciences at Stanford Medicine and co-director of the Inspire Clinic at Stanford. Check out the links in the show notes for more information about psychosis, the Inspire Clinic, and Jake and Shannon's work.

(45:22):

If you're enjoying the show, please subscribe and share with your friends. It helps us grow as a show and bring more listeners to the frontiers of neuroscience. We'd also love to hear from you about what you love or what you hate about the show. We want to know what's working, what's not, what brings you back to the show each week and what you'd like to hear from us in the future. Leave us a comment on your favorite podcast platform, or send us an email at neuronspodcast@Stanford.edu From our Neurons to Yours is produced by Michael Osborne at 14th Street Studios. Production Assistance and Sound Design by Morgan Honecker. I'm Nicholas Weiler. Until next time.