In the premiere episode of DoctoRx Unscripted — Dr. Tania Small sits down with globally respected psychiatrist, Dr. John Kane, to unpack the science, challenge entrenched assumptions, and reimagine what schizophrenia care can be. It’s a forward-looking conversation that equips you with fresh insights — and a new lens on what’s possible in psychiatry.
In the premiere episode of DoctoRx Unscripted — Dr. Tania Small sits down with globally respected psychiatrist, Dr. John Kane, to unpack the science, challenge entrenched assumptions, and reimagine what schizophrenia care can be.
They take a provocative look at the future of psychiatry — unraveling the biology of schizophrenia, early psychosis and relapse, decoding the triad of symptoms, spotlighting emerging breakthroughs, rethinking the dopamine hypothesis, and showing how patient-driven science and partnerships are reshaping what’s possible in treating serious mental illness.
It’s a forward-looking conversation that equips you with fresh insights — and a new lens on what’s possible in psychiatry.
00:00:04:07 - 00:00:22:16
Tania
Welcome to doctors Unscripted. I'm Doctor Tania Small, and I'm here to bring you into a different kind of conversation with some of the brightest minds in medicine and research.
00:00:22:18 - 00:00:58:01
Tania
Today I'm joined by Doctor John Kane, an internationally acclaimed psychiatrist renowned for his pioneering research in early psychosis and patient centered innovation, and with over 900 peer reviewed publications. Doctor Kane is redefining mental health care. We'll explore what drew him to psychiatry, unravel the biology of schizophrenia, decode the triad of symptoms, examine breakthroughs challenging the dopamine dogma, and discover how patient driven science and partnerships are shaping the future.
00:00:58:03 - 00:01:03:23
Tania
Now let's get started.
00:01:04:01 - 00:01:11:08
Tania
Doctor Kane, thank you so much for joining us in downtown New York City for our first episode of Doctors Unscripted.
00:01:11:09 - 00:01:14:01
Dr. Kane
Thank you. My pleasure. Thanks for the opportunity.
00:01:14:03 - 00:01:32:11
Tania
I have a few questions for you today. But I'm starting off with the hardest one, and that is, do you remember when you were med school and you were trying to figure out what you wanted to do? Most of us were trying to figure out at least what we wanted to do, what fields we wanted to practice in.
00:01:32:13 - 00:01:49:02
Tania
And a lot of times, most of our colleagues could guess what fields we were going to. For example, my colleagues figured I was either going to go into ob/gyn or onc, and I ended up going into onc. What did your colleagues believe you were going to go into, and what inspired you to go in to psych?
00:01:49:02 - 00:02:09:00
Dr. Kane
So they didn't have to guess because I told them. I knew when I went to medical school that I wanted to go into psychiatry, and it had been something that I was interested in ever since high school. And rather than just studying psychology, I wanted the medical degree to be able to really have a, you know, a medical perspective on mental illness.
00:02:09:00 - 00:02:32:13
Dr. Kane
But I think as a teenager, I was reading novels and got very interested in trying to understand, why did people act a certain way and what determined their behavior, and why were people so different? And I became fascinated with, sort of the human mind and behavior and, and then trying to understand mental illness.
00:02:32:15 - 00:02:33:23
Tania
Since high school.
00:02:34:01 - 00:02:35:11
Dr. Kane
It was high school.
00:02:35:13 - 00:02:41:12
Tania
Was there anything that really stuck with you while you were in med school or even in residency that really changed your [perspective]?
00:02:41:13 - 00:03:13:05
Dr. Kane
Well, I remember the first time in medical school that I actually interviewed a young man with schizophrenia, and he was pretty much my age and had his first episode of schizophrenia, in the recent past. And I saw him at Bellevue Hospital and, it was a pretty powerful experience because I think I was trying to understand the way he was thinking, and he was quite delusional.
00:03:13:05 - 00:03:18:14
Dr. Kane
And I was asking myself, is it is it possible that he really believes these things?
00:03:18:16 - 00:03:19:18
Tania
Yeah.
00:03:19:20 - 00:03:47:02
Dr. Kane
And then I also met with his parents and I saw the anxiety and the devastation that they were feeling at that time. And it was for me, it would be it would be great if we could figure this out and understand why. Why does this happen? You know, this is a young person with a lot of a lot of promise that becomes psychotic and develops an illness that's really can be quite disabling.
00:03:47:04 - 00:04:16:11
Tania
I remember, when I was learning a lot more about schizophrenia, when I started working in pharma, I learned a lot more about schizophrenia and someone explained it to me this way because, as a pediatric hematologist oncologist, a lot of times you just have so much hope for these kids, and your goal is to get them through it so that they can really fulfill the life that they're meant to live.
00:04:16:13 - 00:04:45:14
Tania
And someone told me you could imagine a newly diagnosed person with schizophrenia, and sometimes immediately it can look like lights out, and their goal is to turn on that light. And I guess my question is like, I know one of the things that you focus on is really early psychosis. And, how did the families actually, feel about it?
00:04:45:14 - 00:04:48:19
Tania
How did the patients get through it in the beginning?
00:04:48:21 - 00:05:09:09
Dr. Kane
It's very hard., We had a grant application for the RAISE Project, but, I had never used a quote from a poem in a grant application. A lot of my colleagues thought that that was not such a good idea. But the quote was, tread softly because you tread on my dreams.
00:05:09:11 - 00:05:34:19
Dr. Kane
That's a quote from Yeats. And I thought that really kind of summed up what we're trying to do here is that, you've got a young person, you've got a family, lots of hope, lots of potential. Parents are always worried. But, you know, you see something like this develop unexpectedly and, it turns out to be a pretty serious illness, and it's devastating, you know?
00:05:34:19 - 00:05:48:04
Dr. Kane
So this led us also to understanding the importance of early intervention. And, you know, can we diagnose this condition early, can we intervene rapidly and try to get it under control?
00:05:48:06 - 00:05:52:07
Tania
Yeah. About what age are people with schizophrenia diagnosed?
00:05:52:10 - 00:06:19:20
Dr. Kane
So the median is in the early 20s. It's usually late teens, early 20s. And, you know, it's occurring at a time, which is really critical in people's development, whether it's educational or psychosocial. And so it has a tremendous influence, tremendous impact on what people can do subsequently.
00:06:19:22 - 00:06:31:11
Tania
And let's talk about that and talk about the biology, because I know a lot of times, again, people hear schizophrenia. They think it's just a homogeneous disease and can't put their finger on it. What do we know about the biology so far?
00:06:31:11 - 00:07:38:21
Dr. Kane
So it is very heterogeneous. I mean there's a very strong hereditary factor, but we don't understand the genetic the dynamics of the genetic influence. There have been many, many genes that have been implicated, but all with very small effect size. So we don't we don't have a major gene or genes that we can point to and say, this is the reason I think I would say that schizophrenia is probably not one illness that right now, we approach it with this sort of diagnosis, but I think it probably includes what we will one day learn are multiple different phenomena with different etiologies and different pathophysiology, so that we're trying to
do research and understand this illness. We don't have great tools yet to really stratify people into different categories. But there is hope with genetics and brain imaging etc. that will come to understand it better. I mean, up until now, we've sort of had the dopamine hypothesis of schizophrenia, the idea that there's too much dopamine being produced in certain brain areas.
00:07:38:21 - 00:08:08:02
Dr. Kane
And so we tried to block that with medication and to some extent it's been effective. And we can treat the acute signs and symptoms of schizophrenia with medication. And it often works pretty well. And then the other problem we get into is people need to take medication on an ongoing basis to prevent a recurrence or a relapse. And I think nonadherence is a challenge in any chronic illness, whether it's hypertension and diabetes or epilepsy or asthma.
00:08:08:02 - 00:08:18:07
Dr. Kane
But in mental illness it's perhaps even more of a challenge with and people with schizophrenia also have cognitive dysfunction. And, that that can make it even more difficult.
00:08:18:08 - 00:08:31:08
Tania
You spoke about the different pathways. You spoke about dopamine and blocking dopamine. Is that where we landed now or do we know a lot more about schizophrenia?
00:08:31:11 - 00:08:55:17
Dr. Kane
Yeah, I think we've learned a lot more. For example, the notion has been that, it's excessive dopamine release, presynapticly, and the way we've been treating it up until now is to block the postsynaptic receptor. So, you know, I think there has been a better understanding of some of the pathways and new approaches to treating the illness.
00:08:55:17 - 00:09:19:23
Dr. Kane
But I think we were left with, as we said before, a very, very, heterogeneous phenomenon. And there may be people who have different mechanism of action. It may be we see the interaction between genetics and environmental factors. And we need to better understand in which category people fall into.
00:09:20:01 - 00:09:24:02
Tania
Are there any biomarkers on the horizon so that we can understand this better?
00:09:24:08 - 00:09:54:19
Dr. Kane
There's certainly excitement about genetics and about neuroimaging and even electroencephalography. But we don't at this point have biomarkers that are useful at the clinic level, to help better understand which treatment to use or which treatment might work or to predict the prognosis of that person. So we're really trying the best we can to take advantage of different treatment modalities.
00:09:54:19 - 00:10:25:00
Dr. Kane
We know that medication can be very helpful. We also know that psychosocial interventions are very important. And ideally we want to combine the two. Even though we consider this a biological illness or a brain disease, we know that psychosocial interventions, therapy, family therapy, family psychoeducation can also be very important in helping people achieve better outcomes.
00:10:25:02 - 00:10:35:07
Tania
Doctor Kane, I want to ask you a little bit about the different symptoms. Can you explain the difference between positive, negative and cognition and how do we manage those symptoms?
00:10:35:08 - 00:11:17:07
Dr. Kane
Well, positive symptoms are things like delusions, which are fixed false beliefs, hallucinations, hearing a voice when no one is speaking, having difficulty communicating in a logical fashion. Negative symptoms involve no motivation, diminished affect, diminished expression, lack of involvement with day-to-day activities. Seeing friends, hobbies, socialization, sometimes poor self-care, and then cognitive dysfunction, which really is a core feature of schizophrenia and affects probably 80% of patients, involves things like, difficulty with attention, with verbal memory.
00:11:17:07 - 00:11:40:12
Dr. Kane
So remembering things like, if I give you a phone number, will you remember it long enough for you to actually dial the number? Attention obviously is very important. And then social cognition, which is how do we understand social interactions? Can I read someone's facial expression in a way that's meaningful? Do I understand my own emotions?
00:11:40:14 - 00:12:15:04
Dr. Kane
So these are all problems that people with schizophrenia have to deal with. And our understanding is that the cognitive dysfunction actually begins long before the other signs and symptoms. And so it really is a core phenomena. The negative symptoms also, which affect at least 50% of patients, also often begin before the positive symptoms. But once when someone gets to a point where the diagnosis of schizophrenia is actually made, we'll often see all three of those things.
00:12:15:06 - 00:12:40:05
Dr. Kane
One of the challenges is that the medications we have had up until now work mostly for the positive symptoms. They don't really help the negative symptoms as much as we'd like, and they don't help the cognitive dysfunction as much as we'd like. So we're very eager for new treatments to be available that can help patients in those particular domains and even positive symptoms.
00:12:40:05 - 00:13:08:06
Dr. Kane
Although medications can often be quite effective, they're not 100% effective. And then in terms of preventing subsequent episodes, medicine is very important, prophylactically. So even when someone improves from their acute episode, they're at risk for having another episode. Could be six months later, could be a year later. It could be two years later. The medicine is very, very effective in reducing the risk of a subsequent relapse.
00:13:08:12 - 00:13:10:19
Dr. Kane
But many people have trouble taking the medicines.
00:13:10:21 - 00:13:16:23
Tania
And why is that? Is it because of the disease itself? Is it because of the side effect profile of the medication?
00:13:17:04 - 00:13:18:00
Dr. Kane
It’s all of the above.
00:13:18:01 - 00:13:18:09
Tania
Okay.
00:13:18:14 - 00:13:43:05
Dr. Kane
So the disease itself, I mean, sometimes people don't fully appreciate what's wrong and they can't really kind of wrap their heads around it. Sometimes people feel better once the medicine has worked for the acute symptoms, they feel better or they're out of the hospital. They're not having those delusions anymore or not hearing voices. So they feel, well, maybe I don't really need to take medicine anymore.
00:13:43:08 - 00:14:23:15
Dr. Kane
Nobody wants to take medicine on a long-term basis. Side effects. I mean, all of these things. And then I think it's human nature to have difficulty taking medicines too long. Whether you have diabetes or hypertension or epilepsy or asthma, it's a challenge. So the cognitive dysfunction maybe adds to that as well. Because I'm not as well organized as I could be. And remembering to do something. So yeah, it's many, many factors. But it's a huge problem. And you know half of our patients have difficulty with adherence. There was one study that was done in Finland, where they followed 2500 patients who were hospitalized for the first time with schizophrenia.
00:14:23:16 - 00:14:31:07
Dr. Kane
And within 60 days of leaving the hospital, they weren't getting their medicine. So it's a big challenge.
00:14:31:09 - 00:14:43:01
Tania
And I want to go into two pieces that you said you spoke about. The first symptom tends to be cognitive dysfunction. Is there a way or is there anything that allows us to diagnose it at that time?
00:14:43:03 - 00:15:12:17
Dr. Kane
It's hard. It's hard because when someone has cognitive dysfunction, unless it's really, really severe, you don't necessarily recognize it because you don't know where they should have been or where they sorted out if there's been a decrement. I think we are getting better at that. And now there's a lot of research going on in what's called the clinical, high risk, population, where we do see that cognitive dysfunction may be a predictor of somebody actually developing schizophrenia.
00:15:12:19 - 00:15:25:03
Dr. Kane
So there's a lot of research going on in these domains looking for early signs so that we can intervene earlier.
00:15:25:05 - 00:15:38:05
Tania
You spoke about the research as well. You said that even getting patients on clinical trials sometimes can be challenging. Why is that and what can we do to improve that to get those answers?
00:15:38:08 - 00:16:07:19
Dr. Kane
Well it's interesting. You came from an oncology background. And I think if you look at, the clinical trials that go on in oncology, it's like many people participate in that because that's something that's brought to their attention very early in their treatment history and psychiatry. That doesn't happen. And I think it would be great if we could develop, you know, more clinical trial and clinical trial networks so that when people come into a hospital, they're offered opportunities to participate in some kind of research.
00:16:07:21 - 00:16:24:01
Dr. Kane
We could do research about anything. It could be access, how did you how did you get here? Who referred you? How long did it take you to realize that something was wrong? How did your parents react? Or it could be a treatment trial. It could be a registry, a long-term study.
00:16:24:01 - 00:16:39:23
Dr. Kane
There's so many things that we could learn from, but the average patient is not participating in research in psychiatry. And I think we need to do a better job of making research available to people explaining to them why it's important. A lot of people think, oh, I don't want to be a guinea pig.
00:16:39:23 - 00:16:47:17
Dr. Kane
You know, that's really not what it's all about. This is how medicine progresses, right? We have to learn from each other.
00:16:47:19 - 00:17:06:08
Tania
I want to learn more about that because, when practitioners are treating patients, they see patients day in and day out. And there's a lot of research that's there. But how do you manage your time to learn all the new information, continue to see your patients and then apply it? Is that a challenge?
00:17:06:08 - 00:17:12:19
Tania
Is it too much information that needs to be distilled? What do you think is the real challenge, when it comes to that education?
00:17:13:00 - 00:17:32:05
Dr. Kane
I think that's a big part of it. I think there is so much - people are just deluged with information. You know, where attention is a challenge, right? What do I pay attention to? So I think we have to help clinicians. We have to synthesize data and present it to them in a way that's meaningful to them.
00:17:32:11 - 00:17:56:19
Dr. Kane
They often react to studies and say, but does that apply to my patient? So we have to do research that's really generalizable, that's real world to help clinicians understand, how does that apply to my patient. That means sometimes being more inclusive in our clinical trials so that we understand the impact of treatment in general.
00:17:56:19 - 00:18:01:06
Dr. Kane
I think we are getting better at these things, but we still have a ways to go.
00:18:01:08 - 00:18:23:22
Tania
So you opened another door because I want to walk through and that is inclusivity. When it comes to clinical trials and even just beyond clinical trials, we know that there's still disparities when it comes to health care, particularly in this patient population. Where are we with that? And then I want to go into how do we make our trials more inclusive.
00:18:24:00 - 00:18:47:12
Dr. Kane
So I think we've made progress. We still have a ways to go, obviously. The US is very diverse. I think people struggle with, who can I trust? And I think we need to make sure that we have people working with us who who can talk in a meaningful way to anyone who's afflicted by a mental illness.
00:18:47:15 - 00:19:05:10
Dr. Kane
I think peer counselors can be very helpful. The idea of having someone else with the same lived experience, but who speaks your language, who comes from your culture, who understands what you're going through on a personal level. I think I think that can be very powerful. I don't think we use that often enough.
00:19:05:12 - 00:19:30:05
Dr. Kane
But we're making progress in that direction, too. I think more people are being trained as peer counselors. I think we're we recognize how important that is. I think there's been more emphasis on including people with lived experience when we design our clinical trials, when we execute our clinical trials to make sure that we're really hearing the patient perspective. Patient reported outcomes are very important.
00:19:30:07 - 00:19:41:03
Dr. Kane
But again, the diversity issue, we need to make sure that all of these things are available to everyone.
00:19:41:05 - 00:20:05:05
Tania
You know, I was speaking to a colleague of mine, and one of the things, again, that he put in perspective for me was, when someone is diagnosed, for example, with cancer, what do we do? We go in and we say, how are you dealing with things? Are you okay? And all of a sudden you have this empathy, more sympathy, at least towards them.
00:20:05:07 - 00:20:25:01
Tania
And then one of the things he told me, though, is what happens when you meet someone who was diagnosed with schizophrenia instead of leaning in, you tend to lean out because of all that is associated with that. So I just wonder, as a health care community, how do we get more people to lean in? Is it a lack of understanding?
00:20:25:01 - 00:20:28:22
Tania
Is it a is it a fear factor? But what can we do?
00:20:28:23 - 00:20:51:16
Dr. Kane
I think it's all of the above, in a sense. There is a fear factor. I think people tend to be afraid of what they don't understand. But we have to recognize that mental illness is an illness like any other illness. We have to treat it the same way, with the same kind of understanding, appreciation and consideration.
00:20:51:18 - 00:21:14:01
Dr. Kane
I think in schizophrenia. We also need to do research and we need people to participate in research and benefit from the research also to make sure that we get the support that we need. I don't think enough funding goes into research on mental illness, for example. I mean, everyone is sympathetic to oncology or to heart disease.
00:21:14:03 - 00:21:25:14
Dr. Kane
But the reality is mental illnesses account for a tremendous amount of disability, not to mention personal suffering and family burden and even shortened lifespan.
00:21:25:20 - 00:21:50:15
Tania
There's something that I like to call patient-driven science. And that is where we develop our drugs for patients. So we move from a product-centered drug development to a patient-centered drug development. And in pharma we create the technology. As a physician, you have the expertise and patients, they understand - they're living their disease.
00:21:50:17 - 00:21:55:09
Tania
How do we come together to really develop the best drugs for patients?
00:21:55:09 - 00:22:22:11
Dr. Kane
So we need to really have ongoing communication between the federal agencies in the US, whether it's NIH or the FDA and industry and academia and clinicians in the field and patients and families all working together for a common goal. Everyone has their role to play in that process. But it's really a collaborative process.
00:22:22:13 - 00:22:40:13
Tania
And I'll say this, one of the things I tell my team all at the time is even though you may not be touching a patient at this time, you are still a part of this treatment team. And the outcome of that patient is still our responsibility collectively, as part of the health care community.
00:22:40:13 - 00:23:01:14
Dr. Kane
And it's really true. I mean, everybody, when we're doing, a clinical trial or we're doing research, the study coordinator or the person working on recruiting has to understand the critical role they play. Everybody plays a critical role. I mean, I think that's true across the board that we need to understand that everybody's important and they need to they need to recognize that.
00:23:02:11 - 00:23:19:19
Tania
But that's so important because I think we forget that. And so how do we all hold hands and make sure that we all feel that responsibility for that human that we are treating?
00:23:19:21 - 00:23:26:23
Tania
What are you most excited about when it comes to innovation for patients living with schizophrenia?
00:23:27:01 - 00:23:48:03
Dr. Kane
Well, I am excited about what we were discussing earlier, which is the evolution of new thinking about how we might manage the dopamine dysfunction that exists in schizophrenia. The development of muscarinic agonists I think is very exciting. There are half a dozen companies now that are involved in developing such drugs. So I think that's very welcome.
00:23:48:05 - 00:24:11:15
Dr. Kane
I think other innovations we're seeing more and more, in brain imaging; trying to understand neural networks and problems in connectivity in various brain regions. It's great to see the innovation that's going on now there. You know, there's been a lot of interest now in a in a new way of looking at the control of dopamine in the brain.
00:24:11:18 - 00:24:19:15
Tania
You spoke about muscarinic receptors. And that's a new mechanism that I know there's been a lot of discussions about. Can you tell us a little bit more about it?
00:24:19:17 - 00:24:39:20
Dr. Kane
There's been interest in muscarinic receptors for years and years, but I think now we're getting a lot closer to fruition. And a sense of what we've seen is that by influencing some of the muscarinic systems, if you will, we can have an influence on that presynaptic release of dopamine.
00:24:39:22 - 00:24:45:11
Dr. Kane
And importantly in the brain areas that are critical to the development of schizophrenia.
00:24:45:13 - 00:24:53:21
Tania
What advice do you have for us in order to improve the patient experience together for those living with schizophrenia?
00:24:53:23 - 00:25:22:06
Dr. Kane
People have to understand what mental illness is, how common it is, how it affects people, how it affects individuals, families. And then, as we were talking earlier, the right collaboration between all the stakeholders. And that means the patients, the families, the pharmaceutical industry, academia, federal agencies, etc., to really go after this problem in a major way and it is getting more attention.
00:25:22:06 - 00:25:35:21
Dr. Kane
I think there's more awareness of mental illness. I think during the pandemic and after the pandemic, there seemed to be kind of an emergence of a better appreciation of mental illness. But, we still have a long way to go.
00:25:35:23 - 00:25:47:01
Tania
Well, I think all of us are ready to lean in to this together. And I just want to thank you for your time. Thank you for your expertise. Looking forward again to continue to move this field forward.
00:25:47:02 - 00:26:00:04
Dr. Kane
My pleasure. Thank you so much for this opportunity.
00:26:00:06 - 00:26:04:18
Tania
What was that novel that you read initially?
00:26:04:20 - 00:26:16:05
Dr. Kane
Well, probably just the Crime and Punishment novels are not necessarily all fiction, right? I mean, a lot of it is actually based on lived experience that people have had. It took me a while to realize.