Dr Daniel Knoepflmacher (Host): Hello and welcome to On the Mind, the official podcast of the Weill Cornell Medicine Department of Psychiatry. I'm your host, Dr. Daniel Knoepflmacher. In each episode, I speak with experts in various aspects of psychiatry, psychotherapy, neuroscientific research and other important topics on the mind.

Today, I'm joined by Dr. George Makari, who is a true multi-hyphenate, a psychiatrist, psychoanalyst and intellectual historian. He's a Professor of Psychiatry at Weill Cornell Medicine and Director of the DeWitt Wallace Institute of Psychiatry: History, Policy and the Arts. He is an accomplished scholar. In addition to his books exploring the history of psychoanalysis, xenophobia, and the Western conception of the mind, Dr. Makari recently published an essay online for the New Yorker on what COVID revealed about American psychiatry.

I'm thrilled to have Dr. Makari on the podcast today to discuss his clear incisive analysis of our fractured psychiatric healthcare system and the ongoing mental health crisis facing our society. George, thank you for coming on and speaking with me today.

Dr George Makari: Daniel, thank you for having me.

Dr. Daniel Knoepflmacher: So before we delve into your New Yorker essay, I'd like to talk about what you do, because you've developed a unique career path for yourself. You found a way to straddle clinical psychiatric practice and active historical scholarship. So, how did you become a psychiatrist historian?

Dr George Makari: That's a question with a long and a short answer. I guess the medium-sized answer is I wanted to integrate both historical scholarship and writing with being a clinical psychiatrist. And I didn't really know how to do that until I discovered that Cornell had such a space that they had created in the late '50s. Believe it or not, as a second year medical student, I transferred to Cornell to actually do work in what was then called the History of Psychiatry Section, and I've never left. So in a lot of ways, my trajectory is very, very specific to Cornell and the wisdom of a bunch of folks who, starting in the '30s, but by 1958, had created this interdisciplinary kind of think tank for how psychiatry intersects with the broader world.

Dr. Daniel Knoepflmacher: I am thinking back to my early 20s. I definitely was not that ambitious and focused. So, you clearly developed a lot of ideas about who you wanted to be at a young age.

Dr George Makari: I mean, you can call it focus, you can call it desperation, you can call it whatever you want.

Dr. Daniel Knoepflmacher: That may be another conversation. Well, I wanted to talk about some of the work that you've done. After you developed this career, your first book, Revolution In Mind, was a history of psychoanalysis. And clearly, there's a through line from that book to your subsequent work. So, how has the focus of your scholarship evolved over the years?

Dr George Makari: You know, I think one of the running issues that I've been obsessed with, if you will, is how psychiatry works or doesn't work with different models of science and medicine and what makes it particular, what makes it peculiar, what makes it sometimes seem like it's an odd duck. So, the model that psychoanalysis presented, at the time, the Freud wars were in full scale, and one of the great questions was, was this a pseudoscience? Was it a science? And, you know, I became deeply interested in trying to contextualize what different models of science were and what different models of medical care were for the mind. And really ended up focusing on this paradox of how can you possibly create an objective science of subjectivity.

So, that interest has followed me. The next book I wrote was really on when did we first believe there was a notion of a natural mind, not a transcendental one or a Cartesian one. Because that's the beginning of mental health and mental illness, only if you have a natural mind. And that again very much is part of the history of science. But I really think of the history of science as part of a broader history that includes social history, political history. And so, I really tried to place that emergence in that context. It led me to the thinking about xenophobia, which is thinking about how we think about broad social prejudices and try to understand them through social psychology and things of that sort. And, you know, I think you could see the New Yorker article that came out as part of that same set of concerns that I've been thinking about for the last 30 years.

Dr. Daniel Knoepflmacher: So, turning to the New Yorker essay, What COVID Revealed About American Psychiatry, what compelled you to write about the current mental health crisis in our country? It's not an easy topic to tackle in a short essay.

Dr George Makari: Agreed. And, I have to say it was an ambitious undertaking to try to get so much in an essay, for the general audience. But I thought it was very important to do. Look, the New Yorker had reached out to me and said, "Would you write something about COVID?" What I think is generally acknowledged, statistics bear it out, that we're really suffering from a kind of post-COVID-- if we are post-COVID, hopefully-- mental health crisis. And it's a lot that's still ambiguous. The data is coming in. Some of it may show decreases in the near--. So, I wasn't 100% sure that I could write something completely solid about what is definitely happening. But I thought that it could be a way of assessing how prepared are we. Where are we in general as a country and as a mental health system to recognize new problems, to deliver care for new problems and to basically be up to the task? And that then took me on a kind of historical journey to try to assess where we've gone right and where we've gone wrong over the last 40 years.

Dr. Daniel Knoepflmacher: So essentially, the COVID crisis, the pandemic was salt in the existing wound. I mean, you're talking about a mental health crisis that was already there, that this just sort of ripped off the veil.

Dr George Makari: That's the conclusion that I came to, is that we have all of these upticks in a bunch of very distressing, markers, suicide, drug relapse, psych ER visits. All of these things are going up. And we presently have a system where we massively undertreat, where we have loads of folks who are psychiatric patients that are either homeless or in prison. And so, yeah, to have more seemed like the camel's back was already broken, and this was more.

Dr. Daniel Knoepflmacher: You had psychiatry in the title of the piece. It's What COVID Revealed About American Psychiatry. And what I think is really helpful in how you dissect this is you point out that really psychiatry is three distinct but overlapping aspects. There's the delivery of community care that addresses the psychosocial needs of those who are suffering from mental illness, which, as you just pointed out, there's been a failure in delivering that care. There are psychiatric treatments, medications, procedures, and psychotherapy that address the symptoms of psychiatric diagnoses. And then, there's the research, investigating neuroscientific underpinnings of psychiatric disorders, efficacy of treatments, and you could be researching other things that I think you allude to. This is a complex tripartite effort. And all three of these parts, I sense, have their own internal fractures, but they're also fractured as part of this bigger system. They're not interdigitating in a productive way. So, can you speak about this more? Because I thought that was a very helpful way of looking at it.

Dr George Makari: I think that one of the things I started hearing, I started interviewing a lot of folks and some people I deeply respected were very rosy and optimistic and some were super pessimistic. And it brought me back to my historical training and the need to say, "Okay, psychiatry is not one thing." In fact, historically, it is not one thing. People started developing social structures to care for those who were mentally ill. You know, 9th, 10th century Baghdad, a lot of people say came from the Islamic world, came through Andalusia in Spain to the West. Those things were the first layer. So, communal care, housing, social support, food, those are things that different societies weigh differently and do a better or worse job at. So, I wanted to start with that because that clearly is a huge problem in our society right now.

The second is, you know, developed in the 18th century, a medical profession that self identifies as treating mental illness, trying to achieve mental health. They're called a number of things, mental medicine in French; alienism, but then they become called psychiatrists, their job is to diagnose and treat illness. They can't really build institutions if the society doesn't give them the money to build institutions, nor do they really focus on the next step really in the evolution of the field, is a research program with a branch of scientists who are really primarily committed to creating new knowledge. And that emerges probably around, you could argue, 1850s in Germany, especially. There becomes this whole research contingent that try to drive the field forward.

Now, ideally, all three should be rowing together. But what we see in our country, and the reason why you could say some things are great and some things are better than they've ever been, and some things are kind of as bad as they've been for many years, is because these three things are not rowing together. And so, when you look at it like that, and you say, "Okay, they're these three things, actually. They look all like psychiatry when they're all in unison, but they break apart into different domains because they're not actually functioning as a unit." And care is obviously with the homeless population where there's some percentage, whether it's 30% or 40% of folks need acute psychiatric care; the problem of the incarceration of people with mental illness, which again, the numbers you can argue about, but it's an embarrassingly high number for us in the United States. The number of people we don't reach who just simply are undertreated, very large. So, that's one part of the problem and that's a problem that's been deteriorating since the institutionalization and the fact that we never built these community mental healthcare systems. So, you can analyze what went wrong there. I think, when you look at the medicine part of it, I think it's fair to say, like, it's as good as it's ever been. We have better medications, better psychotherapies. We have more that we can do, and it's kind of almost a tragic thing to say, like, as we're kind of washing our hands of the poor and the uninsured, which we started to do in the 80s, our treatments got much, much better. So actually, we could help them much, much more.

And then, the third thing that I end up focusing on, because, as you know, our treatments have stalled, especially when it comes to psychopharmacologic agents, is the kind of what I consider to be a massive detour that our scientific community has taken away from either the problems of care, which they should be involved in innovating or the problems of medicine, which obviously we depend on them into the realm of brain science. And the notion that if we understand the brain completely, we'll be able to understand these mental illnesses completely has been a dominating kind of narrative that has meant that the NIMH, which is the central player in funding mental health and illness research, not just in the United States, but on their website, they claim in the world, has really left clinical research in the dust relative to their commitment for very expensive, very fancy, sometimes really interesting, sometimes less interesting brain science.

Dr. Daniel Knoepflmacher: Wow. So, we can delve into all three of those arms. Let's work backwards though, because I want to address what you were just saying about research and the brain and the mind. you've focused a lot of your work on the mind, and you use the phrase mind-brain problem as this tension between these two. And it's obviously central to our field. Can you speak more about that and how that gets overlaid in all of these conflicts that we're talking about?

Dr George Makari: Yeah, that's a big question. So, I like to use the phrase mind/brain medicine, mind/brain science, mind/brain research to refuse the Cartesian split that says the mind is some non-natural, non-biological thing. And really, we can reduce this down to brain stuff. So, that is a very old problem. It's a 2000-year-old problem that psychiatry has had to try to contain. And one of the things I tried to point out is that for us clinicians, it's really not that hard to work on both sides of the aisle there, to do stuff, to help people psychologically, to help them in terms of their social adaptation and to treat their depression with an SSRI.

But the problem for our researchers and it's a real problem is that they have to take a stand on one thing that they're going to make the constant. The variables are going to be one thing and everything else they're going to try to hold constant to try to see if that one thing changes things downstream, the way empirical research works, the way experimental science works is you got to take a shot on one thing. And so, they necessarily have the tendency over the course of the last 200 years to overestimate the one thing that they're interested in and pull the rest of the field towards extremes that actually are not mind/brain, but either mind or brain or sometimes something else. And that's the kind of concern that I have right now about the NIMH.

Dr. Daniel Knoepflmacher: This goes back to that first arm of the community care. I mean, something about the socioeconomic factors, the cultural factors, racism, structural issues, that's almost separate from the mind-brain piece. And there's research that can be done in that area, certainly.

Dr George Makari: Well, see, I would disagree. I would say all of that impacts the ultimate object of our study, which is mind and brain. So, poverty, racism, all of those are the outermost layers. You know, I use this archers target analogy and say, "We start at the bullseye, genetics; move out to neurons and neural nets; and then, the entire brain in the body, the mind in the body as well; the self, which is the mind as we wake up and remember who we are this next day and have self level problems, individual behavior, social impact, and then the non-social environment like COVID.

So, one of the reasons why I thought COVID was an opportunity to think about this is because it literally comes from the opposite end of the spectrum causally, that most of our researchers are looking for biomarkers that are neural biomarkers that are genetic, and they're literally looking at the opposite. And when we get whacked from the non-human environment, by the environment of virus in this case, and it causes massive downstream effects socially, individually, and brain-wise, so it was, I think, a kind of event that in the past, historically, things like this have shaken up our field. It's not the first time. So, war trauma reminds everybody that it's not just heredity. And that happens in the early 20th century. People come back from war. They're all messed up. They were fine beforehand. And people go, "Oh, wow. Mental illness isn't just from heredity." Well, that should have been obvious, but it takes us these reminders sometimes to regroup and recognize we have a super complicated list of suspects.

Dr. Daniel Knoepflmacher: But the research, as you point out with, I think, the focus on RDoC, is not looking at the social determinants of health. That's not what's being funded by the NIMH.

Dr George Makari: Exactly. You know, RDoC was an attempt, and I think it was very honest attempt to go whole hog on the genetics of serious mental illness, basically write off stuff that wasn't going to be either genetic or have stable neural circuit as its cause. And so when that was put forward by Tom Insel and his group at the NIMH and made to be, if not a demand, very close to a demand to get funding from the NIMH that you had to work within the RDoC system. It did two things, it segregated the scientists from the clinicians because now we didn't even use the same language, they were talking about things that were normal functions and you have to rate them and I think they had the basic model that normal functions excessively or to a great diminishment make for pathology, but that was one assumption.

The other assumption is that all of illnesses were going to come from either neural circuits. You know, as the head of the RDoC program right now. Literally, last year, wrote a paper, 2022, saying we have three assumptions. One is that all mental illness comes from neural circuitry. Two, that we have a bunch of really extraordinary technologies to determine that. And three, genetics will help us be more specific about it. I think all of those are astonishing claims that don't at all necessarily hold water, but that's where we've been pouring billions and billions of dollars. And E. Fuller Torrey who's kind of a gadfly psychiatrist, advocate for the severely mentally ill, so he's just published a paper that says during the six years between 2017 and 2022, NIMH funded only one clinical drug trial for the treatment of schizophrenia, and one for the treatment of bipolar disorder. Now, if that turns out to be true, that's shocking.

Dr. Daniel Knoepflmacher: Well, even I'm thinking about the latest issues of the American Journal of Psychiatry, where they were looking at impacts of race or social determinants of health, abuse, trauma, and they're looking at the epigenetics, so they are going down to the molecular level. I'm not hearing about the research that is addressing these social causes.

Dr George Makari: Everyone loves epigenetics because it allows you to save genetic reductionism and incorporate other things that everyone knows they have to be causal factors. And sure, epigenetics is fascinatingly interesting. But if I hear your question correctly, I agree with you that it is still a kind of indication of our deep bias towards genetics.

Dr. Daniel Knoepflmacher: Is there any indication when you had a conversation with Joshua Gordon that there might be a shift in the government funding of research in mental health towards things that are not as focus? I mean, you just quoted somebody else from NIMH that seemed to suggest that it is going to be very gene-focused, but have you had any sense that there may be some shifts ahead?

Dr George Makari: You know, unclear. Tom Insel has repudiated this in the strongest terms. It's rather astonishing. I quote him in the New Yorker piece as saying we published a lot of cool papers, but the cost was maybe 20 billion and we didn't move the needle on suicide or psychiatric suffering. That's from the guy who founded that. And he told me, he really didn't think it had panned out, it'd become an academic exercise. So, that's pretty harsh stuff from the guy who really pushed this forward.

Bruce Cuthbert, who was the interim NIMH head, is now the head of something in the NIMH that is the RDoC program. And he seems as committed as ever from his 2022 paper, I would say. Joshua Gordon was more ambivalent and more concerned that it was potentially in some ways problematic. It was interesting, I asked him two questions. I said, one, "Do you think you're losing good research by limiting researchers to mechanistic target engagement, they call it?" It sounds like warfare, but that's what they call it, that you have to have a claim about a mechanistic target that is going to be the causal claim. And he said he did not think that they were missing out on good papers. I asked him if he thought people were making up mechanistic targets just to get grants, and he kind of giggled and he said he worried about that.

The other really damning, I think, piece of evidence is if you look on the NIMH website, they tout a couple of clinical accomplishments. The most impressive one is this early psychosis treatment that John Kane and others like Lisa Dixon have been involved with. It's a fabulous program. And they've shown that if you treat psychosis early and if you have a raft of social supports and family supports, these people do much, much better. And so Josh said we did that. And I said, "Well, Josh, that got funded before RDoC. And how could that possibly get funded with RDoC?" There's no target. They're saying like, "We're going to use clinical sense and let's see if it works," and it turned out to have worked. So, you would have lost that program if in fact they were required to have target engagement. Now, how much that's a requirement, how much it's simply a preference, how strong is the demand? I've heard a wide range of views on that. Josh says it's not. Some researchers confidentially said it might not be a written requirement, but you're not going to get a grant if you don't have it. So, I don't know what to make of all that. I have to say it's simply unclear to me.

Dr. Daniel Knoepflmacher: Remains to be seen. And that's great example of kind of an overlap of the research arm and the community care arm.

Dr George Makari: Exactly. And, you know, I think we need much more on that. Obviously, the deinstitutionalization and the closing of the asylums had a lot of positives in it. A lot of those people didn't need to be there. But the fact that we never built the community mental health centers obviously has led to this growing problem where now we have to innovate and come up like what's a model for humane asylum that we can come up with because some of these places really were terrible and needed to be closed. But now, is prison the answer? I mean, obviously, that's a horrendous answer,

Dr Daniel Knoepflmacher (Host): It is horrendous and it's not even an answer. I wouldn't call it an answer.

 but speaking to that issue specifically, there's been a lot of talk in bioethics circles, including a recent piece in the Wall Street Journal about bringing back the asylums. Now, nobody is advocating for bringing back the asylums of the past where there was inhumane treatment of patients everywhere.

But, with the failure to replace those asylums with a robust community mental health care system, there's instead been this unconscionable shift towards incarceration of mentally ill Americans. So, given, your understanding of all of these problems, what do you think is the best way for us to address this?

Dr George Makari: It's deeply immoral to put people who are mentally ill in prisons. The founding of psychiatry as a field was supposed to be this enlightenment moment where we recognize that these were people who were sick, not bad. So, I have very strong feelings about that.

Look, I'm not a sociologist, but I think sociology has shown smaller institutions tend to be much more humane. So, I, in my New Yorker piece, call these too big to care uh, asylums. Because as they grew in size, they became more and more brutal. Prisons that are big tend to be much more brutal. Smaller ones, not so much. So, I think that there's a size element to this. And I think that there's got to be like a social investment in figuring out what works, and it might be different in different communities. It might not be one-size-fits-all.

So again, I'm not an expert in this, but the need for an answer and not just like washing our hands of the problem. And that's what I find very distressing about the NIMH. Their initial decree from Congress was to be our country's leaders in research, prevention and treatment. Now, once they split off from SAMHSA, SAMHSA was supposed to be the one that delivered care and they could just kind of wash their hands of all of that. Well, I don't think so. Someone's got to take responsibility for the fact that we have this glaring problem in this country. And I think the NIMH needs to fund a lot of research to figure out what the right answer is. They're supposed to be the ones who break new knowledge and break ground on new knowledge. And we need new answers because you're right, the old asylum is a bad answer. Homelessness or prison is a horrendous answer. So for the last 25, 30 years, it's been obvious we need new answers.

Dr. Daniel Knoepflmacher: And you use the analogy of the AIDS crisis and HIV, and the look for a vaccine versus what ended up making a massive difference in public health in that realm. And kind of end with that, speak more to how that comparison is instructive when we think about psychiatry.

Dr George Makari: I'm a historian, so think about a lot of historical examples, but this was one that I lived through. So, I was an intern during the HIV/AIDS, early part of the epidemic, and remember this disjuncture between the research establishment, which had very strict rules about how to do clinical trials and FDA and, you know, very, very sclerotic, slow process.

And I was an intern in New York and all of these people were dying. And so, it reminded me of that. And then, it kind of also reminded me of how that changed, which was a community rose up in protest, ACT UP being maybe the most obvious example. And they ended up having a dialogue with a guy who happened to want to listen to them, which was Anthony Fauci. And Anthony Fauci said, his relationship with Larry Kramer and other people from ACT UP really made him see that they needed to liberalize some of these very strict rules and that pure science was really not going to be compromised by doing that. And thank God he did because, you know, they were looking for an HIV vaccine and we still don't have one. But what we do have is a whole bunch of medications that were facilitated and I think sped along the way by these more liberalized criteria that really showed that the science establishment was working with the community. And so, that was maybe my hopeful way of saying perhaps a popular, pushback about these obviously deeply dysfunctional things that COVID only makes worse, that maybe a community that makes us stink will get some of these people's attention. And then, obviously, that's why I wrote the article, to try to get people to recognize our scientists are off on this hundred-year mission to learn about the brain. And meanwhile, our patients are suffering and some of them are suffering very badly.

Dr. Daniel Knoepflmacher: So, it's about advocacy, public policy, organization, that there's perhaps some hope in going down that road.

Dr George Makari: I think so, because I think humans, are basically decent people when they hear like, "Oh my God, really? You're going to spend 20 billion dollars for a couple of cool neurosci--" I love neuroscience, by the way. This is not an argument against doing great brain science. And great neuroscientific work is great for all of us. But the problem is they've been commandeered by an ideology. And that's been a problem throughout the history of psychiatry. Ideology stands in for more balanced uncertainty in this unbelievably complex field. And so, I worry that they become domineered by an ideology that's blinded them to how, in fact, desperately we need help.

Dr. Daniel Knoepflmacher: And that ideology is on one side of that mind-brain problem.

Dr George Makari: It is on one side of it and, even worse, it's turning out to not be the answer we hoped it was so that, for instance, we could have hoped that genetics would explain schizophrenia. That would be fabulous. It turns out that there are so many genes that confer a tiny little bit of risk. And we're talking about over 200. That in fact, it's not going to be the answer. So that they went for it, you know, I think is perfectly understandable in that domain. But what they then walked away from are things that aren't nearly as genetic in their causal nature. And anything that's way down on the other side of the spectrum that's not epigenetic, yeah, that's nothing, that's invisible.

Dr. Daniel Knoepflmacher: Well, George, I have a lot of other questions. And I'm going to have to stop because we're going to run out of time. But it was just really great to have you on this episode of On The Mind. And that is the name of the show after all. I guess we're going on the other side of that dichotomy. But your article really, it's just a thoughtful dissection of the problems that are facing our field and our country, and it's a call to action. And as you said, this is hopefully the start of something that can be more of a movement in really rethinking these fractures in our system. So, I hope we can meet the challenges that you've skillfully laid out. And for those listening, be sure to read Dr. Makari's essay for the New Yorker online on what COVID revealed about American psychiatry.

George, always a pleasure to speak with you, whether that's in the hallway or here recording on this podcast. Thank you so much for being here today.

Dr George Makari: Daniel, thank you for having me. It was a lot of fun.

Dr. Daniel Knoepflmacher: Thanks. And thank you to all who listened to this episode of On The Mind, the official podcast of the Weill Cornell Medicine Department of Psychiatry. Our podcast is available on all major audio streaming platforms, including Spotify, Apple Podcasts, and iHeart Radio. If you like what you heard today, tell your friends, give us a rating and subscribe, so you can stay up to date with all of our latest episodes. We'll be back soon with another episode later this month. Thank you.

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