Hi everyone, welcome. I think I just got the go-ahead that we've started the recording, so we have some folks joining us online. I'm going to try to keep an eye on the questions that might come in, so I'll be sitting down. Thank you all for coming. We're of course getting close to the end of the Congress, and I've learned a great deal in the last four days. I hope to be able to contribute to the learning of those of you who are here in person today and virtually as well, and of course it's a great honor to be speaking to this audience and to have the opportunity to share my research and thoughts here at the APA. I will say it will be an even greater honor to have your participation in the discussion and receive your feedback. I know that the true benefit for me when presenting my thoughts are the responses, challenges, and the furthering of discourse that happens. The discussions that are generated in the coming days and months, I look forward to that as well. I stand to benefit greatly from the discussion and I wanted to thank you in advance for that as well. Since I would prefer this to be somewhat of a discussion, we'll have an open forum generally. If you're able to maybe kind of congregate together so that when there are opportunities to exchange some ideas, you can be near one or two people to have some discussion, that would be great if you're able. But I see that generally we've selected our locus in a certain location of the room. So yeah, please feel free to contact me after the session with questions, comments, or requests for anything, collaboration, sharing of sources, clarifications. If you need streaming recommendations on Netflix, anything, just you can reach me. There's my email. And on that note, I hope this session encourages some reflection and discussion. Since I'm the only one up here, I hope I can do whatever I can to help you feel empowered to join the discussion as part of the symposium. And don't worry, I don't plan to take the full 90 minutes. It's a beautiful day and we're getting towards the end of the Congress and I'd like to leave some time at the end for some open discourse. So a little background about me and my relation to this topic. In the spirit of full disclosure, I'm barely a doctor, if you couldn't tell. I just graduated medical school last week, so I'm under no delusions regarding my seniority or lack thereof when it comes to sharing a symposium here at the APA. But luckily this presentation doesn't aim to be a purely medical or technical talk or glean too much from my clinical experience, which is surely limited compared to many in the audience. But my background prior to medicine is in philosophy, especially phenomenology. And it's through this philosophical lens that I hope to present and critique precision psychiatry. I've spent the last 12 years working on the philosophical reasons for and explanatory gaps in science, particularly as they relate to consciousness and the mind. I've also spent the last 10 years working on the potential abilities and limitations of AI, artificial intelligence, and machine learning from the perspective of existential phenomenology. So in other words, while many of my peers were figuring out what computers can do and getting rich and retiring in their early 30s in the process, I was working on what computers can't do and getting no closer to retirement whatsoever. So without further ado, we can start this discussion. Well, I firmly believe that a critique that is the establishment of the limits to technological advances in psychiatry is crucial. It's important to understand the limits of technological advances in order to best use those technologies most productively. So by understanding the limits of the capabilities of our innovations, we can use them for the purposes for which they are suited. And we don't have to worry so much about trying to apply it in every instance, including in instances where they might lack any benefit or be harmful. So by knowing the limits of the applications, we don't have to go through the trial and error of applying a new technology in an instance outside the scope of its application and suffer through the unfortunate scenarios when it might cause harm to a patient. So one of the... First, I have no financial disclosures or disclosures otherwise, but I will admit that I am somewhat skeptical of some of the approaches in precision psychiatry. That's the only disclosure I do have. I'd like to talk about one of the heroes in the history of the Western philosophical tradition. The hero is Immanuel Kant and his magnum opus called The Critique of Pure Reason. It's a formidably titled, famously impenetrable, and dreadfully thick book that laid out the ambitious goal of determining the limits of our scientific understanding. He claimed that by framing, in other words, outlining the boundaries of where reason, empiricism, scientific inquiry can be applied, we can then address the incredibly rich content of science. And on the other hand, by understanding what is outside the scope of scientific understanding, we won't waste our time with applying science nonsensically. The history of knowledge and science has essentially followed as a response to Kant. And in short, this is the topic of the discussion this afternoon. What are the limits and boundaries of our so-called precision approaches in psychiatry? I want to argue that by defining those limits, we can help open our capacities for where we might be able to more thoroughly apply our empathic and human communication capacities. But more on this towards the end. So I have the definition of precision psychiatry on the board, and this is the Oxford English Dictionary definition of precision medicine, just with mental health care replacing health care in general. So precision psychiatry is mental health care designed to optimize efficiency or therapeutic benefits for particular patients, especially by using genetic or molecular profiling. It promises to be a kind of revolution in the field, so I have some qualifiers for this definition in quotes. It wants to create new paradigms, new ways of understanding mental illness. It does not aim to be a mere advancement of our present projects in psychiatry, but a new project altogether. Finally and importantly, many of the claims of precision psychiatry fundamentally rest on the assumption and presupposition that mental illness is a brain disease, or brain circuit malfunction, some kind of neuronal circuitry. So in order to improve our understanding of mental illness, we need to shift away from the terminology of mental altogether and talk about brain disease, if we're going to buy into this approach. So I'll share a little anecdote to articulate the deep roots of this divide between an understanding of the mental versus the brain processes. It was the mid-1970s and my grandfather had completed his residency training in neurology in the country of Iran, our home country. However, he had grown quite interested in the concept of mental illness, and during this time, around the time he was finishing his residency, he experienced the trauma of losing his oldest son in a tragic accident. His tremendous mental suffering at the time, along with witnessing my grandmother's acute psychological response, which included what may have been called at the time, hysteric paralysis, and what we might now call a kind of conversion disorder, or functional neurological impairments, all of this encouraged him to pursue a second residency training in psychiatry. In Iran, where my grandparents lived at the time, there was no pure psychiatry residency program. Rather, the system was based on the French model of training in neuropsychiatry, with a heavy emphasis on brain and neurological disorders as the basis for psychiatric illness. What fascinates me is that at that time, 50 some odd years ago, my grandfather recognized that the answers he was seeking to mental suffering would not come from his own discipline of neurology, in which he was training. He'd completed the residency at that time. Or the predominant model of neuropsychiatry that was being advanced in Iran, and instead, he chose to pursue a psychiatry proper residency training in the United States, and probably the reason why I'm sitting here today. He chose to, well, there was a greater degree of emphasis on the mind in the psychiatry training program, and less reduction of mental states and pathology to brain disease. It's quite interesting to me then that this very same debate regarding the reduction of mental disorders to brain disease, and mental states to brain states, has remained and reemerged more than five decades later. I'm sure many in the audience have have seen this debate or topic through the years, and how it's been reformulated. For me, obviously, in a very early stage of my career, it's, I have to glean from the experience of those those before me. So let's, let's think about this definition, and I'd like to open the discussion here. If, if you can talk amongst yourselves, and I'll keep an eye out for the, for the chat. I understand there are some folks online currently. What do you make of this, this particular definition? How applicable might the products of this research project be in in your practice? And what do you make of the reduction of mental illness to brain disease? So maybe five minutes to discuss among yourselves, and I'd love to hear what you think responses to these questions following the discussion. So I'm also getting some comments in the in the chat, including mental illness is not brain dysfunction. And regarding the definition on slide two, it is useful but not sufficient. We have an elaboration on that comment. Reducing mental illness to a brain disease does not allow for the natural, everyday human experience, interaction of the human being with others and their brains, perception of what is happening between them that may be diseased or impaired. We just had another comment come in. For me, it is difficult to imagine it is just a gene or molecular impairment. So I'd like to hear some comments from the live audience as well. And if, if you're able to use the microphone, that would be great. If, if not, I can repeat your question in the microphone here so that everybody virtually can hear as well. I did see some nice discussion in the audience. Hi, so we were discussing a bit, I'm a resident psychiatrist in Italy, and we're discussing a bit, you know, what we feel precision psychiatry, how, how precision psychiatry is affecting clinical work. I'm very skeptical too. I feel like I've done some work on like molecular profiling of bipolar disorder or speech biomarkers, but I still feel like all these research projects are very far away from my clinical daily experience. And I can't really find significant applications. I was sort of sharing this with the other people around me. But at the same time, you know, maybe it's a, it's a, it's a question of time that most of these things are in their very early stages. And so there's a lot of enthusiasm, but we can't see the real clinical significance because it's so, so early. That's, I think, a synthesis of what we said. Thank you for that comment, doctor. So I'm, I guess, gleaning some comments in the, in the, in the chat forum here from the virtual audience that are questioning or undermining the definition. And I'm also hearing some comments about in the live audience here from, from the doctor that it's, it's possible that we're just not there yet. The, the research programs are in their early stages and the applications right now might be a little premature, but potentially they can mature to something very useful. Great. Yes. Yeah, I would just add kind of a counterpoint to that. So from my perspective, ultimately there are many ways to affect brain circuitry. So it could be sociological factors, could be psychological factors, could be brain injury, could be genetics. There are many ways to get there, but ultimately if you have a mood, behavioral or cognitive disorder, a psychiatric disorder, it's through those brain circuits. So I don't, I think it's a kind of a false choice between it's all reductionism, it's all the brain versus it's not the brain. It is the brain because what else would it be? It's not going to be the liver or the heart. It's got to be the brain, right? But how you cause problems in those circuit, in those circuits are very variable. And that depends on the person's brain, of course. It depends on their background, their experiences, because the brain is very neuroplastic. It's changing all the time with experiences. So everyone's brain is going to be different because experiences are different. But that doesn't mean that the, that the problem is not in the brain. Great. Thank you for that comment. Yes. So we have several perspectives to go over and outline further. And this is, this is very helpful because this highlights the argument from, from one of the leading perspectives. And I think the, the major perspective that's particularly a powerful perspective and, and interesting. And I think it's, it's quite difficult to also argue against the, the role of the brain as a central source of the mechanisms that lead to mental illness, yeah. We have another comment that says we are a sum total of bio-psycho-social influences. And I think the response from the first perspective that I'll outline might be that even the psycho and social elements that we're talking about, we need to be reformulating those in terms of the kinds of brain circuitry that's involved. I'm maybe speaking in your turn, sir, but that's what I imagine the response might be. So I have found two and a half perspectives through the literature that are predominant. So it initially had three perspectives, and then the philosophical critique is what I hope to outline more fully. But I have the gung-ho approach, which is full steam ahead approach, what we just heard, I think, in this first discussion. The gung-no approach, which is the perspective that I tried to present a little earlier about the impossible, the notion that it's impossible to reduce mental acts or psychological acts or psychological types of entities to their reduced brain states. Finally, the philosophical critique, I'll try to at least illustrate how neither of these perspectives maybe give us the fulfillment or adequate response that we need in order to go full steam ahead with precision psychiatry or stop the research programs altogether. Before explaining those perspectives further, it's useful to go to the roots of where this field was founded. So precision psychiatry finds its roots in the field of precision medicine, which has been proposed as the future for our therapeutics. And it started really taking shape after several landmark studies, including this 2010 study with patients who had a very advanced end-stage metastatic melanoma. So they were recruited into a study and a subset of patients specifically who had a specific mutation in the BRAF valine 600 or V600E mutation, specific mutation of these terminally ill patients. They were started on an experimental drug, PLX4032. It was a kinase inhibitor to treat this specific subset of patients with metastatic melanoma. So people who had this specific mutation, BRAF mutation. The drug therapy targeted specifically at that genetic mutation. And you can see the PET scan results, and I don't think you need to be a radiologist to see that before the mets are profound, and after several weeks of treatment, the patient has an incredible improvement in the degree of metastasis. So this kicked off the belief, kind of, this became kind of, especially in the popular press, there was a, I think, three-week New York Times series written about this project and started the field of precision medicine. So this first approach, the all-in, the gung-ho approach as I call it, asks for adoption of the same approaches from precision medicine to precision psychiatry. So we'll go full steam ahead in much the same way as the other disciplines who have adopted precision approaches, such as oncology, immunology, and other fields have already benefited from the advanced therapeutic and diagnostic technologies in precision medicine. So the vision of precision psychiatry should be to use similar models. We should adopt the advances from the disciplines like oncology, rheumatology, immunology that have used these markers. And since those disciplines have already lessened the translational gap, psychiatry is in kind of an advantageous position. We won't make the same errors and benefit from the advances already made in the other fields. But implicit in this approach, which was mentioned earlier in the audience, is that mental illness is brain disease. Essentially, the full steam gung-ho approach takes this as a matter of fact. Mental illness is brain disease. So let's stop wasting our time with the nonsense about mental or psychological terminology. Importantly, our overestimations of the importance of the realm of the mental are mere underestimations of the capacity of the brain. It's true that mental states and processes are incredibly complex, but this complexity maps onto the incredible complexity of our neuronal circuitry. So if we don't understand enough about the mind, it's because we don't know enough about the brain, essentially. The usage of the term mental disorder reflects our limited understanding of the real-time coordination of the brain and our limited knowledge of how psychiatric disorders are functional expressions of subtle pathologies, specifically in brain circuits. So given the advent of brain imaging techniques with sufficient spatial and temporal resolution to quantify neuronal connections in vivo, it is the right time to reformulate our understanding of mental illness as disorders of brain functioning. So now is the time. Let's go. So of course there is an objection. One common objection might be, well, we haven't been able to make this reduction of mental illness to brain disease until now. Much of our evidence, in fact, points to this not being possible. So what's new? What's new with our understanding? Well, the response from the gung-ho precisionist will be the odds of turning this ideal into reality have considerably increased with the development of powerful biological tools, methods, the brain imaging and physiological techniques that we have, as well as assessment of behaviors and life experiences to characterize patients along with the advanced computational tools capable of analyzing large data sets. So now the availability of massive information, so-called big data provided by the acquisition of biological data and by incorporating data from electronic devices like your smartphones, your credit card histories, et cetera, is one of the multiple factors that now allows the analysis of diverse patient characteristics to be considered. And ignoring any questions about privacy that might arise, this is the approach. So this approach should make it possible to investigate, predict or treat groups that are biologically, that is, they're similar in structure and function rather than phenotypically, that is, in symptomatic appearance as we've gotten used to in the tradition of psychiatry. So the homogeneity is in the biological structure rather than the phenotypic structure. This approach is possible through the foundation set by multi-omics, that's genomics, proteomics, exposomics I think is the newest omics I heard, neuroimaging, big data and high-density data approaches, molecular epidemiology and physiology, they should all converge to make specific biomarkers that can lead to biological stratification and ultimately precise person-specific treatments. And maybe it's worth mentioning that this approach builds on the objectives of the research domain criteria of the NIMH, so funding will likely not be a problem for these projects. So as I mentioned, there were initially three perspectives that I considered, but on further investigation I kind of decided to consider the second approach as kind of perspective 1.5, kind of a toned-down gung-ho approach in which we can envision a future where clinical decision-making is complemented by tools and measures that help to diagnose individual clinical biotype profiles and tailor the treatments to these profiles. If the hard stance is that clinical decision-making will essentially be replaced, the toned-down stance offers some reprieve. The goal of the toned-down approach is to build a foundation for a future in which one-size-fits-all treatments are replaced by modalities that are optimized for individual patients across all stages of a disorder, with the clinical decision-making ultimately guided by a physician. So this approach still aims to incorporate so-called expososome, I'm liking this word now, data, environmental factors, and another information in a guided kind of digitized biometric or biosociometric profile. So that part of the approach still would be kind of standardized and digitized. An understanding of the environment, social background of the patient becomes reduced to the basic digital information. So further critique of this approach, a major pitfall, may be the overestimation of biological dominance in mental health generally. So critics have mentioned the overestimation of the prevalence of the syndromes and pathologies that have a predominantly biological root. So we might sometimes refer to these as mainly organic pathologies in mental illness, is maybe the terminology we're used to using. And perhaps this doesn't make up the majority of cases of mental illness. It also rests heavily on the advances in neuroscience, kind of at the expense of perhaps some foundations that we've already built in the fields of psychology, sociology, our understanding of social psychology and psychiatry. And one perhaps semantic and political criticism is that this approach promises a great deal of interdisciplinary collaboration and convergence, but denies the validity and progress that has been made in the fields of, as we mentioned, social psychiatry and psychology. At the expense of those in favor of a more in-depth approach with a neuroscientific background. Of course, I think it's obvious that there is a far more limited consideration of social determinants of health because those social determinants are also somehow incorporated into the digitized information and sometimes even understood as part of the neuronal circuitry malfunction. The opposite to this approach is what I'm calling the gung-no approach. It questions the legitimacy of investing substantially in the field of precision psychiatry. So this field relies on progress in biological research, so the critics say. This field relies far too heavily on the biological research, but confuses the certainly undeniable progress in neuroscience with progress in its applicability to mental health care. So decades of research in the field of markers, brain regions, genes, and developmental precursors have not produced any latent disease entity, biological subgroup, or ideological essence for the main psychiatric syndromes. The main outcome of much of the research is therefore the absence of valid, replicable, and useful association between biology and mental suffering, despite significant progress in brain research per se. So the absence of valid and replicable data should be telling us that mental illness cannot be reduced to specific biological markers or brain circuitry problems. In fact, one of the most important replicable biological findings in psychiatry is that every human being has thousands of genetic risk variants for transdiagnostic mental suffering. It's part of the human condition to have a broad, elusive biological vulnerability to develop mental suffering. The DSM workgroups have therefore not been able to include biological evidence in the criteria for the most important mental disorders. Given the situation, without clear hypotheses or directions to guide us towards future findings that would be able to yield discrete clinical distinctions, it remains debatable whether precision psychiatry, using the same translational approaches, will ever be able to provide any diagnostic, prognostic, or therapeutic benefits to clinical practice. So our colleagues commented earlier about the potential for future benefit and these approaches being early in their research and development, it's kind of brought under question with this approach, that fundamentally there is a lack in the validity of these research programs. Scientific findings provide a powerful case for mental suffering as broad, poorly delineated syndromes that show high levels of variability and low levels of predictability. And the implicit premise of precision psychiatry is that phenomena of the mind, this is somewhat of a more fundamental philosophical discussion, the implicit premise is that phenomena of the mind are physically represented and that these representations are relevant to our understanding of mental suffering. The question, however, is whether phenomena of the mind are physically represented and whether finding biomarkers is of relevance in understanding mental processes at all. The point here is that the representation of mental process in terms of biomarkers is not only reductionist, poor, and insufficient, but also not relevant enough for the understanding of mental processes. So apart from the fact that this problematic starting point does not testify to a basic critical scientific attitude, it inevitably leads to poorly grounded solutions. So the arguments of this critique seem for the most part sound and valid. The pitfall of this approach is that even if it is a valid critique, it does not offer a novel solution. Basically, it offers a carry-on as we do stop focusing on neurobiology and understand the importance of psychology and social factors. But it's reasonable to understand that a precision approach may limit the trial and error problems of, say, for instance, starting a patient on an SSRI or a neuroleptic. Which one do you start with? Perhaps if we do have enough biometric data and all the other omic data, we could come up with a kind of algorithm that starts a patient on the right SSRI or neuroleptic on their first presentation rather than waiting several months and thus reducing patient suffering. This critique, the gung-no approach, doesn't consider this. And so there may be certain people with pathologies heavily rooted in organic processes and it may be reasonable to suggest that we can gather biometric profiles of these patients and make certain improvements in our therapeutic programs. Another critique of this approach is its over-reliance on the validity of present descriptive pathology. So it appeals to the ICD and DSM criteria that exist. But a gung-ho precisionist might say we need to overcome these labels, look beyond them. And that's what the prospects of precision psychiatry give us, looking beyond the descriptive analysis that we have presently. So if the gung-ho precisionist has a shaky ground on neurobiology, according to the dissent, then we can say that the gung-no has a shaky ground on the phenomenological approach that isn't adequately validated either. So, do you think that there is one approach you favor over the other? Are there pitfalls and limitations that you would like to address that weren't addressed? Do you think you align with the all-in or all-no or somewhere in between? I put the in-between with the gung-ho approach with basically some modifications. You know, you can have some minor adjustments. So if you'd like to discuss, then I'll keep an eye out for the chat. Yes, doctor. Hello. I just wanted to comment on something about these approaches, especially brain imaging. So that's why it's about the brain. As a person who did a couple of brain imaging research and published some papers about brain imaging and who still have collaboration with a brain imaging group, I can say that – by the way, I'm now doing neurology. I'm a PGY-1. After seeing a couple of patients with brain lesions and seeing the psychiatric symptoms of them, I can say that sometimes it doesn't match. Brain imaging studies say that the default mode network is important about this and that. But when I see the patient with a brain lesion, I usually say that, oh, this patient must have this attention problem or psychosis in terms of the brain lesion. But most of the time, I feel like the patient doesn't have any symptoms in a psychiatric sense, even though the lesion is there, causing brain damage. But at the same time, some patients have different psychiatric symptoms without brain lesions. But, yeah, it's a pretty interesting topic because there is no balance. And my approach is we can't dismiss the psychological and sociological effects on that because without psychological problems, patients don't develop psychiatric symptoms with just brain lesions. Interestingly, I'm saying that as a person who is really interested in neuropsychiatry and neurological problems and psychiatric problems at the same time. So, yeah, good approach, actually. Very interesting. Personally, I hadn't come across this objection in the literature, actually. You don't see the same kind of presentation or the phenomenology of the presentation with, let's say, a mere brain lesion without any other reasons for the psychiatric manifestation. So, I think this could add a dimension to possibly the second approach, the critical approach, and more likely, I think, the philosophical critique that I'll present. It's all about the interaction between two things. So, it's like, you know, nature and nurture, genetics and epigenetics, like maybe in cancer we say that, what is that called? You need the two damage in the gene to develop cancer. But in psychiatry, biological damage may not be enough for developing psychiatric symptoms. You need to have some sort of sociological and psychological problems to develop psychiatric symptoms after having a brain lesion. So, yeah, it's really hard to determine the outcome with just checking the brain areas. I agree that. So, we need to merge these things to conclude the patient's prognosis and predicting the symptoms. So, a kind of two-hit or multi-hit hypothesis for psychiatric illness. And this could really, you know, we don't have to make such clear distinctions about the approaches. I think the further we progress, we realize that there's a lot that can be shared, and we should actually be working on developing a shared language. And that's what I'll get into in the last portion. But it seems like either approach could adopt what you just mentioned, because the revised gung-ho approach says we need more data from the environment, and with enough of that data, then we can develop more precise therapeutics. How we arrive at that data is part of that hypothesis, which we might be able to question. But thank you for that input. Anything, anybody else? I do have a comment in the chat. Treatment through structural network of symptoms, symptomics, rather than treatment of nosological entities, the relationship of symptoms with risk factors, biomarkers, impairment of functioning, and treatment response. So, it's symptomics. I hadn't heard that before. Thank you. The relationship of symptoms with risk factors, biomarkers, impairment of functioning, and treatment response. So, all of this can be added data that can support the project of precision. There's another comment. Evolving methodology of the network analysis of symptom structure, this approach is based on the premise that mental disorders are the result of the causal interplay between symptoms. For example, worry leads to insomnia, which leads to fatigue. So, I'll present a bit of my approach. It's... I think... So, it's based on the premise that mental disorders are the result of the causal interplay between symptoms. So, I'll present a bit of my approach. It's... I think... So, it's based on the premise that mental disorders are the result of the causal interplay between symptoms. So, it comes at a different direction, at least the way I've tried to conceptualize it and the way I'll try to describe it. It comes from a different direction than the two other approaches. It's a kind of philosophical critique. So, we started with the slide on the definition. I think, for me, that was intentional. Because having those definitions lets us define our limits. Like our hero in philosophy, Kant, who thought it's the most important thing to define the limits in order to know the bounds of the application of our scientific understanding. So that we don't try to apply scientific reasoning to something that lay beyond the bounds of scientific reason. So, we need to define our limits with precision psychiatry as well. Knowing these limits can help open room for our more, let's say, human capacities clinically. So, what I'll try to show is that it's very worthwhile to pursue this research project as long as we identify what we're being precise about in our precision therapeutics. The medical understanding of psychiatric illness has always shown, at least by certain communities within the field, an understanding of the limits of medical therapeutics and the need for adjunctive therapies. The role of social structures, relationships, and factors intrinsic to the person's coping abilities. Personally, I don't think there's an urgent need or any place for dismantling this tradition that values a comprehensive approach to the patient through human understanding rather than digitizing. Perhaps more than any other discipline, our presence with the person suffering from mental distress, our human ability to connect, matters in psychiatry. We need not define precision psychiatry as a global revolution in the field, but rather think of precision as a goal of our therapeutic research programs. We should not give up the mind in exchange for the brain as the strength of psychiatry rests in our ability to join the biophysical understanding in the social and environmental context. To this extent, we should distinguish between our tools and our paradigms or programs. Is precision a global qualifier for our programs or a qualifier for specific elements within the same project? I think it's more worthwhile to identify and solidify precision as a term that defines our tools, not our programs. Let me give an example. So I visited the barber yesterday. That's why I look, you know, so sharp. And shout out to Gabriel, who probably would have never thought he'd be featured in a talk on precision psychiatry. And I was sitting in the barber's chair and thinking about how the barber and I, the person sitting in the barber's chair, have benefited from, say, a sharper razor, a new set of clippers with various capacities, or a shiny new set of scissors made of some kind of new metal alloy. That makes the barber's work easier. The barber can tailor the shave and haircut better for the person sitting in the chair, not only through his tools, but also through his very human capacities of understanding who I am as a person sitting in that chair and what an appropriate or adequate haircut and shave might mean to me. How much time I might have, what level of conversation we might be able to share, and so on. So the sharper, more precise tools aren't just giving him the ability to cut with more precision or trim a beard with more precision, but also opening up the capacity for those human connections by allowing more time and resources to be able to make that approach. So I find the promise of precision psychiatry very similar to this promise of better tools for the barber. And just as the barber should rely not only on sharper, more precise tools, but also the capacities that having those tools opens for our very human connections, our conversations, empathic understanding, or in the case of the barber yesterday, calming someone's nerves before a presentation, we too need to understand precision of our tools as an augment to the very human capacities that make all the difference in improving the lives of patients. This is to say the barber, with his sharper, more precise tools, and of course his ability to use those tools efficiently, which is also important, can focus his time and energy on connecting with the person in the chair, understanding his situation, what would be appropriate and what would not be, and not have to worry as much about the proper functioning or adequacy of his tools. In our precision programs, our aim should be to maintain this understanding that what we are making more precise are exactly our tools, our physical diagnostic and therapeutic tools, but the goal should not be to try to replace our very human capacity, which indeed, I'd like to argue, provides the most precise tool for understanding the person sitting across from us, whether it's in the office or maybe virtually sitting across from us. So, in the language of what I'm most comfortable with, existential phenomenology, right now as you all and I are engaged in this conversation, which you're all probably thinking feels more like a lecture at this point, we are each attuned to an infinite amount of information and can distinguish between the relevant and irrelevant without blinking an eye, without feeling the least bit exhausted. In every instance, our attunement to what is relevant, the tone of a speaker's voice, the volume, the content of the discussion, the posture, the confidence with which one speaks, all of this is understood and contextualized in a meaningful set of appropriate cultural and social practices. And this is done in a way that no system that can manipulate data could possibly be programmed to understand and distinguish all the elements within the environment that are relevant and those that are irrelevant. So, right now, as we're sitting here, you're doing some incredible kinds of gymnastics, mental gymnastics, in which you're attuned to the relevant information. You're not worried maybe about the lighting because the folks here have done such a great job. You're not worried about it going out. You position your body in a way to show that you're attuned to the conversation. And this is infinite levels of data that no algorithm processor can handle, this level of infinite data. So, this is all to point out that within our human capacities, we already have the most precise tools for assessing situations within context, and we can exercise those capacities with ease. On the other hand, by creating the precise tools, the therapeutics that leave less room for error, less need for trial and error, we can open the exercise of these human capacities more thoroughly. So, neither gung-ho nor gung-no, I think, with this approach, we're trying to view precision therapeutics as not an entire paradigm shift, But much of what we've been doing with developing new therapeutics and seeing those as tools within our arsenal rather than the design of the whole process. So knowing where we might be able to stop applying those, where human beings, the human capacities are actually our sharpest tools, that's where we can draw the line between what the precision programs can provide and what they should kind of leave for us. So I'll mention the theoretical and philosophical foundation for this approach. And in kind of memory of a dear contemporary philosopher by the name of Hubert Dreyfus, who taught in, until recently, passing at nearby Berkeley, I had the honor to collaborate on a project related to this very topic with him, which came to an unfortunate halt with Professor Dreyfus's passing. He was long-time chair of the Department of Philosophy at Berkeley and chair and distinguished fellow of the other APA, the American Philosophical Association. He was a scholar of phenomenology, especially the existential phenomenology of Martin Heidegger and its application to cognitive science through the work of Merleau-Ponty. He became world-renowned for his critique of the limits of artificial intelligence. And in a way, I think that critique is incredibly relevant at this juncture in medicine and in psychiatry in particular. The philosophical basis for this story can be said to have started about 100 years ago in 1927, when Martin Heidegger, with whom Dreyfus later studied, published his seminal work, maybe the most influential book in 20th century philosophy, titled Being and Time. In it, he rejected the subject-object dualism that had been presented by Descartes hundreds of years earlier through the famous statement, cogito ergo sum, I think, therefore I am, which cemented an understanding of the world that separated entities into res cogita and res extensa, that is, thinking stuff and extended stuff or matter. Importantly for Descartes, for his conception to work and make sense, it required something to create the connection between the thinking stuff and the extended stuff. And the heirs of this ideology adopted a framework that requires some kind of mental representation of the extended stuff. So Descartes' theory gave a certain preeminent role to the cognitive capacities that can manipulate the so-called representations of the world. So we have no, in Descartes' world, we have no connection with the outside world outside of our mental capacities that can create certain representations. And I feel fairly confident saying that we are all heirs to this conception of the world, especially as scientists and particularly as psychiatrists. We buy this theory that at least in our scientific theories of the mind and brain, that the world is not immediately accessible by us, but through certain representations. This has shaped not just philosophical research, but our very neurobiological conceptions. So even though this seems so far, this philosophy, I strongly believe that it has shaped all our neurobiological research programs from day one. Now Heidegger rejected this whole tradition and the framework he established that was adopted by Merleau-Ponty did not buy into this farce of dualism, claiming instead that the most important or interesting thing about us human beings is not that we can represent the world in our minds or that the world is something separate from us that we can represent in our minds, but that we are always already in the world. And the world presents itself as meaningful, always already meaningful. That's to say the meaning isn't something we somehow create through some sort of cognitive capacity, but instead it is out there in the world. The world is rich and pregnant with meaning. Now back to Dreyfus before I get back to the barbershop and our talk of precision. Dreyfus' genius and what brought him to prominence in the late 70s while he was teaching philosophy at MIT was that he saw the adoption of the Cartesian philosophical framework by the artificial intelligence labs in MIT. And while the AI labs wanted anything but to listen to a riled up philosopher talk Heidegger and Merleau-Ponty, they had to finally take his argument seriously. A major government think tank working on the contracts that funded the AI labs hired Dreyfus who wrote a report which ultimately after a series of failures in the AI labs proved to be correct articulation of the inadequacy of those AI programs. Now, just as those original AI labs were focusing on a kind of global program without understanding the limits of their conception, I suggest that precision psychiatry lacks the kind of focus that is required for it to make meaningful impact. In the same way that those programs required a critique to outline the limits of their capacities, precision psychiatry requires an understanding and delineation of its limits. So I understand that the, you know, whenever you mention these philosophers' names, it's easy to look out and watch some eyes glaze over. I hope that I was at least to some extent able to clarify the philosophical approach of delineating the limits of our, definitions of, say, a research program like artificial intelligence in the 70s as Dreyfus was able to critique and draw the outlines in order for those programs to ultimately be successful in their approach. And this is the tradition I'm adopting when trying to delineate and critique precision as applied to the therapeutics in psychiatry. That by limiting our notion of what precision psychiatry is able to do, where it should be applied and where it shouldn't, we actually expand the possibilities and the very real possibilities of its application. Of course, I think it's also important to remind ourselves what that opens up. Once we do have those limits, we can be more open to the very human capacities of empathy and language that are already providing us with incredibly precise diagnostic and therapeutic validity. I'd like to thank you all very much and also hear from you to gain from your perspective, your disagreements, your reservations, any points I can clarify, particularly about the philosophy. I am very grateful to have finished this presentation. I think philosophy is absolutely necessary to have it for us as mental health workers or psychiatrists. And I think the problem that precision psychiatry or DSM and all the psychiatry that's scientifically or most of all scientifically based and precision medicine and psychiatry as an extreme of that has to do with determinism. And I think as psychiatrists we have to make the question, not answer it, we have to have always the question about liberty. And what does that mean? I mean we can speak here about liberty and we could have different understandings of that. And I think what I'm not comfortable when I hear most of the presentations I've heard here is that liberty is not thought and it's like human beings could finally be put, I don't know, it doesn't matter how much data, but in some amount of data. And I think that answers the question of liberty as not being or a conditioned liberty. And there's one philosopher that goes, in my belief, farther from Heidegger, that's Levinas, Manuel Levinas. And I think when one thinks, I don't know, psychiatry or mental health or human being with Levinas, infinity appears, what doesn't take form, and the relation with other. And I think it's very interesting to think about even attachment, it's a very biological grounded theory, but rethink it with Levinas and their, well Levinas doesn't, the term liberty is not much of him because it's an autonomous liberty how he thinks it, but it gives the opportunity of still thinking in psychiatry, still, because the biology of human beings is unquestionable, but how taking that, still you can think of a liberty that is not conditioned. And well, my question is, what do you think about liberty in this context? That's amazing, thank you for your comment. It's incredibly rich, this point that you raise. I'm particularly moved by what you mentioned about the, when is it enough, especially when considering data in this way, just because we can gather these billions and billions of bits of data, do we need to do that and do we give up our belief in the abilities and capacities that we have ourselves to make incredibly sophisticated decisions and judgments in the blink of an eye, and should we in every instance replace it with so-called reliable evidence that comes in the form of bits of data? I know I'm not directly answering your question, but that gives me actually some hope, because I hope that we can stay in contact and maybe address this question, this very deep and thoughtful question more thoroughly, and perhaps cite some pages from Levinas as we do. I think implicit in what I'm trying to explain is that we owe a lot to those who came before us. A lot of our present approaches might be so exciting because it seems like we're revolutionizing the field in a really meaningful way, because now we understand that changes in somebody's diction are so predictive of such and such, but we can't throw out the baby with the bathwater, I guess. You know, just because our programs are inadequate, and maybe some of our precise programs are inadequate, doesn't mean that we have to disregard all the progress that we have made in the realm of philosophy, psychology, our understanding of the mind. Thank you for that question, again. I think I was preempted a bit, but first, thank you for a great provocative presentation to end this discussion. I think what I was thinking along the lines of his question was the idea of limits, especially in Kant. In Kant, you have the limit sort of being the transcendental, and that is a very fraught philosophical topic that has been brought up throughout the philosophic history. Again, for Kant, it was sort of beyond the limits of sense data, and it becomes sort of a paradox. How do we know what that is? So in my opinion, maybe some of the core questions in precision medicine is around this central idea of the confusion around the limit, and the reason people are taking the gung-ho approach is they don't know what the limits of the pushing can be, because it's inherently fuzzy. Although I do sort of agree with you in the spirit of Dreyfus that there is some limit out there, but I guess my question to you, how do we get around that kind of paradox around limits? Yeah, thank you, Dr. Shum. I think that's a question that, one, remains to be answered, but also I'd like to pose it to the audience as well. Is it that, and maybe I'll reframe that question, as even if there are no clear boundaries or limits, is there utility in trying to define those limits for the sake of our research programs, or do we keep those research programs kind of boundless? On the one hand, it seems like the optimistic, hopeful approach to leave them boundless because we want them to develop in any direction possible. On the other hand, I think that's a bit of an immature perspective, because you don't do that when you're raising a child, you don't leave them with infinite possibilities because they might not be able to grow in the correct direction, or I'm thinking of this movement in French literature. Maybe somebody in the audience can help me, remind me of the name, in the mid-20th century where authors would work on writing entire essays and even a novel was written without the letter E, for instance, and by imposing those limitations, it induced creativity. So this is, I think you're bringing up a key point and a key motivation for this talk to begin with, is by imposing limits on our research programs, we actually can induce creativity, and I think especially here where funding is so important, we've tended, especially in the field of precision psychiatry, toward the research programs that aren't imposing any kind of limitations, and seeing it as, it's why I call it the gung-ho approach, because it's boundless and it's the new frontier, it's the gold rush. So great question, yeah. I think, to try to answer that, I think even if there aren't clear boundaries, it still helps to impose artificial boundaries, like not using the letter E in that novel to induce some creativity. French novelist George Perrick, I just Googled it. Thank you, doctor. It looks like there is. Well, I'm humbled. Remarkable talk from this, well, I won't. Psychiatrists are also intuitive, not sure what neurological pathways are responsible for that. That's interesting. Thank you, Margaret Roberts, for the very kind words. Thank you all. I am humbled and honored.

precision psychiatry

existential phenomenology

technological advancements

Immanuel Kant

precision medicine

individualized treatment

mental illness

neuroscience

philosophical critique

human empathy

clinical practices