The Next Big Breakthrough

Interactive Transcript

spk_0 Welcome to the Insights on Psychiatry Podcast. I'm excited to introduce our guest today, Dr.

spk_0 Charlie Marmer, who is the chair of our psychiatry department at NYU Grosswood School of Medicine

spk_0 and NYU Langone Health. Dr. Marmer, thank you so much for being with us today.

spk_0 Dr. Gowler, it's a great pleasure to be with you. I especially have fun working with you on our

spk_0 shared innovative research projects to advance precision psychiatry, so perhaps we can talk about

spk_0 that too. Yeah, absolutely. And what's really interesting is that we were able to talk two years

spk_0 ago about precision medicine, especially in psychiatry. And can you feel us in, what have

spk_0 been the advances in the last two years in precision psychiatry? And are you happy with the pace at

spk_0 which things are moving? I would say the major advance, separate from specific studies,

spk_0 which aim to try to personalize treatment rather than to apply a one-size-fits-all. Or I would say

spk_0 to go beyond the traditional way in which we've tried to provide treatment guidelines. So we have

spk_0 over the last 30 years or longer been evolving specific guidelines for the evidence-based

spk_0 practice for the treatment of stress, anxiety, depression, psychosis, addiction, etc. And if you

spk_0 look at the guidelines that have been published by the American Psychiatric Association, the American

spk_0 Psychological Association, the World Health Organization, and many others, they will generally say

spk_0 it is recommended for a patient with a new onset of depression to start with the first line

spk_0 treatments. If they're successful, great, if not, go to the second line, then go to the third line,

spk_0 and then if the patients are still very difficult and refractory to treatment, use specialized

spk_0 approaches and special assessments and consultations for the very complex cases. That has been

spk_0 helpful to some extent. It's certainly an advance over one-size-fits-all treatment, but it's not

spk_0 precision medicine in the way that, let's say cancer is treated now. And the major

spk_0 advance, I think, has been a growing recognition in the field of psychiatry of the urgent need to

spk_0 develop precision medicine so that if I refer you a patient with depression, you'll be thinking

spk_0 about that patient not in terms of first and second and third line treatments, but who is the

spk_0 person I'm working with today? What are their unique biological features, age, gender, ethnicity,

spk_0 other features? What are their unique psychological features, their conflicts? What are their unique

spk_0 social and cultural features? Are they highly educated from stable families? Are they from

spk_0 really were disadvantaged in many ways? Didn't have good healthcare growing up and maybe not

spk_0 a great education? They may all present a younger woman, let's say, South Asian woman from a highly

spk_0 educated, prosperous family, presents with sadness, loss of interest, difficulty sleeping,

spk_0 concentration problems, feelings of despair and hopelessness, an older Caucasian male who's had a

spk_0 history of head trauma and comes from a violent neighborhood and has from a poor background,

spk_0 hasn't had great education or the privilege of excellent healthcare, and may also have the same

spk_0 symptoms, but clearly they're very, very different. We talk about the biopsychosocial model,

spk_0 but we're now beginning to ask the question, how are the unique biological, psychological,

spk_0 social and cultural characteristics of my patient that I'm working with today and how do I adjust

spk_0 the treatment? So there is much more buy-in to that. There's progress in some studies where

spk_0 beginning to find certain clinical features, cognitive features, and even genomic and neurosurgery

spk_0 features will help us say which treatment for which person at what time, but the biggest revolution

spk_0 is the understanding that we have to move in psychiatry to where cancer has moved so successful.

spk_0 And almost moving away from trial and error and moving more toward gathering all the data early on

spk_0 and then having a more precise treatment plan for that patient, moving forward and not just,

spk_0 hey, does this work for you or not? And then you have this pile or this grouping of treatment

spk_0 refractory patients who haven't benefited and I think precision medicine is saying we want to make

spk_0 sure that we're not having this group of treatment refractory patients that we don't know what to do

spk_0 with just because they didn't benefit from the first, second, third line treatment. Exactly.

spk_0 And I would say if we go back 30, 40, 50 years into the history of the treatment of psychiatric

spk_0 disorders, psychological disorders, not only was there trial and error approach, there was

spk_0 something even more problematic, which there was a school-based approach. I remember really on

spk_0 as an educator asking my a group of residents, when I was maybe junior faculty and I had a group

spk_0 of wonderful residents at the time I was an assistant professor at the University of California

spk_0 San Francisco UCSF, one of the great medical schools and I asked the residents I was teaching,

spk_0 I presented a case to them and it was a case of a patient, let's say, with a third occurrence

spk_0 of a major depressive illness. And I asked them each to present what they thought would be the best

spk_0 care plan for that patient. And the response actually was not to start with one common treatment,

spk_0 it was completely school-based. One resident was very interested in psychoanalytic psychotherapy

spk_0 and they started with a psychoanalytic formulation of another, was very interested in neuropharmacology

spk_0 and psychopharmacology. They started with a medication approach. Another was a behaviorally interested

spk_0 person. They started with a cognitive behavior therapy and a fourth was becoming interested in

spk_0 some other approach. And fundamentally, the treatment that they would have given that patient,

spk_0 if referred to them, was actually not based on the specific needs of the patient. It was based on

spk_0 the interest, passion, and bias, so to speak, of the clinician depending on the school. So,

spk_0 if they, in practice of a patient with depression at that time was referred with depression to a

spk_0 psychoanalyst, they would get psychoanalysis whether they had bipolar depression or not. If they

spk_0 were referred to a psychopharmacologist, they would get psychopharmacology whether or not the origins

spk_0 of their problems was in childhood trauma. If they were referred to someone with another point of

spk_0 view, they would get that approach. So, and I was thinking to myself as an assistant professor

spk_0 at the time, imagine if I was referring a patient with atrial fibrillation to a cardiologist.

spk_0 And the treatment for that arrhythmia was determined by the cardiologist preferred school of training

spk_0 as opposed to the basic needs of that patient. Yeah. And I think what we are saying is, if the more

spk_0 we can understand kind of the, all of the factors, then we can have a more precise treatment plan.

spk_0 And I think this is also really important. You think of how many people have comorbid conditions,

spk_0 then you add another layer of maybe that trial and error because we're not looking at kind of

spk_0 treating conditions maybe in concert. We have to look at what are the presenting problems?

spk_0 We have to look at all of the complexity of the medical illnesses, neurological illnesses.

spk_0 But we have to look also at education, culture. We have to look at life experience. We have to look

spk_0 at also biology, including sex. For example, there are some developing data to suggest that if a man

spk_0 in their mid-30s and a woman in their mid-30s both present with relatively similar depression

spk_0 symptoms and they are suitable for initial treatment with medication that on average,

spk_0 the woman will do better with a selective serotonin agent anytime from men or ketamine

spk_0 opause. And the man may be do better with some mixed receptor agents, drugs like wild butyimbium,

spk_0 bupropreon, ventilifaxine, pristectin, others because of the difference in the biology. And

spk_0 interestingly, after menopause, a woman who may have done very well with a selective serotonin drug

spk_0 may do less well and may need a drug more like the 35-year-old male may need unless they're also on

spk_0 estrogen replacement therapy after menopause. So just to simple forget about all the great complexity

spk_0 of culture and genetics and family background and brain imaging findings, just the simple age

spk_0 and sex may be profoundly important. And it makes so much sense. I guess the bigger question is how

spk_0 are we getting closer to that? And what are you excited about that's actually happening,

spk_0 getting us closer to kind of taking all this data and understanding the psychiatric complexities

spk_0 in an individual? Two ways, two things have happened which are very, very favorable.

spk_0 One is there's a growing consensus among clinicians, students, and researchers that this is

spk_0 essential to move our field together. The second thing is that there's a growing consensus about

spk_0 the agencies that provide the funding for the research to advance the NIH, DOD, VA, DARPA,

spk_0 and other agencies that fund the majority of psychiatric and psychological research.

spk_0 They are also becoming very, very interested in initiating requests for applications for precision

spk_0 psychiatry proposals. And the final thing is, which is very interesting, is our field is

spk_0 maturing to give us the tools we need. We're leaving aside simpler things like age and

spk_0 sex and education and cultural background, which we've been able to assess for a long time,

spk_0 of course. We now have sophisticated human genomics to study the genome in psychiatric illness.

spk_0 So more and more clinical trials now include collecting DNA and RNA so that we can study the

spk_0 genomic contributions. We also have much more sophisticated non-invasive brain imaging,

spk_0 and we have a whole series of other fascinating ways to try to understand the neurobiology of

spk_0 psychiatric illness. For example, there are brain banks of people who've been visionary and

spk_0 have said at the time they pass away, they'll contribute their brain because they've struggled

spk_0 life long history of bipolar disorder or PTSD or schizophrenia or some other alcoholism.

spk_0 And those studies, those post-mortem studies allow, of course, for a very detailed interrogation

spk_0 of brain structure and functioning, those become published in part of a public databases,

spk_0 and then researchers such as myself and others interested in precision measure can use those

spk_0 as reference samples to say, oh, so these specific genomic pathways may be disturbed differently

spk_0 in these disorders. Now I have the DNA and RNA of my patients and my trials. I can be informed

spk_0 by the post-mortem reference samples to know where to look in the genome in my patients.

spk_0 There are many other ideas. We go along blood. We're starting to learn about exosomes which are

spk_0 actually coming directly from the brain and how genomic cargo on them. We are doing studies,

spk_0 we're planning to do some collaboration at NYU with colleagues at the Mayo Clinic,

spk_0 or in which we're harvesting live cells in our clinical trials. And those cells can be,

spk_0 they will be blood cells, but they can be programmed backwards to stem cells and then forward to

spk_0 neurons. And we can even grow brain organoid sort of brains in a dish. And we can then study those

spk_0 brains. We can expose those brains to alcohol. We can expose them to drug treatments. So we're

spk_0 beginning to triangulate all of those things with animal models. And I believe we'll be able to

spk_0 advance our field and become precise. The goal is to do in psychiatry what is now done in

spk_0 breast cancer. Yeah, you remember how breast cancer was treated in the 50s? Do you have a sense of

spk_0 how if someone presented with breast cancer, how it was treated then? One size fits all. Everyone

spk_0 got some combination of surgery, radiation, and chemotherapy. It was not specific to the person

spk_0 or their general tumor. And it was often associated with great side effects and often not great

spk_0 outcomes. But we didn't know beyond the fact we knew that radiation could help some women with

spk_0 breast cancer. We knew that chemotherapy could help and we knew we had to remove the tumors with

spk_0 surgery where possible. But we didn't know in precisely for a patient has breast cancer now.

spk_0 Obviously we biopsy the tumor. We find his genomic features and we begin with

spk_0 treatments that are highly specific to that form of cancer. As a simple example, estrogen receptors are

spk_0 studied, progesterone receptors are studied, and a set of receptors called HER2 receptors are

spk_0 studied. And if the patient is estrogen negative, progesterone negative, and HER2 positive,

spk_0 they're likely to be started with the drug Horseptin, which is a monoclonal antibody specific to

spk_0 their tumor does not attack other parts of their body, does not attack healthy cells in their

spk_0 gut or their brain or elsewhere. And think of the enormous advance. This is a treatment specific

spk_0 to their form of cancer at which targets the vulnerability of those cancerous cells and does not

spk_0 attack the entire body of living cells. And it seems like psychiatry has not been able to have

spk_0 those advances in part because the animal models has been a possibility. But it seems like with

spk_0 technology and all these opportunities to gather more data in these larger systems or you said even

spk_0 after their death, it might help us to kind of make more of these precision medicine models.

spk_0 It's a wonderful observation. I think there are two major reasons that have limited

spk_0 three that have limited the advance of precision psychiatry. The first dose has been a failure

spk_0 of imagination to understand that we could do that in our field. That's changing. The second is we

spk_0 have animal models, but many of them are not very good representations of the illnesses. There

spk_0 are, so to speak, animal models for psychosis, but rodents don't have delusions. So they're very,

spk_0 very difficult. You have to do an animal model of let's say a circuit disturbance in the

spk_0 hippocampus, but not the illness itself. We have several diseases that are quite

spk_0 amenable to animal disease modeling. The best are trauma because the same circuits in rodents

spk_0 are altered when they're exposed to predator threat as are humans when they're exposed to combat.

spk_0 So that's very helpful. And perhaps the very best animal models are alcohol and drug abuse.

spk_0 Because for example, rodents will become addicted to cocaine. They will become addicted to alcohol

spk_0 and to stimulate other stimulant drugs. And there you can then understand the animal models

spk_0 are very close to what we need to do in humans. So, but the final thing is that has held us back

spk_0 up till now is in precision medicine and all other areas of medicine, we biopsy the organ of disease,

spk_0 breast cancer, prostate cancer. We have access to arrhythmias. We have access to the tissues

spk_0 of disease. In the case of human neuropsychiatric illness, except under unusual circumstances,

spk_0 we don't biopsy the living brain of the patient. So, what we're trying to do is approximate

spk_0 what is happening in the brain by looking very far downstream. Theodomisomy of that story about

spk_0 the person who lost their keys at night and they're looking under the lampost. But they didn't

spk_0 lose their keys. So they're asked why you're looking under the lampost? Well, that's where the light is.

spk_0 But the keys are not there. So the problem for us is when we study DNA and RNA in peripheral blood,

spk_0 the expression of DNA in peripheral blood cells is not necessarily closely related at all to

spk_0 single cell gene expression in specific neurons and specific areas of the brain in a given

spk_0 specific psychiatric disease. So the question is, can we find a proxy for the brain biopsy?

spk_0 We call them just for ease of communication, a liquid biopsy. Is there something in the blood

spk_0 that actually reflects what's going on in the brain? We're very interested in exosomes for that

spk_0 reason because they're in peripheral blood. They can be isolated. They're vesicles that carry a

spk_0 genomic cargo and they have some genomic features on them or markers that would tell us more or

spk_0 less where they're from. Are they from the brain or the liver or the kidney? If they're from the

spk_0 brain, where in the brain? Are they from the hippocampus, the amygdala or the basal ganglia or the frontal

spk_0 cortex, PFC? And maybe even more specifically among those that come from the amygdala, are they from

spk_0 the central nucleus of the amygdala or another nucleus in the amygdala? So that's interesting because

spk_0 in a way, those features are then much closer to what may be dysregulated in the brain. We also

spk_0 like the idea of these postmortem reference samples because they give us clues of where to look

spk_0 because we actually have the genomic features from specific brain cells and brain regions

spk_0 and we like the brain organoids also because they replicate actual brain structures. There may be

spk_0 other strategies, but even you ask me, what's held us back? A lack of understanding that this is

spk_0 critical, that's changing. A failure of animal models to closely replicate human brain diseases

spk_0 in psychiatry particularly diseases with cognitive disturbances such as in psychosis. And then

spk_0 a lack of ability to actually biopsy the organoidylists. We are the only field, psychology and

spk_0 psychiatry are the only field in medicine that does not routinely biopsy the organoidylness.

spk_0 Yeah, it sounds like what you're saying is that's brain scans are not the answer in kind of

spk_0 precision medicine necessarily. We need kind of scalable interventions or scalable ways to assess

spk_0 looking at, you know, like you said, these records are gathering data in these large scale kind

spk_0 of medical records will be. I would say brain scans are becoming more sophisticated, pet scans,

spk_0 MRI scans, other kinds of scans, spec scans. We have a lot. We're making progress. They provide

spk_0 useful information. I would say studying DNA and RNA in peripheral blood is useful. It provides

spk_0 information, but it's not going to be at the level of specificity of actually, for example,

spk_0 you and I have a shared deep interest in post-traumatic stress disorder. We have some pretty good ideas

spk_0 from animal models which circuits are involved. We know that we know the amygdala is involved,

spk_0 we know the hippocampus is involved, we know the insula is involved, and we know the prefrontal cortex

spk_0 is involved among other areas. But when we have, you and I are collaborating together in the clinic

spk_0 on a patient who's not responding well to treatment for complex trauma, we do not biopsy. They're

spk_0 amygdala to find out what's different about this patient. That's the main limitation we have. That's

spk_0 why we are much less advanced than the treatment of prostate and breast cancer.

spk_0 And the hope is that we find ways to make it more accessible and precise by looking at some of

spk_0 these records as well. Yeah, alternative models, more accurate sensitive animal models,

spk_0 post-mortem reference samples, exosomes, brain organised, and other things we haven't thought of

spk_0 but the point for our listeners is very straightforward until we can accurately reconstruct

spk_0 what the neuro transmitter and neurosurcut disturbances are in a patient-specific way.

spk_0 We will be somewhat limited in precision myths. And do you think that would be ultimately what do

spk_0 you hope that we are able to get that information or do you hope that in combination with other

spk_0 factors, I know you're into facial action coding and biovoice markers kind of using other

spk_0 kind of pieces of data to put it all together into a larger model to get more precise if we can't

spk_0 do these biopsies. Well, so great point. So in addition to advances in genomic psychiatry

spk_0 and imaging psychiatry, you and I and others are working together to advance digital psychiatry.

spk_0 The advantage of digital psychiatry of studying voice quality of studying the structure of language

spk_0 with large language models using AI, studying facial expression using facial action

spk_0 coding. I was very influenced by this, interested in this because in my years at UCSF,

spk_0 I got to know and had the privilege of knowing and becoming friendly with and asking for

spk_0 research advice, one of my senior mentors, Paul Eckman actually developed the facial action

spk_0 coding system. He was Paul's a remarkable person. He actually came to the conclusion that there

spk_0 was a limited number of unique human facial expressions. He mapped out the muscles that were involved

spk_0 creating those facial expressions and then he went to multiple different cultures, including

spk_0 South Pacific Island cultures, Asian cultures, many different cultures and found that even though

spk_0 cultural differences were great, even though language was different, that actually the same

spk_0 range or palette of human emotions, anger, sadness, shame, etc. were expressed in all these

spk_0 cultures in the same muscle groups, which is a fantastic discovery. So Paul really inspired me

spk_0 to do this work, but we can also use cell phones, which give enormous amount of information.

spk_0 We know that when people are depressed, they often, their digital location is different,

spk_0 they do less things, they stay home more, they retreat into bad, they avoid social situations,

spk_0 all of that's very interesting and valuable. And the final area, not the final, but another

spk_0 major area which is going to advance precision psychiatry is computational modeling.

spk_0 The ability to use advanced AI and form machine learning and very fast computers. I'm beginning

spk_0 a collaboration now which I hope will be radically interesting. I have a colleague, renowned quantum

spk_0 physicist, Dr. Javit Shabani at NYU, who is one of the world's leaders in developing quantum

spk_0 computing. His laboratory at NYU is developing next generation, Cubots which are like the chips for

spk_0 quantum computing, quantum computing, even in the kind of rough and inaccurate proof of concept

spk_0 models can handle vast amount of information and process it in lightning speed time. So we're going

spk_0 to collaborate together, Dr. Shabani and I on a project in precision psychiatry. In this particular

spk_0 study, it happens to be a clinical trial that was completed by NI AAA, 346 subjects. We have DNA

spk_0 and RNA on every one of them before treatment. They were treated with GABA pen, an anti-convulsive

spk_0 drug which reduces alcohol craving. And we also collected RNA after treatment because it changes

spk_0 with treatment. Okay, so I will ask you a question to be playful. How many unique variables do you

spk_0 think we have on each of these 346 participants, patients, that we could model to try to understand

spk_0 why some people respond well and others don't respond well to GABA pen for AUD, for alcohol use.

spk_0 Take a guess how many uniquely different variables are in the database on each of these patients?

spk_0 200. How many? 200. Okay, how about a little higher? Okay, 2000. How about a little higher?

spk_0 5,000. 22 million. We have 22 million unique features because in designing this study,

spk_0 I had identified, I am my team, other colleagues, had identified 1,300 genes in the human genome

spk_0 that we thought might be relevant for understanding how people respond or fail to respond or get

spk_0 side effects or don't get side effects to GABA pen for the treatment of alcohol use.

spk_0 And I asked the director of our wonderful NYU Human Genomes Genomic Center, Dr. Adriana Hege,

spk_0 a great colleague of ours, and part of this study, to estimate what the cost would be

spk_0 to sequence those specific genes and their transcripts. And she gave me a price that was pretty

spk_0 high and said, you know, Charlie, we can do something much more interesting because we have now the

spk_0 sequencing sophistication to sequence the entire human genome, 22 million features, for less money

spk_0 than the targeted sequencing of those 1,300 genes. And of course, you'll get those genes in

spk_0 their transcripts, but you'll get all 22,000 coding genes in their transcripts. And you will also

spk_0 get all of the so-called dark matter in the human genome, which plays an important regulatory role,

spk_0 even though those genes don't code for proteins and it directly affects cell function. They

spk_0 promote and remodel in transcription, factor regulation, post-transcriptional changes of the

spk_0 structure of transcripts, of proteins, etc. So we have it. And we have also, of course,

spk_0 clinical feature is we have other things, but the big data is the genome itself, right? So we have

spk_0 now we have 346 people with more than 22 million features. Now what were you taught in your statistics

spk_0 courses about how many subjects you needed for the number of variables? In other words, in

spk_0 traditional statistics, you're limited by sample size and you can, you need a certain number of

spk_0 subjects to variable ratio, right? And you remember what you were taught about that in conventional

spk_0 statistics? It's about, you know, you need maybe a 10 to 1 ratio or something.

spk_0 In the world of AI, there's not actually a limit on the number of features you're going to have

spk_0 per subject. There's a limit on the computational resources needed to manage that information and

spk_0 make sense of it. And we think that quantum computing will help solve that problem. So that's

spk_0 the next thing. But even using NYU Langone Medical Center's high capacity imaging, we can do pretty

spk_0 well. But right now when we run a machine learning model to say which genetic features or which

spk_0 imaging features or which clinical features or cognitive features, predict who will and will not

spk_0 be a likely responder to a trubanant, let's say Gabba Penton for alcohol use disorder, it can take

spk_0 weeks to run those models and these quantum computers can run them in a fraction of a second.

spk_0 And can make sense of like you said, and the other thing about quantum computing is it probably has

spk_0 the capacity to create a much more sophisticated map of the interrelationship of these factors

spk_0 than conventional computing. So it's not just light years faster, it's also going to be more

spk_0 precise. And is the goal you think to get even down to go to the complex to get more simple,

spk_0 because it's so many pieces of information and it might be overfitting the model or the data,

spk_0 is the goal then to kind of know what is actually most important and then we can kind of pull that

spk_0 out. The goal is to do some targeted hypothesis testing with a smaller number of features.

spk_0 Then do a very broad exploratory model with all the features and then reduce those to the most

spk_0 important features. Part of the output from AI models is a variable importance plot, which will

spk_0 read out among these 10,000, 100,000 million, 10,000, 20 million features or more, which five are

spk_0 ones carrying the signal. And then we can study those and we can ask which medications or

spk_0 psychotherapy or TMS or remodulation is likely to move those features. Yeah, so going from the

spk_0 complex to the more simple. And just in our final question here, looking ahead, what are you most

spk_0 excited to see happen in precision medicine in the next decade? I think we're actually going to do

spk_0 two dramatically interesting things. The first is we're going to take psychiatric illnesses

spk_0 which are not unitary, they're heterogeneous. For example, we already know that there's six or

spk_0 seven or more forms of depression. There's bipolar and unipolar. There's depression which involves

spk_0 psychotic symptoms or does not involve psychotic symptoms. There's typical and atypical depression.

spk_0 There's others as well. Okay, so we know that depression has multiple subtypes. We suspect that

spk_0 trauma probably does. We know there's PTSD that has prominent cognitive impairment. We know

spk_0 that in simple, those who have a suffer enormous trauma exposure in early development have a different

spk_0 set of problems than a high functioning person who gets survived a traffic accident.

spk_0 We know that there is PTSD with prominent association symptoms and not. So there's not one PTSD.

spk_0 There's probably a half a dozen major types of PTSD. I think we'll be able to confirm what they are

spk_0 and confirm them with biological and psychosocial features. The second thing is we'll be able to do

spk_0 these precision medicine treatment models that say who's likely to respond to which treatment

spk_0 for which subtype? Yeah, which will totally change the way that we're looking at psychiatric illness.

spk_0 And I think even starting with the diagnostics we're already starting to realize like you said

spk_0 there's a spectrum and there's all these different types. So the better that we can diagnose and then

spk_0 treat patients will lead to better outcomes. So a woman with a complex PTSD with associated

spk_0 features whose six years old is not going to be treated the same as a man with a more simple PTSD

spk_0 and a man who came from a very difficult background and had three tours of duty in the military

spk_0 or a woman who was in the military and has a very complex PTSD will not be treated the same

spk_0 as someone who was walking down the street as one of my patients was and tragically as they were

spk_0 walking down the street in San Francisco at the time I was doing the study. Someone jumped to

spk_0 their death from a building from high above and they witnessed this horrible event and the person

spk_0 had gruesome injuries of course and it was completely horrifying to them but they were very high

spk_0 functioning before they went through a period of nightmares flashbacks and startle reactions and

spk_0 but they responded to a you know short course of treatment and were very well obviously that's

spk_0 a different kind of PTSD than someone who was sexually assaulted and abused during their childhood

spk_0 and neglected and has suffered enormously during their lifetime. So yeah I think it's going to

spk_0 give a lot of hope to patients and also I think to doctors and clinicians being able to

spk_0 have more confidence in the treatments that they're actually disseminating and implementing

spk_0 with their patients. If a patient has a solitary nodule of breast cancer which has not escaped

spk_0 the duct they with certain genetic features they're going to be treated they are currently treated

spk_0 very differently obviously than someone who has a very aggressive metastatic breast cancer

spk_0 with other genomic features and so the illnesses are treated as precisely as possible

spk_0 for their stage their aggression their genetic features and other factors we want to be able to

spk_0 treat depression that way. Let me if we have time I'd like to conclude with a very interesting

spk_0 and dramatic example of precision psychiatry in depression. Around 2015 our neurology psychiatry

spk_0 program which we have at NYU where we have experts trained in both neurology and psychiatry

spk_0 their board certified neurologists and psychiatrists were asked to consult and this was on the

spk_0 in the department of neurology initially on a patient who had had roughly 20 years of completely

spk_0 failed treatment for depression. So let's say for the majority of their adult life they were

spk_0 depressed miserable very difficult to work very difficult to maintain love relations and family

spk_0 relations and enormous personal suffering that patient had been treated with all of the evidence-based

spk_0 treatments psychotherapies for PTSD, psychodynamic, cognitive behavioral others that patient had been

spk_0 treated with virtually every type of medication treatment for depression SSRIs non SSRIs other

spk_0 antidepressants mood stabilizing drugs, neuroleptic drugs and others completely failed.

spk_0 Not remembering right now if they had neuromodulation treatments but they definitely had ECT

spk_0 and it complete failure. The patient was thought to possibly have a rare more rare neurological

spk_0 disorder and it was justified to perform a brain biopsy to rule that out. So they had a small needle

spk_0 brain biopsy done under neurosurgical conditions and needle was presented through the orbit and into

spk_0 a silent part of the prefrontal cortex relatively safe thing to do the main complications infection

spk_0 but if it's done under neurosurgical conditions it's safe to do and then the tissue was taken

spk_0 and sent to a neuropathologist and the neuropathology report came back massive invasion of inflammatory

spk_0 cells quite unexpected and the patient was treated with a novel anti-inflammatory drug which crosses

spk_0 the blood brain barrier and for the first time in 20 years had significant relief from their depression.

spk_0 A single biopsy with a single confirmation. We can't do that routinely

spk_0 but I mentioned that case as a proof of concept as an illustration of what could be done

spk_0 if we knew what was actually occurring in the brain. Yeah and I think like you're saying even with

spk_0 that example is kind of the theme of this that going from the complex to the simple and maybe we

spk_0 understand more about the brain when we kind of understand all that maybe it does come down to

spk_0 you know one single biopsy like you said or like in what you're talking about it might come down

spk_0 to just understanding a few different factors and how they integrate together to present for this

spk_0 patient. Correct and if we knew that it was invasion of inflammatory cells in the brain that

spk_0 were causing the depression we might then be able to look in the blood or somewhere else or in

spk_0 brain imaging or in the genetic background to find a marker that was associated with that even

spk_0 though we weren't routinely biopsy. So let me give you another example we talked about it on

spk_0 an earlier drug. Casted it in the 1800s a common reason or perhaps the commonest reason why patients

spk_0 had long term hospitalization in state mental hospitals psychiatric hospitals in America

spk_0 including in New York was turned out to be the neurological complications of syphilis,

spk_0 neuro syphilis and so that was a more common reason to spend end up spending years, decades or

spk_0 your life in a state mental hospital then was let's say schizophrenia. When the the infectious

spk_0 basis of neural syphilis was discovered with the spirochet and treatments were developed of course

spk_0 now that disorder is an infectious disorder it's no longer considered a psychiatric disorder and it's

spk_0 treated and we don't have patients with neuro syphilis in psychiatric institutes if we really understood

spk_0 and that's an example of going from the complex and the treatment completely treatment on

spk_0 response of condition requiring long term psychiatric hospitalization to a clear simple idea of what

spk_0 is disturbed a specific infection of the brain by a specific organism with a specific treatment

spk_0 nothing could be more clear than that right so there is going from the complex and the enormous

spk_0 pain and suffering and a sense of hopelessness to an understanding a treatment and a cure.

spk_0 Well it's exciting for I think patients for clinicians and for researchers and I think it'll be great

spk_0 to see where it continues to grow thank you so much for talking with me. It was a pleasure talking to you

spk_0 and it's an even greater pleasure working and collaborating with you. Wonderful. Well thank you to

spk_0 all of our viewers and listeners and if you liked this episode please rate and subscribe to our

spk_0 podcast where you listen or watch our podcast. Thank you so much from all of us here at NYU Langone

spk_0 Health and the NYU's Grossman School of Medicine.

The Next Big Breakthrough

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