Feeding the Mind: Metabolism in Psychiatry with David T. Liebers, MD, MPhil, MPP

Dr. David T. Liebers – LinkedIn

https://www.linkedin.com/in/david-liebers-7b9706169/

Metabolic Mind

https://www.metabolicmind.org/ 

Patient and clinician resource on ketogenic and metabolic therapies for mental illness, recommended by Dr. Liebers in this episode.

Dr. David T. Liebers is a research assistant professor of psychiatry at NYU Grossman School of Medicine and a research psychiatrist at the Nathan Kline Institute, studying SGLT2 inhibitors in depression, cognition, and dementia risk. He trained as a historian and philosopher of science at Cambridge before his MD and MPP at Harvard. His work has been recognized with the American Society of Clinical Psychopharmacology’s Nina Schooler Early Career Research and New Investigator Awards, plus an NIH Loan Repayment Award.

Ben Everett, PhD, is the creator and host of The JCP Podcast, a series that brings together leading voices in psychiatry to explore the latest research and its clinical implications. Everett earned his PhD in Biochemistry with an emphasis in Neuroscience from the University of Tennessee Health Science Center. Over a two-decade career spanning academia, publishing, and the pharmaceutical industry, he has helped launch more than a dozen new treatments across psychiatry, neurology, and cardiometabolic medicine. His current work focuses on translating complex scientific advances into accessible, evidence-based insights that inform clinical practice and foster meaningful dialogue among mental health professionals.

This transcript has been auto-generated and may contain errors. Please refer to the original audio recording for full accuracy.

00:00 – Introduction: Building on the GLP-1 Conversation

Dr. Ben Everett: Hello, and welcome to the “JCP” podcast. I’m your host, Dr. Ben Everett. In each episode, we sit down with leading clinicians, researchers, and educators to explore the science shaping mental health care today with a focus on the insights that matter most in clinical practice. A few episodes ago, we had a fascinating conversation with Dr. Roger McIntyre about GLP-1 receptor agonist in psychiatry. This is a drug class that was originally developed for diabetes and obesity that has become a major part of the conversation around mood disorders, cognition, and addiction. One of the big takeaways from that discussion was that GLP-1s may just be the beginning of a much broader shift in how we think about psychiatric illness. Rather than viewing metabolism as simply something to manage in psychiatry clinics because of medication side effects, we’re increasingly recognizing that the brain’s metabolic and bioenergetic state may itself represent an important therapeutic target. Today’s episode picks up where that conversation left off, but broadens the lens beyond GLP-1s. My guest today is Dr. David Liebers. Dr. Liebers has taken a unique path into this field. Before his medical training, he trained as a historian and philosopher of science at Cambridge University under Tim Lewens before earning both his MD and a master’s in public policy at Harvard. Today, he’s a research assistant professor of psychiatry at the NYU Grossman School of Medicine and a research psychiatrist at the Nathan Kline Institute, where he studies the potential role of SGLT2 inhibitors in depression, cognition, and dementia risk among people with psychiatric disorders. Similar to the GLP-1s, SGLT2 inhibitors were initially developed for blood sugar control but have subsequently been granted indications for improving outcomes in heart failure and chronic kidney disease in addition to the antidiabetic effect. Dr. Liebers’ work has been recognized by both the American Society of Clinical Psychopharmacology’s Nina Schooler Early Career Research Award and its New Investigator Award, and he currently holds an NIH Loan Repayment Award supporting his clinical research. Dr. Liebers, welcome to the JCP podcast. I’m especially excited for today’s conversation because it sits right at the intersection of evolutionary biology, nutritional biochemistry, and psychiatry. I found the confluence of these disparate areas fascinating for years and have a feeling we’re gonna connect on a lot of dots that our listeners will find both surprising and clinically relevant.

Dr. David Liebers: Thank you so much for having me on, Dr. Everett.

02:30 – An Unconventional Path to Metabolic Psychiatry

Dr. Ben Everett: Oh, great. All right, so we kind of start with, with a little icebreaker to, to transition into this. So you really do have an unusual academic path for someone doing bench-to-bedside metabolic psychiatry research. Biology and history as an undergraduate at Rochester, Cambridge Masters in Philosophy, the history of philosophy of science, and then Harvard for your MD and MPP, and only after all of that, a research career built around a specific class of antidiabetic drugs. So how did those pieces like all fit together for you?

Dr. David Liebers: So I think it’s an open question whether they have. We’ll call it a work in progress. But to answer your question, I think I need to begin during my undergraduate training when I received excellent mentorship, first from evolutionary biologist, Allen Orr, who is a leader evolutionary genetics and specifically has probably contributed the most to the question of how one species splits into two from a genetic standpoint. At the same time he also writes regularly for The New York Review of Books and for New Yorker. So it left a deep impression on me, somebody who was able to stake out of scientific ground and at the same time con-contextualize it and disseminate it to a larger audience. The second mentor I had as an undergrad was Ted Brown, historian of science, who introduced me to Freud during his first lecture in his Intro to History of Science class, made the claim which– the bold claim right at the outset that the three greatest discoveries of all time were Newton’s calculus Einstein’s theory of relativity, and Freud’s discovery of the unconscious. gave us Freud’s Clark University lectures, and it left a major impression on me. So I went from the University of Rochester to the NIH for what was called the IRTA Fellowship in the Human ge– Genome Research Institute, and about six to nine months in there was just feeling a little restless with bench science was starting to question my initial plan, which was to do a PhD in human genetics, and on the suggestion of a, a close friend of mine, I applied for a program called Humanity in Action, which is a human rights fellowship, one month in Europe to study ethnic conflict in the context of the history of the Second World War. As part of the process, they asked me where I’d like to spend the one month, and I said Paris because I had studied French, and I thought that would be a nice place to spend June. And a few minutes later, I got the email that I’d been accepted, and I’d be sent to Warsaw, Poland I, accepted this fellowship ended my time at NIH, and landed in a completely different world, which I found fascinating. Meeting politicians meeting civil society activists heroes of the solidarity movement in Poland survivors of the Nazi concentration camps and medical experimentation, that was conducted in those places. While I was there in Warsaw remember hearing a, a talk from somebody who ran a foundation doing election monitoring in Southeast Asia in the post-Soviet world and supporting pro-democracy media organizations in totalitarian countries, I was just thinking, “This guy’s work sounds a lot more interesting than micropipetting in Bethesda,” and I went up and asked him for a job he thought I was nuts and said, “Go back to DC,” “It sounds like you have a good setup there.” But I kept on it, and eventually he agreed to welcome me into that organization where we mainly focused on supporting, journalists and journalist journalistic outfits in post-Soviet countries. At the same time, I was teaching English to make some money and stayed an entire year in Poland before heading to the UK for this degree in history and philosophy of science, which that process I had already started while at the NIH, the application process. It’s probably too much to say I am a trained historian of science. It was only the master’s level. But I did study evolutionary psychology, critiques of evolutionary psychology and actually d- did a paper on, Freud’s interest in the transmission genetic information and and features of psychology which come out, I argued, in Totem and Taboo and Moses and Monotheism. So all of that started to percolate in my mind. I was thinking about law school, actually, at the same time as a few friends of mine that had their own experiences in psychiatry suggested to me, “Hey, maybe this is something you could do.” And I started to think as I moved back to Poland after my master’s in history and philosophy o- of science, and started to connect the dots that maybe psychiatry connected my interest in genetics, biology, psychology, politics, the law, in a way that almost nothing else did, and also felt like a place maybe I could do some good and where there was a need. And I started to do my research And found that I had very short amount of time left use my college credits before they expired for medical school purposes, in which case I would have to do the whole post-bacc thing. So I wrote about a hundred emails to different psychiatric genetic researchers in the US to try and transition my way back into medicine and create a story out of all these sort of decisions that I had been making over the last couple of years. And received an offer from Fernando Goes, a psychiatrist at Johns Hopkins, an expert in in the genetics of mood disorders, and applied to medical school, where discovered that there are a lot of interesting areas of medicine. In particular, anesthesiology became something that I thought seriously about till the very end of medical school. Had a wonderful teacher Emery Brown. I think he’s of only very few members of the National Academy of Sciences, Engineering, and Medicine and has made fundamental contributions to how anesthesia affects consciousness, and so was really taken in with that. But psychiatry was always there in the back of my mind, I think I realized at some point that the procedural aspects of anesthesia which really exciting as a medical student, where you? get to really help run cases and do intubations and put IVs in, would probably start to wear off in terms of its excitement over the course of a career. the questions that you got to grapple with in psychiatry were just, at the end of the day, more in line with where my interests were and, and I had my choice.

10:30 – Diet in the Asylum Era: A History of Food as Medicine

Dr. Ben Everett: I’m also at a loss for words. A very interesting background to get where you are now. And it is funny how this happens with so many people, I think that, yeah, it’s– you have a bunch of different interests and trying to figure out how to pull everything together to do this. So it’s interesting about anesthesia too, because, you know, I finished pre-med, and I worked at a teaching hospital in the Department of Anesthesiology. I love anesthesia, especially because of this connection with the unconscious. But I ended up doing the PhD route. So thanks for sharing your background with us. I think it gives me a lot of insight into the research that you’re doing now and tying all these different things together. So let’s really start with the history because I think part of your pitch for this conversation was that, you know, metabolic psychiatry isn’t necessarily a new idea. And it’s not a new idea just dressed up in new language. It has real roots in how the field once thought about the body. So I think it’d be good to start there. So there was an era called the moral treatment era that existed in the early to mid-19th century, and it really put a surprising amount of institutional energy into diet, not just as, you know, basic sustenance, but as a deliberate part of the cure. So there were, you know, individuals like Samuel Woodward at, uh, Worcester State Hospital wrote about, you know, violating what he called the laws of life through diet in almost explicitly moral terms. You know, what do you make of that and that period and sort of the, the, the data, if we can say the data that came out of that period and how it set up sort of where we are now and looking back at that, and then applying these new drugs and the new imaging and all the new technologies that we have to look at, you know, bioenergetics in in the brain,

Dr. David Liebers: I remember listening to congressional testimony from former Senate Majority Leader Bill Frist a couple of years ago when he said something like, “We have now entered the era of food as medicine.” So twenty twenty-four or twenty twenty-five, and I remember thinking that the superintendents of nineteenth century asylums would be very surprised that a doctor was saying that in twenty twenty-four or twenty twenty-five because if you read the annual reports of many of the asylums here in the US, certainly in, in Europe as well people were actually extremely interested in food purpose that it filled for individuals with lunacy. And for different reasons. O-one was that it played a role in moral treatment. So there’s this idea, Pinel in France and Tuke in the the United Kingdom, who thought that a disordered mind could be best treated with order in the environment and order in the sensory experiences, diet, fresh air, exercise, being outdoor in sort of pastoral, agricultural environment, returning to some kind of civilizing force under the paternal care of a superintendent, that these things, represented an ability to bring balance to an unbalanced mind. So that in some ways, food filled this part of bringing moral order to individuals entering asylums. But I think what’s less appreciated even in the historical literature on the history of psychiatry, is many of the leading figures of nineteenth century what we would now call psy-psychiatry, had a real interest in how food and nutrition affected the physiology of the brain. Not all of them, and there was discussion and debate about the importance of it, but for example, we see specific prescriptions of specific diets for specific afflictions. We see, the superintendent of the New York State Asylum in Utica who wrote a major treatise in which he argued, among other things, that insanity was caused by a breakdown in cellular nutrition the brain. Now, they didn’t have the language of mitochondria and oxidative phosphorylation, and certainly I wouldn’t describe what they were introducing in terms of dietary interventions as being on a having an evidentiary or scientific basis But nonetheless, they were very curious about these questions. And, for some reason, and I’m trying in some of my spare time when I can invest in this history interest, better understand how this was lost the era of mental hygiene, the influence of psychoanalysis on psychiatry in the United States, and then of course, the era of psychopharmacology. But it does somehow come back, and I think in part that is connected with the environmental movement in the ’70s. There was actually a family doctor in the ’70s Dr. Feingold, who hypothesized that ADHD was caused by food additives and had this kind of minimizing diet that took out risk of food additives to try and treat ADHD. and we may come to this later, but, in the 1960s, there’s a study of ketogenic diet. It’s like a one-page letter to the editor of a, a ketogenic diet in schizophrenia written, I believe… I don’t know the pronunciation. It’s Abel Pacheco. I believe he later became president of Costa Rica the mid-2000s. But there are these little scattered bits of interest as you enter the second half of the twentieth century. And then I think as diabetes is recognized as this major health problem over the last couple of decades that affects not just the endocrine system, but our heart, our kidneys, and yes dementia risk and the brain, there’s a renewed interest. And I think maybe also the influence of people like Michael Pollan, advocating for things like veganism or plant-based diets and showing the effects of this on the brain and how they tie with mood. I think all of this comes together to renew interest in metabolism in psychiatry just over the last of decades. I think it’s worth remembering that even when Medicare Part D was passed by Congress signed into law about, twenty, just over twenty years ago obesity medications were grouped in with hair loss treatments and other kind of cosmetic treatments as not being eligible for reimbursement, which has affected our ability to pr- to prescribe GLP-1 receptor agonists. And so even in the last couple of decades, I think our understanding of the connection between metabolism, whole body health, and brain health has really evolved.

Dr. Ben Everett: I’ll tell you, I completely agree with that, and I’ve come to this evolutionary biology and nutritional biochemistry not through psychiatry, but really through cardiometabolic research in a number of different organizations. And yeah, I find all of this just very, very fascinating. I also find it fascinating that Bill Frist would, would essentially be quoting Hippocrates, who was really the first person, to my knowledge, that said, “Yeah, let food be your medicine.” I think it’s, it’s funny. It’s one of those quotes that’s usually like, “Let food be thy medicine.” But I’m like, no, I don’t think he said “thy.” I don’t think he spoke that kind of English. But,

Dr. David Liebers: Hip-

Dr. Ben Everett: he

Dr. David Liebers: by the way advocates basically a ketogenic diet fasting for epilepsy.

18:00 – Why Metabolism Returned to Scientific View

Dr. Ben Everett: Well, like, and we, we could talk about Ancel Keys and a bunch of other things like World War II era, you know, starvation diets and whatnot. And even though Ancel Keys, you know, advocated for all these things and really started the, the saturated fat is, is, is evil, really all fat i- is bad, he himself adopted a Mediterranean diet. So it’s, it’s interesting. All right, so yeah, let’s get back on track here. So all right, so when we talk about like the level of institutional attention to diet, it, it did– it almost really just disappeared for, for a while as I think we really got more into psychoanalysis and the monoamine hypothesis. And this is, I think, one of those things where, you know, we say technology and new findings often, you know, fuel and, and drive science. But sometimes it’s, it’s not necessarily, you know… I, I’d, I’d say it, it could– it can be difficult because if everybody starts following the shiny new thing and often for good reasons, we, we lose track of, hey, some of these things really did work, and there was really good evidence for them. But to, to that, you know, point, so what actually kind of brought metabolism back into the more serious scientific view rather than just leaving it as a historical curiosity in your mind anyway? There’s probably no one definitive answer to that.

Dr. David Liebers: Yeah, I think a couple of things. is The accumulation of evidence that there is a connection between mental illness and both systemic metabolism and brain metabolism. So even in the ’20s and ’30s when the discovery of insulin translated into insulin shock therapy, there was an observation that people with schizophrenia actually required higher doses of insulin than what would be expected in those without schizophrenia to induce the sh- the coma. And the interpretation of that is maybe there are differences in peripheral metabolism. This is, by the way, before the introduction of antipsychotics that would I think in some ways confound our research on metabolism and SMI today. But then more recently, techniques like magnetic resonance spectroscopy, which allows us to look at specific metabolites involved in metabolism in the brain positron emission tomography CSF studies, postmortem studies of the transcription of specific proteins relevant for metabolism, all have pointed to abnormalities, particularly in oxidative phosphorylation in the brains of individuals with bipolar disorder and schizophrenia, I would say, have the strongest evidence for these abnormalities. So this evidence accumulates alongside what we just mentioned about new understanding about the effects of abnormal peripheral metabolism, insulin resistance on the brain. And, I think all of a sudden there’s an appreciation for potentially targeting these abnormalities, through interventions that perturb metabolism as a possible adjunctive to the reigning monoamine and circuit-based, models of, psychiatric illness, which, you know, I don’t think they’ve been extremely powerful in generating hypotheses and the medications we have that target those systems, have saved lives been e-extremely important, and I prescribe them every day in clinic. And at the same time, there is a substantial number of people that don’t benefit from them. Our definition of benefit from them is different than I think what any of us would be excited about to call a cure. And there are some symptoms which we just don’t have any treatments for. Thinking about cognitive symptoms in some, in, in some ways, the negative symptoms of schizophrenia, where very few options– And even bipolar depression, things that are very difficult to treat with the traditional medications. And the hypothesis, I think, that’s being tested is that maybe there is another perspective to take on those symptoms for a certain subset of individuals, which is that ab– the abnormal mitochondrial function that we’ve, that I just kinda discussed accumulating may be something that could be targeted. And the big challenge, I think, is identifying those interventions that can reliably improve, metabolic function in a way that can be measured and is suitable for randomized trial designs that let us talk about causation.

23:30 – Imaging Brain Energetics: Bridging Peripheral and Central Metabolism

Dr. Ben Everett: I tell you, I think anything that we can do to help address the negative symptoms of, of these disorders, because like you said, there’s, there’s really nothing we can do, you know, treatment-wise for them, and they’re, they’re the absolutely the biggest drivers of, of disability, mor-morbidity, and, you know, just patient you know, dysfunction a-as we think of functional recovery now for these things. So it’s very difficult to try and treat those things that, that are, you know, often the most disabling for the patient. And I think the mitochondrion coming back into focus or, or really coming to focus for the first time is very interesting to me too, because I came out of a dopamine lab in two thousand and five and, you know, very interested in Parkinson’s disease and a lot of these neuro degenerative disorders which are psychiatric i-in their own right. They– We’ve known for a long time that mitochondrial dysfunction is a, is a common hallmark of these, but we kinda didn’t know what to do about it. There was really no way to monitor it or improve it. So yeah, so let’s kinda catch up. You know, mitochondrial dysfunction or function, specifically not metabolism as itself, has moved towards the center of, of a lot of this, which I think is fascinating. So le-let’s move to your… So you recently wrote a review in Neuropsychopharmacology, and you argued for some of these, you know imaging modalities you just mentioned, you know, PET MR MRS others, looking at imaging brain energetics directly rather than treating the mitochondria dysfunction as sort of an inference from some peripheral findings. So what does it actually mean to you to image brain energetics, and why has it been a hard thing to look at sort of in a vigorous, maybe prospective manner?

Dr. David Liebers: So the challenge is that we can look at mitochondrial function peripherally, for example, in blood cells in a dynamic way, actually a way that’s just impossible for the brain. There’s actually an assay called the Seahorse Assay where you can take a, a blood sample and stress mitochondria in various ways and look at the resilience. And it turns out there may be some differences in the way in the blood of individuals with psychiatric disorders respond to those stressors compared to healthy volunteers. But, whether that has anything to do with what’s happening in the brain is unknown, especially when we know there’s a great deal of variation, even in terms of the transcriptional profile between cell types in the brain, between anatomies anatomical locations in the brain. when there’s not full concordance between even within the brain itself, why should we expect that any metabolic changes that we see with a blood test would reflect what’s happening in the brain? I think that is the challenge that is trying to overcome in measuring the changes that any drug or device based intervention targeting metabolism, is, is actually working. And the nice thing is if you can measure metabolic changes in the brain, maybe you can capture some changes before you see a symptomatic response to test hypotheses more quickly, run trials in a way that helps identify the treatments, the doses that are actually gonna move the needle in improving mitochondrial function for individuals with the disorders we’ve mentioned. And this is what the paper is getting at, the perspective argues for greater use for, use of functional, MRI specifically BOLD signal measures that correlate with for example, FDG PET and other more traditional ways of measuring brain metabolism, but in some ways are a little bit more patient-centered because they don’t, require that much time in the scanner. you don’t need to introduce a PET tracer with an IV, and can easily be replicated across different s- study sites. So h- have some advantages in trying to m- measure, whether a specific treatment metabolism is actually doing anything to the brain quickly, reliably, and in a way that meets patients where they’re at. The, magnetic resonance spectroscopy certainly also has a role. unique in being able to look at specific metabolites and in some ways can look at metabolic flux with some specific technologies. But it’s less has lower spatial resolution and for that reason limits the kind of hypotheses that you can test.

28:30 – The Stanford Pilot Trial and the Abrams Follow-On RCT

Dr. Ben Everett: But you can do some of these concurrent, right? And, and so there is an advantage to that also. It’s not like you have to do serial, like, okay, we’re gonna do this scan, and then we’re gonna go down the hall and do a different type of scan, which can be very time-consuming. Uh, and, and, and frankly can just add cost to, to, you know, what you’re trying to do in a study. So so I, I think there’s some advantages there. And yeah, I mean, in, in so many ways of science, we’re always see that the new technologies are, are allowing us to just, you know… A lot of times it’s the same questions that we’ve been asking for a number of years. It could be decades, we’re asking the same questions, but through the new technologies, um, we’re, we’re able to, to think about things a different way and get different answers. So all right. Well, let’s transition a little bit to talking about, you know, the, the evidence for, for the ketogenic diet and, uh, and SMI. So there was a, a good pilot trial study published by Dr. Shebani Sethi’s group at Stanford. It looked at a four-month pilot trial of a ketogenic diet in adults with bipolar disorder or schizophrenia. They were also on antipsychotics and had a metabolic abnormality. So sort of the cream of the crop of patients that could potentially benefit from this in terms of, okay, it can help them from a metabolic, you know diabetic standpoint and potentially, you know, we’re looking at an improvement and, and you know different areas of symptoms for bipolar disorder or schizophrenia, right? And really the first clinical trial of its kind since 1965. So again, this huge gap of, you know, what, 60 years between doing this, this research. Can you walk us through the trial, kinda how it was set up, if there’s anything I left out? My overview was very cursory. And, you know, sort of like what, what they found and, you know, in, in the discussion, what did they get to in terms of hypotheses a-and, and kinda what came out of it from a hypothesis-generating evidence standpoint?

Dr. David Liebers: I, I think your overview is spot on, especially the big picture headline, which is this can be done. It’s feasible and maybe it helps people with psychiatric symptoms in addition to the metabolic effects which are better known with ketogenic diets. You’re right. They looked at a group of individuals both with bipolar disorder and schizophrenia. Was a relatively small study, so I think in terms of completers, it was sixteen individuals with bipolar disorder and five individuals with schizophrenia, and it was an open label design. So everybody in the study got the ketogenic diet and they all knew they were getting the ketogenic diet. this isn’t a blinded study. It doesn’t have a comparator. And the ketogenic diet that they used is similar to what’s used classically. So the classic definition of a ketogenic diet going back to the twenties when the idea was formalized in the scientific literature was a four-to-one ratio in terms of fat to carbs and protein, and meant really keeping the of carbohydrates limited certainly under fifty grams and ideally under, under twenty grams of carbohydrates per day. And what they found is that not surprisingly, individuals circulating ketone levels by beta-hydroxybutyrate is the most abundant ketone and the one of probably the most biological importance increased. That for some of the individuals in this study, it increased above zero point five millimolar, which is considered the threshold for ketosis. And some individuals were less adherent. And notably what they found is those that were adherent and they defined it by a cert– I think eighty percent of measurements were above that threshold. The degree of improvement the CGI Clinical Global Impression scale was greater than in individuals who were partially adherent, say. So they’re finding in this open label study, people are able to do it. There are no serious adverse events so safe. And it’s having a metabolic impact on insulin resistance And those that had a higher degree of ketosis tended to improve more in terms of psychiatric rating scales. So this was the foundation for saying, “Hey this is worth studying in randomized trials,” which can lead us into a recently published, follow-on study Abram et al., was larger, randomized closer to sixty individuals, again, bipolar and schizophrenia. I think this time there were more people with schizophrenia than bipolar that completed, thirty with schizophrenia, nineteen with bipolar. And the design was a little bit different. So they started with one-month placebo-controlled, study, placebo being diet as usual, and, other arm sent eighteen meals per week that adhered to, you know the the framework that we just l- laid out for a ketogenic diet. And they found that individuals in that first month that were in the ketogenic diet arm had improvements in insulin resistance, so the metabolic effects were, replicated. They found that the change in psychiatric symptoms may have been related to, the change in beta-hydroxybutyrate There were not statistically significant differences in the psychiatric rating scales between arms. They did an additional extension beyond the randomized portion of the study, which was open-label, where they found substantial improvements in in psychiatric rating scales and in cognition and continued i-improvements in metabolic markers. And I think this adds to the evidence base that this is something to think about, something to consider. It’s certainly not the final word. I see these two, studies as being an opening move to say this is legit. it needs to be further explored. I would love to see more neuroimaging biomarker studies. There have been a couple one from the UK in bipolar disorder that have used neuroimaging with ketogenic interventions. But but this is just beginning, and I think it’s one of a whole suite of metabolic interventions that is deserving of further study. think, for the right patient it’s something that they can feel empowered to drive forward on their own for individuals that are not improving with traditional a-approaches to the treatment of schizophrenia or bipolar disorder. That’s exciting.

36:00 – Adherence, Meal Delivery, and the Path to GLP-1s

Dr. Ben Everett: Yeah, I agree. And I tell you, one of the things I really like about this is that, you know, getting patients to stay on anti, uh, psychotic medication can be difficult for a number of reasons. Side effects, not just weight gain, but, you know, other side effects as well. A lot of times it’s very challenging to get these patients with serious mental illness to stay on medication. And so to the extent that this would be a different tool in the toolbox that is not a drug in, uh, in air quotes, you know, traditional way, you know, could be appealing, I think, to a lot of patients. Um, probably, you know, a lot of pushback that you’ll hear is, well, it’s just so hard to maintain the ketogenic diet. It’s hard to get on, it’s hard to stay on it. But what I like about the Abrams study that you mentioned as a follow-up is they sent the patients the meals, right? So when you take away the, the obstacle, you make it easy, uh, to maintain to the diet. I think it really helps with the adherence to the ketogenic diet. I think it’s all fascinating. I, I’ll say the other thing kind of borrowing from the cardiometabolic literature is I was thinking when you were talking about Bang and Dyerberg, they were the Danish clinician scientists that studied the Inuit Eskimos and came up with the, the famous Eskimo paradox. I’m not sure they ever really looked at differences in mental health outcomes, but I’m gonna go back in the literature. I’m curious if anybody ever did that with some of their studies, because it would be really fascinating because they did some really amazing groundbreaking studies in the ’70s where they looked at Danish like normal– uh, nationalized Danes, Inuits who had immigrated to Denmark, and then Inuits in their native environment. So it was sort of three different arms study. It was very elegantly done, uh, the w- the way they looked at it. Anyway, so I’m just being curious there. All right, this is really cool. The other point I wanted to make is that, you know, these are, I, I think, really pretty short-term studies for a ketogenic diet. Three months, four months. It can take sometimes, you know, thirty days or so to become fully fat adapted. And so to the extent that we can get to more rigorous and even longer term, you know, studies, I think My hypothesis would be you’re gonna continue to see improvement in the psych, uh, in the psychiatric endpoint as well as the metabolic endpoint. But at this point, it would just be a hypothesis, so really exciting. All right, so let’s move on. So we had you know, Dr. McIntyre on a couple of episodes ago, as I mentioned. He really talked about GLP-1s, you know, anti-inflammatory, already a host of FDA indications, real effects on the brain, reward, mood circuitry. And so we kinda landed on, well, if for no other reason, if you have a patient that could benefit from any of the on-label indications, and as we’ve mentioned, a lot of these patients are more sedentary, they have– tend to be more overweight, obese, have diabetes. So for a lot of these patients, you can just use it on label. You should certainly consider prescribing them. You know, what you’ve told me is that, you know, you wanna make the case that they’re not only or necessarily the best systemic metabolic lever available in, in psychiatry, but they might be the best l- lever available in psychiatry right now. So make that case. Convince me that, hey, we should really be thinking about, you know, SGLT2s and GLP-1s more for psychiatry.

39:30 – GLP-1 Receptor Agonists in Psychiatric Practice

Dr. David Liebers: So I think Dr. McIntyre did a, a really good job in giving an overview of the history of how GLP-1 receptor agonists have entered the conversation in psychiatry and their use, and they’ve now entered expert consensus guidelines addressing the metabolic side effects of antipsychotics have increasing evidence in for example treating the symptoms of alcohol use disorder. For individuals that meet criteria for treatment with GLP-1 receptor agonists on metabolic or obesity grounds, it’s certainly worth using them if there could be an added benefit, for example, in decreasing alcohol use disorder even before we see any kind of FDA indication for that purpose. I will tell you in my practice, which mainly focuses on individuals with schizophrenia spectrum disorders on long-term antipsychotic therapy, quarter to up to a half of individuals on, are on GLP-1 receptor agonists. And I think the evidence is strong, that over the long term, to your point this will provide health benefits not just for their brain but for their heart and for, systemic health in a way that I think is really important for individuals that have a ten to fifteen-year mortality tax because of this psychiatric diagnosis.

Dr. Ben Everett: Yeah. Thanks for that. I couldn’t agree more. So when we look at like both GLP-1 receptor agonist as well as SGLT2 inhibitors, you know, they started off as anti-diabetic drugs. Both have since accumulated evidence about, you know, benefit outside of glycemic control, but they work through completely different physiology. So what’s, you know, actually distinct about SGLT2 inhibition mechanistically that drew you to look at this class of medications versus the GLP-1s?

41:30 – Discovering SGLT2 Inhibitors: A Resident’s Chance Encounter

Dr. David Liebers: I remember the first time I prescribed an SGLT2 inhibitor. It was in July of my intern year as a resident at Bellevue Hospital when my senior resident, a very brilliant oncologist now, told me that for a patient we had just admitted who had preserved ejection fraction heart failure that I would really impress the consultant cardiologist if I went ahead and prescribed empagliflozin. The pivotal studies for preserved ejection fraction heart failure and SGLT2 inhibitors, I believe, had just been published. I was really interested to learn more about this class of medications after for all the years of medical school being told that we have goal-directed medical therapy for reduced ejection fraction heart failure. There’s nothing really to be done about preserved ejection fraction heart failure. how is it that this medication, which is a diabetes medication and targets the kidney, is helping the heart? I discovered that they were unique among antidiabetics in inducing ketogenesis and at the same time started to explore the population-based literature on the relationship between these medications and neuropsychiatric outcomes. I found that they were associated with a reduced risk of dementia, intriguingly also found that in multiple large EHR datasets, a study from Denmark, a study from Japan, a study from Hong Kong, were also associated with the lowest or among the lowest risk of incident depression among individuals with diabetes that were prescribed these medications. And this was enough for… of a signal for me to start doing a deeper dive and seeing the preclinical literature suggesting that they may improve, mitochondrial function, in, in preclinical models in the brain. I wrote an email to Daniel Iosifescu, who is a, a psychiatrist here at NYU with an expertise in clinical studies of metabolic interventions in psych– particularly mood disorders. And he helped me write an IRB protocol to do a small open-label study of empagliflozin in major depressive disorder.

Dr. Ben Everett: All right, so that’s, is really fascinating. ‘Cause so much of the I feel like so much of the discussion right now is around GLP-1s, but because of the different, you know MOAs and, and pathophysiology involved, you know, we could see, we could see disparate, you know, findings, and we might find out in another 10 years that, hey, this patient population really does well on SGLT2s versus this one on GLP-1. So there’s, I think there’s a lot of different hypotheses that, that can be tested with these. And SGLT2s are very different from the GLP-1s in that they can be described as really uniquely ketogenic, and GLP-1s cannot. They can even without carb restriction, they can put a patient into, like, a mildly ketogenic state. Can you walk us through that pathway and how you think that might influence, you know, some of the findings or, or again, hypothesis-generating ideas?

45:00 – The Ketogenic Mechanism Behind SGLT2 Inhibition

Dr. David Liebers: So the main target of SGLT2 inhibitors is the sodium glucose co-transporter two protein, which is in the proximal tubule of the nep- nephron and facilitates reabsorption of glucose back into the blood. So you block the activity of this transporter, and you introduce glucose scarcity, which mobilizes, beta oxidation of fatty acids for fuel, the production of ketone bodies in the liver, and ketone bodies like beta-hydroxybutyrate can cross the blood-brain barrier and be used as fuel. There’s a study which Dr. Sethi, whose paper we mentioned before has cited suggesting that ketones represent a higher energy fuel source per unit oxygen than glucose, which in the heart, for example, translates to something like twenty-five percent higher, efficiency as compared to glucose. the question, and it’s a hypothesis that maybe given that the brain is a similarly energetically demanding organ, two percent of the body mass, twenty to twenty-five percent of energy expenditure by the body, providing an additional fuel source for mitochondria that are already stressed or may be impaired in individuals with psychiatric disorders improve the ability for cells in the brain to meet, the high energetic demands of maintaining membrane potentials, recycling neurotransmitters. So this is the mechanism that I proposed with empagliflozin specifically mimicking the effects of a ketogenic diet. As you point out, it induces a milder ketosis. you know, the studies that we just discussed, average above one millimolar. It’s in my pilot study, it’s not yet published, but we see two, three, maybe four-fold increases on average. Not everybody sees the increase in peripheral ketones. It’s a tricky biomarker. It depends a lot on when your last meal was, following instructions to do the AM blood draw, whether or not they took the medication before the blood draw. I learned a lot about the advantages and disadvantages of the different ways to measure ketones for a study like this. but it also raises the question of the relationship between the peripheral metabolic changes, for example, in ketone levels, and what that actually means for the brain and metabolic flux. It may be that the effects of SGLT2 inhibitors don’t… on the brain don’t require as much peripheral ketones as other ketogenic interventions exogenous ketones, ketogenic diet. We know that SGLT2 and its sister protein SGLT1 are expressed to some degree in the brain. Unknown if and what effects SGLT2 inhibitors may be having directly in that way. These are all open questions for science.

Dr. Ben Everett: I love it. I tell you the biochemist in me just loves the idea of, you know, even an undergraduate biochem, you know, student could tell you, you know, you get a lot more ATP, you know, per cycle of the TCA than you do just from glycolysis. But because of our Western diet, we tend to mostly, you know, we don’t do a lot of beta oxidation. So I think there’s a lot of different implications here just to diet and thinking about these things and some of the diseases of Western civilization even. But all right, let’s get to your pilot study, because you just mentioned your pilot study. So you ran this pilot study to target essentially trial emulation work on empagliflozin, primarily in MDD. Um, and, you know, I don’t want to put a publication at risk, but, you know, what can you tell us about, you know, the study and what you found.

49:30 – Trial Emulation and the Empagliflozin Pilot Study

Dr. David Liebers: So two separate studies. One is the trial emulation that you bring up, which is was recently published in JAMA Network Open. There, what we did is take a cohort of indu-individuals with psychiatric disorders, depression, bipolar disorder, schizophrenia, we asked, “What is the subsequent incidence of dementia?” And then secondarily, psychiatric outcomes like ED utilization and psychiatric hospitalization among individuals on SGLT2 inhibitors versus those that didn’t receive them with a methodology that seeks to remove some of the confounders and biases introduced by traditional population-based analyses. What we found is a replication of what’s been seen in all comers, the decreased risk of dementia risk, but also a signal in decreased psychiatric ED utilization. So my hope with that study was to try and s-provide some kind of support for this idea that among individuals with psychiatric disorders who have a substantially increased risk of dementia is abnormal mitochondrial function, abnormal bioenergetics, an underlying part of the pathophysiology that might both drive the neurocognitive and the psychiatric symptoms in some subset of patients and might SGLT2 inhibitors emerge as a potential intervention that could target that system, thereby decreasing both, symptom clusters. I think it has limitations because it still is a population-based study design, and you can’t talk about causation, it provides an extra handhold as we try and understand the potential role of this class.

Dr. Ben Everett: Yeah. I like that summary. All right, well, let’s transition now to an older drug because we’ve been talking about, you know, SGLT2s, but let’s talk about metformin because metformin really probably has the best evidence base for antipsychotic induced weight gain just because it’s, like it’s a drug that’s been around forever. It’s very well tolerated. It’s cheap. And so when we talk about metformin you know, h-how do you see its place in, in this landscape of SGLT2s, GLP-1s with regard to, to, you know, treatment of your patient population?

52:00 – Metformin’s Expanding Role in Antipsychotic-Associated Weight Gain

Dr. David Liebers: I was really struck by a meta-analysis, I think back in 2016 or so, that showed metformin associated with something like a four-kilogram, weight difference compared to placebo for individuals on antipsychotics, but that it was substantially lower among individuals who had already been on long-term antipsychotic therapy compared with those with early treatment of first episode or early psychosis. Just I think early last year in twenty twenty-five, were consensus guidelines published in Schizophrenia Bulletin, which substantially broadened the scope of who could benefit from metformin among individuals on antipsychotics. I think a lot of people think about it for individuals on clozapine or olanzapine with this, this big metabolic burden, particularly once the side effects are observed. What this set of recommendations says is to go ahead and of course start for those that don’t have contraindications in those starting olanzapine or clozapine right off the bat. But actually, for that group of drugs that are intermediate in their metabolic side effects, so risperidone, paliperidone, quetiapine, there for individuals that have some kind of comorbidity, including a BMI over twenty-five, hypertension, pre-diabetes. So a substantial number of individuals that are starting those moderate-risk drugs should start metformin as well. And for even the low-risk drugs, the lurasidones, the aripiprazoles, if you see weight gain of three percent, might be five to ten pounds of weight gain in the first year of treatment, to go ahead and start metformin there too. what they’re recommending in those guidelines, in addition to the metformin, they recommend GLP-1 receptor agonists for anybody that meets criteria. So if you’re starting an antipsychotic with a, a BMI of thirty, go ahead and start the GLP-1 r-right away. You qualify for it in any case. But what they’re recommending is a, a vast expansion of the number of individuals who would qualify for metformin. the same time, over the last couple of years, we’ve seen studies suggesting that metformin may provide a low to moderate effect size improvement in cognitive performance among individuals with schizophrenia. was a study just a few months ago showing that those improvements not only associated with an fMRI marker of hippocampal connectivity, but also peripheral measurements of changes in TCA cycle metabolites. So they’re starting to pull together the story of moving the needle on metabolic changes observing the circuit-level effects of the change in metabolism, and seeing the cognitive symptoms improve as compared to placebo. So I think is it’s an area of interest of mine. I’ve done some preliminary, queries into EHR databases, and know, I think ten to fifteen percent of the people that should be or would qualify under the new guidelines to get metformin are actually on it. and for that reason, I think it’s a area both in terms of public policy and how to adhere to these guidelines and what we can do to support clinicians in adhering to those guidelines with their patients. but also just an opportunity to better understand the drug and its mechanism an exciting opportunity alongside what we’re learning about GLP-1 receptor agonists.

Dr. Ben Everett: Yeah, I’m actually a really big fan of metformin for a number of different reasons. But on top of, you know, glucose, lipids it has pronounced anti-inflammatory effects. So I, I think similar to how, you know, we’ve talked about SGLT2s and GLP-1s in this at-risk patient population, it, it’s certainly just gonna help them with their underlying metabolic issues. And to the extent that we get any improvement in psychiatric you know, metrics or measures, that’s just… That, that’s a bonus for the patient.

56:30 – SGLT2 Inhibitors as a Complement to Ketogenic Therapy

Dr. David Liebers: A- and maybe I can say just a couple other things about SGLT2 inhibitors that you could move around.

Dr. Ben Everett: Yeah.

Dr. David Liebers: because I feel I think SGLT2 inhibitors are a nice complement to the research ongoing with ketogenic diet. I see them as potentially helping broaden the number of individuals that can benefit from ketogenic therapies. For example it’s true that not everybody can adhere to the ketogenic diet, although I think with the right support to your point, a lot more people could than we might assume. But there’s also some evidence, a recent Nature paper suggested that the increased lipid requirement in a diet for a ketogenic diet for people that have higher risk of GI cancer, for example, could be oncogenic. And so perhaps in individuals with hereditary syndromes that increase the risk of GI cancer or with a family history might be more comfortable with a ketogenic intervention, which maybe combines some dietary changes without having to have the really high fat load required with the keto- traditional ketogenic diet by introducing SGLT2 inhibitors. And and maybe SGLT2 inhibitors when combined with things like medium-chain fatty acids or other ketogenic-promoting interventions could help you achieve the levels of ketosis that you’re seeing with nutritional ketosis. So those I think matter. also the ability to do research with blinded study designs. One of the limitations I think with the studies that we just mentioned for all of their important features is these are not blinded studies, introduces a number of different biases, and I think limits our ability to draw concrete, scientific conclusions. Every study has its limitations. but if we were able to see ef-effects in the brain using some of the neuroimaging techniques that we just discussed, with SGLT2 inhibitors that we also see with ketogenic diets this would be an encouraging signal. And and in fact, we have some evidence that’s the case. There’s a study, Agerinos et al. in 2022 done at the NIH, where they gave empagliflozin to healthy volunteers found significant reductions in GLX, composite biomarker that combines glutamine and glutamate, in fact and this is I think anterior ci- cingulate cortex, which is in fact what was found in a study of ketogenic diet in bipolar disorder also last year in the UK, Campbell et al. So I think the initial signal suggests that despite the differences in what we’re seeing peripherally in terms of metabolism with ketogenic diet and SGLT2 inhibitors, the signature in the brain so far very similar.

Dr. Ben Everett: Yeah. That’s good stuff. And I tell you the, the other thing that, you know, I should have mentioned before, even though you’ve been studying empagliflozin, is that cana- canagliflozin and dapagliflozin have both recently gone generic, so they may be easier to access for certain patients, and especially, like you said, the Part D patients. Now that they’re generic, it might be a little bit easier to do. And sometimes it can make research easier if you’re not having to try and get drug from a, from a study sponsor or something like that, that you know, may not wanna, may not wanna do that kind of research. All right. So been a fascinating discussion so far. Let’s kind of move to the, to the closing, but I want to zoom back out because I think the, the risk with any single mechanism story, whether it be GLP-1s, SGLT2s, ketones, it can kind of start to sound like a silver bullet or like, oh, you know… Although I’d say I think you’ve been very cautious in all of your answers and very diplomatic as to, you know, what the data are, you know, at this point in time. So you’ve said that metabolic psychiatry is really better understood as a perspective than a single treatment. And again, I think this is very very true to the way that you’ve, you’ve answered all your things today. So as we talk about the full toolkit as we see it for ketogenic diet drugs in this, in this metabolic area for psychiatric disorders, exercise. I know we’re seeing exercise as a huge increase or rigorous exercise-based studies a- as interventions, I should say, across a number of psychiatric disorders: schizophrenia, bipolar disorder, depression, really having major improvements. So as you think about all of these things together, diet, drugs, exercise, you know, how are you seeing the toolkit in terms of how you’re approaching patient care?

61:30 – Toward a Whole-Person Model: Diet, Drugs, and Exercise

Dr. David Liebers: Yeah, it’s a great question because I think one of the challenges we face in psychiatry although one of our traditions is what I just discussed in terms of the history of the asylum, the other tradition is that dyad that I think is best exemplified with psychiatrist and the person on the chair from the Freudian and analytic tradition. And a lot of psychiatry happens that way, it’s a psychiatrist in dyad with a patient, a prescription of a medication happens. The expectation is patient takes medication and either improves or doesn’t, and then you decide whether or not to change the medication or change the dose and continue iterating on this process. As you point out, what we’re learning is the best care for individuals, particularly with the most severe, psychiatric illnesses, probably benefit from a whole suite of different ways of supporting them. And that can include exercise, that can include dietary interventions, that can include access to group therapy and, and forms of psychotherapy that are specifically tailored, for example, to bipolar disorder or schizophrenia. And access to those things is not easy to get even in clinic-based models like the one where I practice. The point is to be able to think in different ways using different paradigms, different models about each patient. And I think back to a, a book I was given by Paul McHugh while I was working at Hopkins before medical school called “The Perspectives of Psychiatry.” And what it calls on, practitioners of psychiatry to do for each patient to come at things from, for example, life history perspective. Where are you meeting this person in terms of who they are, where they’re from, and where they’re going? Very difficult to earn somebody’s trust without having that and understanding what’s important to them. A biological perspective certainly is important in trying to understand what’s happening with their brain. But even within the biological perspective, thinking in terms of, monoamine neurotransmitters and thinking in terms of brain energetics might lead you to consider different interventions. I think what we’re doing in psychiatry is returning to something which superintendents of the asylums understood, which is the brain is connected to the body. And when you’re thinking about an intervention like metformin for your patient, it requires that perspective to think I’m called to actually consider something beyond modulating neurotransmitter systems, here’s an opportunity to introduce something that helps peripheral metabolism but may also affect brain metabolism in a way that targets symptoms that our treatments based on a monoamine neurotransmitter premise may struggle to in some way.” so way I see it is, an additional layer of the perspectives of psychiatry for each patient, think about what we’re doing along a number of different axes. And when you do that, it becomes a little bit easier to remind yourself with each individual patient what you’re doing to support their metabolic health, what you’re doing to support their ability to socialize with people, which can be protective. I found this helpful i-in my own practice, and I think if there was a way to build that out further this delta between those that would, for example, qualify for metformin that actually get it might close.

66:00 – Confronting the Treatment Gap: Underused Medications

Dr. Ben Everett: Yeah, I think that could be great. Uh, and I mean, in, in psychiatry we see always, not always, but often… I’m gonna start over You know, it’s, it’s unfortunate sometimes in psychiatry when we look at databases, we look at EHR records, so many patients that would be candidates for a treatment simply aren’t on it. We see it with, um, you know, um, lung What? I’m, I’m blanking on the acronym for the, uh, uh, LA… Uh, uh, uh, uh, LAIs. I, I was– I wanted to say LTIs, and I was like, “It’s not an LTI, it’s an LAI.” Thank you. So all right, we’ll start this over. Yeah, I think that’s fascinating because, you know, when we look at EH-EHR databases, other retrospective analysis, looking at things we often find in patients with psychiatric disorders, they’re very undertreated in terms of medications that are available to them, whether it be a metformin or an LTI or, or other interventions that could, you know, potentially really provide some, some meaningful improvement for those patients. So all right. So,

Dr. David Liebers: Yeah, And just to that point too John Kane at the ASCP meeting this year talking about clozapine. And it is in some ways quite sad when I encounter an individual who’s struggled for decades and with schizophrenia had a single trial. Now, not everybody can tolerate it for whatever reason, but but for somebody not to have had a trial of the best medication we have their diagnosis at fifty or sixty years old and thinking about suicide attempts, hospitalizations, all the rest of it it’s quite sad. And so I think there’s something to be said for, finding these parts of psychiatry where we’re not living up to the best of what we can offer with the treatments we already have, even as we’re trying to explore a novelty in dietary interventions repurposing of anti-diabetic drugs, et cetera.

Dr. Ben Everett: Yeah, I couldn’t agree more. I think anything that we can do to improve outcomes for, for patients is, is best medicine and is really what, you know, we should all be striving to do. And that’s me as a, as a scientist saying we you know, always want to– but I am not a prescriber. But you know but I’m very passionate about this stuff. So all right, well, last thing. So if– let, let’s say if you can look forward ten, fifteen, twenty years, if meta- if metabolic psychiatry succeeds and these mechanisms hold up, does it– you– do you think it ends up replacing or enhancing neurotransmitter circuit-based models of mood and psychiatric disorders? Does it get absorbed into them as a different layer? I think this is an area where it’s like the, you know, the more– what is it? The I’m gonna butcher whatever the saying is. The– it’s like the more, the more we find out, the more questions we have.

68:00 – The Future of Metabolic Psychiatry: Integration, Not Revolution

Dr. David Liebers: My hope for metabolic psychiatry that it integrates into existing models which have some explanatory, force. don’t see it as, sort of a, a scientific or psychiatric revolution which is going to replace the old paradigm in sort of a a Thomas Kuhn sense. I think it starts to help pick up some missing pieces in explaining, in some places the failure of existing paradigms to help all patients with all suffering. And if it can address or alleviate some suffering in some subset, a subset of patients, that would not otherwise find improvement in the treatments that we have on offer right now, then I’ll see that as a great success. I think part of the challenge right now is to help identify patients that interventions like a ketogenic diet, like potentially SGLT2 inhibitors, transcranial photobiomodulation, which is a mitochondrially targeted near-infrared laser intervention with accruing evidence in psychiatric disorders. If we can find the groups of patients that are going to benefit from these things, and maybe it’s a signature of abnormal metabolism in the brain from neuroimaging combined with some peripheral biomarkers or maybe, as, as has been studied i-in a number of randomized trials, just individuals that have, insulin resistance may respond differently to different treatments and better understanding that and integrating that into clinical practice might be a first step. but that’s my hope for it I think it could integrate neatly into existing models because we know that neurotransmission is an extremely energetically expensive process and abnormalities cell and circuit-specific abnormalities or breakdowns or impairments in the ability to meet the energetic challenges of that process will have downstream effects on the regulation of neurotransmission. This has been certainly studied in in vitro, and we’re beginning to better understand that, interesting in silico models and maybe in vivo. So it’s exciting. I think we’re just at the very beginning, but we’re at a beginning where some patients are already finding great benefit from taking their healthcare into their own hands. There’s a great resource called Metabolic Mind that I recommend patients interested in ketogenic diet start with that really lays out how it can be done. And and it will help you connect and collaborate with the kind of experts that can guide clinicians less experienced with it. I think it’s an exciting time to be in this area.

71:30 – Closing Thoughts and Sign-Off

Dr. Ben Everett: Fascinating. Well, look, we’ll have to have you come back on in a couple of years and, and give us an update. Uh, with that, I want to say, you know, Dr. Liebers, thank you. This has been exactly what I hoped for. I, I loved the conversation we had today. We, we really built on, you know, what I talked to Dr. McIntyre about a couple of months ago, and we’ve pushed it into a really different territory that a lot of our listeners might not have encountered yet. So to the extent that this can be, you know, clinically beneficial or, you know, maybe even practice-changing for some of our listeners you know, that, that’s great. That’s, that’s the best thing that we can hope for. And, you know, if you take one thing away from this episode, you know, let it be this, that metabolic psychiatry isn’t a bet on a single drug or diet. It’s a bet that the brain’s energy economy is really a legitimate and increasingly tractable target, and really sits alongside all these other things that we’ve talked about today, and I think that’s what you got to in your closing. So

Dr. David Liebers: Thanks, Dr. Everett.

Dr. Ben Everett: Yeah. This has been the JCP podcast. Insightful, evidence-based, human-centered.