Thank you so much for for coming. Very excited to be here. Hello to everybody who's listening on the stream as well. So I'm Chris Miller. I'm the chair of this session. I'm a psychiatrist, a psychoanalyst, associate professor at the University of Maryland School of Medicine in Baltimore, and I'm the current director of psychotherapy education for the University of Maryland Shepherd Pratt residency program. And I'm joined by my two colleagues, Dr. Hinda Dubin, who is an associate training director for the University of Maryland Shepherd Pratt psychiatry residency training program, and the coordinator of psychiatric education for the state of Maryland. She's a founding fellow of the Academy of Cognitive Therapy. And Dr. Boris Tisenberg is a PGY-2 resident in psychiatry at the University of Maryland Shepherd Pratt program. His interests currently lie in psychotherapy for children and adults, as well as forensic psychiatry. Disclosure standpoint. It's advancing, right? Okay. Dr. Miller and Dr. Tisenberg have no relevant financial relationships to disclose, and Dr. Dubin has the following financial relationship to disclose. She's a principal investigator for Pharmacyte. So basically this session is going to discuss a little bit about a massive topic, and some very difficult choices needed to be made when I was structuring this, because we could have gone down a neural circuitry route, we could have gone down an epigenetics route, we could have gone down an inflammatory marker route, we could have gone down a neuroendocrinology route when we're talking about biological changes in psychotherapy. And I couldn't do all of that. So I had to sort of pick the focus, and we will be focusing a bit more on the circuitry level when we're discussing how it is that therapy can affect change on a biological level. We're still sort of in times of dualistic thinking, unfortunately, but the body of literature supporting biological change with psychotherapy has really been exciting and advancing and increasingly hard to ignore over the past 30 years or so. So I'm going to be talking for about 40 to 45 minutes or so, giving you a little bit of a theoretical foundation, talking about some of the research out there. We'll have, you know, a little bit of time for some reactions, questions, comments, but then we're going to move on to the interactive portion, which is our two clinical vignettes, which will be led by my colleagues to kind of integrate what I'm presenting here in some real-life scenarios that you may have encountered and probably will encounter at some point. Okay, so I'm going to be starting with the neuroscience of early adversity, what it is that can happen when we experience, you know, early life stress, trauma, etc., as a lot of early life events can factor into what we are going to later call depression, anxiety, PTSD, personality disorders, and such, and what is it that psychotherapy is going to do to help redress some of those effects from early life. So I'm going to be focusing on these three different brain areas here, you've probably heard of all of them, starting with the amygdala, which is a little almond-shaped, or at least that's where the name comes from, area in the brain which is associated with assigning emotional valence or salience to events. It's sensitive to signs of threat, and it has a close connection with the hypothalamus, which is the proximal point of the HPA axis, and downstream effects, the release of cortisol, which is sort of our let's deal with stress hormone. So adverse experiences can lead to an early and excessive elevation in cortisol. So ideally, early on in both humans and other mammals, cortisol levels should be low early in life. There's something in animals that's called the stress hyporesponsive period, where our amygdala is supposed to be largely dormant, and quiescent, and not too activated because we're supposed to be protected by the caregivers. But when there's adversity, too much cortisol is released too soon, and that gets the amygdala going a little bit too quickly. The second brain area, and we'll come back to the amygdala shortly, is the hippocampus, which is so named because supposedly it looks like a seahorse. You can decide. But it's an area of the brain that's involved in encoding episodic memory, which is basically autobiographical memory episodes. It's where the name comes from. And it's an area of the brain that's going to provide contextual and spatial data of our experiences. So whereas the amygdala kind of assigns that more immediate valence and salience to the event, our emotional sort of visceral reaction to things, the hippocampus helps to sort of contextualize how these experiences are taking place in a broader way. But one thing that happens in the brain is that the amygdala matures well before the hippocampus. So we're actually going to have potentially very strong emotional reactions to the environment before we really have a cognitive understanding of why. So you ask, and some of you may ask your patients, when's your first memory? Most people are probably going to date it somewhere between the ages of three and six. If people have early life trauma, sometimes it's a little bit earlier than that. But in any event, people sometimes react very strongly to situations, and it's very hard for them to ground themselves. And we don't understand. I don't know why I get scared. I don't know why I get panicky in certain situations. Because again, our brain is playing catch-up to understand how our body is reacting. And oftentimes, this evolutionarily comes down to a matter of safety and survival. It's better to assume the worst sometimes. So the amygdala and the hippocampus have reciprocal connections with one another. And ideally, the hippocampus, in typical situations and typical development, will be able to provide enough of a cognitive contextual understanding to a situation so that we're not so much at the mercy of our emotions. I've been here before. There's nothing to be worried about. I can feel okay. And we can kind of ground ourselves by bringing in some of that contextual input. But if the amygdala is overactive, it may actually inhibit hippocampal activity. So we can see down there with the big inhibition sign. So the amygdala can override anything that the hippocampus might be trying to do to ground ourselves in the situation. And so we may be very stirred up by our emotional reaction to a situation and really unable to think our way through it. I think we probably all have been in situations where we felt so overwhelmed that we can't think straight. As our adrenaline goes up, it stops binding areas that help us think. You know, it's sort of that panicky situation. Help me. What's the number to 911, which is something that happened in my life when you're just so flooded with emotions that you can't think about things that should seem so obvious. And something that we see, for instance, in post-traumatic stress disorder is that there is a hyperactivity of the amygdala and a hypoactivity of the hippocampus. And so people may have very strong emotional reactions and they're really unable to revisit it. And this is where some of the intrusive re-experiencing, the flashbacks, the reliving, the I'm back in that situation again kind of experience comes from. Because it really is as if they're reliving it and they can't ground themselves by providing contextual input to revisit how they're responding. And something that happens with abuse in childhood is that cortisol levels are chronically elevated. Inappropriately early and inappropriate in terms of amount that's released. And as I was mentioning before, this is going to lead to a premature and excessive activation of the amygdala. And as some of you might know, cortisol is neurotoxic. And when there's too much cortisol, it can lead to a decrease in hippocampal volume and activation. So the end result of this is going to be that the amygdala activity is going to predominate when we're responding to environmental stimuli. And it's very hard to inhibit it from through other cortical means. So the last of the three areas that I wanted to touch upon is the prefrontal cortex. Especially these two areas here. Prefrontal cortex, you know, a lot of different functions, a lot of different areas. So to kind of keep things a little bit cleaner for today, for didactic purposes, I'm just talking about these two areas here. So the dorsolateral prefrontal cortex is that little area up there located on the supralateral surface of the brain. The ventromedial prefrontal cortex is down there on the right, located on the medial surface of the brain. And I'm going to talk a little bit about the functions that they serve. So when environmental stimuli come in, and we're interacting with something in our surround, there's going to be an interconnection, a dialogue that takes place between amygdala, hippocampus, and also an area of the prefrontal cortex, which is called the orbital frontal cortex, which is involved in risk and reward considerations. Do I approach the stimulus, or do I move away from the stimulus? This all happens very quickly. What is my emotional reaction? Am I able to provide contextual data to inform me about how I'm responding, or how I should respond? And the OFC gets recruited to tell me, what do I do next? How stressed should I feel about this situation? And that's where the HPA axis is going to be triggered. Our locus coeruleus, our brainstem nuclei, our stress response on a broader level is going to become activated. And finally, do I approach, or do I avoid? This all happens very quickly. A lot of it sort of can elude our sort of conscious understanding. We probably have experiences where we're in a room with somebody, and we just feel uncomfortable. We don't quite understand why. Or there are other people that we just feel very comfortable with, and there's no good reason for it that we can think of. We're just able to open up a little bit more, and other people we feel very suspicious of. So there may be a lot of unconscious processing that's going on that we can't quite put our finger on. And the two areas of the prefrontal cortex that I'm going to talk about will become differentially activated depending on how we're sort of negotiating things on this subcortical level. So the first area of those two in the PFC that I'm going to talk about is the ventromedial prefrontal cortex. So this is an area that's key in emotion regulation. So as you can see from that image there, it is involved with a top-down dampening of amygdala activity, and it's also involved in theory of mind, mentalization, empathic attunement. So this is something that I really hope people will be able to hold on to. It's the same area of the brain allowing us to empathize with other people that allows for us to control our sort of own emotional reaction to the environment. So there's something interpersonal about how we deal with our own internal world, which is going to be very relevant when we talk about the mechanisms of psychotherapy. So one thing that has been replicated in a number of research studies is that the brain activation patterns in parents and caregivers can actually shape the activation patterns in their children. And this can happen in benign and adverse environments, so this is very apropos. When we're talking about intergenerational transmission, whether it's of trauma, traumatic templates, or even something that's benign and edifying or an affiliative, there is a good body of research showing that the dyad of the caregiver and the child is very relevant in mapping out how the brain of the child is going to work, and oftentimes there's a correlation with how the brain of the parent works. So a secure mother, when interacting with her own child, this may seem fairly intuitive, when she's interacting with her child she's going to process this bonding experience as something rewarding. So on a brain level that means that your little ventral tegmental area is going to be releasing dopamine onto the nucleus accumbens. So there's an increase in dopamine which is associated with reward. So bonding with her own child is experienced as rewarding in the securely attached mother. And, and this is relevant for what I was mentioning before too, when the infant is distressed the securely attached mother activates her own ventromedial prefrontal cortex, because what I was mentioning is this is a brain area involved with mentalization and with empathic attunement. So she's able to read the state of mind of the child, understand the distress, and help to contain it, help to process it so that the child feels settled. And importantly, she's not too stirred up by her own emotional reaction to her child, because it can be very difficult for a parent to see the child, you know, going through so much and feeling so uncomfortable. And for some parents it can become too much, it's sort of here you take care of it kind of thing, or let me walk out of the room, but it's not always something that is that easy to navigate. So, but in the securely attached mother, she's able to empathize with the child, contain the experience, and control her own emotional arousal as she's doing it. And this is the VMPFC's territory. So, I was mentioning that the, the mapping can happen between parent and child in benign and adverse environments. So in this particular instance that I was mentioning, maternal sensitivity during infancy, when the mother is able to provide that presence that I was showing in the previous slide, this has been associated with functional connectivity within the child's medial prefrontal cortex. So the fact that the child was empathized with by a caring provider will actually inform development of their own area of the brain that's going to allow for them to empathize with others later on as well. And, you know, on a larger level, people who are empathized with during childhood and feel understood and such are able to provide that presence for other people later in life. So, and there's a corresponding neurobiological equivalent that takes place. So the second area of the brain that I want to talk about is the dorsolateral prefrontal cortex. So when we think about the prefrontal cortex, and if you, you know, ask somebody what, what does it do, one of the first things that might come to mind is executive functioning, which is sequencing, organizing, abstracting, planning, that sort of thing. So, you know, we need this area of the brain. But there are instances in which it can become overly activated when we're dealing with things. And if we're at the mercy of kind of an overactivated amygdala and we're not able to kind of control our emotional response, we may overly prefer this area of the brain, which can be associated with emotional avoidance and rigid thinking. So people who, you know, come to treatment and they're kind of stuck in those thought loops where I'm the worst person in the world, you know, this is terrible, nothing's ever going to get better. That might be sort of that overly active dorsolateral area, and they just have such an uncomfortable emotional response and they're not able to do anything with it other than kind of stick with those very strong, rigid ways of thinking. And we talked about what happens with the secure mother, but what happens with the insecurely attached mother? So when she's interacting with her child, what happens is, very differently from that first scenario where the VMPFC, the empathy area of the brain is preferred and she's able to attune to the child, the VMPFC in the insecurely attached mother is actually under-recruited and the dorsolateral area is preferentially activated. So it's much more of sort of an intellectual cognitive reaction to things as opposed to being able to access the sort of interpersonal elements to attune to the child, which she's not able to recruit quite as much. Instead of dopamine being released, there's actually a decrease in signal in the ventral striatum, which is the, again, the reward processing area. So it's not experienced as rewarding for this mother when she's interacting with her child. And the anterior insula, which is a little bit of a new area for us today, is activated. And this is an area that is involved with our sense of self, our body sense, our interoceptive sense. And it's also associated with feelings of shame, feelings of guilt, social feelings of injustice, feelings of pain. So interacting with the child is deeply unpleasant in these situations here. That image up on the right is from Edward Tronick's still face experiment, where he instructs the mother not to react to her child. And it's profoundly disorganizing for the child when that happens. Edward Tronick and Beatrice Beebe, these are researchers who have looked at the moments of attunement and misattunement between parents and their children and what the sort of subsequent psychopathology can be when there isn't attunement between the two. So what I was talking about before in terms of how the parental activation patterns can become mapped onto the child, this is also relevant for stressful adverse situations in childhood. So I mentioned that the mother who's insecurely attached has difficulty recruiting her own VMPFC. And a child who undergoes early lifehood adversity stress will likewise have difficulty recruiting their own VMPFC. They will have a decrease in reward anticipation and processing, so they're able to enjoy things less. And they will also have overly active amygdala and insulae, which, again, are associated with very heightened emotional responses to stimuli, and also that same sort of feeling of shame, disgust, poor self esteem, et cetera. So there's a close mapping between what goes on in the insecure parent and what is going to get shaped in the child's brain moving forward. Which comes back to that same intergenerational transmission that I was mentioning before. And in this case, the adverse environment is going to have an enduring effect on the child's default circuitry. And from a sort of symptomatic standpoint, what this can look like is the person sort of gets stuck in thought loops. They may be very suspicious or worried about how others are viewing them. They may have limited cognitive flexibility, because again, they're preferring those cognitive control areas over the more flexible ventromedial areas of the prefrontal cortex. Because there's a decrease in reward processing, they may have a lack of interest or enjoyment in activity in life and interacting with other people. They may have very poor self esteem. And because of the amygdala overactivity, they can have very strong emotional reactions to the environment. So a lot of this might sound very familiar from work with adult patients too, because this can happen in a number of our very common psychiatric disorders, major depression, anxiety, PTSD. What I was listing in that previous slide might be applicable to all of these, actually. And being stuck in thought loops, being suspicious or worried about how others are viewing the self, may be because of a preferential and heightened activation of your dorsolateral prefrontal cortex. The limited cognitive flexibility, it's like, oh, this is never going to work. I'm never going to be able to see things differently. I'm horrible. Everybody's better off without me sort of thing. Difficulty revisiting your cognitions can be because of an under recruitment of the ventromedial prefrontal cortex. The lack of interest or enjoyment can happen because of a decreased activation in the ventral striatum, the basal ganglia. Poor self esteem can derive from an overly activated insula, and the heightened emotional reactions from an overly activated amygdala. Now, I'm listing these psychiatric conditions here, and I'm putting them all on the same slide, because these are activation patterns which have been shown across these different categorical diagnoses. So the people who argue for the much more sort of dimensional approach to how we think about psychiatric pathology would find a lot of support in this slide here. The research domain criteria argues that we look at things much more dimensionally as opposed to categorically, because there is a lot of overlap in terms of brain activation patterns, even in things that we think of as discrete psychiatric conditions. And those are a lot of references. OK. So what does therapy do? If I told you nothing, that would be incredibly anticlimactic. So that's not the case. So people come to therapy, and oftentimes, they're stuck in kind of this situation where they have very strong emotional reactions. They have very strong emotional reactions. They have very ingrained beliefs. They have a lot of difficulty sort of revisiting what their cognitions are. And that's the person we have to work with. So they might have, as I'm mentioning, the emotion-based reasoning. And they may have a very limited cognitive flexibility. They may have very rigid expectations and templates about what's going to happen. Oh, you can't help me. I've done this before. Medications have failed. Everybody tells me I'm a loser. Everybody's against therapy. So that's basically where they are. But they did come into treatment. So that's already something not to be underestimated. And the DLPFC really is the entry point for psychotherapy because we need to meet patients where they're at and welcome the content that they're bringing. I doubt that really anybody here would say if a patient came into the office and said, I'm the worst person in the world, that the intervention we should be using is no, you're not. Stop thinking that way because it's not going to work. And if it does for you, I'd be happy to hear it. But oftentimes, what we say is tell me more or what makes you feel that way. Let's think about that together. We don't necessarily try to dispel what their belief is because it's coming from somewhere. It's not in a vacuum. It might have been ingrained and consolidated over their entire lives. And nobody's done anything to help them think differently. So we lean into the cognition. And we try to understand it more. So that's the DLPFC, generating those very rigid thoughts. But that's what we have to work with. So that's what we mean with the entry point for psychotherapy. And what I was mentioning before is in the interpersonal attunement model that I was showing earlier, this is the area of the brain, the VMPFC, that's involved with attuning to another person and being able to utilize the mind of the other person to reflect on our own internal world. And it's actually the area of the brain that's involved with developing conversational synchrony with other people, a rhythm. So if I start talking to any of you, we may adjust our conversation according to how the other person's presenting and vice versa. So this is the VMPFC. It's sort of a social dance that takes place as we're sort of adjusting ourselves according to the person who's in front of us. So we mentioned it with parent and child. But this is also what happens in therapy between the therapist and the patient, that we're kind of both trying to attune to one another in a way and utilize the mind of the other to sort of think through what the situation is, what the conflicts are. And what happens over the course of therapy is that the maladaptive templates and thought patterns that patients bring in are going to be challenged and not reinforced. So because we're not just reinforcing those very rigid cognitions that are driven from an overactive dorsolateral part of the brain, we're actually sort of kickstarting that VMPFC so that we can actually start thinking together through things. We can break up those thought loops. New perspectives emerge. And one thing that I was mentioning before is that the VMPFC is involved with attuning to the other person and being able to think through things in empathic attunement. But it's also involved in controlling our own internal emotional reaction. It's the same area of the brain. So if we're sort of experiencing an increase in distress and we're not able to think our way through things on our own, when we start interacting with another person, as we build a rapport, develop a relationship, and can utilize their mind, concurrently, we're also less at the mercy of the sort of internal state that we have difficulty controlling. And again, I'm putting a lot on one slide here. But there are converging psychotherapeutic effects with a number of different forms of psychotherapy for a number of different conditions that show, increasingly, over the course of successful therapy, that the medial PFC, the area of the brain involved in that empathic attunement and with controlling our emotional response, is going to become increasingly activated. There's an increase in the coupling between the VMPFC and the amygdala, which helps to dampen our emotional reaction. And concurrently, there's a decrease in amygdala activity, which makes sense, and in insula activity, which is that area of the brain that I mentioned was involved with feelings of shame, feelings of injustice, feelings of guilt, et cetera. So we're able to have a much more flexible kind of understanding of our internal state. We're able to think about things differently. And we're not so caught up in those very entrenched, pessimistic ways of viewing self, others, and the future. A lot of synthesis for this slide, as you can see. So a couple of questions might be emerging as I'm going through this. One being, I'm talking about the interpersonal elements, and I'm lumping a bunch of different therapies for different conditions together. Does that mean that rapport is the most relevant treatment aspect? The other question you're probably having is, why is there a dodo bird there? So there is something called the dodo bird verdict as it applies to psychotherapy. It's something that Julia and Jerome Frank talked about in their book Persuasion and Healing. And it's the notion that there's sort of an empirical equivalency between all different forms of psychotherapy in some ways. The name comes from Alice in Wonderland that when the animals had a race, the dodo bird's verdict was everybody gets a prize. So that's kind of the idea here. That ultimately, for certain patient groups, if we start looking at it, every single therapy that's kind of been validated probably has some good research backing it. And we may quibble about the technique of this, and people can have very strong views on which form of therapy is better. But ultimately, the one thing that we can't escape from is that every single form of therapy has the provider and the patient dyad, and that that aspect is very important in terms of shaping outcomes. Now, if AI takes over, anyway. And one thing that I pose to psychopharmacologists as well is, how do you explain that? That a strong alliance can also improve responses to meds. So what we're prescribing to people cannot be divorced from the environment in which these medications are being taken. And the alliance makes a big difference. I mean, you may have experienced it yourselves. I mean, I certainly do going to a provider. They don't look at me. They're on the computer the whole time. They're like, here, take this medication. Are there side effects? I don't know, look it up, sort of thing. It's like, I'm not taking your medication. Or if I take it, I'm going to sort of amplify it just to prove them wrong in some way, what could go wrong with the medication. So the alliance is very, very relevant in terms of shaping outcomes. And it's relevant across settings. So positive alliance has been associated with fewer re-hospitalizations for patients, better inpatient experiences, and improvement at discharge, and greater medication adherence, both in the short and long term. From a counter-transferential standpoint, patients who are perceived as difficult actually show less improvement on inpatient units. There's an interesting study from 06 by McKay that showed the attitude of the provider may actually differentiate outcomes more than the specific medication selected. So there's something about what we're bringing to the encounter, which is very important in terms of determining what the result of anything that we may prescribe is going to be. Which brings me to my final little section here. How do medications and psychotherapy synergize? So one thing that we've learned is that there still is neurogenesis and plasticity in the adult brain. It's not something we've always known. But it can happen over the lifespan through enriched environments, through learning. Hopefully, I'm hoping everybody's brain grow a little bit today. Through exercise, one of the areas that's been focused on is the hippocampus, which has shown continued neurogenesis into adulthood. But one little caveat that we may not pay attention to too much is that just because we're generating new neurons, it doesn't mean that they're going to be used in adaptive ways. So these new neurons actually need to mature for at least two weeks before they can contribute to plasticity and memory function. So this is sort of what we're looking at here. So we have neurogenesis. And then we have this little, I don't know if it's going to show up or not, never mind. That big middle arrow there, which shows that that's the maturation period. And at the other end of it, then we have the changes in the brain that are going to be more enduring. But during that maturation time, the environment is going to continue to exert some sort of influence. And that's going to shape what happens down there at the end on the right. So antidepressants can increase hippocampal plasticity. So there was a study which was done in chronically stressed rats, created a depressed rat. And they put this depressed rat on fluoxetine, an SSRI. And they then put the stressed rat on fluoxetine in an enriched environment, something akin to an intelli-cage, which is down there on the left. So the enriched cage has sort of a rat pier. It has two stories, a ladder, a ball, a wheel, a lot of fun stuff, right? And in this enriched environment, what they showed is these rodents had a decrease in depression-like behavior. They had an increase in the brain-derived neurotrophic factor in the hippocampus, which promotes neurogenesis. And they had lower stress hormone levels. So that makes sense, right? They're on the SSRI. And they're in a positive reinforcing environment. So happy outcomes, right? So when there's a positive continued environmental input, as in that slide, we will have adaptive consolidated plastic changes. That's what we're hoping for, that things will turn out OK in the end and that those new neurons will be used to increase sort of the adaptability of how circuits are activated in the brain. But if these stressed rats are placed on fluoxetine, and then they're put in an adverse environment, you can see down there on the left, very small, cramped cage. You have a huge intruder rat just hovering overhead. Or you put them through the forced swim test. What happens is that they're actually going to have an increase in depression-like behavior compared to baseline. So they get worse than they were before you put them on the fluoxetine. They will have lower levels of BDNF in the hippocampus. And they'll have an increase in the stress hormone levels. So you actually have made things worse with the presence of the medication in this model. You've increased plasticity. But you've really increased sensitivity. You've increased responsiveness. The brain, under stressful circumstances, shuts itself down to protect itself. It's one reason why children who are in adverse environments, traumatizing environments, have a much shorter sensitive period. Because the brain kind of locks things down a lot quicker. Because otherwise, it's exposed to a lot of glutamate, a lot of cortisol. And it locks things in. So reopening a sensitive period increases vulnerability, in a way. And that's what we can be doing with some of our medications. So this is just a summary slide here. That the medications that stimulate plasticity increase responsiveness to the environment. Whether this environment is adverse or enriching. And this environment is going to, to some degree, and this is one model of how things work. But this environment will determine how these neural paths are shaped. And things can go well or things can go very poorly. This is in rodents. Are there corollaries in humans? So it has been shown that children and adolescents who have environmental disruption do have a poorer response to fluoxetine. And if there are higher measures of family functioning, they have better recovery rates. But we'll take it a little bit further. D-cycloserine, which is a drug which is antibiotic. It's used, actually, for tuberculosis. But it's an NMDA agonist, D-cycloserine. And it increases brain plasticity. It's been used as an adjunct to cognitive behavioral therapy and exposure therapy in anxiety disorders. So it's used as an adjunct to increase and accelerate the effects of successful therapy because it's increasing responsiveness. And that is what happens when therapy is successful. That it actually does consolidate fear extinction quicker. But if therapy is unsuccessful, it may actually strengthen fear memories. So because you're more responsive to what's going on, if you have a very triggering kind of course of therapy, if you leave early, if something happens, you can actually be worse off because you had this medication which was increasing your responsiveness. MDMA is a drug which has also been used as an adjunct for forms of therapy for PTSD. It can reopen neuroplasticity windows. It increases oxytocin release. There was a very exciting study that came out a couple years ago in Nature Medicine, a phase 3 study, where people received three doses of MDMA or a placebo in conjunction with supportive therapy. And the effect size was really outstanding. It was 0.91. Whereas the effect size for SSRIs, not from this study, but just generally speaking, is usually about 0.56. It decreased depression scores as well as a secondary measure. So I don't have a but for this. This is just one instance where the use of medications or drugs to sort of enhance the effects of therapy can actually be very beneficial. Psychotherapy for PTSD, cognitive processing therapy, prolonged exposure, they have high dropout rates because they can be very activating for people. They can be very distressing when you're revisiting your traumatic scripts. So what MDMA does, MDMA is called an intactogen and an empathogen. An intactogen means I'm more in touch with my own emotions and I'm able to access them more to share. An empathogen, as the name suggests, I can empathize more with others. So I'm able to access my own internal state and share it more with the psychotherapist. So you really only use MDMA to sort of kickstart the therapy. These sessions are very long. In this study they were eight hour sessions. And it's just to sort of get things going, you know, at the beginning to facilitate retention and to facilitate engagement and to build rapport. And then you continue with the manualized protocol. Psychedelics, which have been, you know, resurging for a while now. The classic psychedelics, the serotonin psychedelics, are 5-HT2A agonists, LSD, psilocybin, mescaline, dimethyltryptamine. And this causes an increase in glutamate and also an increase in brain-derived neurotrophic factor. So there is an increase in neuroplasticity with use of psychedelics. But the drugs don't work in a vacuum either. So there really is a lot of thought that we need the work of psychotherapy, the preparation sessions before using the psychedelic and then the integration sessions after using the psychedelic in order to consolidate the benefits of these drugs. So ordinarily, our cortical-cortical circuits, our areas of the brain, you know, that we sort of lay down as kind of our map of how the world works, you know, this is where our preconceptions, cognitive constructs come from. We have the thalamus down there, which is, you know, sort of doing some gating. That's why there's a gate there. It filters the stimuli from within and outside of the body to make sure that we're not too inundated with information. Okay, so this is how all of our brains are kind of operating under ordinary circumstances. So then you come along with a drug like LSD or one of the 5-HT2A agonists, and that just breaks everything up. It's going to disrupt those cortical-cortical circuits. It's going to break up our preconceptions of how the world works. And the gating is going to be altered through the thalamus, and there's going to be much more of an influx of information. So we're sort of, you know, overwhelmed in the psychedelic state by things just kind of coming from the inside. You know, during the session, you know, you have the blindfolds, and you have the headphones, you know, with the very nicely curated psychedelic playlist, you know, to maybe control a little bit about what's coming from the outside. And set and setting is so important for the use of psychedelics to actually be therapeutic. But the thalamus really is on overdrive here. There's an enhanced flow of information coming from it, and there's that disruption of prior beliefs that I was mentioning. And a lot of the things that are going to be coming to mind during the psychedelic session are autobiographical memories, relationship patterns. But because we're not so weighed down by our preconceptions, and because, you know, we're able to think about things so differently and view many different possibilities, we're able to develop new cognitions and alternative narratives. And, you know, we come out with a different sense of purpose. You know, we may be visited by some sort of guide during the actual session telling us what we need to be doing, things like that. People want to heal relationships. There's more pro-ecological behavior on the other end of psychedelic sessions as well, more openness and connectedness with others. And this is relevant for the integration sessions that happen post-psychedelic session, because there's something which is called the afterglow period, which is after the psychedelic state, where the person does have an increased energetic mood, and there's a greater willingness to enter close interpersonal relationships. The afterglow period can last two to four weeks after the session, and importantly for our purposes, the effectiveness of psychotherapeutic interventions can be greater during this time. It's very important to have those integration sessions later. The drug isn't just going to work on its own. And importantly, in psilocybin use, the strength of the therapeutic alliance with your provider who you were doing the prep work with before the actual session and then with whom you do the integration sessions later, if you have a good rapport with the provider going into the psychedelic session, that actually predicts emotional breakthrough, mystical experiences, and improvement in depression scores. So even for psychedelics, which is so ostensibly an intrapsychic journey, there is an interpersonal element which is shaping the outcomes. So that's what I have for right now. We're at about halfway here, and I'm putting the references here, but there's a little green folder over there at the end of the session if anybody wants. I've listed most of those as well, but we'll have a couple minutes if anybody has a comment or a question, but thank you for listening. And if anybody does, please use the microphone. If there are no comments at this time, we'll... Yes, yes, please, please, please. I'll ask a quick one. So in October 2021, the Orange Journal actually published about escitalopram increasing the connectivity between the ventromedial PFC and the amygdala. And ever since then, I've been counseling my patients on that, and then I've also supposed that the connection is increased by therapy, and I've been counseling on that too. So I appreciate the fact that you have validated my assumption that therapy actually does that. Any other, I guess, significant changes that you've seen through therapy in terms of dealing with intense emotion or dealing with some of that stuck nature of the thought process that you mentioned, specifically with the dorsolateral prefrontal cortex? Yeah. Thank you. And it is interesting in terms of the medication bit because, you know, there is some similarity in terms of what the end result is with that increased connectivity between VMPFC and amygdala, but the way that it happens is different. It seems that the SSRIs, for instance, are going to be tackling the amygdala in a way, where they're going to be decreasing sort of the expression of like excitatory receptors such as 5-HT2A. Those get downregulated over time, which sort of frees up the VMPFC to kind of increase some of those connections. And with the psychotherapy, we're working on the VMPFC to build that up, and over time that can start having a top-down effect. So it's a little bit of a bottom-up versus a top-down but the end result is very similar. So I think in terms of the second question, you know, I guess it's part of the just nature of, you know, how psychotherapy evolves. I think that, you know, some people can become very stuck in, you know, in ways of thinking and we really only have access to them one to two hours a week sometimes. You know, even if you're doing analysis, you know, Freud would talk about the Monday crust because he would see people six days a week and then not on Sunday. And he's like, well, come Monday morning, we got a lot of work to do because you weren't analyzed on Sunday. So, you know, these patterns get, you know, laid down very early on in life and, you know, I think it's the topic for a different discussion altogether. Just, you know, how the brain protects itself against further change, especially in adverse environments because it can be a matter of survival. You know, I can't have too much flexibility early on in a dangerous environment. I can't be sampling it endlessly. So I think that's kind of what we're up against in a way. But, you know, it helps. It's a process. Yes, please. Good afternoon and thank you for doing this lecture. I had a question. When you did the slide on the D-cycloserine and some of the outcomes were related to, well, I was just curious about the causality of is it successful, unsuccessful therapy that determines outcome or was there consideration for actually the D-cycloserine itself causing, like a sick person just doesn't do well in therapy versus someone who's doing better, less fear response. Those are the people more likely to successfully complete therapy as opposed to saying it's the therapy that caused the bad outcome. Did that make sense? Yeah. So I think in those models, what the thought process is that the therapy that maybe proves a little bit too overwhelming or a little bit too activating for the person and they're not able to kind of complete it successfully, that their anxiety is going to potentially be compounded and that they may, you know, be in a worse situation because the medication was also sort of increasing just how bad of an impact that distress was going to have on them, so to speak. So the thought is that it can accelerate, like if you were in just a regular course of like CBT for anxiety, for instance, you know, it might take, you know, a time X to get to that end point, but under D-cycloserine, it would take a little bit less time because it's there to sort of increase your responsiveness. So if you have a good course of therapy, you might not need to be in therapy as long and you can consolidate those changes quicker. But on the other end of things, you know, if things go poorly, you know, you might have had a little bit of a worsening of anxiety, you know, a little bit of disappointment if the therapy wasn't going well, but because there was this medication that was increasing your susceptibility, you know, you might be in a little bit of a worse place, you know, because it's going to consolidate things, you know, even stronger if things don't go well, if that makes some sense, if that was what you were asking, if I understood your question. Okay. One more and I think then we'll transition. Yes. Yes. These days, a lot of our patients are on medical marijuana plus different psychotropic medication plus psychotherapy. Can you comment on that, please? Effective combination of medical marijuana and other psychotropic medication. Okay. So the question is, if I understand, the combination of medical marijuana with psychotropic agents. Yes. And psychotherapy. Yes. You know, I often joke that we're probably doing cannabis-assisted psychotherapy a lot more often than we think. So, yeah, it's a big question. And, you know, I think it's sometimes, I think, you know, the cannabis is something, you know, just like any drug that the person has at their disposal, it's predictable, it's reliable. You know, it's there at midnight when they're distressed, you know, it's something therapists can hear often. It's like, and you're not, you know, that's why I turned to the marijuana. But, you know, I think it gives us, it's challenging, you know, to know just how much our medications are actually making the difference and such, you know, people who are under the influence, you know, during sessions, which, you know, has happened, you know, it certainly is harder to engage. You know, there is a very interesting study that came out, which looked at people who are using psychedelics and have used cannabis concurrently, that the use of cannabis can actually hinder some of the benefits from psychedelics, particularly reaching states of grief, which are actually important in terms of some of the healing process that the person goes through in terms of interpersonal templates and such. So, at least in that model, and, you know, I've known people who, you know, tell me, you know, that I use marijuana really to just numb myself, you know, because otherwise it's all just too much, you know. So, I think that it's a medication, it's, I mean, medical marijuana in itself might be a way of, you know, just kind of tamping things down because it's so difficult to think through things, potentially, at least in some instances. But it's hard to generalize, I think, you know, and I imagine there are a lot of people who use it judiciously. So, but it's not something that I prescribe, so. But that's my perspective for now. Yeah, hi. David Hellerstein from Columbia. So, really interesting talk. It's interesting to see how the kind of neuroscience component of psychotherapy has really, I think, matured as a, you know, in terms of understanding and kind of bringing together diverse theoretical and practice-based kinds of interventions. I'm curious, one of the things since the pandemic has been a proliferation, sorry, proliferation of web-based treatments and, in particular, ketamine being sent to people who've never met a therapist. There's web-based therapy that's being conducted. And, actually, many of my colleagues in New York are also telling me, oh, yes, I'm getting ketamine lozenges made up by local compounding pharmacies and so on. And so, it seems that there's a kind of, I don't know if it's a movement or a fad or development or whatever of this being integrated into routine practice, both through these internet-based kind of startups and also just clinicians in practice. So, I'm wondering what your thoughts are in terms of the efficacy of this and if there's studies going on and kind of risk benefit and, you know, how that might fit into the model that you're talking about. In terms of, like, web-based psychotherapy. Well, do you think that that kind of combining of medication and therapy is likely to be an effective kind of treatment and, you know, would it enhance the kinds of outcomes that you're describing in psychedelic and other kinds of combined treatments? Yeah, the neuroscience of web-based therapy, you know, I think there's probably still a lot to be done in that regard. I think just from a subjective standpoint, you know, in person, the feel of having somebody in person is very different, you know, from having somebody on a camera, you know. It's like I have the experience often of saying she's looking right into my eyes and yet, like, the eyes are completely off because it's, you know, it's so, it's just very different, you know, you don't have the eye contact, you know, you don't have that sort of presence, you know, which is just, it can feel very powerful, you know, sort of containing someone's emotional response in person versus, you know, on the internet, you know, and people can, you know, be in very weird environments, you know, meeting patients where they're at gains a different meaning when they're, you know, at work or in their car or, you know, in bed with their cat on their head or something, you know. Or at the local grocery store. Or at their local grocery store, right. It's just, oh yeah, there's my credit card. Oh, what were you saying, doc? Right. So, I mean, the frame, you know, and, you know, we can think dynamically about, you know, what that means, but it's, you know, but there is a lot of research showing that, you know, like virtual therapy is effective and, you know, that, you know, the difference may not be as pronounced as we might think and, you know, even like psychoanalysis training, you know, there's some institutes that might allow cases to count without you ever seeing your patient in person once, you know, and there are a lot of opinions about that. So, I think it's sort of an evolving situation. It has allowed a lot of people to remain in therapy who might not have been able to otherwise. And what about the ketamine component? Ketamine? Yes. In other words, these companies are doing, they're mailing people ketamine and the assisted psychotherapy of the therapist who they've never met in person is done with ketamine ingestions as sort of a way to provide the treatment. So, I don't know if, have you been aware of that? I mean, it seems like a pretty rampant practice. Yeah, yeah. There, it is, yes. And there's sort of a BYOK therapy situation going on where it's like they'll do the therapy, you have to bring your own ketamine though. And, you know, and I, you know, there are case reports out there in the literature, you know, where they will use, you know, doses which, you know, can, you know, be much more sort of dissociative in a way because ketamine is a different drug at different doses. You know, at 0.5 mg per keg, it's one drug. At 1 mg per keg, it's a different drug. At 2 mg per keg, it's a different drug. And, you know, there's a lot of variability in terms of the doses that are used during therapy. You know, in the same case report, you can read they used a low dose and it sort of allowed them to, you know, relate to me very differently. In another session, I gave them a blanket, they used a much higher dose and they tripped and we talked later, sort of thing. So, you know, and they would use it to sort of get out of sort of stalemates in some ways or gridlocks and break things open up again. And, you know, for some people, it's very helpful. You know, I've talked to therapists who use ketamine, their patients use ketamine, and they have found it, you know, striking in terms of what it can do. I don't have personal experience treating patients who have used ketamine. So, I have an open mind about it, but, you know, the variability and, you know, sort of the lack of controlled studies in terms of, and it's a different drug than the psychedelics really. So, it's a different mechanism and I think it's a different consideration. We do have to move on to the vignettes though, but we can certainly talk more later. Yes. Okay. Well, I believe Dr. Tisenberg is going to guide us through our first vignette and we're going to have an interactive portion here. So. Good morning, everyone. So, we were hoping to have some vignettes put in to kind of take some practice with thinking about the neuroscience and how we want to communicate it to patients in helping build rapport for some patients. It's really important to understand how this works and how it's different than medication. I think it's important to kind of conceptualize how we want to communicate that before we're kind of in a position where we're doing that. So, the first vignette, V is a 24-year-old transgender male to female person with a reported history of treatment-resistant depression who was admitted voluntarily for worsening suicidal thoughts with a plan to hang themselves. They have struggled with chronic suicidal thoughts since early adolescence, have never attempted, but have come close several times. They often call crisis hotlines when they feel overwhelmed by suicidal thoughts and sometimes get admitted to psychiatric hospitals. They have been trialed on multiple antidepressants, mood stabilizers, antipsychotics without significant improvement. They deny any substance use because they are too impulsive and worry they would easily become addicted. This is their fourth admission. The patient and their family feel desperate that nothing has helped and want to try transcranial magnetic stimulation or psilocybin. When asked how we can be of help, they respond, all you psychiatrists do is try to drug me up and it doesn't change how I feel. For this patient how would you encourage them to consider therapy amongst their frustration with treatment? They've tried various medications, nothing's really been effective, they're kind of reaching out. Sure, sorry. So with this patient who's been admitted multiple times, been called on crisis hotlines, they have been trialed on various medications from different classes, how would you go about encouraging them to consider therapy in a setting where they're very frustrated with treatment, they're hospitalized again, they're not really seeing any benefit from engaging in treatment, and this is something they haven't tried yet? So, I think the biggest thing I would need to get them to engage in therapy or try to convince them to engage in therapy is I need some kind of hook. So I would be trying to talk to them, trying to delve into essentially kind of like we were talking about, like that dimensional thinking, like get a dimension that we can actually work on in therapy, explain how that would work, and use that as the motivation to try to get them in therapy rather than vaguely saying, you know, I mean, maybe they just need someone to talk to, maybe they just need some support, but they sound like they're looking for what can you actually do for me, what's this actually going to do, don't just throw something at me, don't just throw a med at me, don't just throw therapy vaguely at me, give me something we're actually going to operationalize and work on, right? And I don't know what that is with this person yet, because I don't know enough detail about them to really say, oh, here's the thing we're going to work on, and here's how we're going to be able to help you with that. But I think in talking to them, you could get there pretty quick. Yep. Thank you. Absolutely. I concur that trying to establish some degree of a relationship, a therapeutic relationship is going to be important going forward, based on what we had just talked about. I think there's an opportunity to get a little bit more detailed history about how their previous hospitalizations went, the length and the duration of the follow-up, and then try to provide some psychoeducation about that neuroplasticity that we've been discussing about the environmental context in the weeks after initiating a therapy or initiating that kind of level of engagement, both to offer them a chance to hear them more, to develop that relationship, be empathic about their previous experiences, and then try to set up some degree of how this is going to be different, how we're going to try to plan around that follow-up care to utilize that period of the neuroplasticity. Thank you. Hello. So, building on that idea of like psychoeducation, kind of coming from a personal standpoint, I know that for me, like rationalizing things helps a lot, and it seems like for this patient, based off of their comment about kind of avoiding substance use because they think that they're too impulsive, it seems like they already have that kind of train of thought that's very scientific and rational, so I feel like presenting them with information regarding the combined approach of psychotherapy with medication could probably be beneficial, because based off of the information presented, it seems that just like medication alone hasn't been helping, and this would be kind of like, okay, let's build on the approach we've already taken. So looking at the chronic history of suicidality, their attempts to reach out for help, that ambivalence with life or death, I would really propose reassessing diagnosis to consider if there's maybe some borderline personality disorder. In individuals with borderline personality disorder, they seem to really resonate, because it, oh my gosh, this fits me so much better than any depression or bipolar diagnosis, but the catch is, with borderline personality disorder, the treatment interventions, we got to do more DBT-oriented, but of course, there's still this kind of, they need the medicines as well, but if they feel connected with borderline personality disorder, then the DBT is what it was designed for. So probably reassessing diagnosis to let them know there's a different treatment modality that medicines just don't have the same evidence for. I think I would be interested in how they handled the transgender piece. We've already been through something that is, I think probably combines a certain amount of talking and trying to think through and feel through a complicated situation that I imagine was, added some medical treatment with that. I don't know where they are in their transgender process, but I think that might be a, if it was a successful process or one that they felt they were supported in, you could use that as an example of something that could be helpful for, I guess, the state of the chronic suicidal thoughts and thinking, can we combine a relationship and thinking more about what this means and medically trying to help you at the same time. And they work, they reinforce each other. I might ask more about that. I wanted to build on the statement that was said about reevaluating diagnosis to consider at least some contribution from borderline personality traits in someone who themselves is endorsing impulsivity, chronic suicidality, unclear from the vignette whether there's any affective instability, identity disturbance type issues. But what I would say is the hook that I sometimes use in cases like that is starting with a chapter of a DBT workbook that I think they might really resonate on, one about impulsivity or something like that, and being able to give that to them and say, I just want you to read this chapter. And as the previous person noted, omnibus, they very much resonate with that. So you could say, hey, this is something that I think might be useful to you. And while they're on the inpatient ward, oftentimes they have some time to read it. And if it does resonate with them, then you can say, hey, well, this is actually part of this larger therapeutic process, dialectical behavioral therapy. If this chapter resonated with you, if you feel like this was something that spoke to you, then I think dialectical behavioral therapy actually could be a significant contribution to your treatment plan. Hi. Your description and the case vignette basically takes the viewpoint from the symptoms and then thinking, what are you going to do after that to fix the symptoms? One of the comments in an earlier session about psychedelics that I found very useful was they talked about this paradigm shift from symptoms or your illness being simply an expression of an imbalance of neurochemicals and that you put in medications to rebalance that and then what you end up with is chronic use of medication in an attempt to kind of rebalance, when actually what is happening, and I guess it kind of consolidated my own thoughts and feelings about the emerging neuroscience and the link between the thoughts and the chemicals, of course, and so what I'm at pains to do now with my own patients is to explain to them, yes, they have symptoms, and yes, their symptoms, which are their thoughts and feelings, which are distressing, are mediated by chemicals, so thoughts are formed by chemicals, but chemicals are affected by thoughts, and it's an interlocked system. It's not like thoughts are out here in some ether and that you are embodied in your kind of neurochemical fleshly self. They're one system. So, yes, you have symptoms, but the thing is something is causing those symptoms. Something is causing those thoughts, and that's inevitably in their past or in their development or in their life experience that they've had. So, yes, chemicals are great, and medications are great, and they can work, but that's not the whole picture. Your illness is a fire, and yes, medications, I always explain to my patients, they're a crutch, so if you've got a broken leg, you can't walk, you take medications, they can help you to walk, but they don't get you down the road. You know, they don't fix the leg. Therapy will fix the leg, but the thing is that if your leg is so broken you can't even get up, then yes, medications can help, but they don't get you down the road. They don't make the road any smoother. They don't get you around the bumps, so the medications can get you on there, but you still have to get down the road. Medications are not a magic carpet that will transport you. You've still got to do the work, which is psychotherapy of whatever sort. So that, for me, is how I explain that link that, you know, it's not all about the chemicals. Yes, for some people, they are so damaged that all you can do is use medications because, you know, we talk, obviously, about having the psychological strength or ego strength to get through therapy, and some people are so damaged that really, you know, there's no opening of that door because that amygdala is just way overactive. In those cases, then absolutely, maybe chemicals is all you can do or your therapy is about keeping that door shut, but having said that, for most people, it is possible to open that door, and that's what psychotherapy is about. So I heard people speaking about, you know, how you explain these different things and you're going to be able to appeal to this person's cognitive, you know, intellectual skills and understand why these things didn't work and why they're going to work, but I think unless you engage the person initially in terms of why, what didn't work, and why do they think it didn't work, and start hearing them, and so that you're engaging, I forget the ventral medial part, you know, in that, and hearing what they're saying and getting a connection using their cognitive strength that you've seen that they have some abilities there. Then you can decide to pick and choose, you know, is it a borderline issue that you need to, and some people get really, felt rejected by that, some people feel really embraced by that, depends, but, or is it the fact that they dropped out of therapy in their vulnerable times, as described by someone else. You have to hear from them what it is first, and that really does match your model of that initial engagement, and then speak to the learning process and how this, how we might proceed that might be different to engage the person, and that's kind of how I would start, I think. Thank you. I'm going to pass the microphone to Dr. Dubinoza, another vignette. Good morning, and thank you for those who lasted more than 50 minutes. It's really a pleasure to be here. Thank you, Dr. Miller and Dr. Zisenberg. I have to say that I love this case because I feel like it reflects so often and so much of what I see, and I've really enjoyed the comments thus far, and I hope to hear from you about this. So case number two, and this is really about institutional bias against psychotherapy. Jeff A. is a 24-year-old single male who has just made his third visit to the emergency room for chest pain accompanied by diaphoresis and tachypnea. Cardiac workup has not revealed any pathologies or abnormalities. He's given five days' worth of benzodiazepines, started on an SSRI, and of course referred to the resident clinic because this is a great case, although it so happens to be that it is. Upon presentation to the clinic, the resident evaluates him and notes that the patient's symptoms began right after he got a promotion at work. The patient is the youngest of four children. Growing up, he had been labeled the goof-off child. Also, not long before the chest pain began, the patient had gone through a difficult breakup in his first serious long-term relationship. In parting, his former partner told him, you are a big-time loser, and you will never amount to anything. The patient states that this has made him feel worthless and unworthy. The patient also complains of decreased libido on the SSRI, but would really like a reflow on the benzodiazepine. The resident presents his case to a psychopharm attending, along with his initial psychodynamic formulation of the case. The experienced and revered attending states, clearly a case of panic disorder. We need to adequately medicate the patient and get these symptoms under control. We can also switch SSRIs or add another medication for the libido side effect. I would tape him off the benzodiazepine as quickly as possible. The resident adds that he would like to address the underlying psychosocial issues that may be driving some of the anxiety. He would like to explore the sense of worthlessness the patient has come to identify with based on his family of origins label affirmed by his ex-girlfriend. The attending responds, all well and good, but let's address the underlying biological issues with the medication first. We can do a little tweaking later if necessary. Thoughts, comments, how would you respond? What are some key elements to consider? How would you suggest managing this case? In what ways could internalized childhood messages play a role in the patient's current presentation? And what might be the role of psychotherapy for this patient? So one of the things you mentioned earlier was the insula and the way that the insula kind of has this very negative, you know, over activation insula can have these very negative self-concept. I think that sounds like what this person has going on. I think we need to recognize that when people present with patterns of behavior or thought patterns, you know, some people will benefit from actually talking about the fact that there's a reason why and there's a part of your brain that's responsible for this and it has a really great function in some cases. So kind of growing up, if you were always called the goof off, always called worthless, as long as you kind of internalize that, you can laugh it off and goof it off. Just doesn't work when you're an adult, still trying to use those very juvenile ways of shedding all the negativity. And so, I'll commonly start with the line, you have a brain, I have a brain. Both of our brains were designed to survive and there's a part of your brain that has to do with the exact situation you just described. And sometimes that's really freeing for people to realize, like, oh, my brain's actually trying to survive and over a pattern of survival, it created an overactive insula. And let's talk about how therapy can address some of those things and maybe make that fluid again so that you can balance out the other parts of your brain that are supposed to be more healing and protective. I like that empathic way of joining with the patient. And really, like in DBT, we talk about the patient is trying to survive and she's doing the best she can. And that's why we never use the term manipulative. Go ahead. Yeah, I think relative to your first question, you know, what from today's workshop might be key to consider? I think one thing is key to consider is starting an SSRI, having an impact on neuroplasticity, it certainly depends still on what's going on in the environment, right? So without removing the stressor that's going on, or kind of mitigating the response to the stressor that's going on in the environment, the potential of what we're doing is kind of reinforcing the stress response as opposed to helping them to kind of work through that kind of by having a combined approach of medication and therapy. And I think that's my bigger observation about this is that the conversation doesn't have to be mutually exclusive, right? I think that to see, well, you know, we've got medication management and we've got therapy is hopefully something that we're kind of growing out of, right, that our field is recognizing that there's some benefit to the combination of medication and psychotherapy. And I think that's what's interesting about this vignette on a second point to me is that, you know, it's kind of made very specific. Well, this is the psychopharmacology attending who is supervising them in medication management clinic. Because, you know, I'll speak as a resident myself, I'll speak to the fact that like, within our psychopharmacology clinic, a number of our supervising attendings have a lot of interest in psychotherapy, right? And so the way that they present it is it's by no means mutually exclusive. And in fact, some sort of therapy occurs in every medication management appointment, right? So even if it's not like I'm doing a protocolized CBT type therapy, some sort of cognitive behavioral or at least supportive therapy occurs within a medication management appointment. So I think to make it mutually exclusive and say, you know, no, we do psychopharmacology or we do psychotherapy is to miss out on the benefit of the combination of the two. It is. And depending what institution you are in, this patient might end up with very different treatments depending on the biases of the institution, where there is a lot of weight for that combined approach. Thank you for mentioning the CBT. And I think I would be torn with the idea that it's a psychopharm clinic and they probably need to be in and out quickly. But the other part of me is I'm thinking if you could just introduce or tempt them with a printed CBT log, okay. You can use that Benzo, but use the opportunity of the next panic attack to go ahead and try and fill out the CBT log. And of course, by the end of, if they actually make it through it, you know, they may not even need the Benzo. But the idea of pairing the Benzo with some type of attempt to do at least the first few sections of automatic thought log, and then maybe that will get them to whatever automatic thoughts that are occurring to them around the time of the panic attack. But they will probably need to be referred really quickly. This is a CBT log that we need to get you started in the resident psychotherapy clinic, perhaps. Fantastic, because as a CBT person, of course, I really applaud that. I would add a comment that I almost wouldn't want them to use the benzodiazepine as a rescue because I'm giving them the message you need to be rescued from your panic attack, but a finer point, go ahead. Hi, Jeffrey Smith, I'm the leader of the Psychotherapy Caucus. And, you know, there are a couple of things that just jump out in this case. One is if we ask, why is he a goof-off? I'm guessing that it's because he was overwhelmed with the idea of meeting the expectations that were there for him to perform. And the other fact that we know is he just got a big promotion. And universally, human beings feel a need for extra support at times of extra stress, like having to fulfill the demands of a promotion. And this is a guy who's already inadequate in that area. So I think we already have enough to say that there's a major need for human intervention with some understanding and maybe helping him realize that he really is under tremendous stress and at a time when the supports are also disappearing. So just a thought. Thank you, wonderful. Thank you. I too was concerned about some things that jump out with this one. And one is that if you're talking about a vulnerable time where the person is coming in and maybe you're starting them on an SSRI, even though they have some side effects they're not real keen on, and you might be able to switch it around or whatever, but you've sort of also in this vulnerable time begun teaching him that he needs a benzo. And so that's what he's learning right now, is especially if you focus on just the symptoms. And so I think all the previous people's comments about this either psychodynamic way of looking at it, a CBT way of looking at it, and getting the person involved in some kind of cognitive changes, preferably if they have the benzo as a rescue, as someone mentioned, where they don't have to, and I don't think it was mentioned earlier in this, I did come in late, but it does seem like very often, certainly in the PTSD literature, there's concerns about the benzos preventing the laying down of new ways of doing things. So now you've opened it up, but now you've got a benzo that's not gonna let you learn a new thing. And so in some ways, the only thing you're learning is I've gotta have a benzo. And I think most of us know how difficult it is sometimes to moving forward down the line, okay, now it's time for therapy because you're struggling here and this person's stuck. To get new learning on that, they're stuck on the benzo, you have real trouble moving in a different direction. So those would be my biggest concerns and using the model about when new learning is that you've presented gives an explanation for why. Exactly, and we have a saying at our program, I believe originated by Dr. Miller himself, but psychotherapy is a biological treatment, right? That is the whole point. And I think that we can do so much for our patients, especially if we are aware, we're sensitive and we carefully combine the psychotherapy and the psychopharmacology in a way to maximize our patient's results. Other comments or Dr. Miller, did you wanna make some concluding remarks? Well, thank you. We have about five minutes left. Any general questions, comments, any feedback, anything else that pops to mind either about the vignettes or the initial part or anything, use your reverie. I just have like a short question about this case. I realized that we're suggesting that we offer a lot of things to the patient, but taking away the benzodiazepine that he's already been on, how does that fit in your consideration when you're like thinking about a case like this in terms of like, you know, somebody comes to with a few problems, even though it relates to like a life crisis that just happened or like pattern of behaviors, but you're taking away something that he's had right at the initial meeting with the patient and it might be too much for the patient at that point? I think even the way you're saying it is very powerful, the taking away. I think I wouldn't want to be withholding or taking away. I would want to be transitioning him, giving him the awareness that that benzodiazepine was helpful. There was a role for it, but in the long term, we have other approaches for him. But I wouldn't want that patient at that point to feel like anything was being taken away. Rather, we're giving him more. We're giving him tools, we're giving him psychotherapy, we're giving him medication. And I wouldn't feel an emergency like this day we stop it or that day we stop it, but there'd be some sort of a taper. But I think you're right. If their patient pursues it as taking away already, that's going to have a negative impact on the treatment. So thank you. Okay. Thank you for a really clear and illuminating presentation and great vignettes on these core concepts. Yes, everything is, you know, all of this is located in the brain, whether it's medications or the psychotherapy. And the more that as a field we can kind of integrate rather than split all of this, the better it'll be for all of us and for the patients that we're treating. I'm curious, thinking about this, because I know you've been working on this for a long time, I'm curious, thinking about this, because that's what we need to teach the rising generation of psychiatrists, if you could comment on how you integrate this into your psychotherapy training or your, I should say your residency training in general, because it's covering both sides. I feel like we may have planted you here, because this afternoon's lecture is on an integrative psychotherapy curriculum, as is one of our presentations tomorrow. So we are very passionate about this. And, you know, what we want to give our patients is every tool in our armamentarium, not just one hammer, not just one nail. Thanks for the great presentation. I was thinking back to the earlier part of the presentation where there was data presented on, like, fluoxetine and the stressful environment and how that led to more adverse effects. And so I'm wondering what implications that might have for us if we're prescribing SSRIs to people who are having a lot of adverse conditions, like maybe not being housed or having a lot of psychosocial stressors, and if we might be causing harm and if we should be informing patients about that. I know you mentioned the data on the other medication, but I'm wondering how you might think about counselling patients about that. Yeah. Is this microphone working? It is, right? OK. It's a good question, and this is one model. Now, there are other models out there, you know, that may support efficacy of medications even in adverse environments, but I do think that this is useful to me in terms of sort of broadening what our intervention strategy is because I think medications end up being, you know, under a great sort of omnipotent fantasy in our minds in a way that they're going to do everything. You know, you give the medication and somehow that's going to change everything, and it doesn't. And I think, you know, when we're talking about enriched environments, you know, sort of allowing the medications to have optimal benefits, we may wonder how can we do that, right? Because, you know, we can't give them, you know, a different, you know, sort of social support necessarily, but there are things we can do. And, you know, even if it's just focusing on the therapeutic relationship, you know, if you have a 15, 30-minute medication visit, I mean, are you really just going to be talking about meds the whole time? I mean, you're not. I mean, you couldn't, really. So the presence that you offer, you know, having a benign, quiet, welcoming environment for patients is already a form of environmental intervention, encouraging them to come to groups, encouraging them to come to therapy on a weekly basis. You know, we have a sort of community treatment teams that go out to where people are. You know, if noncompliance, nonadherence is an issue, if they're unhoused, for instance, you know, we have mobile teams that, you know, can go out and meet them. Where is it convenient for you? So, you know, really making it collaborative, and I think, you know, the recovery model is very sensitive to the fact that people have undergone a lot of adversity, a lot of trauma, and they probably still are. I mean, the people who have suffered trauma the most are those likely to suffer it again. So I think keeping a much broader awareness of the elements in patients' lives, you know, our philosophy is already going to be very different if we have that in mind when we're prescribing a medication versus, you know, first encounter, checklist approach, this is what's going on, that's what we're doing, goodbye. You know, I think that's where we run into problems, and maybe that's where, you know, some of those adverse outcomes, you know, erratic compliance, I'm having some adverse effects, I'm going to use, you know, substances to kind of deal with it, I'm not going to go back to appointments. So, you know, I think having a much broader awareness of the patient's reality is really what helps the medications work best. Quickly piggybacking on what Dr. Miller said, I think one of the greatest things you can do in your first session, the two greatest things are instill hope and convey that empathy, because all of that will help you overcome the psychosocial and biological issues that you're dealing with. I think we are at time officially, but if anybody has any other, we'll be hanging out for a little bit. Thank you very much for coming. Thank you.

psychotherapy

neurobiology

neural circuitry

psychiatric disorders

therapeutic alliance

neuroplasticity

early adversity

trauma

psychotherapeutic strategies

psychedelics

holistic care

interactive vignettes