Good afternoon. I can't hear you. Good afternoon. You know, when it's so packed, it's so difficult to hear the sounds. Hey, thank you all for being here, and I want to thank Brian Shiozawa Jr. for inviting me to present. I know he can't be here today, chicken, but it really is my pleasure to talk with you. I'm Mark Rappaport. I'm the chairman of the Department of Psychiatry at the University of Utah, and I'm the CEO of the Huntsman Mental Health Institute. We're going to talk a little bit about COVID-19 and the fact that it really has been the second pandemic. You know, what we'll do is review the impact of COVID-19. We'll talk about some intervention strategies that can be used in different circumstances. We'll talk about specific interventions for healthcare systems, and also a little bit about the biology of COVID-19 because I'm a nerd, and also because my lab looks at the interface between the brain and the immune system. You know, one of the things that all of us need to recognize is that none of us ever were prepared to think about an unimaginable life-changing event. We weren't prepared as we grew up. We weren't prepared in our education and feedback, and we weren't prepared in medical school or in our training at all for what happened. And it really had a profound impact on so much of who we are in so many ways. And the other thing that happened, do you guys remember the beginning of this pandemic? You know, there was this fantasy that there would be a wave, and then it would resolve and be over with. I mean, that's what we all believed, right? And our fantasies were shattered, absolutely shattered. So we went from one set of beliefs about what was going to happen to another set of absolutely unimaginable beliefs. And you think of the Delta variant, and then you think of the Omicron variant, and then the B2 variant, and the other variants that are emerging. And I have to tell you, I was so worried about doing research for this talk and talking about the mental health aspects of this, hack, three weeks ago I decided to get COVID. So I can also talk from personal experience now. We actually had an event here three weeks ago, and as it turned out, it ended up being a super spreader event. We had the leaderships of the American Psychiatric, the American Psychological, the Social Work Organizations, the American Foundation Suicide Prevention, and others involved because we're launching a national 10-year grand challenge to eliminate mental health and substance use stigma. Another talk, another time. But it ended up being a super spreader event, and it gave me personal experience with what I'm talking about today. You know, it was world-changing, you know, in terms of supply chain and interdependence. It emphasized the vulnerability we had because of the inexpensive travel that is now available to individuals. You know, it's not as if these types of viruses or infections didn't exist previously. But they tended to be much more circumscribed before we had the types of travel we have today. It changed our business models, our education models, our communication models, how we socialize and develop skills for our kids. It changed housing dramatically. All you need to do is look at the cost of housing right now and also the egress of people from cities into other areas. So it really was world-changing. And it really changed basic assumptions that we had. They were invalidated. The assumptions we had about our lives and the regular rhythm and normal components of our lives. It's completely invalidated work, how work was done, going to an office, unless you were an essential health professional like we were, or the police or fire department or the people bringing food. Our roles. There was role diffusion that occurred that had never occurred before. We went to work. We went home. We had a role at work. We had a role at home. That no longer exists. There was stability of basic resources were invalidated. They no longer, it was no longer, do anyone remember when you were frantically going to Costco to get toilet paper? And there wasn't any. You know? In terms of our society, in terms of the certainty of the future, you know, all of us fantasize that oh, we're going to live this life, we're in control of what our future is going to be. And all of a sudden, with this pandemic, there was this remarkable shift. There was a foreshortening of future for many people. A lack of thinking for the first time, I don't know if I have a future. These led to experiences of vulnerability, both for the individual, but also vulnerability about the people we love. You know, there are so many people that who worked in hospitals who found other places to live initially because they were frightened of exposing their family to COVID. Mortality all of a sudden took a different feel. Most of us have this feeling of omnipotence about our lives, and, you know, we sort of deny mortality. COVID-19 threw it in our face. It was a remarkable shift individually and from a societal point of view. We have these fantasies about certainty in life, patterns in our life, anchor points in our life. All of a sudden, all of that got thrown out the window, remarkably so. The role diffusion we talked about, the isolation, I remember I gave a series of lectures to different companies during the first couple of months of the pandemic because there were all these individuals, particularly single individuals, living alone who were completely isolated from all of their supports and everything else. And it really was a remarkable experience. As were sadness and grief and morbidity, concerns about illness and guilt. These were feelings that hit people in the face in ways that never had previously. And one of the major issues that we faced as individuals and as a society was about inequality. It really brought home the inequality that existed in terms of health care, in terms of access to food, in terms of protection, because many of the most vulnerable people had to go to work every day. They couldn't work remotely. They couldn't work in their home. It really highlighted the tremendous inequalities that exist in our society and the inequalities that exist between industrialized nations and nations that were becoming industrialized. So what's the impact in terms of individuals, family, workplace, citizens, society? For the individual, there was a loss of agency, a loss of a sense of control of somebody's life. We normally have this fantasy that we're in control of our lives, and all of a sudden, for most of us, for the first time in our life, we didn't feel in control. And that's a horrifying feeling for individuals. The role of the fusion we've talked about, the uncertainty about future, there was disruption in sleep, disruption in life patterns, disruption in social supports, exercise. And for many of us, there were feelings of true grief and trauma. And it's important for us to realize that as individuals. For our family and friends, there was increased activity with the nuclear family, but decreased activity with one's friends, one's loved ones, one's grandparents, and others. You know, there was isolation from loved ones. There was fear of exposing loved ones to COVID. And our children really were devastated by what we saw. You were saying? A little more projection? I can do that for about 30 seconds, and then I'll go back into my therapeutic voice. If we look at workplace, the unemployment that people in restaurants, people working in hotels experienced, remote working, inequalities in workplace exposure, burnout, helplessness, grief, confusion, trauma. And you know, it's really interesting, the breakdown of culture. The breakdown of the culture of, think of your health systems, the breakdown of culture within your health systems, the breakdown of culture within companies. There was a real change, and we haven't figured out yet how to deal with it. You see it as people have decided, rather than to work for large corporations, or rather to work, you know, in healthcare or something, people are doing their own thing. This is a real change in our society and what happened in the workplace. If we look at cities, there was an increase in violence. There was a disrespect for law enforcement, a disrespect for social norms that developed. There were huge conflicts, and we see it all the time. You know, just think about all the contradictory information and rules, depending on what city you were in, what building you were going in, what state you were in, about what safety was. This is tremendously disconcerting and had never occurred in our society before. I'm old enough and gray enough to remember the swine flu epidemic. I remember the mass immunizations that occurred and how we as a country mobilized to do that. That was certainly not the case, what we saw this time. There was this tremendous fracturing that we saw in terms of conflicting rules, and there were also the blurred boundaries of authority, the crisis of homelessness, and those population shifts we talked about earlier. You know, it was amazing to go into downtown Manhattan in the height of this epidemic. One of my best friends is the COO at Columbia Presbyterian, and she takes the subway in every day, and for months, there was no one on the subway. They'd walk on the streets, and there was no one on the streets. It's remarkable what happened to cities and states, and if we look at countries and societies, there was a schism in societal beliefs and norms, similar to what we talked about earlier, but if you think about it, it became even more extreme during COVID-19, and it wasn't just in this country. Think about what happened with Canada with the truckers blockade. Think about what's happened in China right now with the response the government has, and also the reaction of people to that response. There are these schisms that have never occurred in terms of beliefs and norms. There's the polarization that we saw, you know. Some people absolutely refused to wear masks. People refusing to get vaccinated, even though it was clearly to their advantage to get vaccinated. That speaks to the anti-science movement, the relativism of truth. Good Lord, have any of you looked on the internet and seen all the crazy things on the internet? You know, some people think this is a virus that you can protect with a vaccine. Well, I happen to be one of those people. But the point being that there's been a shift in where information comes from and what is said, and that has had social implications for people in our society. And it has caused challenges for people in our society. And racism and hatred were exposed in ways that they had never been previously in our society in recent times. So what are the implications for adults? First it's important for people to recognize that it's okay to feel out of control because they do. A lot of people have financial anxiety, personal anxiety, as well as grief and guilt and sadness. And for many people, for the first time in their lives, there was trauma. They lost their social supports. They lost their usual positive coping mechanisms of exercise, entertainment, religion, clubs. They lost the anchor points in their lives, i.e., if you think about your life, you usually get up to go to work at a certain time. There usually are certain activities, whether it's seeing patients or other activities you have during the week. When you lose these anchor points, you start to actually change your circadian patterns. And those changes in circadian patterns can actually be detrimental for individuals. So what does it lead to? It led to increased symptoms of anxiety, depression, guilt, and grief, increased amounts of substance abuse, anxiety disorders, depressive disorders, alcohol use disorders, and more overdose deaths. If we look at children, the impact has been absolutely staggering and problematic. The developmental, you know, it depends on the developmental age of the child, the resilience of the family, the resources of the family, and the quality of the educational experience that exists. If you really want to think about the inequalities in our society, just think about what's happened to our children. Think about how many children were left alone because their parents were essential workers. Think about how many children didn't have real access to Internet in order to continue their learning at home. The impact has really been profound on kids. It's been profound in terms of social and developmental delays. You see it in the pandemic that is occurring in terms of childhood depression and anxiety disorders right now. The numbers are staggering, what we're seeing there. They didn't have a place or an opportunity to develop social and emotional skills. So you see these high schoolers who never went to middle school. And because of that, they're actually acting out and acting as middle schoolers while in high school. And it's causing a tremendous amount of chaos. They fell behind in learning. We talked about the inequalities. And these kids were exposed to things that, think about your childhood. Think about your own childhood. How many times were you exposed to the type of loss or grief or anxiety about the future during your own childhood? For most of us, it was very little. But for our children today, it's been an exposure that is incomparable and really has had tremendous ramifications in terms of anxiety and depressive symptoms, the presence of depressive disorders and PTSD and substance use disorders. These have all become a pandemic. You've seen this in the Surgeon General. You've seen ACAP talk about this and many others. And we need as a society to recognize that. So what can we do about these things? One, if you look at public interventions we can do, you can acknowledge the experience that everyone's having. Give people permission to have feelings and thoughts that are unusual for them, thoughts of grief, thoughts of loss, thoughts of being out of control. Give them permission to talk about it and give them permission to understand that this is normal, that most people have these feelings. They're not alone. They're not abnormal. And it's important to know. There are people that we will return to some state of normalcy, just not the ones we're used to. And it's really important to understand that different aged people are going to have different needs and different types of interventions are going to be appropriate for them. And also that there can be a phased approach to the treatment interventions we use. There was a paper by Rauch and Rothbaum that was published at the beginning of the pandemic and it talked about the different types of phased interventions that one could have. The importance for most people of very simple interventions and how you would layer on others as people became more ill or more distressed. But the key is that the assessment of the individual needs to be done so you can tailor the intensity and the type of intervention that you're giving individuals. If you look at a systems-based approach, you need to be able to create comfortable places to vent, discuss, give support, and receive advice. And some health systems and some other systems were better at doing this than others. The supervisors and executives, if you're in a hospital or other settings, they need to walk. They need to tour. They need to listen. They need to encourage dialogue. And there needs to be timely response to those concerns that people have. You saw in dysfunctional systems, whether it's health systems or others, when the executives were isolated, when the executives didn't get engaged, those systems did not do well. And more importantly, the people in those systems didn't do well. You need to think about creating optional brief check-in meetings during the workday with mental health professionals and emphasize the value and importance of wellness programs. You need to consider proactive mental health interventions, webinars, web-based interventions, self-help videos, meditation videos, encourage brief mental health triage visits, and provide either by mobile apps or other approaches, 24-7 access to care. What are the signs that somebody's struggling? Poor or changed performance, social isolation, irritability, anxiety, volatility, alcohol or substance use, absenteeism, presenteeism. These are all signs that somebody's struggling. And we can be aware of that. How do you approach somebody? Gently but persistently ask them if they're doing okay. Reassure them that it's okay if they're not because lots of people aren't during this time. Help them understand that resources are available and confidential. And emphasize, some people, all they need is a brief session and access to self-help things that are online. Others need something a little bit more. I'm gonna show you some data about that in a minute. You can help people by helping them have a regular wake-up time. If you want to entrain a sleep pattern, you don't entrain a bedtime, you entrain a wake-up time. Because if you entrain a wake-up time, what will happen is that the sleep time will then catch up to it. If you intend to entrain a bedtime, it never works. There's no good data in terms of sleep hygiene that suggests that you can entrain using the sleep time as the start there. Regular activities during the work week, differentiating the weekends and holidays is really important. Time to reflect and check in with oneself and time to have fun. If you think about what happened during this pandemic, with this diffusion of roles, with the fact that work and home became one place, what frequently happened, and without these zeitgebers, without these anchor points in one's day in life, and the distinction between work and home, a lot of these very basic aspects of life got disrupted. And because of that, it exacerbated the presence of anxiety and depression and mental illness. You know, there are positive coping strategies that people can use with family and friends, with social activities, book clubs, lots of types of activities, peer support and purposeful activities. One of the most important interventions is really giving people purpose to their lives. So during this pandemic, when it was at its worst, you know, one of the things that we did, I was at that time the Chair of Psychiatry at Emory and the Chief Psychiatric Officer, Emory Health Care. One of the things that we did was take individuals whose work life was really disrupted and worked with them to create, volunteer in other activities that they could have that gave them a sense of meaning and a sense of purpose. Because that sense of purpose so often is what drives us in our lives. And lack of purpose is one of the most destructive things that happens. You know, we need to recognize the fact that parents and older relatives felt very vulnerable and their lives became very circumscribed. And many times, if you were an adult child, you were responsible either remotely or in real time with those individuals. You need to recognize and understand consciously that children, although different developmentally, had disrupted social and educational learning. They had this loss of a sense of omnipotence. You know, you think about when you grew up. Did you ever in your, think about death? Did you ever think about not having a life that was rich and full? These children, young children, these adolescent children, even our young adults, all of a sudden were faced with a concept of morbidity and mortality that none of us had. And it's important to recognize that. Anxiety about integrating back into normal social and educational structures. I can't tell you the number of families I've dealt with where these kids now are concerned and frightened. How do I go back to school? How do I fit in again? How do I do this? Because they don't know how to do it. And there's been tremendous social and emotional delays as we talked about earlier. So the good news is that evidence-based psychotherapies are effective. Brief assessment and time-limited psychotherapy, many times, is all that's really required. If one looks at the work prior to the pandemic that was done in the UK, there was IATAP, which is a National Health Service intervention, and what they showed was that 40% of individuals that had signs and symptoms of anxiety and depression were able to be treated by just a brief intervention with a master's level individual. And bibliotherapy and resources on the internet. So these brief interventions and assessments can be very, very helpful. Individual and group psychotherapy for depression, anxiety, and PTSD. Individual and group therapy for substance abuse. Medications and neuromodulation works. So there are lots of effective treatments. The key is getting people into therapy. Getting people to feel comfortable getting help. So let's talk a little bit about first responders. You all lived this, as did I. You know, early on, it was the fear of exposure to COVID. The inadequacy of protections that we had. Grief for our patients that were dying. How many of you remember watching people die isolated from their loved ones, where their loved ones couldn't come to them? It was horrific. It was absolutely horrific. Fear of isolation, helplessness. And, you know, there was this incongruity. All of a sudden, here we are, dealing with people dying. Dealing with our own inability to help people. Our own inability to cope at times. And we were called heroes. There's an oxymoron in that, that for some individuals was intolerable. If you look later in COVID, people are burned out, exhausted, demoralized. The guilt and the grief. People are traumatized. How many of you experienced moral injury? How many of you experienced circumstances where you had to choose who was gonna get an intervention and who wasn't? Who was going to get surgery and who wasn't? It had tremendous, and has tremendous ramifications, particularly for us as healthcare professionals. It's a real contradiction for people that are trained and who define themselves as healers to all of a sudden feel as if they have to make decisions about who's going to get treated and who's not. There's compassion fatigue. People are burned out. People no longer are able to care because they're so afraid and so tired. This has gone on so long, and this went from being what we thought would be a six-month event to a two-year-plus event and to an event that has not stopped yet. Increased depression, PTSD, anxiety, and substance use in our healthcare professionals. So what are some of the things that can be done? Clear leadership and communication. Using psychiatry and behavioral sciences, faculty and staff assistance, human resources, and health system leadership is critical to the success of this. Let me tell you a couple of examples. One of these is something that was established in Atlanta. It was called Caring Communities. This involved the Emory Healthcare System, the Children's Healthcare System of Atlanta, the VA Healthcare System, and the Grady Health System. And what individuals with expertise in mental health, social workers, psychologists, family therapists, physicians, what they did was engage and organize as a community for the community of Atlanta and for all of the healthcare professionals, the food service professionals, the individuals that were involved in maintenance, because those people were really traumatized. The maintenance individuals had to deal with a lot of the aftermath of what was going on with people dying, with people being ill, with PPE that was infected. What we did there was we created a clear mission, and we created immediate support groups that were available to all types of first responders, from our residents throughout the system to our nursing students to our nurses to, as I talked about, the maintenance individuals. And we had levels of individual and group therapy available to all of them. We identified leaders and teams. We coordinated activities and created accountability, communication, and established meetings and activity cave-ins for all of these health systems. So what we did was, on a regular basis, have individuals go to the meetings of the maintenance staff and work with them. We went to the food service individuals and worked with them. We had meetings of various groups of trainees and faculty because the trainees were tremendously distressed by what they saw. And so we were intervening on a regular basis with all of those groups. What else we did is we integrated a website for the caring communities with all of those health systems' websites so that anyone could go onto any of those websites and be sent to this website where there were tip sheets. One of the things that happened, particularly early on, is people didn't know, what am I supposed to do about my loved ones and the fact that I'm getting exposed and I wanna go home and see my family? How do I deal with telling my family about how I'm feeling, watching these people die? So we created tip sheets that were in English, they were in a variety of, they were in Spanish, they were in about 10 different languages that were available to anyone. And the websites were not just available to healthcare professionals, but to anyone who had questions about this, questions about why am I feeling sad, what does this mean, what can I do about it? We also created on these websites videos, different types of meditation videos, different types of brief videos talking about these issues because some people would prefer to watch a video than not. We had yoga videos on there with just brief interventions available to people. We had virtual group sessions for departments, service lines and the trainees, as well as in-person sessions. We coordinated in-person grief sessions throughout the healthcare systems, the EDs, the wards, the ICUs. And we did a lot of communication to the leadership about what the needs were and what we were seeing. And this facilitated these health systems being much more responsive to individuals than they otherwise would be. Another example of what we organized was an immediate access, the Emory Immediate Access Project. So 24, well actually, seven days a week between 6 a.m. and midnight, an appointment was available for somebody that was in crisis. There was a 30-minute initial screening that would occur within 24 hours of somebody going on the website. They'd immediately, within two minutes, get an appointment set for sometime within that next 24 hours at a time that they picked what was good for them, not what was good for the system, but what was good for them. And during this triage appointment, we would explain online resources, HR, caring community resources. There could be brief, focused psychotherapy interventions, and it also facilitated, when necessary, patients entering into individual medication or group therapy, and it was done for free. It was done for free. During the six-month test of change, the average time it took to schedule an appointment was two minutes. 52% of these appointments occurred during off hours, either 5 p.m. to midnight, or 6 a.m. to 9 a.m. There were 353 individuals that took advantage of this. There were 64 psychotherapy appointments, 47 medication appointments, 56 individuals entered into group therapy, and the no-show rate was only 5%, because the appointments were scheduled at the time that was good for these individuals. Another intervention that was done here, and is available to anyone here, is Safe-UT. Safe-UT Frontline is an app that provides a way for law enforcement, fire, EMS, healthcare providers and their families to confidentially connect with licensed mental health professionals 24-7. There's a geolocation component built into the app. Anyone who has this app can text or call, and will immediately be engaged with a healthcare professional 24-7. And it is a conduit to other types of resources. We initially developed Safe-UT as an app for the schools here in Utah. It is now in every single public school in Utah, and all the universities. It's estimated that Safe-UT saves a life a day. It also has an anti-bullying component, and it also has a component in it that allows people to report if they're concerned about some type of potential mass shooting or untoward event. But this event, this app for healthcare professionals has been critical in helping people that really feel at wit's end to anonymously begin to engage, anonymously know that there's help available. And we're able to plug them into immediate crisis help, or if they need longer term help, we can do that. But these are the types of interventions that are possible. The Caring Communities intervention, the Access intervention, or an intervention like Safe-UT, where we can make a huge difference for individuals. Now we get nerdy, and now we get to where my lab goes. So we know this. If you look at the 30 to 50 month info post-COVID, what you see is PTSD has an incidence of 40%, major depression of about 37%, and OCD, interestingly, is up to about 16%. So what are the mechanisms by which COVID could be affecting the brain? Well, there are two potential mechanisms. One is peripheral inflammation, which is a lot of what my lab does. And the other one is the fact that the SARS virus is a neurotrophic virus. And so there are potential ways of entry we'll discuss in a minute. Let's talk about peripheral inflammation. You guys know this well, but I think what's important to look at here is the fact that if you activate the body, as you'd expect, you know, one of my favorite things to talk about with people is the fact that the mind and the body are connected. That's why God made the neck. What else would you have a neck for, you know? But what we know is that if you have peripheral inflammation going on, you're not only generating M1 macrophages, but you're also generating a whole bunch of cytokines in the periphery. And what we now know, I mean, all you need to think about, so was anyone in here a courageous volunteer like me who got COVID? Raise your hand. All right, a few courageous volunteers. Now, was anyone in here a courageous person that over the last two years had a cold? Raise your hand. We have a disgustingly healthy group here. Well, those of us that have been blessed by a cold or by COVID, we know that you end up eliciting a lot of peripheral cytokines and an inflammatory response, which leads to, in the brain, fever, fatigue, anorexia, anhedonia, and altered sleep disturbance. And that's all from peripheral inflammation. If one looks at the impact of inflammation throughout the body, what you see is that it changes food intake, skeletal muscle mass. It impacts the liver with acute phase proteins and other changes. It changes adipose tissue, steroid axis. You go from a sympathetic, parasympathetic balance to a more of a sympathetic state. You have changes in respiration and bone mass. And the longer that goes on, you shift from what's initially a healthy response because you need that to fight off infection to an unhealthy response if it goes on too long. And you get to a chronic inflammatory state. If you look at the sequelae of inflammatory states, you get depressive symptoms, fatigue, anorexia, malnutrition, cachexia, dyslipidemia. You see alterations in the steroid axis. We talked about the sympathetic, parasympathetic balance. and you get a host of other physiological changes that occur in the body. And what you get is this cycle where you have anhedonia, anorexia, cachexia, cognitive difficulties, fatigue, problems with pain and mood, influencing the body. And conversely, what you have is chronic or peripheral inflation influencing the brain. So you get into this vicious cycle that occurs, and that's partial of what's thought to occur with some people with chronic COVID. It's one of the areas of interest of my group. So what does this mean? So what you see here is a PET scan. And on this PET scan, what one sees is the depression associated with Parkinson's disease, and what's important to look at here is the fact that you're seeing massive increase in activity in the basal ganglia because you have a decrease in dopamine. If you look at individuals that are treated with interferon-alpha treatment, what one sees is a similar picture of increased activity, increased sort of spontaneous and oscillatory activity in the basal ganglia of these individuals that are treated with interferon-alpha. What you also see is that the majority of people that were treated with interferon-alpha, over 50% developed a depressive disorder. If one looks at what's traditionally a hedonic task, a stimulating task, and do an MRI study in the brain, what you see again is in individuals that are treated with interferon-alpha, instead of stimulating an increased release of dopamine with these hedonic tasks, you get both left and right bilateral decrease in release of dopamine associated with it. So this again is the impact of an inflammatory state on the brain itself. This is some work that our group did looking at measures of HSCRP, and what one sees is a relationship between increased levels of HSCRP and increasing levels of glutamate in the brain. And so there's a clear relationship between higher levels of peripheral inflammation and increased levels of glutamate in certain areas of the brain, particularly in the basal ganglia again. So you're seeing decrease in dopamine, increase in glutamate in areas of the brain. Now what this is associated with is increased measures of anhedonia. It's associated with a decrease in the finger tapping test. So you're not able to do finger tapping as quickly as you normally would. A decrease in reaction time, and a decrease in digit symbol substitution tests. All of this suggesting again that there are cognitive effects that we're seeing with increased peripheral inflammation. And what we also see is a dissociation between different regions of the brain that normally are in concordance with each other. So you see a decrease in the concordance between the basal ganglia and the ventral medial prefrontal cortex. The prefrontal cortex is responsible for a lot of our higher order cognitive functions, responsible for control of our affect. And so we see a dissociation of this associated with peripheral inflammation in some individuals. So what you see is how the peripheral inflammation associated with a cold, with influenza, with COVID, for some people may be associated with these types of changes in the brain. Now one of the things that's very important to recognize is it certainly doesn't occur with everyone. But that speaks to the heterogeneity of both our DNA and also our epigenetic changes that may occur within us as individuals. You know this very well because just think about your own practices. There's an increased prevalence of depression associated with rheumatoid arthritis. There's an increased prevalence of depression and anxiety associated with IBS and with Crohn's. It doesn't affect everyone, but these chronic inflammatory states increase depression and anxiety in large populations. And we would contend that one of the reasons why you're seeing this increased prevalence, we've talked about the social reasons for this increased prevalence of depression and anxiety and substance use disorders. The fact that we were fractured as a society in ways that we never had been before, that we were challenged as individuals in ways that we never had been before. And now what we're doing is linking that to some of the biology of it. Now let me remind you, by the way, just out of curiosity, anyone remember taking the boards here? I do, do you guys remember taking the boards? Some, a lot of you have a memory deficit because you didn't raise your hand. Well, for those of you that don't remember taking the boards, it was the most awesome experience of my life. I just loved it. Not. Before the boards, all of us got anxious. All of us normally had that response. When you get anxious, when you get stressed like that, what also happens is you elicit increased cytokine responses in your body. So if you remember, you slept like a baby the night before the boards, right? No. Part of the reason you didn't sleep well was that you had an increased inflammatory response going on. So part of the things that we saw with the dissociation within the society, the stress that we were all under was an activation of the inflammatory axis. And so one of the thoughts is, and one of the reasons why even when people didn't get COVID they might experience more anxiety and depression, more sleep disruption, more problems with concentration and memory is because the stress itself activates both the HPA axis and activates the immune axis. And by doing so causes changes similar to what we see here in circumstances where you give somebody alpha interferon or somebody is suffering from a depressive disorder. The other thing we know is that it's a neurotrophic virus. The COVID-19 is clearly a neurotrophic virus. And you see it with the types of problems with smell and taste, with fatigue, with the cognitive impairments that were associated with it. Now, this is a study that just came out and it was just published in Nature and it's based on the UK Biobank sample. So the UK has been doing this large study where they're not only imaging individuals but doing genetics and epigenetics on individuals and have this huge biobank. So this was a study of 785 individuals, 51 to 81. They had a scan prior to the outbreak of COVID. And then approximately three years after that baseline scan and in most cases, four and a half months after a diagnosis of COVID, there were 401 cases and 384 controls. And what they saw with these individuals was a 2% loss in gray matter thickness, particularly in the orbital frontal cortex and the parahippocampal gyrus. These are areas that are associated with smell. They saw tissue damage to the primary olfactory cortex, a greater decrease in whole brain volume in individuals that had COVID and a greater decline in the ability to perform complex tasks that was correlated with atrophy in the cerebellum and across two regions of the cerebellum. Now, there are limitations to the study. This was a study done before there was any vaccines. It only looked at the alpha variant, the first variant of COVID. This was predominantly a white English middle class. And you know, you could say it was older adults but I'm more inclined to think of it as later middle-aged now adults, 51 to 81. The COVID positive group did have subtle lower baseline scores on measures of cognition. And there were some very subtle structural differences present prior to these individuals getting COVID but it didn't account for a 2% change in brain volume, in gray matter brain volume. So what are potential explanations? Reduced sensory impact due to loss of sense of smell, neuroinflammation or viral infection of brain cells. So how could COVID enter the brain? Well, the most obvious way is through olfactory neurons but also it could enter via infected endothelial cells around the choroid plexus or other structures within the brain. We don't know at this point what the mechanism is or mechanisms, but these are the most likely ones. So in summary, the pandemics had profound direct and indirect effects on mental health and substance use. COVID-19 pandemic created this second mental health and substance use disorder pandemic. It really did and it really is disconcerting. There are simple interventions that can be done to help majority of people, not all people, but the majority of people. Age and culturally appropriate interventions are necessary and many of them are available. And in some set of individuals, COVID-19 really is causing brain sequelae and we certainly need to know more studies about preventative interventions, more studies about the etiology in the brain and other stuff. Thank you very much for letting an old psychiatrist talk to a different group a little bit about this second pandemic. I am more than willing to hear your questions and in some cases, I might even be able to answer them. But thank you for your time and attention. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. And increased growth in the number of sensory neurons associated with that smell. And so what you're seeing are epigenetic changes that are going from one generation to the next that are influencing the regulation of genes. And so what we are postulating is going on in humans is something very similar to that. And so you'll get a subset of individuals that are exposed to a trauma. And because of that experience, we'll develop PTSD or depression. Another subset will not. And there will be transmission. Both, not just because of the fact that these individuals have been traumatized, but transmission biologically from one generation to the next. I know it's nerdy, but that's kind of what turns me on. Yes? I'm not very good with the generation. But this is true in terms of two spots. I was actually interested in your point that people either have PTSD or have a past with a lot of events that were very intrusive, very traumatic. Well, my experience currently is that I've seen a lot of complex, so-called micro-complex PTSD and especially in the generation that I'm supposed to be in. Like the millennials themselves that on top of coping also have a fear of environmental changes, which seems to be very devastating. Now we have a war on top of that too. But I mean, to my experience thus far, complex PTSD in general is not a very easy to treat. So you mentioned three interventions that are not very common. Sure. Yeah, post-traumatic stress disorder. So the question or statement was, and it's absolutely correct, that there's an increased prevalence of post-traumatic stress disorder that we're seeing today and that this post-traumatic stress disorder in general is very, very difficult to treat. And that's absolutely correct. However, what we do have are actually very good evidence-based psychotherapies that can be used. So there's very good evidence that exposure-based psychotherapies help about two-thirds of individuals with PTSD if it is done according to the appropriate approaches and manual. There's another group of individuals with PTSD that have a dissociative aspect to it. They don't respond as well to traditional exposure therapy. There's some work going on with acceptance and commitment therapies and other types of therapeutic approaches where people learn to tolerate, initially, some of the symptoms before working them through, particularly for people that have the dissociative aspect to it. But what we know is that right now, the best treatment we have available truly is exposure therapy. There's a form of exposure therapy that actually is being promulgated within the VA right now throughout the country that's a brief form of exposure therapy that can be done in primary care settings. It's a three-to-five-session intervention that is showing actually remarkable work. Sheila Roush is the individual that developed that particular intervention and is the person that's been responsible for leading the trainings throughout the VA system with that model as well. Now, there are certain individuals that, of course, also benefit from medications. The first-line medications for PTSD, again, tend to be the selective serotonin uptake inhibitors and the SNRIs. Many people, again, may require, over time, because it takes a while for these medications to work. But in certain cases, there needs to be augmentation. One of the most common augmenting agents are atypical antipsychotics. The problem you run into there are challenges with metabolic changes that occur, particularly weight gain and insulin problems that occur with that. However, a brief period at times of low dose of one of these atypical antipsychotics, things like risperidone, which has less weight gain associated with it, or some of the newer ones, in combination with an SSRI and an SNRI and psychotherapy, tend to be very effective. The earlier one can begin therapy and treatment, the better the outcome is going to be. What happens, over time, with PTSD is that frequently, it may start with PTSD itself, but frequently adds depressive disorder to it, or adds to it substance use disorders and alcohol use disorders as attempts to treat it. And then it becomes much more difficult to treat. So early intervention is really critical. There also have been studies in looking at trauma that occurred in motor vehicle accidents and other settings in the emergency room, and they were able to show then that brief interventions, in that case, a couple of sessions, were actually preventative for a subset of people in the development of post-traumatic stress disorder. Yeah. Sorry, I'm not gonna have to use my microphone. Yeah, we're running out of time. No, if you use the microphone, others can hear you. Yeah, that's why I refuse this question. I don't know if this is gonna be an interesting question. I'm sorry? We are out of time. Out of time? Okay, so I can ask this question separately, right. Well, thank you guys very much for listening to an old psychiatrist. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you.

Mark Rappaport

COVID-19

mental health

substance use disorder

anxiety

depression

support

intervention strategies

PTSD

biological mechanisms