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This study identifies the Median Raphe Nucleus (MRN)

After working with property management business owners for over a decade, I've realized that the problems they are experiencing tend to be deeper than issues in the business… In this episode of the #DoorGrowShow, property management growth expert Jason Hull sits down with Sam Womack to discuss entrepreneurship, health, and how the two intertwine. You'll Learn [01:57] How stress affects your health [13:48] The impact of oxygen and proper relaxation [17:40] The importance of being able to calm your nervous system [26:10] More health expert insights   Tweetables “Everybody's doing the best they can with their current limited access to knowledge and resources.” “Don't beat yourself up for when you feel stressed out. Just make sure that before you continue that stress rollercoaster, like find some space to find some peace.” “You don't have to like beat all your competitors in a lot of instances, you just need to outlive them. You just need to outlast them.” “High performance isn't just how hard you push. It's about how well you recover and regulate.” Resources DoorGrow and Scale Mastermind DoorGrow Academy DoorGrow on YouTube DoorGrowClub DoorGrowLive TalkRoute Referral Link Transcript [00:00:00] Sam: If you don't find time to balance your nervous system or don't work on implementing tools to balance your nervous system, then you are limiting yourself to lower performance in the short term and decreasing performance in the long term.  [00:00:15] Jason: Welcome DoorGrow property managers to the Property Management Growth Show. If you are a property management entrepreneur that wants to add doors, make a difference, increase revenue, help others, impact lives, and you're interested in growing in business and life, and you're open to doing things a bit differently, then you are a DoorGrow property manager. [00:00:37] Jason: So DoorGrow property managers love the opportunities, daily variety, unique challenges, and freedom that property management brings. Many in real estate think you're crazy for doing it. You think they're crazy for not because you realize that property management is the ultimate high trust gateway to real estate deals, relationships, and residual income. At DoorGrow, we are on a mission to transform property management business owners and their businesses. We want to transform the industry, eliminate the BS, build awareness, change perception, expand the market, and help the best property management entrepreneurs win. I'm your host, property management growth expert, Jason Hull, the founder and CEO of DoorGrow. [00:01:21] Jason: Now let's get into the show. Cool.  [00:01:24] Jason: And I'm hanging out here with sam Womack. Sam, welcome to the show.  [00:01:29] Sam: Thanks for having me on. I'm excited to be here.  [00:01:31] Jason: Cool. So Sam we met at a local mastermind here in the Austin area, which is really cool. And for those that know that I run a mastermind for property managers, I also eat my own dog food and believe in getting coaching and learning and growth and everything else. [00:01:52] Jason: And wanted to connect with some people locally and make some friends as well. So, Sam's one of those friends. So, Sam, welcome to the show. And why don't you give people a little bit of background on yourself and what you do and how you kind of. Got into running businesses and doing cool stuff. [00:02:10] Sam: Yeah, no, thank you. First off, I don't do anything near as difficult as you guys. Managing property and tenants, I think is a feat to be held. And so props to all you guys out there crushing it in real estate. I cut my teeth in entrepreneurship starting at a young age. I was charging like 30 bucks an hour to teach old people how to use their computers, you know, tell their life story. [00:02:29] Sam: They'd pay me 30 bucks an hour while they sat there and henpecked. It was pretty ingenious. Fast forward into later on in life when the pandemic hit the business that I was launching just disappeared overnight. The retail died, everything that I've been working on, all the investors pulled out. [00:02:44] Sam: I was left with a few grand in my name and a baby on the way, living in a studio apartment with my wife. Had to figure something out, went into supply distribution, and a couple years later, fast forward, I did about 20 million in revenue as a solopreneur distributing gloves, masks, COVID test kits, etc. [00:03:01] Sam: But throughout that time, I dealt with like a really serious health issue. Stress had kind of overwhelmed me and I ended up with an autoimmune condition in my brain and through the journey of healing that autoimmune condition that was presenting as like early onset Alzheimer's, it was kind of a mystery. [00:03:16] Sam: They didn't know what was happening. I developed a deep passion for finding the root of health and the root of optimization and root of performance. A lot of that came through working with my mom, who's a preeminent physician focusing on anti aging and regenerative science here in Austin. [00:03:31] Sam: And so I typed her handwritten notes for a couple years and followed the patient journeys of the elite because she has a concierge practice for the elite here in Austin. And as I saw what drove change in their lives, I learned a lot about the human psyche and I learned a lot about how each of our individual unique biologies are very different when it comes to what we choose to do to find optimization or find optimal health. And so now I have a passion for bringing that to the masses. And as the pandemic waned, and as I healed, I became passionate about different physics based modalities and the different systems in the body and how to reach optimal performance. [00:04:07] Sam: And now I have a wellness center here in Austin that focuses on performance optimization, as well as maximizing human potential and transitioning the human experience as well as a research Institute called Human Beaming Research Institute, where we present the stories of the truth about health and where we help bring true health science to light so that people understand what's actually true, not truth that's manufactured by special interests, but truth that's founded in science. [00:04:36] Jason: Got it. Yeah. I mean, there's kind of a battle right now, right? We're like seeing it all play out live real time. Oh yeah. Got this whole make America healthy movement. We've got RFK, Bobby like and it seems like there's some major disruptions that are kind of happening right now and there's a battle and we're waking up. [00:04:58] Jason: A lot of people are waking up that hey, you know, big food, big pharma, you know, big government are not in favor of us being healthy for some reason, which is kind of scary. So yes, yeah kind of waking up to this and I don't know, maybe we're all biohackers now. I don't know.  [00:05:17] Sam: Yeah. No, I you're absolutely right I think that humanity as a whole is kind of done drinking the Kool Aid when it comes to what we've been told is the truth. [00:05:27] Sam: And, you know — [00:05:29] Jason: Yeah. Cause the Kool Aid has like glyphosate in it and like, also like molds and mycotoxins, like it's got bad stuff all over it. And I'm not saying actual Kool Aid. This is metaphorical people. Metaphorically.  [00:05:42] Sam: Yes. And when you look at like where, you know, just briefly to when you follow the money and you see that, like, from a business standpoint, one of the largest mergers and acquisitions in history, if you bring it to current dollar value was when big tobacco bought the food industry and you look at when that transition happened and you see what happened to our food supply and you know, we're fish in a barrel that they're just taking their pick of right now when it comes to what we have that's societally acceptable to put in our bodies and societally acceptable to engage in, in terms of social interaction, et cetera. [00:06:15] Sam: And it, yeah. Kind of funnels us down this path of high stress, which kind of takes us to today's topic with the nervous system. But yeah, I don't don't know if you have anything else you want to discuss before we dive in.  [00:06:25] Jason: Well, I want to point out. So Sam really sharp guy, as you can tell already, Sam's going to be a speaker at our DoorGrow Live conference. [00:06:35] Jason: And he's going to talk about some really cool stuff that we're very holistic at DoorGrow. And so I know that in coaching entrepreneurs and having talked to thousands of property management business owners and coaching hundreds of clients that it's never really the business or that they're spending too little time in their business that's keeping them from succeeding in business. It's everything else, especially health, especially their relationships, especially their marriage. Like these things create a lot of friction for entrepreneurs And they've got a lot going on. You're not really talking about property management when you come to DoorGrow Live, but I do believe it will be a game changer for them to be able to perform more, be able to get more out of their business, be able to get more out of life, which is the goal of having a business, right? [00:07:20] Jason: That's more freedom and more fulfillment. So, yeah. So if you have not yet gone to doorgrowlive.Com and gotten your tickets. Go do that right now. Go get your tickets and make sure you're at that event. Come hang out with us in North Austin at round rock at the Kalahari resort. It's going to be awesome. [00:07:36] Jason: All right. Shameless plug completed. Now, Sam, let's get into talking about the topic at hand.  [00:07:43] Sam: Yeah, I know. And thank you. And I'm really excited to get on stage and speak and I'm going to save some nuggets for the stage. Won't give it all the way here. So I'm really excited about that and helping you guys understand what the true root of your full potential actually is and not from some woo woo space, but actually understanding like the fundamental simple science beneath high performance and beneath fulfillment in life because it really does break down to a very simple equation. One of the key factors is a molecule, and that molecule is actually oxygen. [00:08:13] Sam: And when your brain is in a high stress state you would think that your body would give it more oxygen under high stress, right? But under high stress, you actually have vasoconstriction. Your blood pressure rises, blood gets pumped to your extremities, you got to get away from that proverbial bear, right? [00:08:29] Sam: But for y'all, that bear is the constant wave of tenant complaints, the constant wave of, you know, economic factors interest rate shifting stuff like that And so you have this like constant bear chasing you and if you're always in that state of fight or flight your brain is patterned to operate on survival mechanisms and a lower amount of oxygen and so And then we get this like male, sometimes male and female, but we get this, like this almost masculine energy of like, let's go conquer and do this high stress, high action push, push, push coffee, stimulant. [00:09:03] Sam: And we're really performing with our hands tied behind our back at that point, because our brain has less oxygen in it. And when you look at the other side of the nervous system, which is our parasympathetic nervous system you have this increase of oxygen in the brain. which actually raises serotonin instead of relying on that dopamine cortisol roller coaster, right? [00:09:24] Sam: And so, at the base of this is oxygen, which is bringing us life, which is creating ATP, cellular energy. And, to put it simply, If you don't find time to balance your nervous system or don't work on implementing tools to balance your nervous system, then you are limiting yourself to lower performance in the short term and decreasing performance in the long term. [00:09:48] Sam: Higher relying on stimulants, higher amounts of of just stress and cortisol and dopamine reliance in the long term, which takes away from your ability to connect with others, to find community, to find that real fulfillment that comes in life.  [00:10:02] Jason: And so what you're saying is we shouldn't just overdose on coffee that here in the U. S. probably has mold in it and makes you not feel good and have to pee way too much. And then not, you know, take care of ourselves in breathing effectively and getting too little sleep, too much hustle, too much stress.  [00:10:23] Sam: Yeah.  [00:10:24] Jason: Okay.  [00:10:24] Sam: Yeah, we can get addicted to that pattern because stress actually can feel really good. [00:10:30] Sam: When you have dopamine augmenting that cortisol, right? Without dopamine, cortisol feels really crappy. You know, you look at high anxiety. You look at that restlessness feeling where you don't feel good. You're on edge. That's when your cortisol's high and your dopamine is kind of low because you've been exhausting the dopamine stores by just pushing it. [00:10:50] Sam: Dopamine is supposed to be a short term reward to get us out of the stress back into a parasympathetic state. Dopamine was never meant to be the consistent ongoing reward. Because, like, think about it for survival, right? If you're, you know, trying to get away from the bear, and you're running, that needs to somewhat feel good, in order to get you through that stress. [00:11:11] Sam: So dopamine kicks in when oxygen lowers in the brain. And then, when you get out of the stress, you find that parasympathetic state again, you calm down, oxygen rises in the brain, serotonin rises, which is that more deeper, long term fulfilling chemical, that actually leads to creativity as well. But our society tells us that love is dopamine. It tells us that success is dopamine. It tells us achievement is dopamine. It gives us these dopamine triggers for all of the cultural hierarchy and the cultural validation, that external validation when you do something to succeed and you show it off, that's a dopamine trigger. Social media is a trigger. So all of these things, society is structured in a way that says, "dopamine's the reward. Now go buy shit, right?" Like almost all the financial economy is driven surrounding dopamine, which is a ultimate losing game because you guys all know that it doesn't really provide that end fulfillment, but since it feels good, we're kind of stuck in that loop. And so. What I want to help illuminate is where true fulfillment can be found and help with some kind of practical tools and a practical understanding of this foundational science so that when you're looking to perform at your best, you can give yourself a break and allow yourself to relax. [00:12:22] Sam: You know, before you have that next cup of coffee to keep yourself going, take some deep breaths, find some space to relax. Don't worry that your brain doesn't feel a hundred percent on. And give yourself some space to allow that peace in knowing that you're raising oxygen in the brain. You're opening oxygenation to areas that are going to drive creativity, that are going to allow for connection, that are going to allow for more presence in your body. [00:12:44] Sam: You'll be a different person in the home. You'll be a different person towards yourself. And so these are critical components of understanding the power of the nervous system when it relates to performance. Because high performance isn't just how hard you push. It's about how well you recover and regulate, and it's about how you create that balance that pushes for longevity and pushes for long term endurance and strength. [00:13:09] Sam: Because if you want to succeed and grow your business 5x, 10x, 100x, you need endurance. Sympathetic, nervous system tone, high stress does not create endurance. It's short term bursts, you crash out or you keep hitting the stimulants. And it keeps you in this narrow window of potential. You find that parasympathetic, you find that relaxation, you get creativity going in your brain, you get higher oxygenation in your brain, you're shifting gene expression towards longevity. [00:13:33] Sam: So it's a pretty powerful tool. And most people think, "oh, I don't want to meditate, you know, or I don't want to relax", or they don't feel safe when they're calm. And it's something to just work on shifting your perspective on because there's true power in that state of peace.  [00:13:48] Jason: A while back, I read this book. [00:13:50] Jason: I don't know if you heard of this. It's called the Oxygen Advantage. It's by a guy named Patrick Mckeown and it's got a forward by Dr. Joseph Mercola, but it's interesting because basically the book is about how he trains athletes to breathe through their nose while working out instead of their mouth, which like exercises the lungs and increases lung capacity. [00:14:15] Jason: But if they're, if we're constantly operating with our mouth open and working with our mouth open, we actually decrease our lung capacity. And so, athletes are just burning out really quickly and they don't have the ability or the capacity to, you know, absorb as much oxygen. So like working out those muscles, like breathing through your nose, you know, is something that talks about, but that's interesting that when we're not calm, we're not getting enough oxygen that we're not recovering, we're not regulating our stress, our body probably starts to eat itself a little bit and, you know, and then we get addicted to dopamine and you know, in business, most businesses fail and really you don't have to like beat all your competitors in a lot of instances, you just need to outlive them. You just need to outlast them. And that, that endurance aspect. And so I think, you know, I think we're going to go through some financial turmoil in the marketplace. Things are probably going to get worse before it gets better as we're cleaning up all this mess financially that is going on in the government. [00:15:18] Jason: And the U S dollar is like, I think it's been going down from its original value down and down as they've been stripping value out of it through inflation and giving that money to who knows who. And so. I think there's going to be a big transition. It's going to get really stressful. [00:15:33] Jason: And I think the businesses that are just able to last through this transition and endure and they're focused on the long game are the ones that are going to win.  [00:15:43] Sam: Absolutely.  [00:15:44] Jason: And there's going to be a lot just eaten up.  [00:15:46] Sam: Yeah. And if you don't allow that perspective of what you just explained about business to apply to your own self and your health, you know, what got you here won't get you there. [00:15:54] Sam: And if you want to sustain and succeed through the turmoil, then you need to adapt. And when you have a high stress state, you actually lose BDNF expression in the brain brain neurotropic factor and brain derived neurotropic factor. And that is our adaptability aspect and factor in our brain. And it literally decreases its efficiency, the higher, the more chronically stressed we are. [00:16:18] Sam: And so it's super important. You guys can look up BDNF and understand its role with oxygenation in the brain. And so fundamentally, you know, the more oxygenated your brain is, the greater your access to intuition, memory, and high level thinking. And those are key components to succeeding in business. [00:16:33] Sam: And when you are in a state of constant survival mode, constant reactivity, constant push, hustle, you lose that space to develop creative longterm solutions. You lose that space to be able to get that spark of inspiration on how to pivot around the corner and see around that corner or do something a little differently than what other people are doing. [00:16:55] Sam: And that's why even you look at like Thomas Edison, Benjamin Franklin, like they would love to access that like state estate, the theta state just akin to sleep. They would put like a lead ball in their hand over a metal plate. And then as they were falling asleep. It would drop and the ball would hit the metal plate wake them up and they'd have their pen and their quill and ink on the table with a candle and then they'd have their formula or problems they were trying to solve and then they'd go to solving it because that was deep parasympathetic state where that creativity was opened up brain oxygenation was opened up. And me, just like so many of y'all out there, like, I'm like, man, I do not like meditating, I do not like calming down, like slowing down.  [00:17:31] Jason: I mean, especially if we're addicted to dopamine and adrenaline, like slowing down feels like a waste of time.  [00:17:39] Sam: Oh yeah, it does. And so you, most of you have heard of dopamine, serotonin, and adrenaline slash norepinephrine, right? That's only 20 percent of our neurotransmitters. [00:17:51] Sam: Okay. What's the other 80 percent glutamate and GABA, right? Glutamate is the exitory neurotransmitter. So that's what animates our body. Think glutamate animate, but then GABA is what balances that. So GABA helps slow things down, shut things down. And it's kind of interesting that popular culture slash society, like you don't hear much about GABA. [00:18:13] Sam: And the reason why is because they're selling us GABA in the form of alcohol. Alcohol is a huge GABA receptor connector, so it just hits the GABA and you feel kind of calm and relaxed. And so people love alcohol to be social because you want to be in a slight more parasympathetic state to be social, right? [00:18:30] Sam: Because high stress doesn't lead to—  [00:18:32] Jason: What about scrolling on social media?  [00:18:33] Sam: Social media is going to be hitting dopamine, not so much the GABA. But scrolling social media is going to be giving dopamine, new information. Ooh, new information. I learned something new, like boom, like that constant external input stimulus. [00:18:45] Sam: But when you look at the importance of GABA and you understand that a lot of us aren't making it on our own, which is why we're staying in such a high stress state all day. Yeah. And then we take a GABAergic, like GABA or a benzo or some weed or something that, that can hit that, that GABA receptor instead of making our own endogenous GABA. [00:19:02] Sam: And that's what happens when you're in a parasympathetic state is your body is creating its own GABA to balance out the brain. And that's what drove me to developing a suite of tools called Peace on Demand that I have at my wellness center that are physics based modalities that drop you into that parasympathetic state without sitting there fighting against your brain and trying to force yourself to meditate. [00:19:21] Sam: And then also with hyperbaric oxygen therapy, that's another tool that induces a parasympathetic state over the course of the treatment. And so I found tools because my brain, I had a hard time controlling with the autoimmune disease that I had and how stressed and on fire my brain was, I had a lot of difficulty finding that space, but without those tools, you can still utilize things like breath work, even if it's just longer exhale than the time you're inhaling or like four seconds in, you know, hold for a little bit and then eight seconds out or seven seconds out. [00:19:48] Sam: That, that's just like the simplest form of breath work to kind of activate the vagus nerve and slow down that that nervous system and get you into a more parasympathetic state but it's really interesting when you see that some of the most creative people and the most successful people, they're not super high strung. At a certain point, you'll see a lot of successful people that are high strung. Push, push hustle. [00:20:10] Sam: But then you go to that next level. You look at like the Elon's of the world, or, you know, so these people are on that next level. You watch them speak. They're calm. They have this, you know, they go hype on at times to like reach certain goal. But then they also have that balance. So the key is balance. [00:20:26] Sam: Don't beat yourself up for when you feel stressed out. Just make sure that before you continue that stress rollercoaster, like find some space to find some peace, do some breathing, take a pause, give yourself that chance to take a break. That'll start developing some resiliency in your nervous system so that you don't burn out. [00:20:42] Jason: Yeah, it does seem like really high performers are highly adaptable to, you know, situations. So they move and adapt quickly. It seems like they are able to maintain some calm, but they also are really quick thinkers, like their thinking seems to be faster than normal. I notice for me, I get really frustrated with team members when they're not— [00:21:05] Jason: I'm like, "come on, this is super quick. Like, look how fast I can do this." And I'm like, "keep up." And so that becomes a little bit of a frustration. I'm like, why is everybody slow? I saw this really interesting thing. My son sent me this and he's really into football. And I guess there's some quarterbacks that are now training with VR. [00:21:23] Jason: Playing the game in VR and but they're doing it at 1. 5 speed. And so they're getting used to everything being fast and they've adapted to that. So then when they go and play, it feels like everything's in slow motion. And I was like, wait a sec. I listen to telegram messages at two speed. I listened to audio books at two, between 1.8 to two speed. Like, so my brain is probably more adapted to speed.  [00:21:49] Sam: Yes.  [00:21:50] Jason: And and so I'm able to process, I was just hanging out with somebody who has a lot more money than me, who runs, who's the CEO of Real, Sharran Srivatsaa. And he talks really fast and he thinks really fast. Like this guy is sharp. [00:22:03] Jason: And I'm like, how does he move so fast? You know? But also and he doesn't seem like stressed out or anything. One of the things I've noticed, maybe like sparks this GABA sort of thing is just for me, reading? Just reading, actually reading not like high speed audiobooks, but sitting down with a book and processing information, my body's in a calm state. I feel a really deep calm where I'm in a flow sort of state reading and absorbing and processing information. So I found that can be a really good tool for me. [00:22:34] Jason: Sarah and I go do your peace on demand thing, which is just awesome. And a game changer. It's really been helpful for Sarah. It's kind of, I compare it to doing a float session, having a really good float session which doesn't happen every time you do a float session, but it happens every time you do Peace on Demand and you don't have to get wet and naked, and nothing gets in your eyes or ears on accident sometimes and stings. [00:22:54] Jason: So that's nice. The other thing I've noticed is just walking. So I went and did EMDR therapy for a while, for like a year with a therapist, bilateral stimulation, both sides of the brain is the concept. And then I noticed like, well, walking is bilateral stimulation. And so that's like a free, very cheap version of EMDR therapy is just to go on walks. [00:23:14] Jason: And rather than running, which is like, Hey, stress response. I found walking is very calming, especially if I'm really stressed. If I go for a walk, it kind of signals to my body, "Hey, you're okay. You're not being chased by a saber tooth tiger right now." So your fight or flight, calm down. So those are the things that work for me. [00:23:32] Jason: I don't know, but those are great tools. I don't know.  [00:23:35] Sam: Yeah. So what those are doing are like, you mentioned a keyword there and that's safe, right? And so you're creating these environments. One, you're reading a book, gaining new knowledge, and you're not cramming the book in a stressed out state to try to memorize it for a test, right? Which so much of us get programmed in school at an early age, that like reading means like, focus hard and stress out over what you're reading. [00:23:56] Sam: But if you allow yourself to relax into that flow state, and you mentioned flow state as well, flow doesn't happen when you're in super high stress state. Some people We'll try to say, "Oh yeah, I'm in flow" because they've got like dopamine coursing and cortisol coursing and  [00:24:10] Jason: they're like manic and going crazy.  [00:24:12] Sam: Yeah, exactly. [00:24:13] Jason: They're busy, but they're not productive.  [00:24:15] Sam: Yeah. And when you get productive and when you feel like you're going fast and your team isn't responding fast enough, like you have that adaptability, you have that BDNF that's really efficient in your brain because you practice going in and out of these states and you spend a lot of time in this flow and in this GABA balanced state Where you're not hyper stressed out and one one thing that also on a biochemistry level explains some of this is: in a sympathetic nervous system response, your body is trying to find as much glucose as possible to burn glucose for fast quick energy, which creates oxidative stress on the body, which creates inflammation. And then your body has to like go clear out all the junk but it doesn't care that it's creating a bunch of junk to clear out, because it's trying to help you survive short term. [00:24:59] Sam: When you're in a parasympathetic state, you're looking at a—  [00:25:02] Jason: Does it make you crave sugar then?  [00:25:03] Sam: Yeah, so high stress makes you crave sugar. Whereas parasympathetic state, you're on a more fat burning metabolism. You're not creating as much oxidative stress. You're like expressing longevity genes. You're expressing anti inflammatory genes. [00:25:16] Sam: Your body literally shifts into almost a different state, not just mentally, but biophysically and biochemistry wise all throughout your body. You adapt based on the nervous system state that you allow. And that's where it does come down to personal responsibility to make the choice to start practicing finding this state that will empower so much more potential for your life than that narrow band of, you know, survival programming and high stress thinking. [00:25:46] Sam: And then it's better for your health longterm too, because you're not just compounding oxidative stress nonstop and then needing those negative inflammatory inputs to make your dopamine stay high. And you can just find that peace. And then you'll find a much higher level of performance and that flow state will start just happening naturally constantly, which is what's been happening for Jason as he's been practicing these things as well. [00:26:08] Jason: Got it. Okay. Very cool. So little teaser, what are you going to talk about a little bit at DoorGrow Live that will be revelatory or helpful for people that might be a little bit stressed in their business or are wanting to take their performance to the next level? And I just, I want to point out, the difference I've noticed just in clients doing time studies and things like this. [00:26:32] Jason: Some of my clients will, we can see in their time study that they, it takes them in the latter half of the day, like the afternoon, an hour to do stuff that takes them 10 minutes in the morning. They're just, they're running out of brain chemicals. They're running out of like, what are neurotransmitter chemicals that they produce while sleeping? [00:26:51] Jason: They're now no longer productive and efficient, even though they're working really hard and they're really busy. And so, so yeah, maybe you could tease a little bit. What could we talk about there that might optimize their productivity so that they could actually feel superhuman and get two to three times the amount of output with the same amount of work or stress or effort? [00:27:14] Sam: Yeah, so we're going to go into a little bit more detail on some other aspects of the foundations of performance. So today we focused on nervous system, which is key. But. Controlling our nervous system isn't just as easy as thinking about it. There's some environmental factors. There's some lifestyle choices we can make. Often, we have a really hard time making those changes due to the, those well worn grooves, like, you know, skis on a slope that are really hard to get out of. And so I'm going to help with some simple truths that you'll understand and make it a lot easier to start making small shifts that will create massive change and that don't have to be stressful or induce anxiety or feel hard. It'll actually feel easy. So I'm going to help you understand some fundamental truths about your biology and That will unlock unlimited potential.  [00:28:03] Jason: Yeah, because I think every entrepreneur listening, myself included, I'm sure you as well, have been in those time periods where you feel like you're working so hard and you're investing so much time and energy, and you're going nowhere like it feels like you're just treading water and you're burning yourself out and you're like, "why am I not adding hundreds of doors? Why am I not growing my business? Why am I not getting ahead? Why am I seeing idiots get further along than me?" You know, like, " why is this not working for me?" And and I think that all plays into that like that. Everything you're talking about plays into that.  [00:28:41] Sam: You'll find yourself having permission to make some changes and the permission is a key aspect of that courage and that bravery to choose something different to focus on something different. [00:28:56] Sam: I mean, we all hear where you, where your attention goes, your focus grows, you know, and what you focus on is what you create, you know, all these things. What does that fundamentally and literally mean when it comes to the way we choose our life experience? And what can we create when our choices change and how can we be empowered to make those choices? [00:29:16] Sam: Those are some of the more intricate topics that we'll discuss.  [00:29:19] Jason: Got it. Almost like shifting from feeling like, "Hey, I'm giving up something or sacrificing in some way that in actuality, you're getting more."  [00:29:30] Sam: Oh, so much more. Exactly. So much more. Yeah. Cool.  [00:29:34] Jason: So. Those of you listening, I'm guessing you're growth oriented, growth minded. [00:29:39] Jason: You want to get more. Come to DoorGrow Live. Come hear Sam talk. So cool. Sam, appreciate you coming here on the #DoorGrowShow. If people are hanging out in Austin or curious about what you're up to, how can they find you? Peace on Demand. Tell them about your stuff and how people might be able to follow you or get in touch. [00:29:58] Sam: Yeah. So we have a small wellness center here. It's a private, you know, high touch concierge space, very comfortable here in Austin. And it's open for business by appointment only but just go to beamhyperbarics.Com and you can book an appointment. If you want to reach out to me I am Sam Womack. [00:30:15] Sam: On Instagram or you can send a message through the website. Easier website to remember is beam.do B E A M dot D O. And yeah, just reach out, come hang out. You don't even have to buy something to come in. Just hit me up. We'll make sure that I'm around and we can sit on the couch in the back and talk life. [00:30:34] Jason: All right. Awesome, Sam. Appreciate you coming on and excited to have you at DoorGrow Live.  [00:30:40] Sam: Yeah. I'm excited as well. Looking forward to it. I love what you're doing. And I think the steps that you're taking to help empower people beyond just showing them tactics and strategies, but helping them live a more fulfilled and empowered life. [00:30:50] Sam: That's what it's all about. So thank you for that work you're doing.  [00:30:53] Jason: Yeah, absolutely. We've just noticed like we can give them all the right tactics and strategies, but if they don't incorporate the other things, it's kind of like you're trying to run a race up the mountain with rocks in your backpack, like boulders, you know, it's just, it's so much more efficient if we get everything else in alignment and usually it's never the business piece that's really what's holding them back. It's not the tactics it's mindset. It's their mental health. It's like everything else, their family. Yeah. So we're excited to bring you and some others that are going to just unlock a lot of things for our clients and for non clients that are coming to DoorGrow Live. [00:31:32] Jason: So appreciate you.  [00:31:34] Sam: Yeah, you bet. Thank you. And just one last thing is you guys are all doing such a great job too. Like, don't think of this as any type of a criticism or, "Oh, you're not doing good enough." Like you're doing such an excellent job with the tools that you were programmed with the upbringings you had with the environment you're in. [00:31:48] Sam: So like, just look at it as a chance to learn something new and be empowered by it. But you guys are all doing such a great job. And so keep it up.  [00:31:56] Jason: Yeah, everybody's doing the best they can with their current limited access to knowledge and resources that they put out. Whatever. All right, cool. Awesome, Sam. I'll let you go. All right. So, if you are a property management entrepreneur and you're wanting to add doors or increase your profit or lower your stress, reach out to us at DoorGrow we would love to help you grow and scale your business. You can check us out at DoorGrow. com. And if you're wanting to join our free community, get a little bit more info about us, hang out with some other property managers, go to DoorGrow club. com to join our free community and connect with other property managers and get some cool free stuff. And until next time to our mutual growth, everybody. Hope you all crush it. Bye everyone. [00:32:38] Jason: You just listened to the DoorGrowShow We are building a community of the savviest property management entrepreneurs on the planet in the DoorGrowClub Join your fellow DoorGrow Hackers at doorgrowclub.com Listen everyone is doing the same stuff SEO PPC pay-per-lead content social direct mail and they still struggle to grow at DoorGrow We solve your biggest challenge getting deals and growing your business Find out more at doorgrow.com Find any show notes or links from today's episode on our blog doorgrow.com and to get notified of future events and news subscribe to our newsletter at doorgrow.com/subscribe until next time take what you learn and start DoorGrow hacking your business and your life.

Today we're talking about methylene blue—aka the stuff that biohackers love, and journalists love to call "fish tank cleaner."  Discover how methylene blue functions as a redox cycling agent, enhancing mitochondrial function, supporting immune health, and even boosting mood.   What We discuss:  Focus on methylene blue and its benefits ... 00:04:33 Introduction to delivery systems and troches ... 00:09:00 Mitochondria's role in health ... 00:17:49 Methylene blue's impact on mitochondria ... 00:26:31 Dosage and its effects on different health issues ... 00:33:45 Cordycepin and immune support ... 00:50:39 GABAergic system and TroZ ... 01:00:59 Travel stack and recommendations ... 01:19:49 Closing thoughts and top tips for longevity ... 01:24:01   Our Amazing Sponsors: Profound Health - Nature's Marvels have been making bioregulators for over a decade, working directly with Prof. Khavinson, the pioneer of Bioregulator science! They're manufactured in the UK. They're GMP and HACCP certified and FDA-compliant. Whatever your health needs, there's a bioregulator for you. Head to profound-health.com and use code LONGEVITY15 for 15% off your first order.   LVLUP: The secret to CREvolution? It's all about GAA. This powerful compound helps you get more creatine into your cells faster than traditional creatine. Ready to crush your next workout? Head to lvluphealth.com and use the code NAT for 15% off.   BiOptimizers - Magnesium Breakthrough: It's the only full-spectrum magnesium supplement with 7 unique forms of magnesium that your body can actually use and absorb. Go to  bioptimizers.com/bionat and enter the coupon code BIONAT to get 10% off your order.   Nat's Links: YouTube Channel Join My Membership Community Sign up for My Newsletter  Instagram  Facebook Group

Today, I am excited to connect with Dr. Scott Sherr, a board-certified internal medicine physician certified to practice health optimization medicine. He is the COO of Troscriptions, a range of physician-formulated, pharmaceutical-grade precision-dosed supplements containing innovative ingredients like methylene blue, with various formulas for energy, focus, sleep, stress, immune support, and more. Our discussion today focuses on the GABAergic system, the parasympathetic system, and maladaptive responses to stress. We explore the importance of GABA and its interaction with progesterone, looking at the impact of stress, lifestyle, alcohol, and benzodiazepines on GABA health. Dr Sherr also explains the role of methylene blue and shares his insights on supplements that support GABA.  This insightful show is the first in a series of valuable and informative podcasts with Dr. Sherr. IN THIS EPISODE YOU WILL LEARN: Dr. Sherr describes the autonomic nervous system, highlighting the sympathetic (fight or flight) and parasympathetic (rest and digest) systems. The two major types of GABA receptors, GABA A and GABA B, and their roles in the brain How GABA calms the firing of neurons and regulates information processing The link between GABA deficiency and conditions like depression, anxiety, and insomnia How progesterone increases GABA tone and leads to better sleep Why women need to support the GABA system during perimenopause and menopause Lifestyle strategies to support the GABA system How most GABA supplements are too large to cross the blood-brain barrier Why GABA supplements can work for those who have leaky gut or brain How alcohol negatively impacts the GABA system How methylene blue enhances mitochondrial function Connect with Cynthia Thurlow   Follow on Twitter Instagram LinkedIn Check out Cynthia's website Submit your questions to support@cynthiathurlow.com Connect with Dr. Scott Sherr Dr. Scott Sherr on Instagram Home Hope Troscriptions Troscriptions on Instagram

In this episode, host Dr. Seema Khosla welcomes Dr. Danny J. Eckert, a sleep and respiratory physiologist and professor at Flinders University in Adelaide, Australia. Dr. Eckert is a leading expert in his field and the recipient of the 2023 European Respiratory Society Gold Medal in Sleep-Disordered Breathing. As the Director of the Adelaide Institute for Sleep Health, he discusses his groundbreaking work on OSA endotyping and the PALM classification system (Pcrit, Arousal threshold, Loop gain, and Muscle recovery). Discover why 70% of OSA patients have non-anatomical causes and how understanding these distinct endotypes can revolutionize treatment approaches. The conversation delves into practical applications for clinical settings, examining the roles of obesity and nasal obstruction in sleep apnea while discussing targeted therapeutic strategies, including GABAergic medications.

Lemon balm (Melissa officinalis L.) has garnered significant attention for its potential to promote psychological well-being. Research suggests that this herb may exert anxiolytic and antidepressant effects, improve sleep quality, and enhance cognitive function. These benefits are attributed to its diverse phytochemical profile, including compounds like rosmarinic acid, citral, and terpenes. While further rigorous clinical trials are needed, preliminary studies indicate that lemon balm may offer a safe and effective non-pharmacological approach for managing mild to moderate psychological concerns. #LemonBalm #mood #anxiety Mathews IM, Eastwood J, Lamport DJ, Cozannet RL, Fanca-Berthon P, Williams CM. Clinical Efficacy and Tolerability of Lemon Balm (Melissa officinalis L.) in Psychological Well-Being: A Review. Nutrients. 2024; 16(20):3545. https://doi.org/10.3390/nu16203545 Alchepharma,Ralph Turchiano,citation,research,study,Melissa officinalis,lemon balm,herbal medicine,phytotherapy,anxiolytic,antidepressant,cognitive enhancement,sleep disorders,stress reduction,GABAergic system,cholinergic system,serotonergic system,neurotransmitter,phytochemical,rosmarinic acid,citral,clinical trial,randomized controlled trial (RCT),placebo-controlled trial,psychological well-being,mental health,quality of life,herbal supplement --- Support this podcast: https://podcasters.spotify.com/pod/show/ralph-turchiano/support

Stiff Person Syndrome (SPS) is treatable if managed correctly from the outset. It is essential to distinguish SPS spectrum disorders from disease mimics to avoid both overdiagnoses and misdiagnoses. In this episode, Allison Weathers, MD, FAAN, speaks with Marinos C. Dalakas, MD, FAAN, author of the article “Stiff Person Syndrome and GAD Antibody–Spectrum Disorders,” in the Continuum® August 2024 Autoimmune Neurology issue. Dr. Weathers is a Continuum® Audio interviewer and associate chief medical information officer at the Cleveland Clinic in Cleveland, Ohio. Dr. Dalakas is a professor of neurology and director of the neuromuscular division at Thomas Jefferson University in Philadelphia, Pennsylvania; a professor of neurology and chief of the neuroimmunology unit and the National and Kapodistrian at the University of Athens in Athens, Greece. Additional Resources Read the article: Stiff Person Syndrome and GAD Antibody–Spectrum Disorders Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media @ContinuumAAN facebook.com/continuumcme Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology.  Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME.   Dr Weathers: This is Dr Allison Weathers. Today, I'm interviewing Dr Marinos Dalakas about his article on stiff-person syndrome and GAD antibody-spectrum disorders, which is part of the August 2024 Continuum issue on autoimmune neurology. Dr Dalakas is a world- renowned expert in neuromuscular diseases and, really, the first name any neurologist thinks of when they hear the diagnosis of stiff-person syndrome. Dr Dalakas, this is such an honor to be able to speak to you today. Welcome to the podcast, and would you please introduce yourself to our audience?   Dr Dalakas: Yes, thank you very much. I'm so happy to participate in this interview. I'm the Chief of the Neuromuscular Division at Thomas Jefferson University in Philadelphia, and I am interested in autoimmune neuromuscular diseases for many years and also on disease mechanisms and immunotherapy.   Dr Weathers: Thank you again for talking with me today. So, given how very rare stiff-person syndrome and the GAD antibody-spectrum disorders are, prior to December 2022, I would have started our time together by asking you to explain this collection of diagnoses to our listeners and by also talking about how often they occur. It feels like that's a bit unnecessary ever since Celine Dion went public with her diagnosis - that moment really changed the public awareness of what was previously outside of neurology and almost unheard-of disease. So, instead, I'll start with, what is the key message of your article? If our listeners are going to walk away remembering one thing from our discussion, what would you like it to be?   Dr Dalakas: Well, I think the publicity has been very good for the disease, this disease spectrum. On the other hand, there have been some misleading messages, like, it's extremely rare, it's untreatable, it's disabling – which, they are partially correct, so, my message is, first, to make sure the neurologists make the correct diagnosis, because there are a lot of diseases similar to stiff-person, but they are not stiff-person. So, to make sure the diagnosis is correct and to make the patients aware of what to expect when they have this disease and what therapies we have and what we may have in the future. So, the number one message is the correct diagnosis and then to avoid overdiagnosis or misdiagnosis, because now we see both - we see overdiagnosis and misdiagnosis.   Dr Weathers: I think that's such a critically important point, and one you really delve into really beautifully in the article, so I encourage our listeners who do have access to it to really read through it. As I said, you do a great job really explaining that - and, actually, to go into that further, could you explain how you approach the diagnosis of a patient with possible stiff-person syndrome or one of the other GAD antibody-spectrum disorders? And I know you probably get asked that on a daily basis. As I was telling you before we actually formally started recording, I remember back when I was a resident and saw my first case of a suspected patient with stiff-person syndrome, my mentor advised me to look up your case series, your articles at the time, and really use that to guide my diagnosis. What do you feel is the most challenging aspect of diagnosing a patient with one of these conditions?   Dr Dalakas: Well, the first is the clinical symptomatology. We say the patients present with spasms and stiffness, but also, there are phobias. They are very hyperexcitable to sudden stimulations, to sudden noises, to unexpected touches, and all of them can cause spasms, and then when you examine the patients, they have stiffness. Now, the stiffness (if there is a true stiffness) results in gait abnormalities (the patients are falling because they're so stiff), and also, the hyperexcitability causes a lot of anxiety and a lot of phobias (they're afraid to cross the street, they're afraid to make a destination promptly) – so, all these things are sort of suggestive of stiff-person. So, these are the symptoms that you hear, you listen, and you ask the patients, and then, when you examine the patient, you look for certain signs that there are, specifically, like stiffness of what we call agonist muscles and antagonist muscles, which means there is stiffness of the abdominal muscles and at the same time, stiffness of the back muscles - so, this concurrent stiffness of these opposing muscles is very specific, very characteristic of the stiff person, so if you see that, and then you listen to the history, you're very close to the diagnosis, and then you do the antibodies. And the antibodies (the specific antibodies, the GAD antibody), but it is specific as we say in the article, and we tried to make this very clear to the neurologists, that it's the high titers that matter, because low titers are not necessarily specific. So high titers of antibodies in the serum, above 10,000 by ELISA (or whatever method they use; but it has to be this many times above normal), and then if you have high serum titers and all the symptoms they mentioned, it is stiff-person. On the other hand, if the titers are low, then you may want to do a spinal tap to see if there is synthesis of antibodies in the spinal fluid. That helps you. Now if the GAD antibodies are negative, then you start wondering, is this seronegative SPS? And how do you confirm the seronegative SPS? You do electrophysiology, and the electrophysiology is, again, to see if there is activity (muscle activity) concurrently from the agonist and antagonist muscles - in other words, from the, let's say the tibialis anterior and the gastrocnemius (so, it's two opposing muscles, eg, biceps and triceps) - and if you see activity in both of these opposing muscle groups, and you see also hyperexcitability (you touch the patient, you stimulate just a little, and you see activity in other muscle groups). So, the electrophysiology is very important if the patient's antibody negative, but they have the other symptoms that I mentioned before.   Dr Weathers: I can imagine how challenging those must be (those seronegative cases) to try to really make sure you're identifying and carefully determining that you have the right disease as you alluded to at the beginning. I know how hard it must be for patients to want to at least have some answers to have a diagnosis.   Dr Dalakas: And this is the main thing today, because the publicity, as I mentioned, the beginning, increased the receipt of some information, so they overdiagnose it, like, “Oh, you have this and this and this, so it may be stiff-person”. And so, in fact, recently, we had a series of patients together with the Mayo Clinic Group of out of 173 patients referred to the Mayo Clinic for stiff-person – that's referred to them - only 28% had stiff-person. It's a low percentage, but it is an indication that the neurologists now refer patients to us for stiff-person, but we need to be very careful to correctly make a diagnosis.   Dr Weathers: On one hand, it's good that people are aware and considering the diagnosis, but it does highlight that risk of overdiagnosing.   Dr Dalakas: Yeah. It's the opposite of when I started this stiff-person syndrome (was close to 30 years ago at NIH) - at that time was underdiagnosed. This was the most rare disease, and I collected patients because at the NIH, I was also the Chief of the neuromuscular division there, and I was doing a study, so it was easy to collect patients (I collected more than 100 patients), but at that time, it was misdiagnosed. So, we had patients that I was seeing and they're really disabled, because they have been having the disease for many years, but they had been diagnosed either for Parkinson disease, for anxiety disorder, for psychiatric diseases, or for MS, or for myelopathies, or for myelitis - so many different things, and of course, they didn't have the correct diagnosis and they were disabled.   Dr Weathers: The side effect of having one of the most famous celebrities in the world having this rare disease - you know, the downside of the increased awareness, as we've said. So, moving on from the diagnosis to treatment - again, you do a, obviously, you know, an incredible job in the article, really going through the treatment options and your algorithms - what would you say is the most common misconception you've encountered in treating patients with this disease?   Dr Dalakas: The most common is now (with the publicity) is that it is a disabling disease. Well, it is disabling, but if you treat the disease correctly and early on, I'm not saying we're curing the disease - many diseases (autoimmune diseases), we help a lot, so there are some we make the patient feel normal, but the disease is there - so, if we start the correct therapy early, a good number of patients respond very well. But by the time the patients come to us, they are so stiff, they walk like a statue, or they come in a wheelchair - of course, it's difficult to reverse this, although we have been very happy to see patients with immunotherapies to get out of the wheelchair, to walk, to enjoy normal activities. So, we have made enough progress with the therapists to help a good number of patients. Now, what is the first therapy we do? Well, is what we call the antispasmodics - these are drugs that relax the stiffness that patients have, sort of a symptomatic therapy. It's not going to address the disease itself, but we address the symptoms. And of course, the symptomatic therapy in SPS is not just to relax the patients - it is related to the so-called GABAergic inhibition. So, the drugs that we use (like the benzodiazepines, or the baclofen, et cetera), these are the drugs that work on the GABAergic pathways. So, it is symptomatic therapy, but it works also on the mechanism, so it's not just a relaxing basis - but since the patients have a lot of phobias, the benzodiazepines also help the phobias. The anxiety and the phobias make the patients worse - they make them more stiff. And in the beginning, they go to psychiatrists because they are so phobic - they're phobic to walk. They hear something, they get so stiff. And I have patients coming at the National Airport in Washington to come to there needing aids in getting out of the plane - some of them get so stiff, they have to get an ambulance to come to the hospital because they're stiff everywhere. So, these phobias and anxiety have triggered a lot of my interest to the point of asking the investigators at the National Institute of Mental Health to see if there is any such thing like autoimmune phobias, because these patients have an autoimmune disease, so, well, maybe we can treat the phobias of immunology - well, we did not find anything, but I just sort of brought the idea maybe we have an autoimmune phobia. But on the other hand, when the patients get better, the phobias are reduced and they're more comfortable to walk. So, it's a very interesting complexity of the symptoms altogether.   Dr Weathers: That is – and, actually, that leads into my next question somewhat, that, as I mentioned in your introduction, you are the world expert in this rare disease. How did that happen? You talked about it a little bit just now. But how did you develop this particular interest and expertise? What drew you to this particular disease?   Dr Dalakas: Yes. It's interesting. I was interested in autoimmune neuromuscular diseases (many of them) and neuropathies and myopathies, and one day, I had a good friend of mine who was the clinical director of NINDS at that time, Dr Hallett. So, he saw patients in the movement disorder clinic and they had stiff-person (I don't know why they went to the movement disorder, but they went there), and Dr Hallett said, “Well, this is an autoimmune disease. You should work on this.” And then, I started seeing one or two patients, and I was very impressed. Really, the symptomatology is so interesting. The patients are suffering, and they sort of give the impression that they're neurotic. So, it's just a combination of when you listen to the symptoms, I was very impressed with the depth of the discomfort that they have and without seeing anything - but, when you examine the patient, you see the stiffness and nothing else. They're not weak, like, we see patients with MS, with myopathies, with neuropathies - they have weakness. They may use a cane, they may use two canes, they may use a walker, because they're stiff. So, it's a different disability than you see in patients who are weak. So, this really made me so interested to understand the mechanism - what's going on here - and that's the reason I started and I put the protocol. And then, we did a lot of immunological studies to understand the mechanism, electrophysiological studies to look at these agonist and antagonist muscles - and of course, we named it also. You know, in the beginning, the syndrome was described as stiff man (stiff-man syndrome), and they're all women. They are most of them, women. In fact, there is an article in a major journal, three women with stiff-man syndrome - and this was many years ago. So, stiff-person will be a more proper term. And then we're seeing a lot of patients or more women, but also we have enough men.   Dr Weathers: So, we've talked a lot about the change with this disease in public awareness. How has that changed your day-to-day life - has it (with the change in public awareness)? Are you bombarded with media requests?   Dr Dalakas: Well, it has stimulated me to write more about the disease and more articles, but also to highlight certain things that were not known before. For example, I had recently a paper on late-onset stiff-person. So, people, we see now patients who develop stiff-person at the age of seventy - they are above sixty or so, overall - and they have more severe disease. These patients also have not good tolerance to the medications we use - so, it's a more challenging group, so it is important to make the diagnosis even in patients with late-onset. These people do less well, because, first of all, they're all misdiagnosed, because if you're a little stiff at the age of sixty-five or seventy - well, you have a bad back, so you all have degenerative disc disease, so you don't think of stiff- person in that age. So, the stimulus was to identify some other issues with the stiff-person. The other is to think of new trials - and I have been working on two new trials. They're not out yet. I'm working to see how best to apply the new therapies. And also, it came up the idea of what are the best ways to assess, objectively, to assess the response, because this is an issue from the beginning. When I did controlled trials at the NIH, and we had established the so-called stiffness index to see how stiff they are measurably, but it is still subjective. It's not really objective, it's not (weakness to measure). So, we have gait analysis, we have the time to walk. So, I think establishing objective criterion to assess response to therapy, it's an important one - and so, I have been working on this how to make it more objective or as subjective as we can.   Dr Weathers: I think that's fantastic. And you actually, I think, have already answered my question - which is, what is the next breakthrough coming in the diagnosis and management of patients with stiff-person syndrome and the GAD antibody-spectrum disorders - and I think it's going to be the outcomes of these trials. Is there anything else that you're really excited about coming along in this field?   Dr Dalakas: Well, I think that the hope is, then, better immunotherapy, because the patients respond to IVIG based on the controlled study. We did one with anti-B-cell therapy - it was not statistically positive, but we had some placebo effects, because that second trial included some patients who did not have severe disease, so it was difficult to assess mild response. So, I'm interested in other similar immunotherapies, and we were approaching companies to see if they can sponsor such a trial. I think the publicity helps a lot, because if I was going to approach a company before the publicity, nobody would be interested in - there's no, you know - it's money-driven, so they will not do it. But at the NIH, I did it, because NIH had the grants there to sponsor the trials. So, I think the publicity will help us. And I know talking to companies, there are one or two companies that they have expressed a lot of interest, and, hopefully, we can do some new trials and go work on it, but I don't have any clear drug at the moment. I cannot discuss a real drug.   Dr Weathers: Of course, of course, more to come, but still very exciting. And so, still to learn more about you - again, you're so well known, obviously, for what you've done for the field of neurology. What do you like to do outside of seeing neuromuscular patients in your research career? What do you do for fun for your hobbies?   Dr Dalakas: Well, I have two hobbies. One is I'm an art collector of abstract expressionism. So, I go to a lot of auction houses, and I bid often for certain artists that I'm very interested, some French artists, some at the New York School of Modern Art. The eras of the forties and fifties of the abstract expressionism - so that's my collection and my interest in not missing auctions. And the other was I have a interest in wine collection – but, so, most of the time, I read art and I collect art.   Dr Weathers: That is a great answer. I appreciate art. I am not (fortunately) at the auction and collecting stage yet, but that I will have to learn from you. That's wonderful.   Dr Dalakas: Yeah. I'm originally from Greece, and I have also a professorship at the University of Athens, and also I go there. I also have some European artists in my collection.   Dr Weathers: That's wonderful. We have one more modern piece that we've been lucky enough to have.   Dr Dalakas: Yeah, I started with the impression impressionistic art, but I evolved into abstract.   Dr Weathers: Who is your favorite artist?   Dr Dalakas: Well, it's, you know, Rothko and Newman. So, these are very expensive artists, of course, so I can, but in that school, so these artists are not alive now, but people who are working with Rothko and Newman in the other group - so, there are four or five of them that I collect.   Dr Weathers: I feel like we need a whole separate interview just to talk about that.   Dr Dalakas: But, they are very stimulating, because the colors talk to you, and it's not like an impressionistic piece that, sort of, their flowers are nice, et cetera - so the colors talk to you differently.   Dr Weathers: They do. I love Rothko. Well, thank you, Dr Dalakas, for joining me on Continuum Audio. This has been a wonderful conversation. Again, today, I've been interviewing Dr Marinos Dalakas, whose article on stiff-person syndrome and GAD antibody-spectrum disorders appears in the most recent issue of Continuum on autoimmune neurology. Be sure to check out Continuum Audio episodes from this and other issues, and thank you to our listeners for joining us today.   Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at Continpub.com/AudioCME. Thank you for listening to Continuum Audio.

Hear about research into a new way of inhibiting temporal lobe seizure activity through GABAergic interneuron cell therapy! With epileptologist and neuroscientist David Spencer. ------------------------------------------

The release of the fast-acting antidepressant Auvelity got us thinking about an older strategy to speed up antidepressants, benzodiazepines. So we're bringing you this Thursday throwback, do benzodiazepines treat depression? Benzos and sleep meds rarely earn a mention in textbooks on depression these days, but that has not always been the case.Today, in part one of a two-part series, we'll open up a forgotten repository of psychiatric research, where a stack of about 50 controlled trials has been archived away, suggesting that the GABAergic benzos might actually treat depression.CME: Take the CME Post-Test for this EpisodePublished On: 02/15/2024Duration: 27 minutes, 43 secondChris Aiken, MD, and Kellie Newsome, PMHNP have disclosed no relevant financial or other interests in any commercial companies pertaining to this educational activity.

Please visit answersincme.com/NFP860 to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, an expert in managing postpartum depression discusses strategies to optimize the use of novel GABAergic neuroactive steroids for the management of patients with postpartum depression (PPD). Upon completion of this activity, participants should be better able to: Recognize the rationale for incorporating the GABAergic neuroactive steroids in the treatment of postpartum depression (PPD); Review the clinical evidence for the novel GABAergic neuroactive steroids in patients with PPD; and Outline patient-centered strategies for personalizing treatment with the novel GABAergic neuroactive steroids.

In this episode of the Epigenetics Podcast, we talked with Francesca Telese from UC San Diego and Jessica Zhou from Cold Spring Harbour about their work on the molecular underpinnings of human addiction. Francesca Telese worked on neuronal enhancers and their pivotal role in governing gene activity. She sheds light on her remarkable findings concerning the epigenetic signature of neuronal enhancers that are intricately involved in synaptic plasticity. Jessica Zhou joined Francesca Telese's lab as a PhD student where she worked on elucidating the effects of chronic cannabis use on memory and behavior in mice. She takes us through the fascinating correlation between THC and gene co-expression networks. Francesca and Jessicathen discuss the utilization of genetically diverse outbred rats in their research, along with the crucial exploration of cell type specificity in gene expression studies. They then delve into the long-term changes that occur in the brain after drug exposure and the profound implications for relapse. Additionally, they touch upon the challenges they face in analyzing single-cell data.   References Zhou, J. L., de Guglielmo, G., Ho, A. J., Kallupi, M., Pokhrel, N., Li, H. R., Chitre, A. S., Munro, D., Mohammadi, P., Carrette, L. L. G., George, O., Palmer, A. A., McVicker, G., & Telese, F. (2023). Single-nucleus genomics in outbred rats with divergent cocaine addiction-like behaviors reveals changes in amygdala GABAergic inhibition. Nature neuroscience, https://doi.org/10.1038/s41593-023-01452-y Wang, J., Telese, F., Tan, Y., Li, W., Jin, C., He, X., Basnet, H., Ma, Q., Merkurjev, D., Zhu, X., Liu, Z., Zhang, J., Ohgi, K., Taylor, H., White, R. R., Tazearslan, C., Suh, Y., Macfarlan, T. S., Pfaff, S. L., & Rosenfeld, M. G. (2015). LSD1n is an H4K20 demethylase regulating memory formation via transcriptional elongation control. Nature neuroscience, 18(9), 1256–1264. https://doi.org/10.1038/nn.4069   Related Episodes The Role of Histone Dopaminylation and Serotinylation in Neuronal Plasticity (Ian Maze)   Contact Epigenetics Podcast on X Epigenetics Podcast on Instagram Epigenetics Podcast on Mastodon Epigenetics Podcast on Bluesky Epigenetics Podcast on Threads Active Motif on Twitter Active Motif on LinkedIn Email: podcast@activemotif.com

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete NCPD/CE/AAPA information, and to apply for credit, please visit us at PeerView.com/EUC865. NCPD/CE/AAPA credit will be available until November 11, 2024.Realizing the Potential of Rapid-Acting Treatments for Depression: Key Clinical Evidence, Practical Considerations, and Best Practices for Individualized, Patient-Centered CareOptimal management of depression begins with adequate screening and early introduction of appropriate therapy. However, monoaminergic antidepressant therapies, which are currently considered the standard of care, have several limitations, such as slow therapeutic response times, suboptimal efficacy and remission rates, and adverse effects that may impact patient adherence.Recent research has focused on novel pathways involved in the etiology of depression, including glutamatergic and GABAergic modulation. For example, neuroactive steroids such as zuranolone act as positive allosteric modulators of the GABA-A receptor. In 2023, zuranolone became the first and only oral therapy to be approved for the treatment of postpartum depression. There have also been advances in glutamatergic antidepressants, with the approval of esketamine nasal spray for treatment-resistant depression in 2019 and for depression with acute suicidal ideation or behavior in 2020, as well as the approval of dextromethorphan-bupropion for the treatment of major depressive disorder in 2022.In order to help clinicians remain abreast of the latest treatment options for depression, PeerView recently held a Candid Conversations & Clinical Consults educational symposium, featuring a panel of psychiatric–mental health nursing faculty. These depression experts paired compelling, real-world case scenarios with practice-changing evidence to illustrate how to integrate novel and emerging treatments for depression into clinical practice, including strategies to identify patients who may benefit from these treatments, and how to use shared decision-making to craft individualized treatment plans. If you couldn't watch the live event, this on-demand version is available now!Co-Chair & ModeratorJosh Hamilton, DNP, RN/PMH-BC, FNP-C, PMHNP-BC, CTMH, CNE, CLNC, FAANPThe Hamilton Group Behavioral Health LLCLas Vegas, NevadaCo-Chair & PresenterRhone D'Errico, DNP, MBA, APRN, FNP-BC, PMHNP-BC, ENP-C, CNE, ACUERasmussen UniversityBloomington, Minnesota In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Sage Therapeutics and Biogen.Disclosure PolicyPVI, PeerView Institute for Medical Education, disclosure policy adheres to The Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to control the content of a CE activity, including faculty, planners and reviewers are required to disclose all financial relationships with ineligible companies (commercial interests) that as an entity produces, markets, re-sells or distributes healthcare goods or services consumed by or used on patients. All relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerJosh Hamilton, DNP, RN/PMH-BC, FNP-C, PMHNP-BC, CTMH, CNE, CLNC, FAANP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Alkermes and Point of Care Network, LLC (POCN).Speaker for Myriad Neuroscience and Point of Care Network, LLC (POCN).Co-Chair/PlannerRhone D'Errico, DNP, MBA, APRN, FNP-BC, PMHNP-BC, ENP-C, CNE, ACUE, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Point of Care Network (POCN).Speaker for Lippincott Clinical Pulse and Practical Updates in Primary Care.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete NCPD/CE/AAPA information, and to apply for credit, please visit us at PeerView.com/EUC865. NCPD/CE/AAPA credit will be available until November 11, 2024.Realizing the Potential of Rapid-Acting Treatments for Depression: Key Clinical Evidence, Practical Considerations, and Best Practices for Individualized, Patient-Centered CareOptimal management of depression begins with adequate screening and early introduction of appropriate therapy. However, monoaminergic antidepressant therapies, which are currently considered the standard of care, have several limitations, such as slow therapeutic response times, suboptimal efficacy and remission rates, and adverse effects that may impact patient adherence.Recent research has focused on novel pathways involved in the etiology of depression, including glutamatergic and GABAergic modulation. For example, neuroactive steroids such as zuranolone act as positive allosteric modulators of the GABA-A receptor. In 2023, zuranolone became the first and only oral therapy to be approved for the treatment of postpartum depression. There have also been advances in glutamatergic antidepressants, with the approval of esketamine nasal spray for treatment-resistant depression in 2019 and for depression with acute suicidal ideation or behavior in 2020, as well as the approval of dextromethorphan-bupropion for the treatment of major depressive disorder in 2022.In order to help clinicians remain abreast of the latest treatment options for depression, PeerView recently held a Candid Conversations & Clinical Consults educational symposium, featuring a panel of psychiatric–mental health nursing faculty. These depression experts paired compelling, real-world case scenarios with practice-changing evidence to illustrate how to integrate novel and emerging treatments for depression into clinical practice, including strategies to identify patients who may benefit from these treatments, and how to use shared decision-making to craft individualized treatment plans. If you couldn't watch the live event, this on-demand version is available now!Co-Chair & ModeratorJosh Hamilton, DNP, RN/PMH-BC, FNP-C, PMHNP-BC, CTMH, CNE, CLNC, FAANPThe Hamilton Group Behavioral Health LLCLas Vegas, NevadaCo-Chair & PresenterRhone D'Errico, DNP, MBA, APRN, FNP-BC, PMHNP-BC, ENP-C, CNE, ACUERasmussen UniversityBloomington, Minnesota In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Sage Therapeutics and Biogen.Disclosure PolicyPVI, PeerView Institute for Medical Education, disclosure policy adheres to The Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to control the content of a CE activity, including faculty, planners and reviewers are required to disclose all financial relationships with ineligible companies (commercial interests) that as an entity produces, markets, re-sells or distributes healthcare goods or services consumed by or used on patients. All relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerJosh Hamilton, DNP, RN/PMH-BC, FNP-C, PMHNP-BC, CTMH, CNE, CLNC, FAANP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Alkermes and Point of Care Network, LLC (POCN).Speaker for Myriad Neuroscience and Point of Care Network, LLC (POCN).Co-Chair/PlannerRhone D'Errico, DNP, MBA, APRN, FNP-BC, PMHNP-BC, ENP-C, CNE, ACUE, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Point of Care Network (POCN).Speaker for Lippincott Clinical Pulse and Practical Updates in Primary Care.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete NCPD/CE/AAPA information, and to apply for credit, please visit us at PeerView.com/EUC865. NCPD/CE/AAPA credit will be available until November 11, 2024.Realizing the Potential of Rapid-Acting Treatments for Depression: Key Clinical Evidence, Practical Considerations, and Best Practices for Individualized, Patient-Centered CareOptimal management of depression begins with adequate screening and early introduction of appropriate therapy. However, monoaminergic antidepressant therapies, which are currently considered the standard of care, have several limitations, such as slow therapeutic response times, suboptimal efficacy and remission rates, and adverse effects that may impact patient adherence.Recent research has focused on novel pathways involved in the etiology of depression, including glutamatergic and GABAergic modulation. For example, neuroactive steroids such as zuranolone act as positive allosteric modulators of the GABA-A receptor. In 2023, zuranolone became the first and only oral therapy to be approved for the treatment of postpartum depression. There have also been advances in glutamatergic antidepressants, with the approval of esketamine nasal spray for treatment-resistant depression in 2019 and for depression with acute suicidal ideation or behavior in 2020, as well as the approval of dextromethorphan-bupropion for the treatment of major depressive disorder in 2022.In order to help clinicians remain abreast of the latest treatment options for depression, PeerView recently held a Candid Conversations & Clinical Consults educational symposium, featuring a panel of psychiatric–mental health nursing faculty. These depression experts paired compelling, real-world case scenarios with practice-changing evidence to illustrate how to integrate novel and emerging treatments for depression into clinical practice, including strategies to identify patients who may benefit from these treatments, and how to use shared decision-making to craft individualized treatment plans. If you couldn't watch the live event, this on-demand version is available now!Co-Chair & ModeratorJosh Hamilton, DNP, RN/PMH-BC, FNP-C, PMHNP-BC, CTMH, CNE, CLNC, FAANPThe Hamilton Group Behavioral Health LLCLas Vegas, NevadaCo-Chair & PresenterRhone D'Errico, DNP, MBA, APRN, FNP-BC, PMHNP-BC, ENP-C, CNE, ACUERasmussen UniversityBloomington, Minnesota In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Sage Therapeutics and Biogen.Disclosure PolicyPVI, PeerView Institute for Medical Education, disclosure policy adheres to The Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to control the content of a CE activity, including faculty, planners and reviewers are required to disclose all financial relationships with ineligible companies (commercial interests) that as an entity produces, markets, re-sells or distributes healthcare goods or services consumed by or used on patients. All relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerJosh Hamilton, DNP, RN/PMH-BC, FNP-C, PMHNP-BC, CTMH, CNE, CLNC, FAANP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Alkermes and Point of Care Network, LLC (POCN).Speaker for Myriad Neuroscience and Point of Care Network, LLC (POCN).Co-Chair/PlannerRhone D'Errico, DNP, MBA, APRN, FNP-BC, PMHNP-BC, ENP-C, CNE, ACUE, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Point of Care Network (POCN).Speaker for Lippincott Clinical Pulse and Practical Updates in Primary Care.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete NCPD/CE/AAPA information, and to apply for credit, please visit us at PeerView.com/EUC865. NCPD/CE/AAPA credit will be available until November 11, 2024.Realizing the Potential of Rapid-Acting Treatments for Depression: Key Clinical Evidence, Practical Considerations, and Best Practices for Individualized, Patient-Centered CareOptimal management of depression begins with adequate screening and early introduction of appropriate therapy. However, monoaminergic antidepressant therapies, which are currently considered the standard of care, have several limitations, such as slow therapeutic response times, suboptimal efficacy and remission rates, and adverse effects that may impact patient adherence.Recent research has focused on novel pathways involved in the etiology of depression, including glutamatergic and GABAergic modulation. For example, neuroactive steroids such as zuranolone act as positive allosteric modulators of the GABA-A receptor. In 2023, zuranolone became the first and only oral therapy to be approved for the treatment of postpartum depression. There have also been advances in glutamatergic antidepressants, with the approval of esketamine nasal spray for treatment-resistant depression in 2019 and for depression with acute suicidal ideation or behavior in 2020, as well as the approval of dextromethorphan-bupropion for the treatment of major depressive disorder in 2022.In order to help clinicians remain abreast of the latest treatment options for depression, PeerView recently held a Candid Conversations & Clinical Consults educational symposium, featuring a panel of psychiatric–mental health nursing faculty. These depression experts paired compelling, real-world case scenarios with practice-changing evidence to illustrate how to integrate novel and emerging treatments for depression into clinical practice, including strategies to identify patients who may benefit from these treatments, and how to use shared decision-making to craft individualized treatment plans. If you couldn't watch the live event, this on-demand version is available now!Co-Chair & ModeratorJosh Hamilton, DNP, RN/PMH-BC, FNP-C, PMHNP-BC, CTMH, CNE, CLNC, FAANPThe Hamilton Group Behavioral Health LLCLas Vegas, NevadaCo-Chair & PresenterRhone D'Errico, DNP, MBA, APRN, FNP-BC, PMHNP-BC, ENP-C, CNE, ACUERasmussen UniversityBloomington, Minnesota In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Sage Therapeutics and Biogen.Disclosure PolicyPVI, PeerView Institute for Medical Education, disclosure policy adheres to The Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to control the content of a CE activity, including faculty, planners and reviewers are required to disclose all financial relationships with ineligible companies (commercial interests) that as an entity produces, markets, re-sells or distributes healthcare goods or services consumed by or used on patients. All relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerJosh Hamilton, DNP, RN/PMH-BC, FNP-C, PMHNP-BC, CTMH, CNE, CLNC, FAANP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Alkermes and Point of Care Network, LLC (POCN).Speaker for Myriad Neuroscience and Point of Care Network, LLC (POCN).Co-Chair/PlannerRhone D'Errico, DNP, MBA, APRN, FNP-BC, PMHNP-BC, ENP-C, CNE, ACUE, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Point of Care Network (POCN).Speaker for Lippincott Clinical Pulse and Practical Updates in Primary Care.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete NCPD/CE/AAPA information, and to apply for credit, please visit us at PeerView.com/EUC865. NCPD/CE/AAPA credit will be available until November 11, 2024.Realizing the Potential of Rapid-Acting Treatments for Depression: Key Clinical Evidence, Practical Considerations, and Best Practices for Individualized, Patient-Centered CareOptimal management of depression begins with adequate screening and early introduction of appropriate therapy. However, monoaminergic antidepressant therapies, which are currently considered the standard of care, have several limitations, such as slow therapeutic response times, suboptimal efficacy and remission rates, and adverse effects that may impact patient adherence.Recent research has focused on novel pathways involved in the etiology of depression, including glutamatergic and GABAergic modulation. For example, neuroactive steroids such as zuranolone act as positive allosteric modulators of the GABA-A receptor. In 2023, zuranolone became the first and only oral therapy to be approved for the treatment of postpartum depression. There have also been advances in glutamatergic antidepressants, with the approval of esketamine nasal spray for treatment-resistant depression in 2019 and for depression with acute suicidal ideation or behavior in 2020, as well as the approval of dextromethorphan-bupropion for the treatment of major depressive disorder in 2022.In order to help clinicians remain abreast of the latest treatment options for depression, PeerView recently held a Candid Conversations & Clinical Consults educational symposium, featuring a panel of psychiatric–mental health nursing faculty. These depression experts paired compelling, real-world case scenarios with practice-changing evidence to illustrate how to integrate novel and emerging treatments for depression into clinical practice, including strategies to identify patients who may benefit from these treatments, and how to use shared decision-making to craft individualized treatment plans. If you couldn't watch the live event, this on-demand version is available now!Co-Chair & ModeratorJosh Hamilton, DNP, RN/PMH-BC, FNP-C, PMHNP-BC, CTMH, CNE, CLNC, FAANPThe Hamilton Group Behavioral Health LLCLas Vegas, NevadaCo-Chair & PresenterRhone D'Errico, DNP, MBA, APRN, FNP-BC, PMHNP-BC, ENP-C, CNE, ACUERasmussen UniversityBloomington, Minnesota In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Sage Therapeutics and Biogen.Disclosure PolicyPVI, PeerView Institute for Medical Education, disclosure policy adheres to The Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to control the content of a CE activity, including faculty, planners and reviewers are required to disclose all financial relationships with ineligible companies (commercial interests) that as an entity produces, markets, re-sells or distributes healthcare goods or services consumed by or used on patients. All relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerJosh Hamilton, DNP, RN/PMH-BC, FNP-C, PMHNP-BC, CTMH, CNE, CLNC, FAANP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Alkermes and Point of Care Network, LLC (POCN).Speaker for Myriad Neuroscience and Point of Care Network, LLC (POCN).Co-Chair/PlannerRhone D'Errico, DNP, MBA, APRN, FNP-BC, PMHNP-BC, ENP-C, CNE, ACUE, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Point of Care Network (POCN).Speaker for Lippincott Clinical Pulse and Practical Updates in Primary Care.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete NCPD/CE/AAPA information, and to apply for credit, please visit us at PeerView.com/EUC865. NCPD/CE/AAPA credit will be available until November 11, 2024.Realizing the Potential of Rapid-Acting Treatments for Depression: Key Clinical Evidence, Practical Considerations, and Best Practices for Individualized, Patient-Centered CareOptimal management of depression begins with adequate screening and early introduction of appropriate therapy. However, monoaminergic antidepressant therapies, which are currently considered the standard of care, have several limitations, such as slow therapeutic response times, suboptimal efficacy and remission rates, and adverse effects that may impact patient adherence.Recent research has focused on novel pathways involved in the etiology of depression, including glutamatergic and GABAergic modulation. For example, neuroactive steroids such as zuranolone act as positive allosteric modulators of the GABA-A receptor. In 2023, zuranolone became the first and only oral therapy to be approved for the treatment of postpartum depression. There have also been advances in glutamatergic antidepressants, with the approval of esketamine nasal spray for treatment-resistant depression in 2019 and for depression with acute suicidal ideation or behavior in 2020, as well as the approval of dextromethorphan-bupropion for the treatment of major depressive disorder in 2022.In order to help clinicians remain abreast of the latest treatment options for depression, PeerView recently held a Candid Conversations & Clinical Consults educational symposium, featuring a panel of psychiatric–mental health nursing faculty. These depression experts paired compelling, real-world case scenarios with practice-changing evidence to illustrate how to integrate novel and emerging treatments for depression into clinical practice, including strategies to identify patients who may benefit from these treatments, and how to use shared decision-making to craft individualized treatment plans. If you couldn't watch the live event, this on-demand version is available now!Co-Chair & ModeratorJosh Hamilton, DNP, RN/PMH-BC, FNP-C, PMHNP-BC, CTMH, CNE, CLNC, FAANPThe Hamilton Group Behavioral Health LLCLas Vegas, NevadaCo-Chair & PresenterRhone D'Errico, DNP, MBA, APRN, FNP-BC, PMHNP-BC, ENP-C, CNE, ACUERasmussen UniversityBloomington, Minnesota In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Sage Therapeutics and Biogen.Disclosure PolicyPVI, PeerView Institute for Medical Education, disclosure policy adheres to The Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to control the content of a CE activity, including faculty, planners and reviewers are required to disclose all financial relationships with ineligible companies (commercial interests) that as an entity produces, markets, re-sells or distributes healthcare goods or services consumed by or used on patients. All relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresCo-Chair/PlannerJosh Hamilton, DNP, RN/PMH-BC, FNP-C, PMHNP-BC, CTMH, CNE, CLNC, FAANP, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Alkermes and Point of Care Network, LLC (POCN).Speaker for Myriad Neuroscience and Point of Care Network, LLC (POCN).Co-Chair/PlannerRhone D'Errico, DNP, MBA, APRN, FNP-BC, PMHNP-BC, ENP-C, CNE, ACUE, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Point of Care Network (POCN).Speaker for Lippincott Clinical Pulse and Practical Updates in Primary Care.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

This is an episode of the Frontier Psychiatrists Podcast. It's a conversation between my Fermata team member, Chelsey, and Myself. This conversation is about us, at work, trying to understand neuroscience together. We recorded this one! An edited version of the transcript follows.Owen Muir, M.D.: So we were chatting about the amygdala, and if you want to ask me any questions about it, I can answer them and edit it together. And that's a podcast. Chelsey Fasano, BA: There's a lot of discussion in the field right now about location neuroanatomy or chemistry neurobiology. And I'm always thinking about how the two crossover, so we're talking about the up-regulation or down-regulation of the amygdala.What are the neurochemical aspects of how the amygdala would be up- or down-regulated?Owen Muir, M.D.: Neurochemistry is a great way of selling drugs and selling explanations that are easy to understand.When we talk about neurochemistry, we're talking about a synapse between two nerves that are trying to communicate. There's a tiny little gap, and the way a nerve communicates with another nerve cell is a neurotransmitter is released from one and floats its way across a tiny little gap, and then hits a receptor on the other side, and that creates a change in that subsequent cell, which makes it either more likely or less likely to fire.What's happening next is within that cell. There are intracellular changes that lead to an increasing likelihood of reaching an action potential and itself firing and effectuating the next change in its neighbor cells. We focus narrowly on neurochemistry, because we can look at and modify it.We're getting obsessed with answerable questions— not with important questions. For example, we don't give people “hyper-glutamate,” the excitatory neurotransmitter in the brain. They'll have a seizure. Those excitatory impulses open ion channels that cause immediate depolarization and firing of neurons. Uncontrolled depolarization leads to seizure and death. GABAergic drugs do the opposite thing. So, anything binding to the GABA receptor opens a chloride channel. Chloride's negatively charged.And that changes the inside of the cell's voltage to negative, which means it's less likely to fire because you need more glycine and glutamate to increase the voltage. GABA is safe to agonize, because you're not going to get a seizure—but withdrawal is dangerous because now you're more likely to fire in the absence of the GABA drug.We're focusing on other compounds like serotonin, norepinephrine, and dopamine, which functionally regulate the internal cellular environment, making firing more or less likely. And we focused on it because it's safer. We got obsessed with what we knew we could do and not immediately kill somebody— as opposed to what might actually be effective or is happening naturally because, on their own, our cells are firing and releasing neurotransmitters and pulling them back up and regulating their voltage without us messing with it at all.For example, the chemistry argument at the amygdala level is part of the story. But when we're talking about what information the amygdala is kicking out, it's really how fast it is firing. That's my kind of argument. It's a rhythm answer. If we looked at the stage plot for AC/DC and saw they had a lot of cables and started worrying about which cable plugged into the guitar as opposed to they are going to play in time --and you can replace the strings, the guitar, the cables. You do not have a good AC/DC show if they play at a time, and if they're playing in time, even if the guitar cuts out like bass drums, Angus is still locked in, and it rocks.We've focused on what's focused-on-able, not what matters.Chelsey Fasano, BA: The primary neurotransmitters of the amygdala are precisely the ones you were talking about!Owen Muir, M.D.: The n methyl D aspartate receptor is a binding site that modulates glutamine.Chelsey Fasano, BA: So that makes sense as to why ketamine would strongly affect PTSD since it works primarily on NMDA and GABA. That would downregulate the amygdala, which would help to buffer against the overactivity associated with PTSD and subcortical areas.Owen Muir, M.D.: The firing rate functionally comes down because each nerve in the amygdala firing becomes less likely by some amount. Chelsey Fasano, BA: Is the feeling something to this whole hippie thing of vibration and vibe?Owen Muir, M.D.: It's true at the level of the neurons in the brain. Yes. I think wavelength is an accidental term. I don't know. But it's the literal truth.Chelsey Fasano, BA: We know that neural firing from some research that I've read affects motor movements and speech patterns, and so there probably is some truth to the fact that upregulation of specific circuits is going to cause speech pattern and motor movement differences that are going to be the bodily rhythmic reflection of the brain activity. We would pick up a vibe because we all sense those things about each other through our brains.Owen Muir, M.D.: We're building a model of the vibe. I propose that a firing pattern represents everything in the brain. It's click click of one nerve group, right? And in the other person's brain, it's click click.But in our brains, we build a model of our click. And then, we make a model with clicks in our neurons of the other person. We're constantly building models of other people's minds in our minds with our pattern of firing. Then, we pick up signals from their motor movements and behavior. We're resynchronizing our model. with their model, and we're constantly just getting it a little bit wrong and getting back into sync, and what humans love is feeling in sync.When we dance, we're dancing in time. Like the guy who dances badly, we find displeasure. When we dance together, we find it joyous. When we're dancing to the beat, we enjoy that because our brains all represent the beat simultaneously. We can look and see and feel with high bandwidth sensory cortex and high bandwidth motor cortex that we are together, and that lets us not bump into each other when we're dancing and emotionally not bump into each other's feelings when we're communicating.The dopamine system, for example, which profoundly regulates ventral striatal activity around motor gating, is also implicated in not just motor gating but also the gating of behavior. Some of that behavior is our feelings, how we react to the feelings, and how we talk, think, or sing.This is how we can do things like lie to each other politely and not get enraged. Because there are times when someone lies to you, and it's bad, and how dare you lie to me. There are times when someone says, thank you so much for calling. And we recognize that their thanks may not be sincere.And both of us are definitely on the same page about that, but the underlying intent we have modeled for the statement is beneficent.We're both on the same page about that metadata, which is, oh, the person's lying to me, but it's because they care and want me to feel good. And so I'm going to think this lie is kind in this context, and in other contexts, my internal model was that they shouldn't have lied as opposed to should have lied.So it's not the lie; it's the intent that we model and can reconnect to that allows human behavior and motion. To go well. If someone's a lousy dancer because they have Parkinson's, you're not going to love it, even if you don't know they have Parkinson's, and you may feel more positively inclined to them if you understand they have a reason for it.But it doesn't feel good. We feel good when we move together.Chelsey Fasano, BA: We've had some discussions about this previously about you not valuing agreeableness or not liking that quality of when people pretend to be polite, and I tend to be more like that.And I think when I do that. Often, when I attempt politeness or I attempt positivity, even in a situation where things feel pretty dire, and I don't think that way, what I'm doing, my intention, is I'm trying to slow down the dance. I'm trying to introduce something to the dyad that I'm a part of that is not necessarily totally authentic in that I'm not feeling it at that moment, but I want both me and the other person to handle it.I desire. So, I create the desired state in affect, hoping the dance will move in that direction. It often works. If you fake it till you make it, and you choose grace, and you choose to give someone calmer and more positivity than you might feel like they deserve, they often follow suit by giving it back to you.Owen Muir, M.D.: What mentalizing and Peter Fonagy would say about this is like the way to do that most successfully because some people will interpret it because their experience and trauma, for example, as a lie—an aversive lie— and that'll create mistrust, and they'll get agitated, right?Like, how dare you be polite to me, right? For those individuals and people who like politeness, you can do the same thing: mark your intentions. I'm going to be polite now. It's just that much—set it up. “I am behaving in a way because I hope it will be helpful.”You can tell me if that's different from how it comes across. You can do whatever you want, and you have the spoonful of acknowledging the rationale for your behavior that gives them the additional information that you're doing it within the intent of XYZ, as opposed to just being polite. They can assume you're scamming them with your politeness.Because they're people who've been harmed, scammed, and traumatized by polite people who wanted to abuse them. Thus, politeness for them may be a signal of risk. And so it's the ability to mark that I wonder if politeness is the right way to go, but I will try it out. That is the kind of permission slip to behave; however, you need to behave and also eat if it goes poorly… in a tolerable way.“Wow, my politeness came across badly there. I can see by the look on your face that politeness was the wrong approach,” Then suddenly, they feel understood and don't want to argue with you anymore.Chelsey Fasano, BA: We've talked before about having a mini version of the other person in your head, which, according to this conversation, the mini representation of the person that we have would be not only our conceptions of them and abstract representations but be a literal rhythmic firing of neurons, which explains sort of emotional contagion and how you can feel someone else's feelings.Owen Muir, M.D.: Mirror neurons are a metaphor for mirror patterns of circuits firingChelsey Fasano, BA: When we're looking at different schools of therapy, and some people are saying all of the feelings that you're feeling are definitely counter-transference are all coming from your past. It sounds like what you're saying is that's not accurate. What is happening is that we're getting rhythmic representations of the person that are combining with the conceptions that we previously had of what those rhythmic representations mean to create a sort of mini person inside of us that then informs both Our immediate affect as well as our ability to predict another person's behavior across time.Owen Muir, M.D.: a million percent correct. So it's yes. Therapy is neuromodulation using the sensory experience of another plus the representation they have of us and the representations we have of them, and the desync/resync on repeat —is what therapy is. If you've seen projective identification when you come across that term, the ability to invoke in another person Psychodynamically a behavior that's true because of my ability as a human to create a model of you and perturb that model and react to the perturbances. I see it in a way that's in keeping with my internal representation.It's a fish swim in schools. They're not sending a letter to all the other fish in advance, being like, okay, so in second 17 — turn left. They're modeling all of the other fish and then swimming in context with the model and then adjusting the model in each fish, so there's the constant adjustment of how much the school is moving because we're all building models of the school and checking them with each of the nodes in the network.In therapy, you have a dyad that's doing the same thing. I move left, and I expect you to move right, and you move right as far as you move right. And then that hits or doesn't hit the model I have, and then we move back to the center and do it repeatedly. That's the misunderstanding that is the neuromodulatory agent in psychotherapy. Still, it's brain rhythms in both people's brains firing and then checking, and error checking against the visual sensory interpretation as presented to consciousness and heavily edited by subcortical structures that make that dance happen. It's the getting it wrong, just like in meditation, -- we're attending, losing the attention, bringing it back to the flame. And bringing it back to the flame is why we meditate, not simply “staying on the flame.” It's supposed to be challenging.It's better if it's hard because it's a workout. -- Therapy is better if it's hard because it's a workout. But it's not just for attention regulation; it's a process of re-syncing to better inter-human and intra-personal things because when you do it in therapy, you get to do it out in the world when the therapist isn't there to help. So, being a therapist who's a little bit wrong all the time and then gets back to it is the honest answer. Ta-da! How's that?Chelsey Fasano, BA: Good.Owen Muir, M.D.: Let's see if it turns into anything. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit thefrontierpsychiatrists.substack.com/subscribe

While the pathophysiology of idiopathic hypersomnia is unknown, emerging science suggests that nighttime sleep dysfunction may contribute to daytime sleepiness in patients with idiopathic hypersomnia. A systematic review and meta-analysis that included 10 studies found that, on average, several sleep architecture hallmarks were different in patients with idiopathic hypersomnia relative to controls.Total sleep time and percent of REM sleep were increased in patients with idiopathic hypersomnia compared with controls.Sleep-onset latency and percent of slow-wave sleep were decreased in patients with idiopathic hypersomnia compared with controls.Sleep efficiency and REM latency were similar between patients with IH and controls.In addition to nighttime sleep dysfunction, other physiological changes have been observed in some patients with idiopathic hypersomnia and theorized as possible contributors to its pathophysiology including:Dysfunction of the GABAergic systemAutonomic system dysfunctionAltered functional or regional connectivity in the brainCircadian system dysfunctionDysfunction of energy metabolismThis episode is produced by Sleep Review and is episode 5 of a 5-part series sponsored by Jazz Pharmaceuticals. Visit Jazzpharma.com and SleepCountsHCP.com for more information. In episode 5, listen as Sleep Review's Sree Roy and neurologist-sleep specialist Isabelle Arnulf, MD, PhD, discuss:Science doesn't fully understand the pathophysiology of idiopathic hypersomnia. Research has revealed potential clues, however. For example, idiopathic hypersomnia is associated with changes in sleep staging and architecture. What does emerging science suggest are differences in nighttime sleep?How might the arousal index differ in idiopathic hypersomnia versus in people without it, and why might that matter?In addition to nighttime sleep dysfunction, other physiological changes have been observed in some patients with idiopathic hypersomnia and theorized as possible contributors to its pathophysiology. What is the GABAergic system and its possible role?What are some emerging findings surrounding idiopathic hypersomnia and autonomic system dysfunction?What is the evidence that supports the idea of altered functional or regional connectivity in the brain in people with idiopathic hypersomnia?There were fascinating studies done on skin fibroblasts, suggesting that circadian period length may be different in people with idiopathic hypersomnia versus in people without it. What role might circadian rhythm dysfunction have in idiopathic hypersomnia?What has science discovered about the possible role of dysfunction of energy metabolism in idiopathic hypersomnia?What further research would you like to see conducted on the pathophysiology of idiopathic hypersomnia?Listen to Episode 1: Symptoms of Idiopathic HypersomniaListen to Episode 2: Diagnosis of Idiopathic HypersomniaListen to Episode 3: Differential Diagnosis of Idiopathic HypersomniaListen to Episode 4: Burden of Idiopathic Hypersomnia

While the pathophysiology of idiopathic hypersomnia is unknown, emerging science suggests that nighttime sleep dysfunction may contribute to daytime sleepiness in patients with idiopathic hypersomnia. A systematic review and meta-analysis that included 10 studies found that, on average, several sleep architecture hallmarks were different in patients with idiopathic hypersomnia relative to controls. Total sleep time and percent of REM sleep were increased in patients with idiopathic hypersomnia compared with controls. Sleep-onset latency and percent of slow-wave sleep were decreased in patients with idiopathic hypersomnia compared with controls. Sleep efficiency and REM latency were similar between patients with IH and controls. In addition to nighttime sleep dysfunction, other physiological changes have been observed in some patients with idiopathic hypersomnia and theorized as possible contributors to its pathophysiology including: Dysfunction of the GABAergic system Autonomic system dysfunction Altered functional or regional connectivity in the brain Circadian system dysfunction Dysfunction of energy metabolism This episode is produced by Sleep Review and is episode 5 of a 5-part series sponsored by Jazz Pharmaceuticals. Visit Jazzpharma.com and SleepCountsHCP.com for more information. In episode 5, listen as Sleep Review's Sree Roy and neurologist-sleep specialist Isabelle Arnulf, MD, PhD, discuss: Science doesn't fully understand the pathophysiology of idiopathic hypersomnia. Research has revealed potential clues, however. For example, idiopathic hypersomnia is associated with changes in sleep staging and architecture. What does emerging science suggest are differences in nighttime sleep? How might the arousal index differ in idiopathic hypersomnia versus in people without it, and why might that matter? In addition to nighttime sleep dysfunction, other physiological changes have been observed in some patients with idiopathic hypersomnia and theorized as possible contributors to its pathophysiology. What is the GABAergic system and its possible role? What are some emerging findings surrounding idiopathic hypersomnia and autonomic system dysfunction? What is the evidence that supports the idea of altered functional or regional connectivity in the brain in people with idiopathic hypersomnia? There were fascinating studies done on skin fibroblasts, suggesting that circadian period length may be different in people with idiopathic hypersomnia versus in people without it. What role might circadian rhythm dysfunction have in idiopathic hypersomnia? What has science discovered about the possible role of dysfunction of energy metabolism in idiopathic hypersomnia? What further research would you like to see conducted on the pathophysiology of idiopathic hypersomnia? Listen to Episode 1: Symptoms of Idiopathic HypersomniaListen to Episode 2: Diagnosis of Idiopathic HypersomniaListen to Episode 3: Differential Diagnosis of Idiopathic HypersomniaListen to Episode 4: Burden of Idiopathic Hypersomnia

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.02.551706v1?rss=1 Authors: Perez, C. I., Luis-Islas, J., Lopez, A., Diaz, X., Molina, O., Arroyo, B., Moreno, M. G., Lievana, E. G., Fonseca, E., Castaneda-Hernandez, G., Gutierrez, R. Abstract: Obesity is a major global health epidemic that has adverse effects on both the people affected as well as the cost to society. Several anti-obesity drugs that target GLP-1 receptors have recently come to the market. Here we describe the effects of tesofensine, a novel anti-obesity drug that acts as a triple monoamine neurotransmitter reuptake inhibitor. We investigated its effects on weight loss and underlying neuronal mechanisms in mice and rats using various techniques. These include behavioral tasks, DeepLabCut videotaped analysis, electrophysiological ensemble recordings, optogenetic activation, and chemogenetic silencing of GABAergic neurons in the Lateral Hypothalamus (LH). We found that tesofensine induced greater weight loss in obese than lean rats, which was associated with changes in LH ensemble activity. In Vgat-ChR2 and Vgat-IRES-cre transgenic mice, we found for the first time that tesofensine inhibited a subset of LH GABAergic neurons, reducing their ability to promote feeding behavior, and chemogenetically silencing them enhanced tesofensine's food-suppressing effects. Unlike phentermine, a dopaminergic appetite suppressant, tesofensine causes few, if any, head-weaving stereotypy at therapeutic doses. Most importantly, we found that tesofensine prolonged the weight loss induced by 5-HTP, a serotonin precursor, and blocked the body weight rebound that often occurs after weight loss. Behavioral studies on rats with the tastant sucrose indicated that tesofensine's appetite suppressant effects are independent of taste aversion and do not directly affect the perception of sweetness or palatability of sucrose. In summary, our data provide new insights into the effects of tesofensine on weight loss and the underlying neuronal mechanisms, suggesting that tesofensine may be an effective treatment for obesity and that it may be a valuable adjunct to other appetite suppressants to prevent body weight rebound. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.13.547220v1?rss=1 Authors: Arias-Hervert, E. R., Birdsong, W. T. Abstract: Activation of opioid receptors in the anterior cingulate cortex (ACC) mediates aspects of analgesia induced by both exogenous and endogenous opioids. We have previously shown that opioids signaling disrupts both afferent excitatory and indirect inhibitory synaptic transmission from the medial thalamus (MThal) to the ACC, but the effects of endogenous opioids within this circuit remain poorly understood. The goal of the current study was to understand how the endogenous opioid, [Met]5-enkephalin (ME), modulates thalamic-driven excitatory and inhibitory synaptic transmission onto layer V pyramidal neurons in the ACC. We used pharmacology, brain slice electrophysiology and optogenetic stimulation to study opioid-mediated modulation of optically evoked glutamatergic and GABAergic transmission. The results revealed that ME inhibited both AMPA-mediated excitatory and GABA-mediated inhibitory synaptic transmission in the ACC. However, inhibitory transmission was more potently inhibited than excitatory transmission by ME. This preferential reduction in GABAA-mediated synaptic transmission was primarily due to the activation of delta opioid receptors by ME and resulted in a net disinhibition of MThal-ACC excitatory pathway. These results suggest that moderate concentrations of ME can lead to net excitation of ACC circuitry and that analgesia may be associated with disinhibition rather than inhibition of ACC subcircuits. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.11.548438v1?rss=1 Authors: Peerboom, C. N. E., Wijne, T. B., Wierenga, C. J. Abstract: During the first two postnatal weeks intraneuronal chloride concentrations in rodents gradually decrease, causing a shift from depolarizing to hyperpolarizing {gamma}-aminobutyric acid (GABA) responses. GABAergic depolarization in the immature brain is crucial for the formation and maturation of excitatory synapses, but when GABAergic signaling becomes inhibitory it no longer promotes synapse formation. Here we examined the role of chloride transporters in developing postnatal hippocampal neurons using furosemide, an inhibitor of the chloride importer NKCC1 and chloride exporter KCC2 with reported anticonvulsant effects. We treated organotypic hippocampal cultures made from 6 to 7-day old mice with 200 M furosemide from DIV1 to DIV8. Using perforated patch clamp recordings we observed that the GABA reversal potential was depolarized after acute furosemide application, but after a week of furosemide treatment the GABA reversal potential but was more hyperpolarized compared to control. Expression levels of the chloride cotransporters were unaffected after one week furosemide treatment. This suggests that furosemide inhibited KCC2 acutely, while prolonged treatment resulted in (additional) inhibition of NKCC1, but we cannot exclude changes in HCO3-. We assessed the effects of accelerating the GABA shift by furosemide treatment on inhibitory synapses onto CA1 pyramidal cells. Directly after cessation of furosemide treatment at DIV9, inhibitory synapses were not affected. However at DIV21, two weeks after ending the treatment, we found that the frequency of inhibitory currents was increased, and VGAT puncta density in stratum Radiatum was increased. In addition, cell capacitance of CA1 pyramidal neurons was reduced in furosemide-treated slices at DIV21 in an activity-dependent manner. Our results suggest that furosemide indirectly promotes inhibitory transmission, but the underlying mechanism remains unresolved. The furosemide-induced increase in inhibitory transmission might constitute an additional mechanism via which furosemide reduces seizure susceptibility in the epileptic brain. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.05.547662v1?rss=1 Authors: Zhao, X., Zhang, Y. E., Yang, L., Yang, Y. Abstract: The mammalian neocortex receives extensive cholinergic projections from the basal forebrain. Although it has been shown that acetylcholine (Ach) participates in learning-associated cortical plasticity, it's not clear whether Ach can directly modulate structural changes of cortical synapses. Using in vivo two-photon microscopy, we show that optogenetic and chemogenetic stimulation of cholinergic neurons in mouse basal forebrain leads to an increase in spine formation on apical dendrites of layer (L) 5 pyramidal neurons in auditory cortex and posterior parietal cortex, and these newly formed spines follow similar spatial rules as the spontaneously formed new spines. Selective blockage of Ach receptors (AchRs) revealed that nicotinic AchRs, but not muscarinic AchRs, are involved in the stimulation-triggered spine formation. Furthermore, {gamma}-Aminobutyric acid (GABA) transmission is required in this process, indicating that acetylcholine acts through GABAergic connections in promoting spine formation. Together, our findings demonstrate that acetylcholine can induce spine formation in both sensory and higher-order cortices, via activating nicotinic AchRs through GABAergic local circuitry. Our work established a direct link between Ach release and cortical spine formation in vivo, and shed light on synaptic mechanisms underlying Ach-associated cortical remapping and learning-induced plasticity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.04.547705v1?rss=1 Authors: Labarre, A., Schramm, E., Pilliod, J., Boyer, S., Lapointe, M., Maios, C., Leclerc, N., Parker, A. Abstract: In several neurodegenerative diseases including Alzheimer's disease (AD), tau, a microtubule-associated protein (MAP) enriched in the axon, becomes hyperphosphorylated, detaches from microtubules, redistributes to the somato-dendritic compartment and self-aggregates. The mechanisms leading to neuronal dysfunction and death by tau pathology remain to be fully elucidated. C. elegans has been successfully used by several groups including ours to identify mechanisms involved in neurodegeneration. We generated three strains, one overexpressing wild-type human tau (WT Tau), one a tau mutant mimicking hyperphosphorylation (hyperP Tau) and one preventing phosphorylation (hypoP Tau) in GABA motor neurons. A significant reduction of body size and egg laying was noted in these tau strains. Starting at day 1, we found that the worms overexpressing hyperP Tau were smaller than the N2 control strain and the worms either overexpressing WT Tau or hypoP Tau. Starting at day 5, the worms overexpressing WT Tau were smaller than control and the worms overexpressing hypoP Tau. Egg laying was reduced in both hyperP Tau and WT Tau worms. Survival was only decreased in WT Tau worms. Motility deficits were also observed. For age-dependent paralysis, a difference was noted between control and hyperP Tau. Swimming activity and speed were increased in hypoP Tau and decreased in hyperP Tau strains. Axonal integrity was altered in all tau strains. In the case of synaptic activity, at day 1, it was increased in the hypoP Tau strain and decreased in the hyperP Tau one. Collectively, our data revealed that overexpression of tau exerted neuronal and peripheral defects indicating that tau dysfunction could affect cell cell communication. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.03.547522v1?rss=1 Authors: Bryson, M., Kloefkorn, H., Idlett-Ali, S., Garraway, S. M., Hochman, S., Martin, K. Abstract: Spinal cord injury (SCI) leads to hyperexcitability and dysfunction in spinal sensory processing. As hyperexcitable circuits can become epileptiform we explored whether such activity emerges in a thoracic SCI contusion model of neuropathic pain. Recordings from spinal sensory axons in multiple below-lesion segmental dorsal roots (DRs) demonstrated that SCI facilitated the emergence of spontaneous ectopic burst spiking in afferent axons, which synchronized across multiple adjacent DRs. Burst frequency correlated with behavioral mechanosensitivity. The same bursting events were recruited by afferent stimulation, and timing interactions with ongoing spontaneous bursts revealed that recruitment was limited by a prolonged post-burst refractory period. Ectopic bursting in afferent axons was driven by GABAA receptor activation, presumably via conversion of subthreshold GABAergic interneuronal presynaptic axoaxonic inhibitory actions to suprathreshold spiking. Collectively, the emergence of stereotyped bursting circuitry with hypersynchrony, sensory input activation, post-burst refractory period, and reorganization of connectivity represent defining features of epileptiform network. Indeed, these same features were reproduced in naive animals with the convulsant 4-aminopyridine (4-AP). We conclude that SCI promotes the emergence of epileptiform activity in spinal sensory networks that promote profound corruption of sensory signaling. This includes sensory circuit hypoexcitability during the refractory period and ectopic hyperexcitability during bursting via spiking in afferent axons that propagate bidirectionally via reentrant central and peripheral projections. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.29.547069v1?rss=1 Authors: Rodriguez, L. A., Tran, M. N., Garcia-Flores, R., Pattie, E. A., Kim, S.-H., Shin, J. H., Lee, Y. K., Divecha, H. R., Montoya, C., Jaffe, A. E., Torres, L. C., Page, S. C., Martinowich, K. C. Abstract: The lateral septum (LS), a GABAergic structure located in the basal forebrain, is implicated in social behavior, learning and memory. We previously demonstrated that expression of tropomyosin kinase receptor B (TrkB) in LS neurons is required for social novelty recognition. To better understand molecular mechanisms by which TrkB signaling controls behavior, we locally knocked down TrkB in LS and used bulk RNA-sequencing to identify changes in gene expression downstream of TrkB. TrkB knockdown induces upregulation of genes associated with inflammation and immune responses, and downregulation of genes associated with synaptic signaling and plasticity. Next, we generated one of the first atlases of molecular profiles for LS cell types using single nucleus RNA-sequencing (snRNA-seq). We identified markers for the septum broadly, and the LS specifically, as well as for all neuronal cell types. We then investigated whether the differentially expressed genes (DEGs) induced by TrkB knockdown map to specific LS cell types. Enrichment testing identified that downregulated DEGs are broadly expressed across neuronal clusters. Enrichment analyses of these DEGs demonstrated that downregulated genes are uniquely expressed in the LS, and associated with either synaptic plasticity or neurodevelopmental disorders. Upregulated genes are enriched in LS microglia, associated with immune response and inflammation, and linked to both neurodegenerative disease and neuropsychiatric disorders. In addition, many of these genes are implicated in regulating social behaviors. In summary, the findings implicate TrkB signaling in the LS as a critical regulator of gene networks associated with psychiatric disorders that display social deficits, including schizophrenia and autism, and with neurodegenerative diseases, including Alzheimer's. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.29.547095v1?rss=1 Authors: Fan, R., Sportelli, C., Lai, Y., Salehe, S., Pinnell, J., Richardson, J. R., Luo, S., Tieu, K. Abstract: Dynamin-related protein 1 (Drp1) is typically known for its role in mitochondrial fission. A partial inhibition of this protein has been reported to be protective in experimental models of neurodegenerative diseases. The protective mechanism has been attributed primarily to improved mitochondrial function. Herein, we provide evidence showing that a partial Drp1-knockout improves autophagy flux independent of mitochondria. First, we characterized in cell and animal models that at low non-toxic concentrations, manganese (Mn), which causes parkinsonian-like symptoms in humans, impaired autophagy flux but not mitochondrial function and morphology. Furthermore, nigral dopaminergic neurons were more sensitive than their neighbouring GABAergic counterparts. Second, in cells with a partial Drp1-knockdown and Drp1+/- mice, autophagy impairment induced by Mn was significantly attenuated. This study demonstrates that autophagy is a more vulnerable target than mitochondria to Mn toxicity. Furthermore, improving autophagy flux is a separate mechanism conferred by Drp1 inhibition independent of mitochondrial fission. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

5.04 Depressants (Types, Intoxication, and Withdrawal) Psychiatry review for the USMLE Step 1 exam. Depressants decrease neuronal activity in the brain. They can work by stimulating GABAergic neurons or binding to opiate receptors. Common GABA-promoting depressants: alcohol, benzodiazepines, barbiturates, and inhalants. Opioid depressants include heroin and morphine derivatives. Alcohol enhances GABA receptor effects, inhibits glutamate activity, and causes intoxication symptoms such as disinhibition, slurred speech, impaired motor control, lethargy, respiratory depression, and coma. Alcohol withdrawal symptoms include anxiety, agitation, insomnia, nausea/vomiting, tremors, autonomic dysfunction, seizures, and can be life-threatening (delirium tremens). Benzodiazepines bind to the benzodiazepine receptor, enhance GABA effects, and cause intoxication symptoms similar to alcohol. Benzodiazepine withdrawal symptoms include anxiety, agitation, insomnia, and seizures, which are treated with a gradual tapering of the drug. Inhalants depress brain activity and cause symptoms such as disinhibition, paranoia, lethargy, dizziness, ataxia, slurred speech, and high doses can lead to respiratory depression and brain damage. Opioids bind to opioid receptors, reduce pain, improve mood, and cause intoxication symptoms like drowsiness, constricted pupils, seizures, and respiratory depression. Opioid overdose can be reversed with naloxone, an opioid receptor antagonist. Opioid withdrawal symptoms include dysphoria, anxiety, weakness, sweating, dilated pupils, and diarrhea, and can be managed with medications like methadone and buprenorphine. Alcohol withdrawal is an emergency and requires prompt treatment with benzodiazepines.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.05.04.539488v1?rss=1 Authors: Gayden, J., Puig, S., Srinivasan, C., Buck, S. A., Gamble, M. C., Glausier, J. R., Tejeda, H. A., Dong, Y., Pfenning, A. R., Logan, R., Freyberg, Z. Abstract: Striatal dopamine (DA) neurotransmission is critical for an array of reward-related behaviors and goal-directed motor control. In rodents, 95% of striatal neurons are GABAergic medium spiny neurons (MSNs) that have been traditionally segregated into two subpopulations based on the expression of stimulatory DA D1-like receptors versus inhibitory D2-like receptors. However, emerging evidence suggests that striatal cell composition is anatomically and functionally more heterogenous than previously appreciated. The presence of MSNs that co-express multiple DA receptors offers a means to more accurately understand this heterogeneity. To dissect the precise nature of MSN heterogeneity, here we used multiplex RNAscope to identify expression of three predominantly expressed DA receptors in the striatum: DA D1 (D1R), D2 (D2R), and D3 (D3R) receptors. We report heterogenous subpopulations of MSNs that are distinctly distributed across the dorsal-ventral and rostral-caudal axes of the adult mouse striatum. These subpopulations include MSNs that co-express D1R and D2R (D1/2R), D1R and D3R (D1/3R), and D2R and D3R (D2/3R). Overall, our characterization of distinct MSN subpopulations informs our understanding of region-specific striatal cell heterogeneity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.05.03.538908v1?rss=1 Authors: Martinez de Morentin, P. B., Gonzalez, J. A., Martynova, Y., Sylantyev, S., Heisler, L. K. Abstract: Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.05.01.538959v1?rss=1 Authors: Dorsey, S. G., Mocci, E., Lane, M. V., Krueger, B. K. Abstract: There is an increased incidence of autism among the children of women who take the anti-epileptic, mood stabilizing drug, valproic acid (VPA) during pregnancy, moreover, exposure to VPA in utero causes autistic-like symptoms in rodents and non-human primates. Analysis of RNAseq data ob-tained from fetal mouse brains 3 hr after VPA administration revealed that VPA significantly [p(FDR) less than or equal to 0.025] increased or decreased the expression of approximately 7,300 genes. No significant sex dif-ferences in VPA-induced gene expression were observed. Expression of genes associated with neurodevelopmental disorders such as autism as well as neurogenesis, axon growth and synapto-genesis, GABAergic, glutaminergic and dopaminergic synaptic transmission, perineuronal nets, and circadian rhythms was dysregulated by VPA. Moreover, expression of 400 autism risk genes was significantly altered by VPA. In addition, expression of 247 genes that have been reported to play fundamental roles in the development of the nervous system, but are not linked to autism by GWAS, was significantly increased or decreased by VPA. The goal of this study was to identify mouse genes that are: (a) significantly up- or down-regulated by VPA in the fetal brain and (b) known to be associated with autism and/or to play a role in embryonic neurodevelopmental processes, perturbation of which has the potential to alter brain connectivity in the postnatal and adult brain. The set of genes meeting these criteria provides potential targets for future hypothesis-driven approaches to elucidating the proximal underlying causes of defective brain connectivity in neuro-developmental disorders such as autism. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.29.538824v1?rss=1 Authors: Ganley, R. P., Magalhaes de Sousa, M., Ranucci, M., Werder, K., Öztürk, T., Wildner, H., Zeilhofer, H. U. Abstract: Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Understanding how our body senses and interacts with the world. Scientists are only now beginning to understand how our body senses the world, hence the '21 Nobel Prizes. This Nobel prize wining research helped others find a connection between the gut and our sense of touch. Internal organ pain can be crippling and require side effect laden treatments. How do organs like the gut detect and transmit pain signals? The same mechanism to detect soft touch is used by your organs to send pain signals. How does our body precisely control temperature? What region of the brain measures and control what temperature to set itself to? Zili Xie, Jing Feng, Timothy J. Hibberd, Bao Nan Chen, Yonghui Zhao, Kaikai Zang, Xueming Hu, Xingliang Yang, Lvyi Chen, Simon J. Brookes, Nick J. Spencer, Hongzhen Hu. Piezo2 channels expressed by colon-innervating TRPV1-lineage neurons mediate visceral mechanical hypersensitivity. Neuron, 2022; DOI: 10.1016/j.neuron.2022.11.015 Yoshiko Nakamura, Takaki Yahiro, Akihiro Fukushima, Naoya Kataoka, Hiroyuki Hioki, Kazuhiro Nakamura. Prostaglandin EP3 receptor–expressing preoptic neurons bidirectionally control body temperature via tonic GABAergic signaling. Science Advances, 2022; 8 (51) DOI: 10.1126/sciadv.add5463

https://astralcodexten.substack.com/p/highlights-from-the-comments-on-unpredictable [Original post: Unpredictable Reward, Predictable Happiness] 1: Okay, I mostly wanted to highlight this one by Grognoscente: I think really digging into the neural nitty gritty may prove illuminative here. Dopamine release in nucleus accumbens (which is what drives reward learning and thus the updating of our predictions) is influenced by at least three independent factors: 1. A "state prediction error" or general surprise signal from PFC (either directly or via pedunculopontine nucleus and related structures). This provokes phasic bursting of dopamine neurons in the Ventral Tegmental Area. 2. The amount and pattern of GABAergic inhibition of VTA dopamine neurons from NAc, ventral pallidum, and local GABA interneurons. At rest, only a small % of VTA DA neurons will be firing at a given time, and the aforementioned surprise signal alone can't do much to increase this. What CAN change this is the hedonic value of the surprising stimulus. An unexpected reward causes not just a surprise signal, but a release of endorphins from "hedonic hotspots" in NAc and VP, and these endorphins inhibit the inhibitory GABA neurons, thereby releasing the "brake" on VTA DA neurons and allowing more of them to phasically fire.

My guest this week is Jim Poole, President and CEO of Solace Lifesciences, Inc. In this episode, Jim and I discuss NuCalm. It may just be the most revolutionary, stress melting system that you have never heard of. In just 20 min a day you can change the course of your entire day by putting your brain in a stress free state. I have been trying it for a couple months and it's made a huge difference in my sleep biometrics. It can also be used to elevate performance and promote laser focus! Learn more about NuCalm at  https://nucalm.com/ and use discount code “NN10off”. This code will give you 10% off any subscription.   Follow Jim: https://www.linkedin.com/in/jim-poole-7526305/ https://www.instagram.com/nucalm_official/ https://www.facebook.com/NuCalm www.nucalm.com     Sponsor Deals   Sponsor 1: DrinkHRW Molecular Hydrogen addresses the foundations of health through its ability to manage reactive oxygen species (ROS), inflammation and improve metabolic balance.Anecdotally we have seen improvements in blood sugar control, pain from arthritis and even cognitive function in a Parkinson's patient. Sponsor offer: visit https://bit.ly/drinkH2NN and use code “Longevity” for 15% off.     Sponsor 2: BioOptimizers The fourth-generation formula of magnesium breakthrough now includes cofactors vitamin B6 and manganese that support the absorption of magnesium. Magnesium is involved in 85% of the body's metabolic reactions. Magnesium breakthrough has seven unique forms of organic, full spectrum magnesium which helps to reduce stress, improve sleep, and give you abundant all-day energy. Visit www.magnesiumbreakthrough/bionat and use code BIONAT10 at checkout to save 10%.     Episode Takeaways   [06:16] What is James' story?.. [17:04] Dr. Hollaway the creator of Nucalm set out to address PTSD ... [28:00] NuCalm's applications in the medical field… [30:15] Should I do NuCalm before surgery?.. [32:30] Can NuCalm even chill out a monk?.. [35:15] What is NuCalm and what makes it special?.. [36:30] Activating the GABAergic system… [50:30] What is the healing zone?.. [55:57] Does NuCalm feel like your brain is being tickled?.. [67:23] What are the three options on the NuCalm App?..     Follow Nat Facebook Facebook Group  Instagram Work with Nat: Book Your 20 MInute Optimization Consult

Go online to PeerView.com/AFZ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, experts in psychiatry discuss recent advances in the management of patients with major depressive disorder and postpartum depression. Upon completion of this activity, participants should be better able to: Recognize the burden of major depressive disorder and postpartum depression and the impact of delayed or suboptimal treatment on patient outcomes, Describe the role of GABAergic dysregulation in the pathophysiology of depression and the rationale for GABA-A receptor modulation with neuroactive steroids, Evaluate the mechanisms of action, efficacy, safety, and tolerability of current and emerging treatments for major depressive disorder and postpartum depression, recognizing potential implications for the future treatment landscape, Implement evidence-based, individualized treatment plans for patients with major depressive disorder and postpartum depression.

Go online to PeerView.com/AFZ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, experts in psychiatry discuss recent advances in the management of patients with major depressive disorder and postpartum depression. Upon completion of this activity, participants should be better able to: Recognize the burden of major depressive disorder and postpartum depression and the impact of delayed or suboptimal treatment on patient outcomes, Describe the role of GABAergic dysregulation in the pathophysiology of depression and the rationale for GABA-A receptor modulation with neuroactive steroids, Evaluate the mechanisms of action, efficacy, safety, and tolerability of current and emerging treatments for major depressive disorder and postpartum depression, recognizing potential implications for the future treatment landscape, Implement evidence-based, individualized treatment plans for patients with major depressive disorder and postpartum depression.

Go online to PeerView.com/AFZ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, experts in psychiatry discuss recent advances in the management of patients with major depressive disorder and postpartum depression. Upon completion of this activity, participants should be better able to: Recognize the burden of major depressive disorder and postpartum depression and the impact of delayed or suboptimal treatment on patient outcomes, Describe the role of GABAergic dysregulation in the pathophysiology of depression and the rationale for GABA-A receptor modulation with neuroactive steroids, Evaluate the mechanisms of action, efficacy, safety, and tolerability of current and emerging treatments for major depressive disorder and postpartum depression, recognizing potential implications for the future treatment landscape, Implement evidence-based, individualized treatment plans for patients with major depressive disorder and postpartum depression.

Go online to PeerView.com/AFZ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, experts in psychiatry discuss recent advances in the management of patients with major depressive disorder and postpartum depression. Upon completion of this activity, participants should be better able to: Recognize the burden of major depressive disorder and postpartum depression and the impact of delayed or suboptimal treatment on patient outcomes, Describe the role of GABAergic dysregulation in the pathophysiology of depression and the rationale for GABA-A receptor modulation with neuroactive steroids, Evaluate the mechanisms of action, efficacy, safety, and tolerability of current and emerging treatments for major depressive disorder and postpartum depression, recognizing potential implications for the future treatment landscape, Implement evidence-based, individualized treatment plans for patients with major depressive disorder and postpartum depression.

Go online to PeerView.com/AFZ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, experts in psychiatry discuss recent advances in the management of patients with major depressive disorder and postpartum depression. Upon completion of this activity, participants should be better able to: Recognize the burden of major depressive disorder and postpartum depression and the impact of delayed or suboptimal treatment on patient outcomes, Describe the role of GABAergic dysregulation in the pathophysiology of depression and the rationale for GABA-A receptor modulation with neuroactive steroids, Evaluate the mechanisms of action, efficacy, safety, and tolerability of current and emerging treatments for major depressive disorder and postpartum depression, recognizing potential implications for the future treatment landscape, Implement evidence-based, individualized treatment plans for patients with major depressive disorder and postpartum depression.

Go online to PeerView.com/AFZ860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, experts in psychiatry discuss recent advances in the management of patients with major depressive disorder and postpartum depression. Upon completion of this activity, participants should be better able to: Recognize the burden of major depressive disorder and postpartum depression and the impact of delayed or suboptimal treatment on patient outcomes, Describe the role of GABAergic dysregulation in the pathophysiology of depression and the rationale for GABA-A receptor modulation with neuroactive steroids, Evaluate the mechanisms of action, efficacy, safety, and tolerability of current and emerging treatments for major depressive disorder and postpartum depression, recognizing potential implications for the future treatment landscape, Implement evidence-based, individualized treatment plans for patients with major depressive disorder and postpartum depression.

We start off our January 2022 series of AMiNDR with this episode highlighting 9 papers on changes to synaptic transmission in Alzheimer's Disease. In this episode, Anusha will cover topics including changes to GABAergic and glutamatergic transmission and calcium flux in AD-affected neurons. We also have papers looking at age-dependent changes in synaptic function in AD. End neuro-transmission ;) Sections in this episode:  Changes to GABAergic transmission (2.41)  Changes to calcium flux (6.42)  Changes to glutamateric transmission (8.38)  Age-dependent changes in AD (13.11) -------------------------------------------------------------- To find the numbered bibliography with all the papers covered in this episode, click here, or use the link below:https://drive.google.com/file/d/1hUH8nXFf-O73pJlkHH4u9d0kBb3ibNUZ/view?usp=sharingTo access the folder with ALL our bibliographies, follow this link (it will be updated as we publish episodes and process bibliographies), or use the link below:https://drive.google.com/drive/folders/1bzSzkY9ZHzzY8Xhzt0HZfZhRG1Gq_Si-?usp=sharingYou can also find all of our bibliographies on our website: www.amindr.com. --------------------------------------------------------------Follow-up on social media for more updates!Twitter: @AMiNDR_podcastInstagram: @AMiNDR.podcastFacebook:  AMiNDR  Youtube: AMiNDR PodcastLinkedIn: AMiNDR PodcastEmail: amindrpodcast@gmail.com  -------------------------------------------------------------- Please help us spread the word about AMiNDR to your friends, colleagues, and networks! And if you could leave us a rating and/or review on your streaming app of choice (Apple Podcasts, Spotify, or wherever you listen to the podcast), that would be greatly appreciated! It helps us a lot and we thank you in advance for leaving a review! Don't forget to subscribe to hear about new episodes as they come out too. Thank you to our sponsor, the Canadian Consortium of Neurodegeneration in Aging, or CCNA, for their financial support of this podcast. This helps us to stay on the air and bring you high quality episodes. You can find out more about the CCNA on their website: https://ccna-ccnv.ca/. Our team of volunteers works tirelessly each month to bring you every episode of AMiNDR. This episode was scripted, hosted and edited by Anusha Kamesh, and reviewed by Christy Yu and Ellen Koch. The bibliography was made by Anjana Rajendran and the wordcloud was created by Sarah Louadi (www.wordart.com). Big thanks to the sorting team for taking on the enormous task of sorting all of the Alzheimer's Disease papers into episodes each month. For January 2022, the sorters were Jacques Ferreira, Christy Yu, Kate Van Pelt, Kira Tosefsky, Dana Clausen, Eden Dubchak, Ben Cornish, Elyn Rowe and Ellen Koch. Also, props to our management team, which includes Sarah Louadi, Ellen Koch, Naila Kuhlmann, Elyn Rowe, Anusha Kamesh, and Jacques Ferreira for keeping everything running smoothly.Our music is from "Journey of a Neurotransmitter" by musician and fellow neuroscientist Anusha Kamesh; you can find the original piece and her other music on soundcloud under Anusha Kamesh or on her YouTube channel, AKMusic.   https://www.youtube.com/channel/UCMH7chrAdtCUZuGia16FR4w   -------------------------------------------------------------- If you are interested in joining the team, send us your CV by email. We are specifically looking for help with sorting abstracts by topic, abstract summaries and hosting, audio editing, creating bibliographies, and outreach/marketing. However, if you are interested in helping in other ways, don't hesitate to apply anyways.  --------------------------------------------------------------*About AMiNDR: *  Learn more about this project and the team behind it by listening to our first episode: "Welcome to AMiNDR!" 

Can electrical current stop seizures, or make seizures less severe? How does it work, and who can benefit?  Dr. Laurent Sheybani interviews Dr. Robert Fisher about deep-brain stimulation for epilepsy.Disclosure: Dr. Fisher is a consultant for Medtronic but receives no compensation for using its deep-brain stimulation devices.Deep-brain stimulation (DBS) is the newest of three types of neuromodulation for epilepsy, and targets a part of the thalamus called the anterior nucleus. In DBS treatment, targeted electrical pulses inhibit  a network in the brain  involved in starting and spreading seizures. This interference is linked with a reduction in the number and/or severity of seizures in some people who haven't found relief with anti-seizure medications.In a randomized, double-blind study of DBS, the SANTE trial , 43% of people had significant reductions in their seizure frequency after one year, and 74% had reductions after 7 years. The treatment also had high patient satisfaction (84% after 7 years).The mechanisms of DBS are still largely unknown, though pre-clinical studies have found synaptogenesis, receptor changes, and changes in gene expression, suggesting the growth or regeneration of neurons. DBS is usually well tolerated, acceptably safe, and associated with improvement in quality of life.Research discussed during the episode:Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy (2010) Epilepsia (Fisher R, Salanova V, Witt T, for the SANTE study group)Experience and consensus on stimulation of the anterior nucleus of thalamus for epilepsy (2021) Epilepsia (Fasano A, Eliashiv D, Herman ST, et al.)Closed-loop stimulation of the medial septum terminates epileptic seizures (2021) Brain (Takeuchi Y, Harangozo M, Pedraza L, et al.)Medial septal GABAergic neurons reduce seizure duration upon optogenetic closed-loop stimulation (2021) Brain (Hristova K, Martinez-Gonzalez C, Watson TC, et al.) Other resources:ILAE/YES webinar on neurostimulation with Dr. Robert Fisher (January 2022)This episode was reported by Dr. Laurent Sheybani, and edited and produced by Nancy Volkers.Sharp Waves content is meant for informational purposes only and not as medical or clinical advice. The International League Against Epilepsy is the world's preeminent association of health professionals and scientists, working toward a world where no person's life i  The International League Against Epilepsy invites you to explore the ILAE Academy: Interactive, practice based online courses for health care professionals who diagnose and treat epilepsy. Find more information at ilae-academy.org. Support the showSharp Waves episodes are meant for informational purposes only, and not as clinical or medical advice.The International League Against Epilepsy is the world's preeminent association of health professionals and scientists, working toward a world where no person's life is limited by epilepsy. Visit us on Facebook, Twitter, and Instagram.

Go online to PeerView.com/TTU860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in psychiatry discusses the evidence for the use of GABA-modulating neuroactive steroids for major depressive disorder. Upon completion of this CE activity, participants will be able to: Summarize the evidence supporting a role for GABAergic dysfunction and altered neuroactive steroid signaling in major depressive disorder (MDD), Recognize the burden of MDD and the impact of delayed or suboptimal treatment on patient outcomes, Evaluate recent safety and efficacy data related to emerging treatment options for MDD, recognizing potential implications for the future treatment landscape.

Go online to PeerView.com/TTU860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in psychiatry discusses the evidence for the use of GABA-modulating neuroactive steroids for major depressive disorder. Upon completion of this CE activity, participants will be able to: Summarize the evidence supporting a role for GABAergic dysfunction and altered neuroactive steroid signaling in major depressive disorder (MDD), Recognize the burden of MDD and the impact of delayed or suboptimal treatment on patient outcomes, Evaluate recent safety and efficacy data related to emerging treatment options for MDD, recognizing potential implications for the future treatment landscape.

Go online to PeerView.com/TTU860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in psychiatry discusses the evidence for the use of GABA-modulating neuroactive steroids for major depressive disorder. Upon completion of this CE activity, participants will be able to: Summarize the evidence supporting a role for GABAergic dysfunction and altered neuroactive steroid signaling in major depressive disorder (MDD), Recognize the burden of MDD and the impact of delayed or suboptimal treatment on patient outcomes, Evaluate recent safety and efficacy data related to emerging treatment options for MDD, recognizing potential implications for the future treatment landscape.

Go online to PeerView.com/TTU860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in psychiatry discusses the evidence for the use of GABA-modulating neuroactive steroids for major depressive disorder. Upon completion of this CE activity, participants will be able to: Summarize the evidence supporting a role for GABAergic dysfunction and altered neuroactive steroid signaling in major depressive disorder (MDD), Recognize the burden of MDD and the impact of delayed or suboptimal treatment on patient outcomes, Evaluate recent safety and efficacy data related to emerging treatment options for MDD, recognizing potential implications for the future treatment landscape.

Go online to PeerView.com/TTU860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in psychiatry discusses the evidence for the use of GABA-modulating neuroactive steroids for major depressive disorder. Upon completion of this CE activity, participants will be able to: Summarize the evidence supporting a role for GABAergic dysfunction and altered neuroactive steroid signaling in major depressive disorder (MDD), Recognize the burden of MDD and the impact of delayed or suboptimal treatment on patient outcomes, Evaluate recent safety and efficacy data related to emerging treatment options for MDD, recognizing potential implications for the future treatment landscape.

Go online to PeerView.com/TTU860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. In this activity, an expert in psychiatry discusses the evidence for the use of GABA-modulating neuroactive steroids for major depressive disorder. Upon completion of this CE activity, participants will be able to: Summarize the evidence supporting a role for GABAergic dysfunction and altered neuroactive steroid signaling in major depressive disorder (MDD), Recognize the burden of MDD and the impact of delayed or suboptimal treatment on patient outcomes, Evaluate recent safety and efficacy data related to emerging treatment options for MDD, recognizing potential implications for the future treatment landscape.