Mental Health, Serotonin, Dopamine, and Neurodegenerative Disorders

I'd like to welcome everybody today's presentation on mental health, serotonin, dopamine and the neurodegenerative disorders. I AM your host, Dr. Donnelly Snipes. In this part of the presentation, we're going to define neurodegenerative disorders, explore the bidirectional interaction of mood and neurodegenerative disorders, review the functions of serotonin and dopamine in mood and neurodegenerative disorders. I'm going to call them NDS from here on out so I don't trip over my own tongue. Describe the symptoms of NDS and explore primary, secondary and tertiary prevention. So really we're going to get, get a broad overview and I know I've done other courses on dementia, for example, but, but I think it's important that we explore a little bit deeper or broader into the nds. Neurodegenerative diseases occur when nerve cells in the brain or the peripheral nervous system lose function over time and ultimately die. So the name pretty much says it all. Degeneration of the neurons, that's what we've got. And depending on which neurons degenerate is going to affect which symptom the person experiences. Alzheimer's disease will impact approximately 11% of people. Amyotrophic lateral sclerosis or ALS.002% Friedrich ataxia.002% Huntington's disease 0.01% Lewy body disease 2% of people. Parkinson's disease 1% Spinal muscular atrophy 0.01%. Multiple sclerosis is not technically classified as a neurodegenerative disorder at this point, but they are investigating some neurodegenerative aspects of it and chronic traumatic encephalopathy, and the prevalence of that is unknown according to the cdc. So there are a lot of different disorders that are neurodegenerative in nature and these are just the most common. And I think it's important that we recognize that because as we go through this presentation and we start talking about neurodegenerative disorders and mood, you're going to hopefully recognize that the people that you are seeing in clinic or in the hospital, wherever you work are likely more at risk for the development of NDS because of their pre existing mood disorders and, or people with NDS are likely to have comorbid mental health issues as well. So we, we want to recognize this from a prevention as well as an effective treatment standpoint. Depression and anxiety as well as NDS are linked to an imbalance of neurotransmitters and hormones including low levels of dopamine, serotonin, and or estrogen. So remember that males as well as females have estrogen, and our gonadal hormones are actually neuroprotective. So when there is an imbalance in our gonadal hormone levels, which unfortunately, we do see decline for both genders beginning, you know, in the mid-40s, generally, we're also losing some of the neuroprotection from that. So, you know, that is an interesting little thing to consider. Mental illnesses and nds, and I thought this was really interesting, have overlapping de. Neurodegenerative mechanisms. I don't think of mental illnesses as neurodegenerative, but. But they do have a lot of similar physiological pathologies, which mean. Which means that it. It is more likely that people with significant mental health issues are more likely to develop NDS later in life because of the oxidative stress. Remember, oxidative stress is what happens when your body is not able to clear out the free radicals quickly enough because you're making too many. How does that happen? Well, when that HPA axis is activated and you are just full bore, you are burning through energy and neurotransmitters and everything else, your body is in overdrive, which means it's making extra byproducts or free radicals, and that those excess free radicals, your body's not prepared to clean out as quickly. It's kind of like after a. After a parade. You know, normally the city staff is able to keep the city looking really nice. At least in our city, it's great. However, after a parade, it looks like, you know, a tornado hit it because there's trash everywhere and everything, because there was an influx. You can think of that trash kind of like those free radicals. When there is an influx, when there is extra stress on the system, it produces extra free radicals. When those free radicals aren't cleared out, it produces oxidative stress, which leads to inflammation. And we know that inflammation is associated with both NDs as well as mood disorders. Mitochondrial dysfunction and inflammation are also two other overlapping aspects between mental illnesses and neurodegenerative disorders. So the functions of serotonin and dopamine. Mood regulation for serotonin is mood regulation, cognition and concentration, sleep, circadian rhythms, pain perception, immunity and inflammation, gonadal hormones, heart rate, impulse control, and hunger and satiation. So let's just think about serotonin for a minute. With people with dementia or Parkinson's or other neurodegenerative diseases, how many of these symptoms do they have? Well, there's obviously Difficulty with cognition and concentration. There can be some mood lability. Their sleep and circadian rhythms typically get all kinds of wonky. We have seen in experiments and testing that people with neurodegenerative diseases, as well as people with anxiety and depression, have higher levels of inflammation, which means the immune system is malfunctioning. Because the immune system is what's involved in deciding when those inflammatory cytokines go out, gonadal hormones can be imbalanced. Now, that's, you know, that's generally not a symptom of neurodegenerative disorders, but you can see there are several symptoms that, that are common in mood disorders as well as neurodegenerative disorders that can be caused by an imbalance in serotonin. Now, dopamine, dopamine is involved in motivation, attention, energy, muscle contractions, cognition, again, pain perception, and opioid release. It modulates blood flow and glucose metabolism. So one thing that I do want to point out, and I think we're going to talk about it later, but I can't remember heart rate. Remember, your heart pushes the blood around. The blood carries the oxygen. When enough oxygen is not getting to the brain, it causes cognitive difficulties, which is why people who have cardiovascular disease tend to have more issues with cognition and concentration. Well, we go over here to dopamine. Dopamine doesn't necessarily impact the heart rate, but it does modulate blood flow to certain, to a certain extent, modulating the blood pressure and the contractions of the arteries or however the blood moves. Obviously, I didn't go to medical school anyhow, so it's important to recognize that low dopamine levels may contribute to low blood flow, and low blood flow can contribute to difficulty with cognition and concentration, as can low dopamine levels and glucose metabolism. Our brain is one of the primary utilizers of blood glucose. At the end of the day today, you're probably going to feel kind of tired, and you're going to be like, I was sitting in, in, in a seminar for four hours. Why do I feel tired? Because your brain was working and because your blood probably wasn't circulating as much as usual, because you're not up walking out to the waiting room, seeing patients, cleaning the house, whatever you generally do in a day. So glucose metabolism is important to recognize because if your brain is not able to process the glucose as effectively, it's not able to function as effectively. It's kind of like trying to run a car without oil. So we do want to understand the overlapping symptoms that can be caused by either an Imbalance or inadequate serotonin or dysfunction in the serotonergic system or dysfunction in the dopaminergic system that that can lead to mood disorders and neurodegener ne that neurodegenerative problems. I told you I would trip over my tongue on that word yet. So let's talk a little bit about serotonin and neurodegenerative disorders. 5ht. Remember, 5ht is the precursor to ser. It's the joke general thing for serotonin. Serotonin receptors come in multiple categories. 5 HT 1, 2, 3, 4, 5, 6, 7, etc. I believe there's 19 different types of serotonin receptors. Don't quote me on that. But it's important to recognize that. Why? Because not all serotonin is created equal. If you upregulate serotonin 5 HT1, it's gonna have a much different impact than if you upregulate 5 HT3. This is important to recognize in people with mood disorders who start taking antidepressant medication because not every medication works exactly the same way or on exactly the same receptors. That being said, when you have people who have neurodegenerative disorders, they're often prescribed antidepressants, and that can have some effects. We'll get there in a minute. But so 5ht and serotonin in general, and that encompasses everything. May it be involved in the development of epilepsy, Parkinson's disease, multiple sclerosis, als, adhd, autism spectrum disorders, and Alzheimer's disease? That's a lot. But we also know that serotonin is involved in just about everything that we do. Serotonin dysfunction is also associated with sleep problems in neurodegenerative disorders. Serotonin is a interesting molecule because serotonin is broken down to make melatonin. Melatonin helps people get sleepy so they can go to sleep. Serotonin is secreted and triggered to break down into melatonin by the pineal gland when all the conditions are right to start winding down. So if there's not enough serotonin or if there's a breakdown in that system, there could be a problem. So we do need serotonin in order to make that melatonin. However, serotonin reuptake inhibitors, SSRIs and SNRIs and S. ARIs are also shown to inhibit REM sleep. So melatonin helps us get to sleep, but serotonin inhibits REM sleep, which is important because. Because we need REM sleep just like we need deep sleep and light sleep. There's a reason we have all those phases. So I digress. Lower serotonin levels contribute to cognitive decline. Well, let's go back and look at this. Why might that be? Well, serotonin is directly involved in cognition and concentration, but lower serotonin also can lead to reduced heart rate, which leads to reduced oxygenation, which can impact cognition. Lower serotonin can lead to or corresponds to, I shouldn't say can lead to corresponds to imbalances and go nadal. Hormones, estrogen and testosterone tend to make serotonin more available. So when estrogen and testosterone are low, serotonin may be low. So it's important to recognize that all of these things may be interrelated and those gonadal hormones are responsible for neuroprotective factors. So when serotonin is low, that means gonadal hormones are probably low, which means we're missing some of that neuroprotection. Welcome to the All CEU's education channel where you will find long form counselor education training videos as well as shorter overview videos geared toward the general public. We have over 900 videos so using the search function that is underneath the subscribe button on our homepage can help you find the videos that you really want to watch. You can also find an alphabetized set of some of my most popular playlists@allce.com YouTube-playlists I absolutely love hearing from you, so keep those comments coming. We actually do read all of them and try to respond within a few days. Have a fabulous day and don't forget to click subscribe and the bell if you haven't already so you can be notified when I release new videos. Treatment with SSRIs Selective serotonin reuptake inhibitors or SNRIs Selective norepinephrine reuptake uptake inhibitors significantly slows the progression of cognitive impairment in neurodegenerative disorders. Now why SNRIs? Well, because SNRIs don't just target norepinephrine, they actually also correspondingly but not as strongly increase serotonin in the brain. And they found that some people respond better to SNRIs than SSRI. SSRIs trazodone, which a lot of our clients have probably been on. At least where I've worked it was a very common medication for the doctors to prescribe for people who had insomnia. Trazodone is often used for sleep and is associated with improvements in neurodegenerative disorder sleep related dysfunction. Now it's important to Recognize that trazodone is a serotonin agonist, which means it actually tries to get more serotonin into that synapse. And it's a reuptake inhibitor. So it's a double whammy for serotonin. But since serotonin is a REM inhibitor, yes, trazodone can help people get to sleep and potentially stay asleep. However, they need to be monitored for the impact of any reductions in REM sleep. Some people getting any sleep is way better than what they were doing, so you're going to see improvements. Other people may start to develop more confusion and irritability because of the lack of REM sleep in sleep. And I, I know I'm just kind of going off on, on tangents today. When we sleep, remember we have that light sleep where you're just kind of dozing, you're easily awakened. You have REM sleep, which is when you dream, and then you have that deep sleep. And that deep sleep is when the adenosine is cleared out of your brain. It's when the cleaning crew comes in and cleans out all of the residual junk from the day in terms of, you know, adenosine and byproducts and free radicals and other stuff comes in there and does that during the deep sleep period. So when people take trazodone, we know that it does, does not negatively impact their deep sleep. In fact, it improves their deep sleep. So by improving it, making sure they're getting their deep sleep, making sure they're cleaning that adenosine out, which makes you feel groggy the next morning, if it's still sticking around. People often see an improvement in cognition. So cognition and deep sleep are much more strongly related than cognition and REM sleep. But, you know, like I said, some of the studies have shown that REM inhibition can be problematic for some people. In people with neurodegenerative disorders, there's a degeneration in serotonergic axons, axons and dendrites. Back to Neuropsych 101. You may remember it. You know, not a huge point, but just for a refresher, Axons take information and pass it along downstream. They keep the message going where it needs to go. Dendrites take the information and send it to the cell. So when the axons start to degenerate, that means the message is not getting passed along in the nervous system. Okay, so think about back when you were in grade school and you used to play telephone or whatever they called it, wherever you were, and you passed a Message from person to person to person. Well, in this case, at some point, the person is just not listening and is not going to pass that message along, which obviously causes problems. Reductions in 5ht, 1, 2, 4 and 7. And no, you're not going to be quizzed on this. But I thought it was important to recognize that reductions in certain types of serotonin and increases in all other types of serotonin receptors or receptor activity improves cognition. So it is way overly simplified to say that too little serotonin contributes to neurodegenerative disorders, too much of certain types or too little of other types of contributes to neurodegenerative disorders. And there is no way, unfortunately, right now, we still have no way of accurately and adequately measuring the amount of neurotransmitters that are in the brain, because neurotransmitters and their receptors are throughout your body. So we don't know, we can get a general idea through a blood test about how much serotonin or dopamine or whatever a person has. There are some blood tests that they've done for that, but we don't know how much of that is in their body versus actually working in their, in their brain receptors. Dopamine dysregulation is involved in nds as well as schizophrenia, depression, adhd, and addiction. We talk a lot about dopamine and I spend a lot more time on serotonin because a lot of times when people think of Parkinson's disease, especially, they think of dopamine only. And the research is really showing that, no, that's not the case. But remember, with depression as well as anxiety, and now we know neurodegenerative disorders, imbalances in serotonin can contribute to symptoms. So it's likely that the serotonin imbalances in people with nds are also going to contribute to comorbid mental health issues, and vice versa. Parkinson's disease is a neurodegenerative disease characterized by loss of dopaminergic neurons. In fact, 60 to 80% or more of dopamine producing cells are gone by the time the person presents with actual symptoms. So their ability, their body's ability to pass on, pass along those dopamine signals is, you know, 60 to 80% gone by the time they actually get diagnosed. And, and that's significant. My thought is, as clinicians, if we notice people are having significant depression, lack of motivation, low energy, you know, a lot of them, symptoms of depression, especially if it's accompanied by cognitive changes, it's probably worth referring Them to be screened for any neurodegenerative things that might be going on, especially if the cognitive issues started, you know, recently. We know that cognitive dysfunction, you know, difficulty concentrating, difficulty focusing, making decisions, are common symptoms of clinical depression. So there is a lot of overlap. But if we can get people diagnosed before they've lost 60% of their dopamine producing cells, they probably have a better chance of delaying the progression of Parkinson's. Excessive dopamine. We've talked about excessive glutamate before, but excessive dopamine can also create a neurotoxic environment, which leads to dysregulation of the dopaminergic system. Wow. So there is such a thing as too much fun. Remember, dopamine is your motivation chemical. It's your energy chemical, it's your I want to do that again chemical. Endorphins. Dopamine. When we do something that's positive or enjoyable or is designed to keep us healthy and safe, dopamine is, is released. But endorphins are too. And endorphins are what provide the pleasure. Dopamine gives you the energy and the desire to do it again. So dopamine is more motivation, but when you've got that going on, dopamine increases energy. We've talked before with glutamate about how the excitatory neurochemicals can make it neurotoxic. And it doesn't literally get too hot in the brain, but it's a decent analogy. It gets too hot and with all that excitement and some of the neurons start dying. When that happens, then people aren't getting enough dopamine through their system. It's interesting to note the parallel between this and delirium tremens. When people quit drinking, if they've been heavy drinkers, they have been flooding their brain with dopamine, just flooding their brain with dopamine. And that has caused a neurotoxic environment. They have developed a level of tolerance. So the brain is not letting as much dopamine through. The tissues have become resistant to the effects of dopamine, which means they need to drink or do something to increase the amount of dopamine being sent through in order to feel normal. When they quit drinking, their body is not making or sending enough dopamine through anymore because it's so used to getting it exogenously that they have a precipitous drop in dopamine levels. We know that low dopamine is associated with tremors, with Parkinson's disease, and with delirium. Tremens. So you can see kind of the overlap here. You can see how people who abuse substances particularly interestingly enough, and we'll talk about this in a minute, Amphetamines are at a much higher risk of developing neurodegenerative disorders later on because they have created that neurotoxic environment. Are there questions? I know I get really excited about the neuroscience aspect of mental health issues because I like to understand how things work and why, you know, some symptoms seem to be so ubiquitous to so many different disorders. Do you have any questions about dopamine? Any of the neurodegenerative issues that we've talked about this thus far, or serotonin and the involvement? Remember, on the zoom interface, you can click on the reactions button to raise your hand and I can unmute you. If you want to talk or if you want to type, that's fine too. And I can just read whatever you're more comfortable with. One of the other things I think is interesting and we need to consider and feel free to raise your hand or type while I'm talking. I'm just filling time here is when we're working with people who present with depressive depression, clinical depression, a lot of times we don't even think neurodegenerative. A lot of times we don't even think dopamine. We instantly think serotonin. And when people present with nds, we automatically think dopamine and don't think serotonin. But in actuality, either way, it could be either neurotransmitter, which is important from a pharmacological perspective. And it's also important to recognize that people with NDS can have low dopamine and low serotonin because a lot of times they work in tandem. And so they may do better potentially on a serotonin dopamine reuptake inhibitor or even a serotonin norepinephrine dopamine reuptake inhibitor. And yes, they are in existence. The sndris. Kind of like throwing the whole kitchen sink at it. Sheila asked, should regular blood work be done to monitor appropriateness of SSRIs or SNRIs, or level of dopamine or serotonin? Unfortunately, since we can't tell where the neurotransmitters are that we're measuring with the blood test, that's not going to give you a lot of information. If you have a client who tends to be treat treatment non compliant, then it's always helpful to monitor the levels of the SSRIs or SNRIs. But for most patients, just judging and having them judge scale themselves as to how they feel each day on the medication can give you an idea of what's going on, whether it needs to be increased, whether it needs to be decreased, or whether it needs to be changed completely. Unfortunately for a lot of people, psychiatrists only see the patients at once a month at best. So they're not getting a minute by minute, so to speak, understanding of or picture of what's going on. And especially with people with advanced neurocognitive, neurodegenerative or neurocognitive disorders, they may not be able to effectively keep a journal or a diary or a log. And their caregivers may be so overwhelmed trying to help the person stay safe and have the highest quality of life that they have difficulty completing it. So any kind of journaling or logging that we ask people to do, I find regardless of the diagnosis, I try to make as simple and, and quick and dirty as possible. You know, on a scale of 1 to 5, 1 being no symptoms at all, they're having a great day, or you can do it, five, however you want to do it, two being some symptoms, but they're having a really good day, three, they're having symptoms, it's impacting their functioning, four significant symptoms, and five, just completely over overwhelmed or overcome by their symptoms. It's important to anchor your Likert scales for people and, and try to make it as easy to differentiate as possible. I hate it when I look at a, a Likert scale and it says a little, some, much, always, whatever. I'm like, give me numbers, 10%, 25%, 50%, I can do that. But maybe that's just because I'm, I'm a little bit too rigid that way. I don't know. But they have found that people do tend to be much more accurate on self report if they are given something that's anchored and it's actually better. They have found that if you give somebody an anchored scale that you do it with an even number, preferably four. Once you get above four, people have difficulty. The, the differences can be too minute to be accurate. But if you give people a five point Likert scale, a lot of times they'll choose three. And so you're not getting as good of a picture. So either use really good definable anchors or, and, or keep it to four points of, of reference, that'll make it a lot easier. And, and people can just, you know, circle a number and maybe jot down a little bit about why or maybe even not even if you can just look at the numbers over the course of a week and you see that John is a 22224, then you can go, okay, what happened on Thursday? That and do backward chaining and figure out what happened with medication. Knowing that when people start medication, it takes up to six weeks to really fully get in their system. And the first week is generally pretty lousy anyway because most people, when they start taking antidepressants, SNRIs, SSRIs, tend to feel kind of fluish those first few days. So while their body adapts to the new medication. So we expect the first week to not be so great. We want to look at what's going on after that in terms of figuring out what they need. And I think that's kind of what. What you were hinting at, Sheila, is it's really important to communicate as best as possible with the client to identify what their presenting symptoms are, what their most prob. Problematic present in their perception presenting symptoms are, and how the medications impacting that. So, well, that, that. That's pretty straightforward there. And if the medication is not helping with the symptoms that they find most bothersome, then it's important for them to be able to self advocate or work with their treatment team to look at changing medications or figuring out what's going on. I do think blood work is really important because alterations in gonadal hormones can be identified with blood work, and alterations in gonadal hormones will affect dopamine and serotonin levels. So generally that's not going to contribute to neurodegenerative disorders, but it can contribute to significant mood disorders and cognitive dysfunction. So. And thyroid. Thyroid hormones are the same way, easy to test in a blood test and can impact cognitive functioning. So it's always good to at least start out with a full blood, full panel blood test. The presentation I did a few weeks ago on hepatitis, when the liver becomes inflamed, you can. People can develop hepatic encephalopathy in which basically toxins from the liver back up into the brain. That's overly simplified, but we also want to be aware of that. And a blood test will tell us if the liver is functioning as it should. Because liver dysfunction can contribute to a neurotoxic environment, can contribute to delirium, and cause a whole host of other problems. Now, that's not neurodegenerative, so to speak. That's caused by the toxic effects of that junk going to the brain and identifying that and working with. To Address the hepatitis or the cirrhosis can certainly help that. There are a lot of different types of dementia and there are a lot of different types of neurodegenerative disorders as we already identified. Some of them have genetic components and we can look and say if you've got a family history of this disease, you're more likely to get it. Some of them have virtually no genetic connection at all. So we can't say, you know, unless we, we can't predict somebody's risk for dementia solely on, on genetics. Vascular dementia is one of those that has, doesn't have a genetic component. It's associated with inadequate blood flow. So let's think about what causes inadequate blood flow. Sleep apnea, people stop breathing. It actually contributes to inadequate oxygenation, it and inadequate blood flow. Sleep apnea is associated with some neurodegenerative disorders. When you stop breathing, your brain thinks that's a pretty big issue. And it triggers the HPA axis, triggers all of those excitatory neurochemicals to shoot out to try to get you to start breathing again. Think about somebody who has stopped breathing and when they start breathing again, they, they sit up with a start, or they may not sit up, but they awaken with a start and they gasp, they cough. That's the brain triggering those excitatory neurochemicals. Well, if your brain's doing this 15, 20 times a night, you know, ramping up to try to, you know, get you to breathe that gummet, that can contribute to a neurotoxic environment in the brain. Abuse of depressants can contribute to inadequate blood flow. If people are using especially opioids, if people are using excessive amounts of opioids, it can slow their respiration, slow their heart rate, which means the blood, the oxygenated blood's not getting up to the brain. You know, it's just, it's just not. And that can cause cognitive issues more likely for vascular dementia. We're seeing things like stroke. Now. Stroke can happen because of high blood pressure. It can also happen when people, especially when they're detoxing from alcohol. When the alcohol leaves the body, blood pressure goes up. When people try to detox from binge drinking or long term drinking, their blood pressure is going to go up. If they already had high blood pressure, it may not take much to get up into that stroke danger zone. If they didn't already have high blood pressure, then, you know, they may have a little bit more wiggle room. But that's why alcohol detox is a medical issue. It needs to Be medically supervised to be safe. And it's not an overreaction to say that, yes, it's legal, but it does have some very, very nasty detox side effects. Other people may have strokes for unknown reasons that can contribute to vascular dementia. Lewy Body dementia is due to abnormalities and how the brain processes a particular protein which leads to abnormal del deposits damaging brain cells. So, you know, basically it's caking up in the brain cells and killing them. Frontotemporal dementia is a progressive nerve cell loss in the brain's frontal lobes or in its temporal lobes. So where your temples are, or in the frontal lobe, which is where we know we do executive functioning as well as impulse control in front of frontotemporal dementia. 30% of the cases do have a genetic component to them, but that's still only a third. So two thirds don't. Huntington's disease is a progressive brain disorder caused by a defective gene. Symptoms usually develop between 30 and 50, but can appear between. Yes, no, that's not a typo. It can. Can appear between the ages of 2, toddler, 2 and 80. That's a big issue. Most pediatricians, you know, probably would pick up on this, but we do want to be cognizant of it if we are working with anybody, since it can happen at any age. Dementia can happen at any age. Now, we typically think of neurodegenerative disorders as being something that starts in midlife or late life. And that's typically what happens, but not always. I mean, Michael J. Fox, for example, started developing symptoms of Parkinson's, you know, long before he was in midlife old age, by my definition. So we do want to be. Be cognizant of that fact and not dismiss it, because the earlier we can get people into treatment, the better their prognosis for delaying the progression. Neurodegenerative disorders at this point can't be reversed, but there are medications that are coming out that can slow the progression. And there are things that we can do. Parkinson's disease related dementia is another type of dementia. Not everybody with Parkinson's develops dementia, but a lot of them do. And posterior cortical atrophy is another type. We are not neurologists. We don't need to know, you know, all the specifics of these. The biggest ones we want to know is just the general signs of neurodegenerative disorders. And, and we're going to talk about those and also the risk factors for vascular dementia, because that's by far the most common dementia that, that we're probably going to to see, especially in mental health practice.