Revolutionary New Treatment Strategies for Depression

0:00 Unlimited CEUs $59 @ AllCEUs.com I'd like to welcome everybody to today's presentation on depression prevention and treatment emerging research I'm your host Dr Dawn-Elise Snipes in this presentation we'll review new types of interventions designed to prevent or treat depression or and or treat depression including transcranial magnetic stimulation anti-inflammatory approaches healing the gut microbiome ketamine and esketamine genomic sequencing oxytocin Chiropractic manipulation Vagas nerve stimulation and acupuncture so let's start out with TMS that's the one that seems to be just flourishing around here in Middle Tennessee I don't know about in other areas of the country TMS

0:51 is a non-invasive neuromodulation technique that uses magnetic fields to stimulate nerve cells in the brain targeting areas in involved in M mood regulation TMS devices use an electromagnetic coil placed against the scalp which generates a magnetic field that penetrates the skull without causing discomfort or damage now TMS is nothing like electroconvulsive therapy and that's when people hear about magnetic stimulation brain stuff they think ECT this is nothing like that this will not produce the um physiological response it's a very um sort of benign sort of thing uh people often report feeling a sense of warmth um where where the magnetic field is contacting the scalp

1:43 but nothing painful nothing scary the magnetic field creates small electrical currents in the brain tissue which depolarize neurons in the left dorsal lateral prefrontal cortex now we've talked about the prefrontal cortex a lot that's where we do our executive functioning our thinking we take our our feelings and we can process those feelings to figure out fitkat based on the facts in the current context is this a threat to me people with depression tend to have a um disrupted signaling in the dorsal lateral prefrontal cortex and that is crucial for mood regulation decision making an

2:30 executive functioning TMS influences not only the targeted area but interconnected brain networks and that makes sense I mean when you have an electrical current going through fluid and tissue it's going to kind of meander a little bit they found that it also inter interacts in the subgenual anterior singulate cortex which is associated with depression related hyperactivity the default mode Network which we've talked about a bunch that's your autopilot um and your default mode network is involved in rumination and self-referential thought processes so by indirectly targeting the dmn it can help reduce some rumination and self-referential thought and

3:20 then the salience network remember that's the network that impacts what you pay attention to what is Salient in your mind um and then the cognitive control Network all of these are critical for emotion regulation and cognitive processing so TMS may be targeted towards one particular area but then it branches out and you can think about it as as a network and the network in the brain that typically sends signals to the prefrontal cortex they're they're connected so when the prefrontal cortex is stimulated those areas are going to be stimulated as well in terms of Effectiveness ATMs or accelerated TMS protocols show significant reductions in

4:08 depression system symptom severity now accelerated TMS and Rapid TMS are um treatment protocols that use a more intense level of stimulation again nothing like ex electroconvulsive therapy at all uh but they're finding that when they increase the intensity of the magnetic stimulation there are more rapid results and there is less treatment Dropout and there's more patient satisfaction ATMs protocols can demonstrate symptom Improvement within just a few days Days A lot of times we've been talking with people about okay in the next few weeks hopefully you're going to start feeling a little bit better not with TMS TM ATMs specifically uh a lot of patient

5:00 report starting to feel symptom Improvement I mean it's not you know a magic switch but they start to feel symptom Improvement in days no decline in cognitive functioning has been reported in fact some Studies have even observed cognitive improvements such as enhanced attention and executive functioning well let's think about why this might be if we're rewiring the system we may be unblocking some blocks that could be it but also when people are are stressed when they're depressed they tend to be in a brain fog they tend to have difficulty concentrating so as that fog lifts of it makes sense that people are going to be able to think more clearly and

5:46 pay better attention ATMs does show mixed results for reducing suicidal ideation and there are other treatments that are being explored for people who are acutely suicidal but this is an excellent um approach or protocol that can be used for people with major depressive disorder with postpartum depression with um and with treatment resistant depression it is shown Effectiveness and I don't like the term treatment resistant depression I'll tell you because that implies that the depression can't be healed and what it should say is the standard treatment ain't working because what is causing that person's depression has nothing to do with how quickly the serotonin

6:37 is re-up taken from the synaptic space there's something else that is causing those depressive symptoms and a lot of times it comes back to uh systemic inflammation that is throwing all of the HP axes the HPA axis the hypothalamic pituitary adren hypothalamic pituitary thyroid and hypothalamic pituitary gonadal axis out of whack and that can even include menopause and andropause when the gonadal hormones start to go down it Alters the levels of neurotransmitters in the brain and so there can and and can lead to some systemic inflammation so it's important to

7:27 consider instead of calling it treat treatment resistant depression we need to think well our standard approach which only works for about 50% of people anyway isn't working we must be missing something what is causing this particular person's symptoms neuroimaging insights functional MRI and pet studies suggest that changes in the brain correlate with treatment response indicating potential biomarkers for ATMs efficacy so not only are we relying on patient report which can be affected by the placebo effect they expect it to help them so they're feeling better but they can actually go into brain Imaging studies and they can see changes in the way the brain

8:18 lights up to different stimuli as a result of ATMs TMS is effective for treatment resistance istant depression it's also effective for treatment resistant geriatric depression GD uh with a clinical response rates ranging from 6.7% to 5 54.3% and again you're like wow that's a big range well let's think about that again if the problem is the communication between the neurons in the brain then TMS could be very effective if the problem is something else maybe um the

9:04 person doesn't have any testosterone production anymore which is throwing the system out of whack well no amount of brain stimulation is going to impact that we're going to have to balance those hormones somehow another thing that impacted the variability and outcomes was differences in the TMS protocols patient characteristics and dosing strategies when people get older they may require higher stimulation intensities due to age related brain atrophy as we get older and as we're stressed we start having our brain shrink a little bit uh which is one of the reasons we talk a lot about the importance of cognitive uh stimulation therapy of of staying active in older age because the more we stay active the more we've got neurogenesis the more

9:53 we prevent the brain from shrinking as quickly and we can even build up some reserves so we've got you know a few extra neurons that that we can afford to give up if we have to at some point when we have age related brain atrophy the scalp to Cortex diff distance is reduced so your skull doesn't change at all you know that's going to stay the same size but your brain as it shrinks is further away from the skull so it requires increasing the intensity of the TMS in order to get that signal all the way and effectively to the part of the brain that you want it to get to many studies apparently underdose TMS compared to FDA approved protocols

10:44 for younger adults TMs in older adults has also shown to preserve cognitive functioning and in some cases even improve cognitive functioning especially in executive fun executive areas so again they're targeting that um prefrontal cortex area which is where we do our executive functioning and by stimulating that it actually can potentially generate some neurogenesis and help the neurons communicate a little bit better emerging Trends and recommendations advances in neuroimaging and connectivity mapping with MRI fmri and EEG can produce individualized

11:30 TMS targeting so people can go in and they can have their brains scanned and we know what it should look like if it's a healthy brain and the the doctors can figure out what areas are not lighting up the way they should and then they can Target the TMS for those areas for that particular individual and that is super helpful not only for people who have history of trauma and other things but it's also super helpful for people who've had a traumatic brain injury because the problems or the um disruption disrupted areas in their brain may be very different as a result of uh that TBI as well as their body's adaptation and recovery from that TBI accelerated TMS Protocols are

12:21 gaining popularity due to their rapid effects and potential for reducing lengthy treatment schedules integrating TMS with other approaches May improve outcomes particularly in treatment resistant depre uh populations so again we're going to keep hearing this treatment resistant thing come up because people who respond to ssris we've done that research these new approaches are pretty much only being used when the first line fails and I personally have an issue with that I think we should educate people about all the different options that are available to them so if they don't want to go with the standard firstline treatment that fails 50% of the time they can opt

13:08 for other approaches um combining TMS can also be helpful as I said for example when our hormones get out of whack it can contribute to systemic inflammation now it can also contribute to uh neural inflammation as a result because the brain is a part of the system and TMS can help improve the basically electrical functioning and signaling in the brain but we still have to address that systemic inflammation uh people who've undergone trauma who are struggling with cptsd or PTSD are going to have systemic inflammation almost inevitably um until that's resolved until they

13:55 feel safe and empowered and as a result again we can help the brain communicate but we've also got to address the underlying issues what's causing that brain to have trouble communicating larger well-controlled trials are needed to standardize TMS protocols optimize dosing and identify predictors of treatment responses especially in older adults this is still a new field so people are still sort of experimenting learning uh there are a lot of clinics that are available that do provide this service now not all insurance covers it which can be a bummer for a lot of people so let's look at another approach and based on how many times I said inflammation in the last

14:43 segment I'm sure it doesn't surprise you that I'm going to say the anti-inflammatory approach is actually gaining a lot of traction because we know that when we have inflammation in the body it correlates very very strongly with uh mood disorders causes a brain inflammation include immune system disregulation and plays a central role in the development of depression overproduction of pro-inflammatory cyto kindes your inflammatory markers contribute to this neuroinflammation remember when we're stressed for a long time cortisol that hormone that is supposed to suppress inflammation loses its Effectiveness and when it loses its Effectiveness

15:33 then those inflammatory cyto kindes can kind of run wild because it doesn't have the ability to control them anymore chronic psychological or physiological stress leads to HPA AIS hyperactivity overactivity of that stress response increasing cortisol which paradoxically may induce corticoid glucocorticoid resistance over time promoting inflammation which is a really fancy way of saying what I just said over time cortisol loses its ability to suppress inflammation if it's constantly coursing through your system and so then we have inflammation increase in the system all right well that's not good our body registers that is not good so it turns up the

16:19 stress response even more and dumps even more cortisol so it starts sort of spinning out of control so one of the things we need to focus on is reducing that inflammation and reducing the stress that's causing that inflammation so the um receptors can get a break basically and become more receptive systemic infections can trigger peripheral immune responses that affect the brain via cyto kind signaling remember those are some of your inflammatory markers the vagus nerve or by crossing a compromise ized blood brain barrier so systemic inflam infections and I think a lot of us can think of a few that have been you prevalent recently uh can actually

17:10 contribute to neuroinflammation as and systemic inflammation because the immune system's trying to trying to handle it and is not succeeding it can also cross that when we get stressed our bloodb brain barrier can become more permeable so those cytotoxins can get into the brain trauma during critical developmental periods Alters the HPA AIS regulation and immune function increasing lifelong vulnerability to inflammation and depression trauma even in the mother can impact the fetus because the mother is you know doused in cortisol and stress hormones when she experiences chronic

17:58 stress or trauma and that little peanut is also being doused in those stress hormones so we do see uh infants that are born to parents who were under extreme stress often are born with a disregulated HPA access the beauty is it can heal we can help them help the parents help the child feel safe and empowered reduce the child's unnecessary stress so brain can heal itself trauma-induced epigenetic modifications can lead to persistent immune system disregulation and increased inflammation if we don't address these changes we can see persistent inflammation in some cases the trauma

18:47 is long prolonged enough or severe enough that it actually does cause some genetic changes that can make the person as I just said more susceptible to immune system problems and inflammation in the future okay well we may not be able to change that we can't rewire that DNA or RNA uh we need to help the person learn how to adapt so they can mitigate anything that might trigger the immune system disregulation and inflammation gut microbiome alterations increase inflammation through increased gut and blood brain barrier permeability uh so the gut takes

19:37 in food it breaks it down and it produces byproducts you know there's always waste in a production process those byproducts can be toxic and when the gut becomes more toxic and the bloodb Brain barrier is more toxic then these endotoxins are able to kind of you know filter in to places where they're not supposed to be and we don't want them and cause inflammation a higher BMI now I don't like BMI the way we have historically measured it uh in the Articles they still refer to it as BMI what we're looking at is a higher adiposity a higher percentage of um fat or atopos tissue compared to other tissues increased levels of fat tissues

20:27 are associated with increased estrogen and increased inflammation so when we're talking about anti-inflammatory approaches we need to explore what is causing inflammation for this person is it trauma is it genetic is it from their gut microbiome is it a result of having too much adapost tissue that's causing estrogen dominance there's a lot of things that can can cause inflammation pro-inflammatory cyto kindes interfere with serotonin dopamine and glutamate Pathways reducing neuroplasticity and altering mood regulation so when we have those

21:15 pro-inflammatory cyto kindes just circulating through our body it's going to interfere with our body's ability to regulate those neurotransmitters and it's going to interfere with our body's ability to remodel the brain neuroplasticity is the the brain's ability to remodel itself well those pro-inflammatory cyto kindes those are stressors so we're actually we've actually got kind of a neurotoxic environment instead of a uh neurogenesis type environment inflammation affects key brain areas involved in mood regulation such as the prefrontal cortex amydala and the hip campus when we start getting inflammation it's not real particular it goes everywhere and we

22:05 know the prefrontal cortex that's our thinking our reasoning our attention the amydala that's our mood emotion fear processing hippocampus fear processing sensory so we've got a lot of very crucial areas of the brain that when they become inflamed are going to cause problems in mood regulation reduction of neurot trophic factors is another issue in the brain when we have inflammation inflammatory cyto kindes reduce the level of brain derived neutrophic factors crucial for neuronal survival and plasticity we need to have those buffers in there to protect our brain against excitotoxic environments and

22:50 when we've got inflammation the buffer can't keep up so it becomes neurotoxic now let's talk about how depression causes neuro neuroinflammation we've talked for a while about different things that can cause inflammation that can cause the body to have difficulty regulating neurotransmitters and cause depression but how does depression cause neuroinflammation chronic depression maintains HPA axis overactivation and you may be scratching your head going when I'm depressed I got no energy I don't the breast response doesn't seem to be there ah but it is we've talked in other videos about the flat and the Furious when our HPA axis becomes disregulated

23:39 the body becomes less responsive to what we'll call minor stressors but when there's a major stressor then there's a tsunami of stress hormones that pushes us into the Frantic or Furious so we go from Flat to frantic or flat to Furious underlying all that when we've got inflammation even if we're not feeling stressed our body is stressed and when our body stressed that HPA axis stays turned on and that sustained cortisol secretion and immune system modulation leads to problems and perpetuates inflammation chronic inflammation leads to that sensitivity of The glucocorticoid receptors impairing cortisol's anti- inflammatory effects which

24:29 exacerbates neuroinflammation and depression so we're back to the same place we were before when cortisol can't do its job and we start having inflammation there's going to be a problem so when we think of people as depressed we often miss the fact that that HPA axis is still on overdrive in the background and we need to help them strengthen their vagus nerve strengthen their and we'll get there in a few minutes um and strengthen their ability to turn on that parasympathetic nervous system that rest and digest which will turn off the fighter flight or the HPA axis so what can we do anti-inflammatory medications now most of us I don't know about you but most people

25:19 have difficulty tolerating anti-inflammatory medications yes it's systemic yes it can help a little bit for some people but but it really doesn't do a bunch um some Physicians will use it as an adjunct especially initially to help the person feel a little bit better feel less achy feel less you know heavy if you will but that's not a long-term solution all you're doing is basically doing trying to do cortisol's job for it and suppress the inflammation but that cortisol is still running wild we need to figure out why that HPA axis is disregulated and help it heal moderate aerobic exercise and I know people hate to hear this especially when they're depressed they're

26:08 like you're kidding me right you expect me to go to the gym well maybe not the gym but moderate aerobic exercise modulates cyto kind levels and increases anti-inflammatory markers it reduces systemic inflammation improves mood and enhances neuroplasticity all right so that's a bunch of BL blah blah big words moderate aerobic exercise light to moderate aerobic exercise actually helps reduce cortisol actually helps reduce cortisol now I'm not talking about going to the gym and you know lifting three sets of 10 to failure or something no number one that's not aerobic most of the time what I'm talking about is walking around the walking around the park walking around your neighborhood that actually does increase anti-inflammatory markers

26:57 we often talk talk about the parasympathetic nervous system as rest and digest right but really it's rest digest and repair when the HPA axis is active when we're under stress our body is not repairing on the Fly our body is saying okay let's suppress that inflammation until we can have devote our energy to repair so when we are triggering that relaxation response we're triggering the repair response and we're telling the um inflammatory cyto kindes we got this you know go back to your go back to where you need to be so we start to see uh a reduction in inflammation anti-inflammatory diets are huge rich in omega3 fatty acids fruits vegetables and whole

27:46 grains have been reduced to depressive uh linked to reduced depressive symptoms Mediterranean style diets what they're talking about lots of olive oil lots of walnuts for example and lots of colors the darker the Richer and the more numerous the colors that you're eating the more antioxidants and anti-inflammatory chemicals you're getting into your body probiotics and gut microbiome repair with probiotics or prebiotics may also help reduce systemic inflammation and improve depressive symptoms by modulating the gut brain axis a lot of our neurotransmitters are made in our gut up to 90% of your serotonin is made in your gut and if your gut microbiome if

28:37 the workers in your gut are not healthy um you may not have the or you don't have the right workers to make serotonin then you're going to have a problem so by healing the gut microbiome and healing the um positive or the beneficial microbes in your gut it'll allows your gut to take in the food that needs to be broken down break it down effectively and send it to where it needs to be stress reduction in each piece of life and the book that I wrote and I I distributed the other day well not the other day it's been a few weeks on healing your nervous system has a lot of suggestions for stress reductions in each piece of Life ultimately your stress response your h

29:28 PA axis is going to be activated when you are under stress physical stress sleep deprivation um poor nutrition um pain illness all of those are stressors and when those are going on you're going to have increased HPA access activation interpersonal stress emotional stress mental stress we talked a few couple months ago about how people with hearing loss actually have more inflammation as a result of excess HPA access activity because they're straining to hear they have such a high cognitive effort to try to hear and understand what's being

30:13 said that it actually contributes to increased HPA AIS activation inflammation and neurod degeneration So Physical interpersonal emotional cognitive and we can't forget environment mental stress those are your toxins as well as your sensory environment if it's too hot it's stressful if it's too cold it's stressful we want Goldilocks um if it's too bright or not bright enough you know we're again we're looking for Goldilocks but everybody's just right is not the same my husband and I are very different as far as temperature is concerned I'm about 15° I wanted about 15° cooler than he actually likes it any at any given time so we've had to compromise

30:59 over the years but knowing what works for you and reduces stress is important I remember when my son was little he used to overheat really easily and he would get so angry I mean he was when he was an infant and the first thing we would do is pull off his little socks and try to help him get cool and as soon as he'd cool down he would calm down and and so you could see that HPA axis just you know right in front of your eyes transr transcranial magnetic stimulation like we talked about earlier also reduces neuroinflammation by modulating brain excitability and altering cyto kind production a lot of these you're hearing me talk about things that overlap why do they overlap because they're

31:50 trying to basically accomplish the same thing they're trying to reset the nervous system but we need to figure out what's causing the inflammation and what's going to work for this person to help reduce that inflammation Vegas nerve stimulation is another approach to reducing inflammation because as the Vegas nerve activates as that parasympathetic nervous system rest digest and repair activates we start seeing cortisol go down and the nervous systems start to heal and become more responsive to cortisol again if you will we want cortisol to be able to suppress inflammation

32:35 but first we've got to get rid of our tolerance to it we've got to get rid of our tolerance to it and we've talked in other videos um and I've made the analogy before about alcohol and alcohol the first couple times you drink it you may be able may may be able to get buzzed off one or two drinks if you're drinking regularly over time your body becomes tolerant to it your body becomes resistant to it it your body doesn't even pay attention to the stimulation from the first couple of drinks it's not until your blood alcohol level gets up to like you know 0.12 0.15 that you start feeling buzzed the same sort of thing is true with insulin it's true with cortisol it's true with

33:27 all of the chemicals in our body if the receptors are constantly being bombarded by it eventually they're going to ignore it they're going to say no you know go away you bother me uh until the intensity of those uh of that chemical is turned up and The receptors just can't ignore it anymore so Vega nerve stimulation is really good because it helps the person develop better vagal tone and helps the person basically manually override that stress response and say you know what this is not something we need to be stressed out about right now we're not in objective danger and so you're reducing the cortisol in the body and you're giving those receptors a break the gut microbiome

34:19 consists of trillions of microorganisms including bacteria viruses fungi protozoa which primarily reside in the gastrointestinal tract these microbes significantly influence digestion immune modulation and brain function who knew all that stuff going on in your gut affected everything now wonder when you get why when you get the flu you have a hard time thinking clearly um when your gut gets out of whack it can be a problem now I didn't put a bunch of research in here on it but it's also important to remember when you take antibiotics antibiotics are going to go in and they're just going to wipe things out it's not that the antibiotic is going to specifically

35:05 Target strepto cacus or stafilic cacus or something it goes in and at best wipes out all gram negative or gram positive bacteria or you take one of the you know really strong antibiotics and it goes in and wipes out everything well what are we wiping out we're wiping out a bunch of that bacteria in our microbi iome a lot of it good we're taking out the good guys with the bad guys and that can be problematic they find people may have more mood symptoms um for up to six months and after taking antibiotics and some people's microbiome two years later still hasn't restored to the same balance it was prior to taking the antibiotics uh the gut microbiome regulates d

35:57 digestion and immune responses synthesizes vitamins and interacts with the brain through the gut brain axis we have that vagus nerve that wanders through our body and is attached to most of our major organs but especially our gut and the Vagas nerve communicates to the brain what the status of things down here is and if it's getting toxic down there the Vegas nerve says hey this is no good we're under stress we're under attack we got a problem or it sends the all clear signal the Vegas nerve ax is a communication Super Highway between the gut and the Brain influencing immune responses gut motility and neurotransmitter production think about when you get um really stressed and to not get too graphic a lot of times when we get

36:51 really stressed our vagus nerve is not kicking in because our our HPA axis is kind taking over because we're really stressed what happens to your gut motility um and and for a lot of people it speeds up significantly um for some people who have irritable bowel syndrome it may actually go the other way and slow way down but it changes dramatically and that is partly because the Vegas nerve is communicating to the brain that we need to alter basically alter the crew that's in the gut making hormones and neurotransmitters I said earlier 90% of Serotonin is produced in the gut modulated by gut microbes like interocc cacus and streptococus I know streptococus strep

37:42 bacteria a little bit can be useful especially in that anerobic environment Gaba is produced by lactobacillus and bacterium series species influencing Stress and Anxiety responses well we know Gaba is our sort of internal volume and it's important to recognize that it is produced partly in the gut and if we don't have those microbes in our gut then they're not going to be able to break down the food to make Gaba and then we're going to have a problem over 50% of dopamine is synthesized in the gut and influenced by bacteria like stafilic coccus your St bacteria again I

38:29 know it sounds really gross but really in that anerobic environment those uh microbes can Thrive and actually be beneficial but obviously it's in very very small amounts compared to you know other situations in terms of the microbiome and its influence on depression when the microbiome gets out of whack we call it disbiosis and disbiosis leads to something we we call leaky gut which I talk a lot about it in the in the video on uh on gut health so if you want to know all the nitty-gritty details you can go watch that video but ultimately the um mucus that lines our

39:16 gut becomes much more permeable becomes and and the junction between the cells in our GI system become looser so your toxic material your waste products can actually kind of seep out which you know I think is gross too um but this when that happens your body says oh toxins are here systemic inflammation starts to happen this also leads to disrupted neurotransmitter synthesis contributing to depression if we've got a bunch of iies leaking out and we don't have the right bacteria able to uh in the in the gut able to make the s tonin then we can start having problems with balancing neurotransmitters in terms of depression in the microbiome chronic stress Alters gut composition

40:08 reduces microbial diversity and increases pro-inflammatory cyto kindes now remember even when somebody's depressed they're in that flat stage they're they feel hopeless helpless no energy in the background the HPA axis is still often turned turn up because there's systemic inflammation because there is something wrong in the system and that chronic stress of the depression is going to increase uh inflammation and reduce the microbial diversity it act we actually start seeing the number of good microbes drastically decrease they they quit they're like hey you know I'm not needed here no need to make serotonin right now ain't nobody happy so

40:57 I'm going on strike um the fetal microbiota can also be transplanted now this is a very new technique but it has been shown to be useful in people who are particularly um struggling with with treating the depression so trans transmitting the microbiome of somebody who is healthy into the microbiome of somebody who is depressed has shown to help in improve mood and do not do that at home do not do your own do not and I know there are videos out there don't know um it has to be done very specifically very carefully and very surgically in order to do it effectively and not

41:49 um harm yourself so short chain fatty acids produced by the gut bacteria are anti-inflam inflammatory the good G bacteria when that is flourishing you're it's producing as a as a side effect these short chain fatty acids these short chain fatty acids are anti-inflammatory so that's great we just you know extra bonus um and it influences brain function by modulating the immune responses if there's not as much inflammation then the immune system doesn't have to be nearly as active it maintains the bloodb brain barrier and helps regulate neurotransmitter synthesis disbiosis or disruption of that microbiome causes tryptophan one of the proteins amino acids that we

42:38 eat to be broken down into neurotoxic metabolites which are implicated in depression now that's really interesting because tryptophan can be broken down into positive metabolites but under stress the microbes that act on the tryptophan actually turn it into a toxin yikes probiotics are beneficial bacteria that can improve mood regulate the HPA axis and reduce inflammation they did do a study and you know poor Mouse I'm or rats I'm sorry breaks my heart but they did do a study with some rats where in half the rats they cut their Vegas Nerf in their gut and half the rats they didn't and in that they gave them both probio iotics the rats that had their Vegas

43:30 nerve cut showed absolutely no change in response to the probiotics the rats that did not have their Vegas nerve cut showed improved mood improved activity improved attention so there was a huge change in the intact rats if you will obviously it's not ethical to do that on humans but we can extrapolate that healing you know healing the gut microb getting the right probiotics in there can be very beneficial I will say like everything else Goldilocks principle you actually can overdo it on probiotics too you can eat I found out the hard way at one point you can eat too much yogurt and you know that's not going to have super long lasting consequences but it can be unpleasant for

44:20 a short period of time uh so in our in our society where we think if one is good two must be better and three must be great that ain't it uh you want to start with a low dose and if it works great maybe increase it a little bit but don't go don't go bananas with it prebiotics are non-digestible fibers that promote beneficial bacteria growth enhancing mental health inin is a Prebiotic that is uh prevalent in uh chory root so if you drink drink chory tea you're getting some inin uh there are a lot of other prebiotics that are out there again they're non-digestible fibers but they get

45:06 down into the gut and they can be um consumed if you will by the Ben beneficial bacteria diet's rich in fiber from prebiotics and whole grains and those things polyphenols those are the basically colorful foods and fermented foods support microbial diversity and reduce inflammation when we're talking about fermented foods we're talking about everything from sourkraut to Keir uh whatever it is that you like fermented foods if you can incorporate in your diet can really help the M microbiome as I mentioned earlier fecal microbi microbiota transplantation can in extreme

45:53 circumstances restore a healthy microbiome and improve mood disorders and Vegas nerve stimulation now we've talked a lot in other classes as well as this one about Vegas nerve uh strengthening but Vegas nerve stimulation is actually also can be done and we're going to talk about it in a few minutes through implantation of a device kind of like a pacemaker that regularly stimulates the vegus nerve they've done studies with that and found it to be super helpful we'll get to that phytopharmica theapy for depression basically using Herbal Remedies and plant- derived compounds to manage depression these phytochemicals modulate neurotransmitter path Pathways reduce

46:41 oxidative stress and inflammation and address both neurochemical and inflammatory contributors to depression if you are taking an over-the-counter um supplement recognize that it is not not quote harmless if you're taking an SSRI recognize that it can and probably will interact with these things uh so you need to be very very careful not to trigger serotonin syndrome saffron modulates serotonin dopamine and norepinephrine re-uptake it has anti-inflammatory actions and anti antioxidant properties lemon balm enhances Gaba receptor activity reduces anxiety and promotes relaxation

47:27 lavender modulates the serotonin system and enhances parasympathetic or your rest and digest activity and reduces cortisol levels well if you're enhancing parasympathetic you're going to reduce cortisol gingo baloba improves mood through antioxidant effects enhancement of blood flow to the brain and modulation of the HPA axis it also influences monoamine neurotransmission monoamines are your neurotrans transmitters so it improves communication um and and transmission of signals from your as a result of your neurotransmitters helps with inflammation helps with blood flow all of these things have very similar characteristics panex gensing regul

48:15 regulates HPA access activity reduces inflammation promotes neurogenesis the creation of new brain cells and modulates dopamine serotonin and norepinephrine systems now how much you take how often you take it whether it's even safe to take that's something you need to talk about with your doctor ketamine and esketamine are two more things that are coming on the market or have been on the market in the in in terms of ketamine for quite a while right now ketamine was originally developed as an anesthetic and often times it was used in uh veterinary medicine It produced r rapid anti-depressant effects and they found that it could be administered through uh through an IV

49:03 to uh address acute depressive and acute suicidal ideation in in people well that's great but it's not a resolution it is an acute thing sort of like you use uh Naran for something for somebody who's ODed on opioids this using ketamine to address suicidal ideation it's a very very um shortterm intervention I won't even say fix esketamine is more potent with fewer dissociative effects and administered as a nasal spray it is actually approved for use uh with treatment resistant depression so esketamine is out there but it's very regulated you have to get it by

49:53 prescription and there are only a few places that actually um are able to dispense it both drugs show significant Improvement in depressive symptoms within hours to days unlike traditional anti-depressants which take weeks one thing you need to be aware of with uh ketamine though is a lot of people who are going to these clinics where they can get ketamine to feel better ketamine for depression um if it's not very very tightly controlled and regulated and ethically prescribed people can become dependent on the ketamine I've had a couple of patients come to me who had been taking ketamine regularly for months and they're like I can't function if

50:43 I'm not getting my ketamine dose and I'm like well that that's that's a problem here um so we do need to be careful with that esketamine doesn't have nearly the same um dissociative effects and and um problematic effects which I think is why that one has become um available for and approved for treatment resistant depression another issue that both contributes to depression as well as systemic inflammation is the disruption of sleep and circadian rhythms I know right it's amazing that sleep in your your sleep and circadian rhythms can actually cause depression the Circadian rhythm or the Circadian system coordinated can't speak anymore sorry the Circadian system coordinates

51:33 sleep wake Cycles hormone releases and mood regulation so when your circadian rhythms get out of whack all of those things are going to get out of whack disruptions in circadian rhythms often due to irregular light exposure shift work or sleep disorders can lead to desynchronization between your internal clock and the external environment light temperature and activity all work together to help set your circadian rhythm and provide clues to your body about when cortisol is supposed to be high and when it's supposed to be low sleep disturbances can worsen emotional disregulation and cognitive impairments increasing vulnerability to chronic stress which

52:22 will further impair sleep and circadian rhythms inflammation and DEP depression so I've said it before I'll say it again if your patients are will willing to do only one thing focus on sleep and circadian rhythms at first because a lot of people find huge amounts of relief when all of their hormones and neurotransmitters and signaling actually gets into into a rhythm chronic sleep deprivation activates the HPA axis leading to elevated cortisol disregulation of the cortisol leads to glucocorticoid resistance which increases inflammation disrupts feedback mechanisms that regulate the stress response so we've heard this three times already in

53:08 this presentation inflammation influences the gut microbiome neurotransmitter metabolism neuroendocrine function and neuroplasticity all of which are critical in mood regulation when you've got inflammation a lot of times you've got pain it may just be general aches but it's pain and pain keeps us from getting good sleep and when we don't get good sleep it throws the circadian rhythms out of whack which is triggers a stress response and increase cortisol and so it's a Cascade effect which is why I harp on the fact that we look at a symptom but we don't want to just put a Band-Aid on the symptom we want to say what is causing this symptom what is causing this sleep disruption what is causing this person's CC Rhythm to be out of whack in terms of addressing

54:01 things a sleep rout a sleep routine with the same activities every day the same temperature at night and turning down the lights when it's time to start getting sleepy is really important getting rid of that blue light get having very di dim lights in the evening is super important to reducing cortisol and triggering melatonin release light therapy which includes bright light in the day dim light at night blue light reduction especially 2 to four hours before bed all three of these can work together synergistically to help reset those circadian rhythms melatonin supplementation is often used talk with your doctor before taking any supplements and vegus

54:51 nerve activation activities I.E relaxation activities are also helpful why because as the vagus nerve is activated cortisol is going to go down as cortisol goes down melatonin can go up so we see how these things can work together not everybody likes yoga or stretching or whatever whatever works for them to start slowing their breathing and triggering that vagus nerve can be really helpful um Progressive muscular relaxation for people who don't have trauma histories can be really helpful at triggering that vagus nerve and helping people get to sleep genomic sequencing looks at DNA to find genes that affect how your body processes anti-depressants and responds to

55:39 them it identifies Gene variations that influence how well you produce transport or respond to mood related chemicals the information on this is really promising a lot of people are finding that they get this test done and it comes back and it says well zoft isn't going to work for you and they're like yeah it didn't I was on it and it was awful uh this though over here may work better and everybody I've talked to who's had it done literally everybody has said that it really helped them find an anti-depressant that was more effective it may not have done everything but it was much more effective so they didn't have to try four five six different anti-depressants oxytocin helps regulate emotions and stress hormone levels like cortis

56:26 ol oxytocin goes up cortisol goes down this can help reduce feelings of anxiety and emotional distress also as cortisol goes up serotonin and Gaba go down so as oxytocin goes up serotonin and Gaba also tend to go up oxytocin strengthens the connection between the amydala our fear processing area and the prefrontal cortex leading to better mood stability and less emotional reactivity so they're talking more and the amydala sends a signal to the prefrontal cortex the prefrontal cortex says Nah this is nothing to worry about and it's all good instead of getting stuck in that auto Loop where the person feels anxious and starts to panic oxytocin nasal sprays have shown

57:15 mixed results for use in humans with depression it's shown great results with some other things depression not so much Chiropractics is also a new field that we're looking at that can help restore proper alignment and movement in the spine reducing tension which reduces pain and helps us sleep and improves communication in the nervous system by improving spinal alignment chiropractic care may improve the function of the vagus nerve which is responsible for helping to trigger that relaxation response limited evidence exists for the use of Chiropractics at this point some people love it some people hate it but there's not a lot of really good quality evidence but it is something we're talking about Vegas nerve stimulation as I mentioned before can be

58:05 done via an implanted device that sends periodic signals to the Vegas nerve the elect electrical stimulation increases activity in brain areas related to mood regulation such as the amydala and prefrontal cortex it boosts the release of neurotransmitters and reduces inflammation by decreasing the production of inflammatory cyto kindes and reduces the stress response so again the cortisol is not constantly circulating and the body can start to become less resistant to those to to cortisol when it's released over time vegus nerve stimulation helps retrain the brain's neural circuits to respond more positively to stress improving emotional regulation strong

58:54 evidence exists for using the implanted VNS for treatment resistant depression lots of clinical trials have shown good evidence other methods of vegus nerve stimulation can also be used through vegus nerve activation activities like yoga deep breathing meditation biof feedback and oric vagus nerve stimulation where you're stimulating the vagus nerve that comes out through the trigeminal nerve and like right around your ear acupuncture stimulates nerves muscles and connective tissues that promote natural healing processes the needle insertion activates the body's pain relief mechanisms leading to the release of endorphins which improve mood and reduce the

59:40 perception of pain as endorphins go up dopamine goes up and we also see serotonin start to go up so by triggering one you're increasing some of his budes the needle insertion also reduces levels of cortisol as the endorphins go up cortisol tends to go down increases levels of Serotonin and dopamine and reduces inflammation lowering the levels of pro-inflammatory cyto kindes research has shown that acupuncture can be as effective as some anti-depressants for mild to moderate depression especially when combined with other treatments acupuncture is going to work sort of in the moment to help release that um release those neurotransmitters but in the long haul we need to address the underlying cause of that inflammation evidence for acupuncture in the treatment of mood

1:00:31 disorders is growing but more large highquality studies are needed terms of oldies but goodies these are not new treatments but things we need to rule out if somebody has depression we need to have their gatal hormones tested their thyroid hormones tested their blood tested for nutrient deficiencies like anemia B12 D well iron B12 and D we need to screen them for irritable bowel syndrome Crohn's disease or colitis inflammation in the gut is going to lead to systemic inflammation and alcohol consumption which causes inflammation in the gut diabetes chronic pain hyper parathyroid chronic fatigue syndrome long c um uh and hearing loss are also all things

1:01:24 that can contribute to symptoms of exhaustion and depression and systemic inflammation depression results when the hormones and neurotransmitters get out of balance we need to figure out why are they out of balance one of the main causes of this imbalance is inflammation caused by stress in one or more pieces of Life typical pharmacotherapy does not address inflammation or sympathetic dominance it does not strengthen the vagus nerve and it does not reduce inflammation standard CBT therapists often fail to address non-cognitive sources of inflammation like sleep deprivation uh or chronic pain whatever is going on for many treatment resistant depression simply means the

1:02:12 professionals did not identify the right cause of the problem I don't want people to feel Hopeless by H calling it treatment resistant depression that sounds like we can't fix it well the old way ain't going to work but but it doesn't mean it's not fixable it means means we need to figure out what's causing your depression treatment must be holistic and individualized to be effective all righty back to questions can TMS be used to treat alcohol rated brain changes yes it can TMS can be used for just about anything um and let me see if I can pull something up for you

1:02:59 uh I'll just send you this search uh that shows some of the ways that TMS is being explored in relation to recovery from uh substance use repetitive deep TMS and alcohol dependent patients halts the progression of white matter changes in early abstinence that's super important that that's mind-blowing so there's a lot of stuff that TMS actually can be really helpful for great question

1:04:02 I agree with you Dr Darlene the recommendation for keto must be made very carefully I can't handle it when I try to go go keto um I start having all kinds of increased issues with my heart and it it's very problematic um I can do you know a Mediterranean diet with no problem um but we do need to consider the individual and make sure that they're Consulting their physician Andor a dietician uh before they start making sweeping nutrient changes like that thank you so much Oliver for your support of the channel you have been such a godsend and a great supporter for many years and I really appreciate you

1:05:02 in terms of a protocol for working with clients who are are receiving TMS um obviously working in conjunction with the TMS provider having them log monitor their Baseline symptoms can be really helpful but just like any other treatment helping them identify if they're using TMS for depression help them identify their triggers for depression and things that have been different when they weren't depressed and what they can do in order to start making small changes um I typically we'll go through the pieces pneumonic with people to try to identify sources of stress in their life and I'll

1:05:49 say where do you want to start any change you make in any of these areas is going to have a positive positive effect most likely so where do you want to start and that and and if they wonder why then I explain the whole stress and inflammation connection and everything but ultimately a lot of it has to do with the client having faith in the process and being motivated they're not going to continue to do things that they're not motivated to do or they you know like journaling for me I'm not a journaler so I was never effective at being compliant with regular journaling but exercise yeah I'll do that not a problem uh so finding things that people are willing to stick

1:06:37 with especially in those early days of treatment when their depression is just oppressive can be huge because as they start to feel improvements they're going to have more energy they're going to have more more motivation and I typically um with depressive patients unless they really want to go there I typically want them to get a little more energy and start feeling better before we dive into intense trauma processing that kind of stuff because that's exhausting and that will trigger stress reactions so I want them to try to heal their nervous system a little bit and feel somewhat recuperated before we start trying to run that Marathon

1:07:30 and Adriana is right this presentation was specifically about depression bipolar is a whole different presentation um and bipolar depression is by no means the same as unipolar depression and I agree with you anola exercise comes in many different forms I will go out and garden and you'd be surprised at how high you can get get your heart rate up ho in a garden um playing with your dog playing with your kids cleaning the house you know mopping actually I can work up a sweat when I'm mopping whatever it takes especially if you put on your headphones and you're rocking out while you're cleaning the house you can usually you know hit that level of moderate activity um so that's a great point that we

1:08:17 need to find something that the individual is willing to do and even maybe looking forward to doing there is a lot of Andrew there is a lot of uh research coming out about different um alternative drugs that can be used to treat depression from mushrooms to LSD um and and a lot of other different um chemicals so there is a lot of research or research being done but there really isn't a lot out there that I would consider a a best practice especially not one that's really accepted widely

1:09:04 in the US at this point I hope that some of that is going to change rapidly but we shall see alrighty everybody thank you very much for being here I appreciate your attention I appreciate your questions and I will see you next week same time same station