The Hidden Link in Chronic Fatigue, Long Covid, and POTS: A Deep Dive into the Role of the Brain

chronic fatigue syndrome fibromyalgia long covet Mast Cell Activation pots endless download syndrome neurodivergence what links all of these disorders together the answer might surprise you but it's a key aspect that's often overlooked in the management of these conditions and that aspect is the brain now this does not mean that the symptoms related to all of these conditions are in the patient's Minds not at all this is a medical condition so before we go into the detailed video I want to highlight that this particular condition isn't a typical psychiatric condition but that does not mean that psychiatrists don't play an important role particularly neuropsychiatrists because you see advances in Psychiatry now have led to the emergence of fields such as psychoneuro immunology psychoneuroendocrinology and by understanding the impact of medical conditions and how it affects the brain we can make a significant difference to patients by working together with different Medical Specialists so before we jump into the video keep this aspect in mind I'm Sunil reggae consultant psychiatrist today I'll be talking about chronic fatigue drum CFS and myalgic encephalomyelitis me now we've done a video on CFS and me on this channel and we've got a number of comments uh really insightful comments about the condition based on that I'm going to be talking about really drilling down into some of the pathophysiology of CFS and me because there are certain aspects in the treatment that sometimes aren't taken into account and what I mean by that is that CFS and me really highlights this mind or brain body divides and what happens is most of the treatment focuses on the periphery really almost as if there is a cut off at this level and a lot of treatments focus on the peripheral aspects and really the brain which is affected to a great extent is forgotten and the important thing here to recognize is firstly it is an extremely heterogeneous Disorder so the things I'm going to be talking about it's really important that they should be considered as general educational aspects really derive some insights or as a way of discussion it's really important that is not taken as medical advice because what I talk about generally can't be applied to all patients with CFS or me it is an extremely heterogeneous disorder and it's important to take that aspect into account but some of these aspects may actually help sort of enhance that discussion with treatment providers so with that in mind let's jump into this further discussion what I'm going to be focusing on firstly is a big question you know why should I listen to a psychiatrist in the first place about CFS and me now as psychiatrists we often get this quite a lot most of the patients I see with CFS and me have actually gone through treatment average I would say eight to ten years extensive treatments and then finally sort of seeing a psychiatrist often because they start say have developed mood disorders or other issues now of course many a time they've been told it's in your head which is really a comment that is derogatory because CFS Emmy has real real biological underpinnings but a psychiatrist can play a very very important role in the management of this condition the second aspect I'm going to be talking about is endothelial dysfunction and how its affects perfusion perfusion both to the brain and of course the periphery as well which of course we know leads to a number of symptoms I'll be talking about the pathophysiology of the autonomic nervous system and pots and then enter mast cells because we do know there are subsets of Mast Cell Activation and chronic fatigue syndrome then I'll sort of be bringing this together and be talking about important neurotransmitters such as dopamine noradrenaline and then linking that to the brain and then talking about how sort of that treatment that's focused in the periphery needs to be augmented with treatment that also looks after the brain so with that let's start off with the first aspect you know why a psychiatrist the thing about Psychiatry is that Psychiatry is not just about the mind it deals with the brain so we have Fields such as psychoneuroendocrinology psycho oncology psychoneuro immunology and chronic fatigue syndrome really encompasses the brain and the body body together it just cannot be separated and that's the reason why having a psychiatrist preferably with a interest in psychoneuroimmunology psychoneuroendocrinology consultation liaison Psychiatry someone that can take an overarching view across all the systems will be an important part of the team but once I go through these mechanisms I'm hoping that you'll be a slightly more convinced as well with the role of a neuropsychiatrist or a psychiatrist in that overall management so first let's look at what we know about CFS and me from a perfusion perspective now we know when we look at cerebral blood flow and the perfusion in organs chronic fatigue syndrome patients are known to have reduced cerebral blood flow and what we call orthostatic intolerance and I'll talk about more about that when we come to autonomic nervous system in pots now this abnormal cerebral blood flow and orthostatic intolerance is associated with abnormal vascular regulation and as a result of that we know that both the cerebral aspects are affected leading to a number of symptoms but also the skeletal muscles are affected and these skeletal muscle pH abnormalities are known to be associated with autonomic dysfunctions so firstly we do know there is good evidence for endothelial dysfunction in chronic fatigue syndrome now this is postulated to be an important mechanism by which there is a shift from the vasodilatation aspect that is necessary particularly to counteract just constant sympathetic activity because sympathetic activity is associated with vasoconstriction we need adequate parasympathetic activity to also facilitate vasodilatation so it's really a balance between these two aspects but what happens in chronic fatigue syndrome is that these aspects are impaired leading to a predominant alpha-1 adrenergic activation which means a balance towards vasoconstriction in the skeletal muscle and brain and excessive vasoconstriction would actually reduce perfusion overall both in the periphery and the brain so that's the important thing to take into account secondly we know that excessive vasoconstriction particularly when it leads to consistent hypertension for example leads to impairment of vascular resistance the endothelium actually gets affected now this can be compounded in certain individuals that may have say hypermobility syndrome lsdanos syndrome for example connective tissue disorders which is a common trait in individuals with chronic fatigue syndrome this has been talked about as this endothelial leak which compounds the situation furthermore in certain subsets of patients they have found beta-2 adrenergic receptor antibodies and M3 acetylcholine receptor antibodies which of course when there are antibodies to these major vasodilator components what we see is again a shift towards vasoconstriction so what we're seeing is that there is a shift towards vasoconstriction which can reduce perfusion across organs now if you think about the impact of this hyperperfusion this is where tests such as cpets the cardiopulmonary exercise test that many individuals with CFS will will go through it's a measure of the energy production you know from contributions from metabolic aspects respiratory aspects cardiac aspects Etc right and we also know this links to the mitochondrial aspects we know there is abnormalities in mitochondrial energy production in patients with CFS so you can see how all of these aspects are converging and one of the hypothesis is this endothelial dysfunction now I know a lot of these things are quite complex you know I'm sort of providing this and trying to simplify it as best as I can but please do use the comment section to enhance some of this discussion as well so with antibodies to the beta-2 adrenergic receptor which is necessary for vasodilatation and the M3 acetylcholine receptor we are looking predominantly at vasoconstriction which can lead to reduced perfusion so that's an important aspect to take into account next we know when cerebral blood flow is impacted symptoms such as mental fatigue and cognitive issues such as brain fog can occur which can be compounded by all of these okay so that's the first thing which is the endothelial next aspect is the autonomic nervous system and pots and the reason I'm talking about autonomic nervous system and endothelial dysfunction is because we're starting off we're moving away from Psychiatry and we're looking at sort of the peripheral aspects the kind of aspects that many patients will relate to and say you know what this is something I can completely relate to but I will come later to show you how this is closely linked to the brain so that's where I'm sort of heading just to give you a guide so let's look at the autonomic nervous system and pots next now you see the autonomic nervous system there is a crosstalk between the sympathetic and parasympathetic reflexes and the aim of that is to maintain adequate perfusion to the brain the cerebral blood flow because you see when there are changes say when we are lying down and we suddenly get up we need this to shift really quickly so that there is a sympathetic shift to maintain that perfusion to the brain so this is known as orthostatic tolerance orthostatic tolerance is a measure of the ability to prevent hypertension during bring gravitational stress best example is getting up Suddenly from bed and if there's impaired orthostatic tolerance then individuals can be really prone to these hypertensive episodes that in extreme cases leads to the phenomenon that is known as pots postural orthostatic tachycardic syndrome now pots the core components orthostatic tolerance but pots is defined specifically by a heart rate increments of 30 beats per minute or more within 10 minutes of standing up or a head tilt and this is a test often done by cardiologists to diagnose that in the absence of orthostatic hypotension so I'll go through this again pots is defined by a heart rate increase of 30 beats per minute or more within 10 minutes of standing or head tilts in the absence the head up tilt in the absence of orthostatic hypotension the standing heart rate is often 120 beats per minute or higher so this is that orthostatic tachycardia that occurs now me and CFS is associated with pots which manifest with symptoms of cerebral hyperfusion and excessive sympathetic activation because the body he's really trying to maintain that perfusion to the brain now the thing about orthostatic intolerance is that it may really make patients bed bound I've seen patients wheelchair bound as a result I had a patient that would have hemiplegic migraines I'm on that shift these are transient ischemic attacks but this clearly shows that there is a significant dysfunction of the autonomic nervous system pots which of course affecting cerebral blood flow so you can see that the autonomic nervous system is closely linked to cerebral blood flow as well upright posture results in orthostatic stress and even in the absence of heart rate and blood pressure changes is known to be closely associated with post-exertional malaise which is we know a core feature of chronic fatigue syndrome now an interesting thing is present you might remember that I just talked about this beta-2 adrenergic receptor dysfunction because in some patients there is this subset with antibodies now you see when there's this suspected dysfunction of the beta-2 adrenergic receptors what happens is something known as chronotropic incompetence which means that the heart rate may not even rise proportionally to the sympathetic activity so there is this sympathetic activity excessive activity but the heart rate might not rise proportionally so if we take only the heart rate as a measure of sympathetic activity we might actually be missing the possibility that orthostatic stress and intolerance is present that the phenomenon pots is still present as a contributor to post-exertional malaise and other mental symptoms such as brain fog cognitive symptoms Etc if we just focus on the heart rate so this is an important thing to take into account so to summarize essentially what's happening is orthostatic intolerance in pots results in this impaired sympathetic vasoconstriction that leads to venous pooling venous pooling leads further to hypovolemia and a hyperadrenergic state as a compensatory mechanism so really it's a vicious cycle we have hypovolemia in many cases the body there's a hypovolemia leading to orthostatic stress orthostatic stress will of course lead to sympathetic excitation to maintain blood flow to the brain so therefore that results in excessive hyperadrenergic activity and that excessive sympathetic hyperadrenergic activity is an important part that we will see feeds into many of these symptoms and affects the brain overall so if you're interested in learning more about these conditions don't forget to check out the academy by sightseeing we've got a webinar series a three episode webinar series totaling seven and a half hours that covers chronic fatigue syndrome fibromyalgia long covet Ellis Daniel syndrome pots Mast Cell Activation the role of neurodivergence and we bring it all together and we highlight four medical professionals how we can actually Implement these strategies by using real-life case studies for a single annual subscription you not only get access to these three episodes but you also get access to a range of other accredited courses because we cannot split chronic fatigue syndrome of fibromyalgia and long cover but from all of the other aspects that we need to learn for example we've got a webinar series on ADHD which is again seven and a half hours so by linking the two understanding the neuroscience and the advanced side of pharmacology we can make connections and improve outcomes for patients so don't forget to check out academy.sightseeing.com so let's jump back to the video so once again to summarize autonomic nervous system pots excessive sympathetic excitation a Central hyperadrenergic State next there are two types of pots the postural orthostatic tachycardic syndrome the first one is the neuropathic pots which is known as this autonomy which is due to this autonomy and the second one is the central hyperadrenergic Hots now a subgroup of patients the first one I'll cover which is the neuropathic pots these patients have indirect evidence of peripheral sympathetic denervation in the lower Limbs and we know that take for example in certain hypermobility syndrome ellersdana syndrome there is some evidence of arterial wall stiffness small fiber neuropathy so this small fibon neuropathy may be playing a part here and this condition is often characterized by you know loss of sweating in the feet for example so this peripheral sympathetic denervation is linked to this neuropathic pot why is it important because it's important when we think about medications such as you know when we talk on mitodrine and beta blockers and parody stigmine Etc which are the common ones prescribed so do keep this mechanism in mind when we come to that later on now the primary pathophysiological mechanism of postural intolerance in this subgroup of patients is presumed to be impaired peripheral vasoconstriction leading to pooling in the lower Limbs and this is why sometimes we see phenomenon such as one limb may be sort of almost a libido present there redness are present there or swelling of the feet the other limb not present so we often see this on physical examination as well the second aspect is the central hyperadrenergic pots many patients with pots have elevated levels of norepinephrine or nor adrenaline and this is of course suggestive of a hyperadrenergic state and this is due to hypovolemia as I talked about hypovolemia orthostatic stress bang a compensatory mechanism hyperadrenergic State sympathetic excitation to maintain that blood flow the thing here this group of individuals will have extremely high levels of upright plasma nor epinephrine there is a certain subgroup in addition to this furthermore a specific genetic abnormality has been identified with hyperadrenergic Hots whereby they have a single point mutation leading to loss of function in the nor epinephrine transporter so we know that nor epinephrine transporter you might look at the video that we've done on snris which is serotonin epinephrine reuptake Inhibitors is a common antidepressants prescribed but we know they're evidence-based in say fibromyalgia as well and we know that they inhibit the norepinephrine transporter which means they increase levels of noradrenaline presence now in this individuals with the subset of pots Central hyperadrenergic there is a loss of function of the norepinephrine transporter what happens there is there will be excess nor adrenaline present leading to hyper adrenergic State because the norepinephrine transporter the function is to take norepinephrine from the synaptic cleft and take it into the presynaptic neuron to avoid excess norepinephrine there so when there is a loss of function there is excess norepinephrine so to summarize two types of pots we have the neuropathic pots peripheral vasoconstriction abnormalities and the central hyperadrenergic pots due to hypovolemia compensatory excessive norepinephrine oradrenaline leading to excessive sympathetic activity so this is a really important part now how does this link to endothelial dysfunction and you see the thing about endothelium is that the endothelium has innervation from the nor adrenergic pathway which is for vasoconstriction and also acetylcholine innervation which is the parasympathetic Pathway to balance this excessive sympathetic activity so that's how norepinephrine plays an important part in that overall endothelian sort of dysfunction as well next enter mast cells so just to recap I know there's quite a bit to take in just to recap what we've looked at firstly we've looked at the endothelial dysfunction which links to perfusion abnormalities brain and periphery next we looked at autonomic nervous system autonomic nervous system could be peripheral autonomic abnormalities or the Central hypodrenergic State as well overall the pathophysiology is all around orthostatic intolerance but then I also talked about how the autonomic nervous system has that linked to the endothelium as well due to noradrenergic innervation and also due to the acetylcholine innervation next enter mast cells now what are mast cell mast cells are the First Responders of the immune system and they're omnipresent in the body everywhere they're localized in the peripheral nervous system and within the brain so they play a very very important role you know with neurons and with neuronal processes throughout the body next they're also in close proximity to blood vessels and peripheral nerves and therefore strategically positioned to modulate the sympathetic activity vasculotone and also angiogenesis the production of you know capillaries vessels Etc so what we can see here is mast cells they are in close connection to the stuff that we've already discussed which is endothelium and the autonomic nervous system through the peripheral nerves furthermore mast cells also contain dopamine and we will talk more about dopamine because this is a crucial piece of the puzzle in chronic fatigue syndrome now you see Mast Cell Activation is known to be present in a subset of individuals with CFS and me and Mast Cell Activation actually causes dopamine depletion so it reduces dopamine overall in the body and of course the brain as well and interestingly Studies have found that when you you target the dopamine 1 receptor the dopamine receptors are D1 to D5 when you target the dopamine one receptor on mast cells this can actually inhibit Mast Cell degranulation of course inhibition of mass LG granulation means that dopamine levels don't decrease and the other vasodilator components aren't present there's no muscle Activation so these are promising approaches for the treatment now mast cells we know release histamine histamine is a powerful vasodilator so what's happening when there's cutaneous vasodilatation that occurs with Mast Cell Activation we get flushing so when can one suspect Mast Cell Activation Syndrome usually when patients have pots and they have flushing suspect Mast Cell Activation you see what happens here is that when there is release of these vasoactive dilators such as histamine this may contribute to vasodilatation there's a reflex sympathetic activation then sympathetic activation resulting in central volume contraction Central volume contraction along with norepinephrine release and then orthostatic intolerance so this is a feedback loop that has been proposed so basically there is a specific sub set of patients with muscle activation and chronic hyperadrenergic orthostatic intolerance of pots present the issue here is beta blockers actually trigger mast cell degranulation and worsen symptoms so it's an important one to take into account because we know that beta blockers are often prescribed to reduce the heart rate in patients with pots or chronic fatigue syndrome Etc now in this subset of patients the antihistamines may be more beneficial next just to recap very quickly endothelial dysfunction autonomic nervous system and pots mast cells and now let's look at dopamine as the fourth aspect why is dopamine important often we think about dopamine predominantly when we just think about pleasure reward take for example lots of discussion or dopamine with addiction Etc so that's why we think about a dopamine in the brain but dopamine is a really important neurotransmitter and not just a neurotransmitter it has other functions on the endothelium in maintaining cerebral blood flow we know also plays an important role in the control of autonomic nervous system through the prefrontal cortex so this is what I'm going to be talking about in more detail so first let's look look at cerebral blood vessels and dopamine dopamine has a direct effect in cerebral blood vessels and is plays an important role in the control of cerebral blood flow and this is from the 1998 paper by Kima published in nature the closed association between dopaminergic terminals and cerebral blood vessels raises the possibility that disturbances in central dopaminergic neurotransmission could alter cerebral vascular regulation for example cerebral blood flow and its regulation are abnormal in schizophrenia depression and parkinsonism diseases in which there is dysfunction of dopaminergic Pathways the important thing is not only as a neurotransmitter we know that it's responsible for a number of functions particularly in the frontal lobe which is a hedonic Drive attention concentration cognitive aspects executive function decision making Etc but it also plays an important role in blood flow so this is a really really important Point here and studies that have been done with amphetamine exposure have shown that there were both vascular and microvascular responses to amphetamine increasing cerebral blood flow as well as reducing the diffusion distance for oxygen which means it increases perfusion the oxygen intake the ability uptake of oxygen so to kind of summarize the impact of dopamine on endothelium because we know endothelial dysfunction is a core component of chronic fatigue syndrome right so it is not only a precursor in the production of adrenaline and adrenaline you see dopamine is broken down by dopamine beta-hydroxylase to noreadrenaline we've talked about noradrenaline a bit right so it not only helps in the production of noradrenaline and adrenaline but it is also an important vasodilator and interestingly you see there is an endogenous source of dopamine in the vascular wall so what Studies have shown is that the arterial wall of systemic vessels that is the endothelial cells and the underlying tissue produces a substantial pool of dopamine and this intrinsic release of dopamine happens upon stimulation by decreasing oxygen concentrations which causes a dilatation of the blood vessel thereby increasing blood flow and subsequent oxygenation of the tissue this is a really really important Point dopamine is endogenously released from the arterial system itself in response to hyperfusion so it's an intrinsic vasodilator and you can see what happens if there is an overall reduction of dopamine in the body so the second aspect and we'll come to those aspects and see whether there is a reduction of dopamine in chronic fatigue syndrome so firstly we looked at dopamine and the endothelial aspects second let's look at the prefrontal cortex dopamine and whether the prefrontal cortex actually affects the autonomic nervous system you see the connections of the prefrontal cortex areas are with the hypothalamic areas and the prefrontal cortex can actually influence autonomic and endocrine responses that accompany many emotional processes and the parts of the brain that's been identified as a medial prefrontal cortex where there are projections for the middle prefrontal cortex directly to the sympathetic and parasympathetic brain centers and therefore actually the prefrontal cortex controls many of these autonomic responses so the second aspect of the prefrontal cortex that we need to take into account and how is it linked to dopamine you see the prefrontal cortex really functions on dopamine the striately the striatum has projections to the frontal lobe this is the frontal striatal pathway it's all about dopamine so you can imagine if there's reduced dopamine in this pathway the control on the autonomic nervous system is also affected next dopamine plays an important role in pain see dopamine activity has been found to be attenuated in fibromyalgia we know there's a closed relationship between chronic fatigue syndrome fibromyalgia often coexist CSF levels of dopamine and presynaptic dopamine function are reduced we know that inactivation of dopamine D2 receptors leads to excessive pain sensation hyperalgesia so overall sort of summarize it if we have adequate dopamine or pain thresholds as well is adequate that we will not have hyperalgesia or excessive perception of paint really really important here so the big question is dopamine affected in chronic fatigue syndrome and the answer is yes absolutely firstly through inflammation you see in the brain dopamine is produced in two key areas a substantial part of the brain that's really affected in Parkinson's disease and the ventral tegmental area and take for example there is a dopamine imbalance hypothesis that contributes to fatigue in Ms multiple sclerosis similar aspect plays a part in chronic fatigue syndrome you see in inflammation two key things happen one there is a decrease of the vmat of vascular monoamine transporter this is the important transporter that packages dopamine into the vesicles for later release into the synaptic cleft so it decreases that those levels of the transporter secondly it actually will increase the expression of that and that takes up dopamine from the synaptic cleft into the presynaptic neuron so there isn't enough dopamine available in the synaptic cleft so overall what you get is depletion of dopamine and we know depletion of dopamine in the prefrontal cortex is going to lead to not only mood issues but is also going to lead to anhedonia Cox significant cognitive issues brain fog but we've just talked about dopamine also playing an important role in perfusion it's going to lead to decreased cerebral perfusion as well we also looked at dopamine at controlling autonomic nervous system so imagine dopamine with the front the medial prefrontal cortex is not really able to control those excessive autonomic sympathetic Drive arising from the autonomic nervous system as well so we've got a decrease in that and the rest of the body is you know there's excessive sympathetic activation all these autonomic nervous system symptoms orthostatic intolerance Etc and the frontal lobe is struggling to fix that so we can see that the dopamine overall is reduced in inflammation the second aspect we talked about mast cells dopamine is reduced due in Mast Cell Activation and mast cells essentially contain dopamine the other curious aspects when it comes to risk factors you see ADHD is a known risk factor for chronic fatigue syndrome in fact many patients that I see when I take their history have been really really high functioning sometimes really go-getters go go in terms of personality when a history is taken often there are a number of traits that look like ADHD they've probably never had a formal diagnosis of ADHD but ADHD is really prefrontal cortex dopamine or adrenaline dysfunction and I've done a video on ADHD so you can have a listen to that to that to understand more but individuals with ADHD have a greater risk of chronic fatigue syndrome and particularly females with ADHD can have an increased risk of chronic fatigue syndrome so here hormonal aspects also come into play and we know estrogen is closely linked to dopamine as well so here there's an extra complex relationship that we can see with prefrontal cortex dopamine noradrenaline and we know that the hyperarousal symptoms are quite prominent in ADHD that manifest as hyperactivity and in females we have this cognitive and emotional arousal where mood swings Etc can occur and that's also because the frontal load cannot control that emotional arousal system so again really really fascinating aspects so bringing it together I'll really simplify what we can see here is remember that we've talked about endothelial dysfunction autonomic nervous system but the point that I'm really trying to convey is that the periphery is looked at autonomic nervous system endotheliums looked at from a perfusion perspective Hots Etc mitochondrial aspects are looked at because Etc you know see pets Etc but what about the brain we've just talked about the role of medial frontal cortex in controlling the autonomic nervous system that we just talked about dopamine which is such an important neurotransmitter playing an important role in the brain and we can't afford to forget that the second aspect is the Central hyperadrenergic State that occurs orthostatic intolerance you see it's a Central hyperadrenergic State how do we reduce that Central hypoadrenergic State so we've got to understand what is the connection from the peripheral hypodrenergic state to that Central what part of the brain controls that we'll talk about that in a bit now what's often used often when patients are referred or I've seen them and I've mentioned you know most of the times I'll see patients after an extended period they've had treatment for eight to ten years midodrine is commonly used it's a peripheral alpha-1 Agonist which leads to vasoconstriction now evidence suggests that it is most useful in individuals with that neuropathic pot that's where it's most helpful but it does not really we pass the blood-brain barrier so what about all the cerebral perfusion aspects that are required to be maintained in the brain second beta adrenergic blockers are commonly used in cardiology clinics to control tachycardia which we know is present in pots but it can be associated with side effects such as excessive fatigue or some people just have intolerance you know nightmares can increase and sleep disturbances are a common issue in CFS as well so reducing the heart rate by the way can be counterproductive if the increase in heart rate is meant to be a compensatory mechanism but could be useful if the tachycardia was over compensation for the physiological stimuli so if it's over compensating it can reduce it yes and this is why lower doses tend to be better tolerated than much higher doses now the important thing as I'm talking through this is It's really crucial to look at this as general education only it's very important not to make decisions or think about medications as having side effects just because I'm mentioning this it is crucial to discuss these aspects with a medical professional this may not apply it to an individual this is just an overall sort of insight that I'm providing based on the evidence so because every medication is a risk benefit analysis next we know that beta blockers result in Mast Cell degranulation worsening symptoms of the Mast Cell Activation and Mast Cell Activation pots that's a subset that's present then I often see fluidro cortisone which is a mineral corticoid to increase sort of volume because hypovolemia is an issue so that's often prescribed next pyridostigmines prescribed which we know parody stigmine being an cholinesterase inhibitor with increased levels of acetylcholine what it basically does it prolongs the phasic effects on acetylcholine on the autonomic ganglia basically resulting in helping to counteract that excessive sympathetic drive so acetylcholine remember was had Innovation on the endothelial so what it does is it potentiates that effect counteracting that excessive sympathetic activity so there is evidence that again it can reduce heart rate by doing that and that's often one of the reasons is it's prescribed so often I'll see mitrogen Present part of the signaling present fluid cortisone present and maybe a beta blocker present and a lot of these are really working on the periphery to a certain extent trying to reduce also that Central hyperadrenergic States but let's backtrack to the brain and ask ourselves well hold on we've looked at the periphery but what is the part of the brain that really controls this excessive hyperadrenergic state from the top so firstly what part of the brain controls the autonomic nervous system frontal lobe is one we saw medial prefrontal cortex but the other one is the limbic system and in the limbic system there is a part of the brain known as amygdala and many of you will know that amygdala is closely linked to fear aggression Panic anxiety this is really the seat of that fight and flight response so let's take the example of panic attack we know that the first time there is an exposure to a threat we have that same sympathetic drive but that's the amygdala that is linked to the autonomic nervous system and python flight response sympathetic Drive increased heart rate increased blood pressure you know sweating Etc and we head off run away from there so the question here is that we know that panic attacks after a while and panic in panic disorder they can occur out of the blue why does that happen because in some cases you see the heart rate increase can trigger off the amygdala response so it's a bi-directional link that the periphery can trigger off amygdala response setting up a vicious cycle or the amygdala can set off the periphery so the important thing is that the limbic system and the amygdala has to be taken into account overall in treatment as well so this is the frontal lobe and the limbic system that needs to be taken into account secondly what part of the brain results in the cognitive symptoms frontal lobe right we looked at the cerebral blood flow and frontal lobe is also closely linked to mood so in summary the frontal lobe and the limbic system absolutely need to be taken into account in the overall treatment of chronic fatigue syndrome and me and this is where psychiatrists or neuropsychiatrists come into the picture and this is where a different group of medications come in for frontal lobe we're really looking at that dopamine strengthening Pathways and there is a whole range of dopaminergic agents that can do that centrally secondly that Central hyperadrenergic State right this reduction the center hypo adrenergic States we have Central sympatholytics that reduce that such as clonidine for example president that we use in say post-traumatic stress disorder where a similar mechanism applies so it's important to take into account that the amygdala the limbic system controls basic autonomic arousal processes the amygdala innervates the autonomic networks and produces visceral signs of emotional arousal such as that heart rate increase so what medications potentially and again this is not medical advice this is a discussion but often the important aspect is dopaminergic Agents there's a whole range of dopaminergic Agents you might have heard of bupropion we know stimulants that are used in ADHD interestingly stimulants such as methylphenidate are modafinil modafinil are also evidence-based in pots clonidine is also evidence based in pots can actually stabilize the blood pressure often there are concerns around drops in blood pressure but evidence suggests that it can stabilize heart rate and blood pressure in patients with high sympathetic nervous system activity so we've got stimulants methylphenidate dexamphetamine modafinil are modafinil we've got proprion we've got agents such as snris that increase noradrenaline unless the brand we've got death vanilla vaccine Duloxetine which is Duloxetine malasepram specifically used in fibromyalgia and then other limbic system reducers so for example this is where we have agents that we use for mixed features when limbic system is activated such as mood stabilizers such as Gaba potentiators glutamates a reducers mood stabilizers such as Lamotrigine for example low-dose antipsychotic medications if it's really at an extreme level now this is the armamentarium that we have that we can use to Target specific symptoms centrally because as we saw that all of this autonomic nervous system endothelial dysfunction Mast Cell Activation Etc dopamine aspects all backtrack to the brain and really localize in that frontal lobe that limbic system amygdala sort of aspects that are present so I'm going to summarize this we've taken a lot in I'm sure there's a lot to discuss but I hope that this has given sort of an understanding of how the body and the brain are closely linked so firstly to summarize guys we've got endothelium autonomic nervous systems pots closely linked we've got an underlying Central hyperadrenergic State that's present in many many patients second there is dopamine reduction in the prefrontal cortex and we know dopamine also plays an important role in endothelial function there is dopamine depletion in the periphery as well often due to compounding factors such as Mast Cell Activation as well and dopamine is necessary for prefrontal cortex not only to maintain adequate executive function cognition but also to control the limbic system arousal the autonomic nervous system and to provide adequate cerebral blood flow as well third the autonomic nervous system is connected to the limbic system so it's important we can't forget the limbic system in the overall picture it's important to calm that part of the brain down so the final message is that a multi-pronged approach is required addressing Central and peripheral aspects but in the absence of strengthening the frontal lobe calming that limbic system down and only looking at the periphery it's sometimes difficult to get that full traction or outcomes optimal outcomes in training patients with chronic fatigue syndrome or me at milder ends of course a range of things can work but as I mentioned my insights are derived from seeing patients that have come to see me after 8 to 10 years so a multi-pronged approach a multi-disciplinary team is necessary you know sort of bring all those thoughts together and to have a strategic approach to implement this if you've stayed till the end you know a big thank you listening to it all the way to the end and if you liked the video of course give us a like do leave your comments in the comment section let me know what else your insights are with regards to this really complex condition I look forward to seeing you in another Edition soon in another video in the near future until then take care and stay safe bye [Music] material in Psychiatry to simplify your practice

Channel: Psychiatry Simplified - Dr Sanil Rege

Views: 8,388

Keywords: dopamine, chronic fatigue syndrome, patients, autonomic nervous system, pots, brain, mast cell activation, cfs, reduce, mast cells, perfusion, cerebral blood flow, sympathetic activity, vasoconstriction, long covid

Id: dIspvIMws2U

Length: 36min 32sec (2192 seconds)

Published: Sun Jun 25 2023