Are dopamine and serotonin involved in COVID-19 pathophysiology?

pattismith

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Are dopamine and serotonin involved in COVID-19 pathophysiology? (nih.gov)

L. Attademoa,* and F. Bernardinib
2021

The whole world is being affected by COVID-19 caused by SARS-CoV-2, with unprecedented consequences on health, social and economic systems in all countries.

The COVID-19 pandemic is not only a threat to physical health but mental health as well.1 In fact, scientific evidence is emerging on the potential direct effects of COVID-19 on mental health of people infected, as well as on the psychological impact on people quarantined, on patients with psychiatric disorders and on the health-care workforce.1, 2

Discussion on the first of these points (i.e. the direct effects of the infection on mental health) appears to be rather interesting. Clinical evidence is showing that patients with COVID-19 might experience short- and long-term mental health problems.

Delirium, confusion, agitation, and altered consciousness, as well as depression, anxiety, traumatic stress, and insomnia, have been described not rarely in patients with COVID-19.1, 2

Putative aetiological mechanisms of the neuropsychiatric sequelae of coronavirus infection have a likely multifactorial basis but are still poorly established.

The direct effects of viral infection on CNS, cerebrovascular disease, physiological impairments, the inflammatory response and the immune system reaction, medical interventions, social isolation, physical discomfort, the psychological impact of a novel severe and potentially fatal illness, concerns about infecting others, and clinical/social stigma, might be all involved in the aetiological process, independently or more likely synergistically.1, 2

Interestingly, it has been recently postulated that alterations of both the dopamine and serotonin synthetic pathways might be involved in COVID-19 pathophysiology.3

The possible involvement of these neurotransmitters is suggested by a significant link – based on similarities related to gene co-expression, co-regulation and function – between Angiotensin I Converting Enzyme 2 (ACE2, encoding the main receptor to SARS-CoV-2) and Dopa Decarboxylase (DDC, encoding the enxyme that catalyzes the biosynthesis of dopamine, serotonin and histamine).

In fact, evidence shows that ACE2 and DDC co-express and co-regulate in non-neuronal cell types.

Furthermore, it has been demonstrated that ACE2 receptors are highly expressed in dopamine neurons and that they are reduced in Parkinson’s disease (characterized by dopamine deficiency).4

Hence, a SARS-CoV-2-induced defective expression of ACE2 might be paralleled by a DDC dysfunction, with consequent potentially altered neurotransmitters’ levels in COVID-19 patients.3

Therefore, short- and long-term neuropsychiatric disorders in COVID-19 patients could be explained – at least in part – by neurotransmission dysfunction/dysregulation.

Delirium, confusion, agitation, and sleep-wake disorders, for example, are commonly associated with alterations in melatonin (a product of serotonin), acetylcholine, dopamine, serotonin, and histamine.

Furthermore, it has been demonstrated that viral infections with subsequent cytokine storm may contribute to suppressed serotonin and melatonin availability.5

Serotonin and norepinephrine are the biogenic amines most often associated with depression pathophysiology, but also dopamine play a significant role with data suggesting a reduced dopamine activity in depressed patients.

Serotonin – together with norepinephrine and GABA – is one of the three major neurotransmitters associated with anxiety.

Patients experiencing traumatic stress have chronically low levels of serotonin, and altered dopamine levels contributing to anhedonia, apathy, impaired attention, and motor deficits (when levels are low) and to psychotic symptoms and agitation (when levels are high).

It is obvious, however, that further experimental studies are necessary to elucidate the link between ACE2 and DDC during SARS-CoV-2 infection and to demonstrate the hypothetical alterations in dopamine, serotonin and other neurotransmitters in COVID-19 patients.
More research is needed to explore the potential direct effects of COVID-19 on mental health, using both short- and long-term longitudinal investigations.
 
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I'm not sure what it's called, the feeling you get when you like or enjoy something? When my taste/smell were dulled after getting Long Covid, my "feelings" were more intense. Enough to where salt=meh, sugar=GOOD. So now that my taste/smell has been slowly coming back the past couple of weeks, I no longer have sugar "cravings" or the need to compulsively eat sugar. I think I had this same thing happen to me about 8-10 years ago when I was diagnosed with an eating disorder (compulsive overeating).
 

pattismith

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I'm not sure what it's called, the feeling you get when you like or enjoy something? When my taste/smell were dulled after getting Long Covid, my "feelings" were more intense. Enough to where salt=meh, sugar=GOOD. So now that my taste/smell has been slowly coming back the past couple of weeks, I no longer have sugar "cravings" or the need to compulsively eat sugar. I think I had this same thing happen to me about 8-10 years ago when I was diagnosed with an eating disorder (compulsive overeating).
It may be that your dopamine level was too low...

Here a web site with information on sugar craving:

Craving sugar, sweets, and refined carbs have been associated with anxiety, depression, ADD/ADHD, schizophrenia, and other psychiatric issues. A number of studies, including a 2019 review in the journal Antioxidants, have found a link between high-sugar consumption and depression. And according to 2016 research in the journal Appetite, a diet containing more high-glycemic foods was associated with a higher incidence of depression and fatigue. In addition, when you’re feeling anxious or stressed, you’re more likely to crave sugar. ADD/ADHD has been associated with dopamine deficiency, which can cause people with this condition to seek out activities and foods—such as sugar—that stimulate dopamine.
How to Eliminate Sugar Cravings | Amen Clinics
 
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I guess what I'm trying to say is that I think my smell/taste being dulled actually brought on the sugar cravings. Does that make sense? because now that my smell/taste is returning, I don't have the sugar cravings. I think they somehow have to be related. Thank you for the article! It sounds a lot like the eating disorder therapy I had for many years. I was able to lose a lot of weight and keep it off. Until I got sick with Long Covid. It's like my body just stopped filtering urine and digesting food like it had been. dysautonomia, i think. and i was diagnosed with ME/CFS. Maybe getting my smell/taste back is just a hint that some of the inflammation is going down?. I can only hope.
 

SWAlexander

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I'm not sure what it's called, the feeling you get when you like or enjoy something? When my taste/smell were dulled after getting Long Covid, my "feelings" were more intense. Enough to where salt=meh, sugar=GOOD. So now that my taste/smell has been slowly coming back the past couple of weeks, I no longer have sugar "cravings" or the need to compulsively eat sugar. I think I had this same thing happen to me about 8-10 years ago when I was diagnosed with an eating disorder (compulsive overeating).
"compulsive overeating" could also be a lack of oxytocin.
 
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I assume you see an endocrinologist? If yes, did you ever have had a full panel hormone (catecholamine test) test?
yes i see an endocrinologist. it's a prolactinoma and I'm on meds for it, I also have Hashimoto's and am on meds for that because my thyroid levels have been low. Our last video visit I asked her about a whole bunch of different hormones to see if I needed them checked and she said I would have specific symptoms for them so it wasn't worth testing. Full disclosure I have Long Covid which lead to a ME/CFS diagnosis and have had so many health issues over the years. they had all been fairly under control until Covid.
 

SWAlexander

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GeorgiaLinders "they had all been fairly under control until Covid"
I hear you. I also believed I had my hormones under control until severe sepsis in 2016. Now, I no longer can identify which medical problem is worse. I have to watch my permanent low cortisol and low ACTH, not only because of low muscle strength and low energy but also depression is never far behind. Sometimes I feel standing in an 8 f deep hole where water is seeping in and my muscles are too weak to pull me out of danger.
 

vision blue

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I like articles like that since if covid can do it, likely so can other viruses that many of us are afflicted with. its' just no one paid attention before to the alterations like these that viruses cause.

I find this thread because i was searching for posts on dopamine
(having just gotten back a test result saying my dopamine levels were high. and yes i have high blood pressure and suspect they are connected thru ace 2 )
 

Violeta

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I like articles like that since if covid can do it, likely so can other viruses that many of us are afflicted with. its' just no one paid attention before to the alterations like these that viruses cause.

I find this thread because i was searching for posts on dopamine
(having just gotten back a test result saying my dopamine levels were high. and yes i have high blood pressure and suspect they are connected thru ace 2 )
Did they measure any other neurotransmitters?

This is interesting because I always hear about people with low dopamine, not high. I wonder what one does to correct that.

Not converting dopamine to serotonin to melatonin?
 
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Violeta

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Maybe you have already considered that the dopamine is not being metabolized.

Catechol-O-methyltransferase (COMT), mostly an extracellular enzyme, and monoamine oxidase (MAO), mostly an intracellular enzyme, each metabolize dopamine.
 

Violeta

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They are well known enzymes in pharmacology, since they are the target for the action of a number of monoamine oxidase inhibitor drugs. MAO-A is particularly important in the catabolism of monoamines ingested in food. Both MAOs are also vital to the inactivation of monoamine neurotransmitters, for which they display different specificities.

Specific reactions catalyzed by MAO include:

I think the FAD mentioned in this paragraph is important but atm I can't remember why.

"Monoamine oxidases catalyze the oxidative deamination of monoamines. Oxygen is used to remove an amine group (plus the adjacent hydrogen atom) from a molecule, resulting in the corresponding ketone (or aldehyde) and ammonia. Monoamine oxidases contain the covalently bound cofactor FAD and are, thus, classified as flavoproteins. "
 

vision blue

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@Violeta hi. As usual, great reasoning and questions

They did measure others: will see if can attach here

Yes , know all about mao-a especially, and comt. The reason is for years ive been very tyramine intolerant. Produces spikes in blood pressure and used to cause myoclonus. So i was down the mao route searching for genetic variants but not finding any that would predict low mao -a and never have been on nao inhibitors. But i got evidence a few years back the first time i tested biogrnic amines/neurotransmitters (the test was better before they merged with another company. ) Back then, altho dopamine was not outright high, Dopac was quite low but other metabolites of dopamine also high which suggested at time mao- a low since you need that to convert to dopac. But on subsequent tests, i could not get the sane result

But besides tyramine intolerance and suspected sluggish mao- a, i was suspecting high dopamine. One reason is my norepinephrine and epinephrine levels have been high in the past (usually showing up as elecated metinephrine and nor meteneprine. Since usually its dopamine that gets converted to norepinephrine i had been thinking the whole lot of them were just in excess

And then another reason I was already suspecting hi dopamine was that I do well with gabapentin (although it was on none when I took this test by the way) From what I’ve recently been finding people who do badly on gabapentin are those who have side effects from it of depleted dopamine- muscle rigidy and spasms, word finding issues etc- ie alot of the symptoms those with parkinsons have who are low in dopamine So was thinking maybe indeed my dopamine too high and gabapentin lowers it and feel alot better (i wont use unless emergebcy becaude of dependence issue)!

And then dopamine Actually turned up
High this week surprising me since i rarely get proof from numbers. Know its converting fine to norepinephrine At least . Probably not great at converting to serotonin as in past thats been low
Theres stuff on pattern of results thats a head scratcher Tho and i cannot figure out why the pattern would be that way. N


@SWAlexander Too bad CFS makes it difficukt to do anything about the fourth item...
 
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SWAlexander

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to vision blue,
any hormonal imbalance there must be a transmitter disconnection between the pituitary - hypothalamus - and adrenal gland if there is no pituitary tumor.
Hormonal imbalance can be caused by one low hormone production that influences hypothalamus dysfunction. In my case, it is "corticotropic insufficiency" without a pituitary tumor but ACTH level is clearly reduced.
In two months there will be another hormone panel test to see if hydrocortisone has changed other borderline hormones.
 

hapl808

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Other than gabapentin, what interventions would be helpful? And is there any evidence that the neurotransmitter tests we have available (urine, etc) are at all connected to brain levels? My understanding is that has still never been proven to have any relation, so I still wonder at the utility. If there were a robust connection, psychiatrists would be testing everyone so they can throw 10 SSRI or SNRI drugs at them, but I'm not aware of any testing like that used in dispensing RI medications?
 

vision blue

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@hapl808 Ive seen the debates on whether anything measured in urine is in any way reflective of anything happening in the brain or anywhere other than digestive track. I find merit to the arguments, some summarized by the Townsend reprt years ago, that if youve got some imbalance in gut, often considered the “second brain, ” then it mirrors the same imbalance in brain because whatever the problems you have with enzyme shortages and metabolic issues, ykoure going to have them in whatever system uses the same trqnsmiitrers, like both gut and brain.

In addition, some of the tests here are indeed used in conventional mecicine , like the metenephrines, to screen for pheochromocytoma; ive had them and they agree with the numbers ive gotten with this test

For me theyve been sensible with other results and symptoms. My one and only qualm is i mentioned that after doctors data merged with labrix immskeptical of their results. I have found labrix when on their own to have totally bogus results and cutoffs.

@SWAlexander Thanks but i am not really following what you say. These arent hormones plus why must any issue be in the HPA axis? I will read some of your other posts, perhaps youve answered that elsewhere

update @hapl808 Forgot to also mention on tests for response to psyciathric meds, i do know there's a genetic test they use but i've often thought theyd be better off running tests like oat and aa and amines as a better indicator of what med to take or not take- i've suggested to a ocuple of people who have trouble finding a helpful med that they do just that.
 
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Violeta

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@Violeta hi. As usual, great reasoning and questions

They did measure others: will see if can attach here

Yes , know all about mao-a especially, and comt. The reason is for years ive been very tyramine intolerant. Produces spikes in blood pressure and used to cause myoclonus. So i was down the mao route searching for genetic variants but not finding any that would predict low mao -a and never have been on nao inhibitors. But i got evidence a few years back the first time i tested biogrnic amines/neurotransmitters (the test was better before they merged with another company. ) Back then, altho dopamine was not outright high, Dopac was quite low but other metabolites of dopamine also high which suggested at time mao- a low since you need that to convert to dopac. But on subsequent tests, i could not get the sane result

But besides tyramine intolerance and suspected sluggish mao- a, i was suspecting high dopamine. One reason is my norepinephrine and epinephrine levels have been high in the past (usually showing up as elecated metinephrine and nor meteneprine. Since usually its dopamine that gets converted to norepinephrine i had been thinking the whole lot of them were just in excess

And then another reason I was already suspecting hi dopamine was that I do well with gabapentin (although it was on none when I took this test by the way) From what I’ve recently been finding people who do badly on gabapentin are those who have side effects from it of depleted dopamine- muscle rigidy and spasms, word finding issues etc- ie alot of the symptoms those with parkinsons have who are low in dopamine So was thinking maybe indeed my dopamine too high and gabapentin lowers it and feel alot better (i wont use unless emergebcy becaude of dependence issue)!

And then dopamine Actually turned up
High this week surprising me since i rarely get proof from numbers. Know its converting fine to norepinephrine At least . Probably not great at converting to serotonin as in past thats been low
Theres stuff on pattern of results thats a head scratcher Tho and i cannot figure out why the pattern would be that way. N


@SWAlexander Too bad CFS makes it difficukt to do anything about the fourth item...
One thing I notice about your results is that in the explanation they talk about the problems that low tyrosine causes, but tyrosine is what is converted into dopamine, and dopamine is high. I think they missed something.

Folate can help raise histamine levels.

B3 increases histamine

Folate deficiency decreases serotinergic activity.


methyl-folate helps reduce the activity of the neurotransmitters that are contributing to the high-energy and anxiety

Methylated folate is great for some conditions. Histapenia (low histamine) and over-methylation states respond well to folate and folic acid

Just saw in the comments at the bottom of the page that selenium deficiency can increase the conversion of tyrosine to dopamine.

I don't know much about this, but have you ever considered overmethylation?

And I realize these notes are all over the place but I thought it might start some brain storming. Anyone here have some brain power this morning? Feeling pretty numb here.
 
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