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Comment by francisofascii | Hacker News Reader

My gut reaction (pun intended) or guess on what causes Long Covid is a viral reservoir, possibly in the gut, that the immune system cannot fully clear. Low serotonin is then a downstream effect from the chronic stress on the body. Approx. 90% of serotonin found in the human body is located in the (GI) tract. So people and doctors will throw SSRIs at the problem, and maybe that will relieve some symptoms, but will not address the fundamental cause. Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10171832/

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> [...] is a viral reservoir, possibly in the gut

In that case, a gastrointestinal lavage (as applied before a colonoscopy) could be a potential remedy. It's a long shot, but since the process doesn't have any side effects (other than the inconvenience of having to change your diet for a few days), it'd be worth a try.

> So people and doctors will throw SSRIs at the problem, and maybe that will relieve some symptoms, but will not address the fundamental cause.

Additionally, SSRIs cause severe - and in many cases permanent - side effects. What's worse, we don't even really know how SSRIs work - or if at all (at least, as intended). Nevertheless, they're handed out like sweets.

I can't find anything about permanent side effects of SSRIs

Sexual dysfunction, for one:

https://en.wikipedia.org/wiki/Selective_serotonin_reuptake_i...

Additional potential long-term side effects include, but are not limited to, weight gain, feeling emotionally numb, and an increased suicided risk. Furthermore, there's the SSRI discontinuation syndrome: https://en.wikipedia.org/wiki/Antidepressant_discontinuation...

SSRIs are truly fun stuff.

To add to this, a tiny one-sentence note about post-SSRI sexual dysfunction is actually buried in the prescribing information for Prozac. It’s not just something on Wikipedia, it’s a known issue in the mainstream medical community (albeit maybe not as widely known or discussed as it should be).

Source: https://pi.lilly.com/us/prozac.pdf

Half of the side effects are also the side effects of abating depressions.

It's theorized that the suicide risk from most anti-depressants are from transitioning from so depressed that you have no motivation to do anything, to having enough motivation, but still feeling the related pain from depression.

Likewise with weight-gain. For many depressed people they have a suppression of appetite, and relieving the depression causes return of appetite.

AFAIK, neither the sexual side effects nor the withdraw symptoms are generally considered to be long term much less permanent.

AFAIK, neither the sexual side effects nor the withdraw symptoms are generally considered to be long term much less permanent.

They’re often not permanent, but particularly with sexual problems there is a significant minority of people who do not get better after they stop the drugs. The term to search for is “PSSD” (post-SSRI sexual dysfunction).

I've been off them for a while, but in addition to permanently worsened tinnitus, I've also been left with reduced "tingly" sensations like those experienced during ASMR and orgasms. I experienced no benefit from the half dozen that I tried. It really, really, really sucks, and if I could go back, I would have never taken them. Ironically, they were prescribed to me because my doctor was too afraid to prescribe anything else for fear of side effects.

While most of the body’s serotonin is indeed in the gut, the serotonin that impacts our mood, sleep, and other cognitive functions is exclusively produced and used in the brain.

Was going to say this. My one gripe with HN is that people say incorrect things with complete confidence pretty regularly and you can only Detect it if you know the subject matter.

And I’m going to add, confidently, that low serotonin is just a marker and not a cause.

Any type of inflammation will cause tryptophan to be pushed down an alternative pathway instead of going to make serotonin.

Also, it’s very possible that low zinc after Covid would cause the lack of serotonin as well.

Forgive me, because I don't want to pretend I understand this. No one does. It is still a mystery. This is just a "guess" based on what I've read and experienced first hand. Also, isn't the brain/gut/nervous system all connected anyway. What makes you think only the serotonin in the brain affects mood?

To be fair, this person clearly said it was a "gut" feeling, and it is also ok to be wrong about things, since being corrected on saying a wrong thing is a wonderful way to learn.

My god... WE were the LLMs the whole time.

And so now, how do we tell if you're the person that we should listen to? You're making your point with complete confidence (as is the parent comment)?

References people. Especially when it comes to anything related to subjects outside of tech.

HN used to show vote count. In the past, you'd see something like your GP having a vote count of 14, and your parent (the correction) having a vote count of 53. It was super useful and helped to combat misinformation.

You're right, and I just now realized the crux of why I was so miffed by that change. It indeed helped me better understand (while skimming)... but only for those topics that I don't enough about to make my own judgements.

I undersand the reasons to do it, also, but I think you clearly elucidate what was lost... (T_T)

Vote counts indicate post popularity with the subset of users who are in the thread, they don't indicate truth.

Post that there's no verifiable empirical evidence for aliens in a thread about Navy pilots spinning tall tales and you'll get a lower post score than the people saying that Navy pilots are unimpeachable founts of truth who would never lie, much less get confused. All this reflects is the fact that people who want to believe are more likely to be drawn to a thread about aliens, and people who are skeptical of it tend to ignore those threads or actively stay away because they're afraid of what might happen to their worthless internet point score.

If only we had some way to weight votes from folks we liked!

One finds the Gell-Mann Amnesia Effect in the strangest of places

I cringe nearly anytime I see anything about neuroscience on HN, and yet I keep reading. I almost wish I had studied something else just to avoid that feeling.

While the serotonin used in your gut doesn’t directly impact the brain, it does impact the enteric nervous system which communicates via the vagus nerve to your brain. So I don’t think it’s correct to say this doesn’t (or couldn’t) impact your mood (and indeed murine experiments demonstrate it does).

Perhaps my favorite science experiment, next to dual-slit, https://radiolab.org/podcast/197242-gut-feelings

They cut the vagus nerves of rats and see behavior change.

Which makes sense to me - when "brains" first evolved, the connection to the stomach would've been the prime connection.

Not just that. In mice, SSRIs stop having any anti-depressant effects if the vagus nerve is severed: https://www.nature.com/articles/s41598-019-50807-8

So they also seem to be effective via the enteric nervous system!

The evidence supporting any specific, direct behavioral function of serotonin in the brain is only marginally more substantial than the evidence supporting any specific, direct behavioral function of serotonin in the gut[1]. If anything, the evidence suggests that the behavioral effects of serotonin are more global and abstract, mediated via downstream effects on other neurotransmitters and circuits controlled chiefly by other neurotransmitters, such that behavioral correlations can only be drawn generally and indirectly.

Your confidence is totally and completely unwarranted.

[1] https://www.ucl.ac.uk/news/2022/jul/no-evidence-depression-c...

Yes, this is very clear with recent evidence.

We still need to understand the gut <-> brain connection and why trials like prozac or precursor supplementation helps.

It is already inconclusive that SSRIs help acute covid, but no studies have been done for long covid. That's what the researchers are calling out here.

It also seems likely that at least some of the cases of depressive symptoms and lack of fitness is due to covid isolation, which entailed a precipitous decline in both physical and social activity for a lot of people.

That was exactly my take on this study, and I wasn't happy about seeing the jump to "WE NEED MORE SSRIS, LOOK IT'S SEROTONIN" - it's already been proven that serotinin disruptions in depression are a symptom so this is the same but doctors/pharma continue to cling to the outdated "low serotonin"

The other side effect this may have is delegitimatizing the condition, much like SSRIs are thrown at chronic pain, menstrual issues and more. Since the medical institution doesn't really take these conditions seriously this is going to become another half recognized condition that doctors can say "Maybe it's Long Covid HAVE YOU TRIED SSRIS" vs working with the patient or doing research into the true causes.

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