Disruptions in serotonin- and kynurenine pathway metabolism in post-COVID: biomarkers and treatment, 2025, Carla P. Rus

Conclusion

Disruptions in the serotonin- and KP metabolism in PCS provide a clear direction for advancing this line of inquiry. While it is evident that many scientists who explore the cause of PCS focus on or the KP route or the serotonergic route, they typically overlook the possibility that these two routes are related.

Additionally, serotonin is not a biomarker to choose for diagnostic assessment of PCS, because it cannot cross the blood-brain barrier. Tryptophan can cross the blood-brain barrier and may therefore be a better option. In the case of a comparative study however, the variables should preferably be more comparable.

Toxic KP metabolites in serum are good biomarkers as well, because researchers found a significant relationship between the level of toxic KP metabolites in serum and the severity of cognitive impairment in PCS.

Various researchers advised to examine the treatment of PCS with an SSRI or with a precursor of serotonin. A randomized controlled trial (RCT) on the effect of SSRIs in PCS patients should follow under strict conditions, such as testing the pharmacogenetic profile in advance, since many patients absorb and break down an SSRI too quickly while other patients do this too slowly. This can lead to a lack of the desired effect or too many side effects. These patients should be excluded from an RCT with a specific SSRI and can be treated with another SSRI outside the context of the RCT. PCS patients are more sensitive to side effects of SSRIs than other patients. Therefore, the trial must also provide for an option to stop increasing the dosage if the balance between effect and side effects threatens to tip without affecting the requirements of an RCT.

Furthermore, a treatment with the precursor tryptophan is not recommended because it also stimulates the overactive KP. Therefore, 5-HTP could be a better option.

This opinion article is also a call for better collaboration between immunologists, neurologists and psychiatrists in the study and treatment of PCS through the field of neuroimmunology. There are already many examples of psychiatric and neurological diseases that are treated immunologically, such as schizophrenia, childhood depression or multiple sclerosis

There is still much to unravel in neuroimmunology and treatment of immunological disorders with psychotropic drugs should be considered.
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What are psychiatrists doing in this group? Serious question, not a gotcha..

 

@Utsikt

There are ME/CFs patients trying low dose Abilify (LDA), there might be some medications/mechanisms that improve immunological symptoms?

 

Yes, but why include psychiatrists to figure out treatments for non-psychiatry-patients?

 

Because they are discussing studying repurposing psychiatric drugs that might improve immunological disorders.

I'm not sure what you're asking @Utsikt

 

Why does it matter what the drug has been used for in other cases?

They are discussing studying a neuroimmunological phenomenon. I don’t see how a psychiatrist fits in there, that’s all. How would they provide anything that a neurologist or immunologist can’t, in the context of the proposed use case?

 

Wouldn’t that be an argument for narrowing their scope, rather than expanding it to neurology? I understand why they would have to be involved during the ‘transfer’ of the illness from one field to another, but I don’t see why they would have to be involved in something that isn’t psychiatric at all.

 

Edward Shorter, incase anyone is unfamiliar with him:

The NIH laid a huge egg when someone invited Edward Shorter, a Toronto psychiatrist who makes Simon Wessely look like an angel, to speak on ME/CFS. Shorter not only denies the disease exists but calls ME/CFS patients “groaning victims” and belittles their “tales of woe”.

He’s now slated to speak on the history of a disease he believes constitutes nothing more than a psychic epidemic. His misanthropic and trivializing approach to ME/CFS has no place at the NIH or indeed any other respected medical institution.
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I personally would not want a repurposed psychiatric drug listed on my medical records, but I can understand for some who feel improvement with their ME/CFS symptoms, if that were the case.

 

I don’t have the health to care about the label on the drug. If I need it, I’m taking it. But I understand why you’d want to avoid the stigma.