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

[Mij]

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.
LINK

 

[Utsikt]

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.

What are psychiatrists doing in this group? Serious question, not a gotcha..

 

[Mij]

@Utsikt

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

 

[Utsikt]

@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?

 

[Mij]

There are already many examples of psychiatric and neurological diseases that are treated immunologically, such as schizophrenia, childhood depression or multiple sclerosis

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

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

 

[Utsikt]

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?

 

[SNT Gatchaman]

The line between neurology and psychiatry is blurred and a historical artefact. It might help to frame psychiatry as involving those disorders of brain function, not already established in neurology, such as MS, Parkinsons, stroke.

Some diseases that were the domain of psychiatry have moved to neurology, eg with the increasing recognition of autoimmune encephalitides (such as anti-NMDAR or GFAP astrocytopathy). Psychiatry is moving toward an understanding that many psychiatric diseases are based on dysfunctional immune and metabolic functioning.

Some examples —

Nuclear factor kappa-B cell NF-κB, interferon regulatory Factor, and glucocorticoid receptor pathway activation in major depressive Disorder: The role of cytomegalovirus infection (2024, Brain, Behavior, and Immunity)

Molecular and Functional Analysis of TLR 1, 2 and 6 in Peripheral Blood Monocytes of Patients with Schizophrenia: A Pilot Study (2025, International Journal of Molecular Sciences)

NLRP3 inflammasome mediates astroglial dysregulation of innate and adaptive immune responses in schizophrenia (2025, Brain, Behavior, and Immunity)

 

[Utsikt]

Psychiatry is moving toward an understanding that many psychiatric diseases are based on dysfunctional immune and metabolic functioning.

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.

 

[SNT Gatchaman]

Yes the field of neuropsychiatry is controversial. The author's perspective is given in her bio —

I’m Carla P. Rus (1953) and interested in various research fields. In addition to studying medicine at the Erasmus University in Rotterdam, I studied technical physics two years at the Technical University in Delft. I specialized as a neuropsychiatrist at the University of Maastricht. At the same time, in seven years I went through all directions of psychotherapy, and after that I specialized as a psycho-traumatologist. But I never lost my love for physics and biochemistry, which is why I did research in the field of neuroscience. So I think that there is too much compartmentalization in medicine because of the increasingly specialization. But we still need researchers/doctors with a helicopter view. As specialists we should actually work more together. I think for example it is a pity nowadays in the Netherlands you do'nt study at least one year of neurology when training to become a psychiatrist, and vice versa. As a neurologist you should be able to discriminate for instance between certain forms of epilepsy compared to certain forms of dissociative disorders and vice versa.

In 1996 I became chronically ill after surgery for a tumor in the spinal cord of my neck. After that, in addition to a partial spinal cord injury, I also developed post-traumatic dystrophy (CRPS-2) throughout my body. Fortunately, I was able to continue my work as a psychiatrist from home and later also as a researcher, both pro Bono. So I can give something back to society for all the homecare I need. I am the co-author of two books about my work, have written two books about WWII in Zeeland - a part of the Netherlands where my father took part of the resistance - and a collection of poems entitled: ‘Wind beweegt mijn tak’.

Since the beginning of the Covid-19 pandemy in 2020 I was very struck by the similarity of the symptoms of post Covid syndrom (PCS) to that of ME/CVS. I experimented with the same treatment with antidepressants I gave tot ME-CVS patients and I was surprised by the apparant much better effects in PCS patients. Together with some others I published in 2023 the striking results of an uncontrolled investigation of this treatment and some possible explanations.

That uncontrolled study (subjective / unblinded) was Treatment of 95 post-Covid patients with SSRIs (2023, Nature Scientific Reports)

 

[SNT Gatchaman]

However, perhaps a good argument in favour of neuropsychiatry is that Edward Shorter appears to be against it.

Historian Edward Shorter argues that the view that depression is a brain disorder to be corrected with medication is a product of the pharmaceutical advertising rather than a scientific understanding of depression.[42]

 

[Mij]

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.
LINK

 

[Mij]

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.

 

[Utsikt]

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.

 

[SNT Gatchaman]

Edward Shorter, a Toronto psychiatrist

Just to note he is not a psychiatrist or even an MD, despite being a "professor of psychiatry". He's a historian.