Drug for rheumatoid arthritis may reduce risk of psychosis

Something borrowed, something new: how an anti-inflammatory drug for rheumatoid arthritis may reduce risk of psychosis.

Dr Fabiana Corsi-Zuelli is one of the MHP ECR Fellows, and is based at the University of Oxford. In her work she aims to better understand of how the immune system links to severe mental illness (SMI). She has published a paper working with other researchers showing potential for an existing drug, already in use as a treatment for rheumatoid arthritis, to be repurposed for psychosis prevention [1].

Immune system and SMI

The immune system is made up of a multitude of cells engaged in countless checks and balances to keep you healthy. In incidences of psychosis, it is generally thought that the immune system is overactive. While this observation has been proven time and time again, it lacks the specificity needed to develop targeted and effective treatments. 

Linking this measurable biological factor to psychosis, a  symptom of schizophrenia, holds incredible potential for developing new treatment strategies.  

Impaired Treg function is already a well-studied mechanism behind the autoimmune disorder, rheumatoid arthritis (RA). In RA, Tregs are unable to tell the immune system to stop attacking synovial fluid which lubricates the joints. Therefore, a common treatment for RA is a course of low-dose methotrexate which is a specific anti-inflammatory medication thought to restore Treg function. 

If methotrexate was able to rescue Treg function in RA, Dr Corsi-Zuelli sought to understand if this medication also reduced a person’s risk of experiencing psychosis. 

In this new paper, the team found that people who took methotrexate had lower recorded incidence of late-onset psychosis compared to the other groups. This result also reappeared for incidence of bipolar disorder, major depression, and anxiety. 

Looking back to look forward – a retrospective cohort study

Twenty-five years’ worth of de-identified electronic health records were used for this study. However, not all patient data was used. Carefully chosen rules were used to sort records into multiple comparable groups, or cohorts, of patients taking methotrexate or a different anti-inflammatory medication. 

Then, patient records were analysed up to the five-year mark after methotrexate was first prescribed. Reports of psychosis, bipolar disorder, major depression, and anxiety were the focus for this study.

What does this mean for people with SMI?

Using medications like methotrexate to target underlying biological symptoms like inflammation may serve as a powerful approach to improving both mental and physical wellness. However, it will require many more studies before researchers now it is safe for people with SMI, and that it can be used in the clinic. The team are continuing their work to understand and integrate different facets of SMI to develop the best treatments possible.  

References

[1] Corsi-Zuelli, F., & Deakin, B. (2021). Impaired regulatory T cell control of astroglial overdrive and microglial pruning in schizophrenia. Neurosci Biobehav Rev, 125, 637-653.  

[3] Chaudhry, I.B., Husain, M.O., Khoso, A.B. et al. A randomised clinical trial of methotrexate points to possible efficacy and adaptive immune dysfunction in psychosis. Transl Psychiatry 10, 415 (2020). 

[2] National Rheumatoid Arthritis Society: Methotrexate