How is the immune system linked to psychosis?

This month's guest expert is Dr Katharina Schmack , a psychiatrist and neuroscientist at The Francis Crick Institute and UCL.

Antipsychotics are effective in treating the symptoms of psychosis, a condition that causes people to lose contact with reality, but they can have severe side effects.

In recent years, there has been a wealth of evidence that links psychosis to the immune system. For example, research has shown that in some cases psychosis may be caused by autoimmune diseases like lupus or multiple sclerosis , and that the drugs we use to treat psychosis may regulate immune disbalances .

However, this has been difficult to investigate because the immune system is very complex. It’s challenging to know if a change in the immune system is a cause or consequence of the improvements we see in people with psychosis.

Thanks to brand new methods in immunology and neuroscience, we now have a chance to address this challenge.

That’s why I’m leading a study, funded by Wellcome , to help understand the effects of antipsychotic drugs on the immune system. We want to find out if and how antipsychotics modulate an immune disbalance in psychosis.

Such an understanding could be crucial to developing new interventions that target the underlying cause of psychosis, rather than just treating the symptoms. It could lead to treatments with less side effects.

Identifying what drives a positive treatment response?

In our study, we will recruit people who experience psychotic symptoms, such as hallucinations and delusions, and we will take their blood samples before and after they undergo treatment. We’ll also take samples of cerebrospinal fluid – fluid that surrounds the brain and spinal cord – from some participants.

The next step is to identify the processes in the immune system that play a role in improving symptoms of psychosis. We’ll do so in two ways.

Firstly, by using machine learning and a database to compare the immune responses we find in people with psychosis to those without. This test will be run twice: before the participants begin antipsychotic treatment and after. We can then relate the changes we see in the immune system to improvements they may have experienced during treatment.

Secondly, by working with mouse models, we can then learn if changes in these immune processes drive the positive treatment effects of antipsychotics or if they are a consequence of using antipsychotics.

As well as measuring improvements in people’s symptoms of psychosis, we will also measure how well they are functioning to the degree they want to be functioning. For example, whether they have difficulties returning to work or living their day-to-day life.

To make this research possible, we’ve assembled an interdisciplinary team of neuroscientists, immunologists, psychiatrists and lived experience experts.

Finding better treatments for psychosis

The immune system is fascinating because it is influenced by many lifestyle factors that we know increase the risk for certain conditions. We also know that any medication has some effect on the immune system.

But we don’t know how many people who experience psychosis also have an immune disbalance.

We have only just reached the level of scientific tools and methods needed to start answering questions like this, and the insights we gain through this study could be huge.

If we can understand the immune mechanisms that make antipsychotics effective, we could develop new treatments for psychosis that directly target those mechanisms. We could also run tests to find out if these mechanisms are in play in an individual before we target them with such a new treatment.

It could bring us much closer to personalised treatments for people with psychosis, and that’s a very exciting possibility.

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