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“We urgently need to develop new treatments for schizophrenia”

We caught up with MQ-funded researcher Dr Petra Vértes about her work to find out what’s going on in the brain when symptoms of schizophrenia arise.

She’s joined by Dr Sarah Morgan, her close collaborator from PSYSCAN, an international consortium of researchers dedicated to transforming our understanding and treatment of psychiatric conditions.

It’s great to speak to you both! Could you start by telling me what the aim of your project is?

Petra: Schizophrenia is a severe and long-term mental health condition that affects around 1-3% of the population and can be very distressing. However, it still isn’t well understood – which impacts the quality of the treatments available.

We do know that the brain goes through huge reorganisation during teenage years and that schizophrenia often arises during this period. But we don’t yet have a clear understanding of the specific mechanisms in the brain that go awry and the genes and proteins that could be responsible for them. 

My aim is to investigate how the brains of people with schizophrenia differ from the brains of people without, so we can ultimately create new, more targeted treatments.

So what kind of treatments do we have for schizophrenia at the moment? Are they working?

Sarah: At the moment, schizophrenia is usually treated using antipsychotic medications, often in combination with psychological treatments like cognitive behavioural therapy or family focussed interventions.

While some people respond well to these, unfortunately they don’t work for almost a third of patients. For the other two thirds, although these medications tend to reduce symptoms like hallucinations quite well, other symptoms like lack of motivation may not decrease as much. For these reasons, we urgently need to develop new treatments for schizophrenia.

What does the study involve and what have you found so far?

Sarah: So, in the first part of the project, we analysed MRI scans. MRI brain imaging is an incredible technique, which allows us to see inside a person’s brain in a safe, non-invasive way. However, MRI images can be difficult and costly to collect.

The PSYSCAN consortium is a major international effort to acquire and analyse these images at scale, led by Prof Philip McGuire (King’s College London), Prof René Kahn (UMC Utrecht), Prof Ed Bullmore (University of Cambridge) and around twenty other experts across the world.

PSYSCAN are collecting and analysing brain scans from 330 volunteers who have had one episode of psychosis, as well as 250 people who are at high risk of developing psychotic disorders. The project also brings together hundreds of brain scans that were previously acquired by different groups across the world.

From this large volume of images, we are able to identify particular areas of the brain that showed unique structural changes in people with schizophrenia - changes that didn’t appear in the brains of those without it. For this first study we used two different sets of data from research centres in Dublin and Maastricht in the Netherlands, as well as a publicly available dataset from the USA, which all showed the same structural changes. For this reason, we believe we have a very robust set of results. 

What can you learn about schizophrenia from these brain changes?

Petra: These brain scans can only tell us so much. In order to truly improve treatments, we need to understand what the structural changes they show mean from a biological perspective - what they can tell us about the biological processes that could be disrupted in schizophrenia.

To do this, we cross-referenced the scans with information from the Allen Brain Atlas. The Atlas took over a decade to compile and maps the activity of all known genes across the entire brain. 

This led us to focus in on a cluster of about 40 genes which are known to work together, and which discovered to be particularly prominent in the areas of the brain most vulnerable to structural changes in schizophrenia.

So, what’s the potential now – where can we go with this new information?

Petra: The cluster we identified includes a number of genes that are already known to be associated with schizophrenia, and some of the therapies currently offered to people with schizophrenia.  

We hope that, by exploring the other genes in this cluster that haven’t previously been linked to schizophrenia, we can open the doors to develop new, more effective treatments which target these genes and improve the lives of people living with schizophrenia.  

We’ll also apply this approach to the larger number of brain scans currently collected by PSYSCAN researchers across the world. We hope this will validate our findings and help to identify subgroups of people with psychosis who may benefit from different treatment options.

Sarah: Finally, as part of the PSYSCAN project, we will continue to collect brain images from people who are at increased risk of developing psychotic disorders and who present the early signs and symptoms of illness. By tracking these people over time, we’re excited to learn how the changes in brain structure that we’ve observed in people with schizophrenia develop. This new work could give us important clues about how and when to intervene to prevent people developing schizophrenia in the first place.

To read Petra and Sarah’s recent article in the Proceedings of the National Academy of Sciences journal, click here: https://doi.org/10.1073/pnas.1820754116

Last updated: 30 May 2019

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