Cambridge

Mary-Ellen Lynall & Graham Murray
Academic leads

Immunophenotyping of early psychosis

Objectives

1

Identify gene expression changes in individual circulating immune cells from blood samples donated by people with first episode psychosis. This will enable blood-based biomarker discovery.

2

Use this comprehensive dataset to group people based on their immune cell profiles. This will help explain differences amongst people with severe mental illness for guiding personalised treatment options..

What we are doing

We are collecting blood samples from people experiencing first episode psychosis through a partnership with the Early Intervention Mission Study.

From these blood samples, we isolate a subset of immune cells called peripheral blood mononuclear cells or PBMCs. In each cell, we measure the activity of genes using a technique known as single cell sequencing. These measurements across many genes are referred to as gene expression profiles. We perform this profiling at scale across hundreds of thousands of cells.

These experiments generate large amounts of high-resolution data to identify subtle but meaningful changes in how our immune system contributes to brain health and severe mental illness (SMI). For example, we can assess if the number of specific immune cells changes in SMI and whether immune cells function differently.

What we are planning to do

Using these data, we will catalogue the gene expression profiles of PBMCs in first episode psychosis, this is known as immunophenotyping. We will then analyse this catalogue of data to identify differences in immune cell type proportions and gene expression patterns between case and control donors. We will also consider these data in the context of genetics, demographics (such as age and sex), and clinical observations, to group donors based on these other factors. This process is known as patient stratification.

These analyses will pave the way for multiple advances in our understanding of immune involvement in early psychosis:

Discover underlying biological mechanisms which contribute to the manifestation of psychosis.
Identify blood-based biomarkers for brain and mind disturbances, bridging physical and mental health.
Stratify people into biologically and clinically meaningful subgroups to guide personalised and precision approaches to intervention.

Find out more

The involvement of adaptive immune cells in severe mental illness is an exciting area of research with tangible impact for people living with these disorders, in terms of biomarker discovery, patient stratification, and therapeutic target prioritisation. For example, previous work from our group has demonstrated that genetic risk for schizophrenia is enriched in active regions of the genome in T cells, particularly upon pro-inflammatory stimulation (see research on this here). Our ongoing research will strengthen our understanding of the role of these cell types in severe mental illness.

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