What Happens in the Brain When Symptoms of Schizophrenia Arise?

Principal investigator: Dr Petra Vértes

Location: UK

Funding Period: 2018-2021

Dr Petra Vértes is looking at what’s going on in the brain when symptoms of schizophrenia first arise so we can create novel targeted treatments.

The project

Schizophrenia affects 1% of the population and has life-long impacts. Our understanding of the brain processes behind the condition remain limited, meaning it’s difficult to treat.

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

Dr Petra Vertes and her team at the University of Cambridge are looking at genetic data and brain scans to uncover the biological processes responsible for psychosis and other symptoms experienced by people with schizophrenia.

The process

To begin her research, Petra analysed brain scans collected from hundreds of ‘healthy’ volunteers, people who have already experienced psychosis, and a group of people who have been identified to be at risk.

These scans revealed the patterns in the brain that could be unique to schizophrenia and those at risk. The scans were cross referenced with the Allen Brain Atlas, this was a novel method of linking brain imaging with gene expression data. The Atlas took over a decade to compile and it maps the activity of all known genes across the entire brain.

The project also investigated sex differences in adolescent brain development, using advanced neuroimaging and transcriptomic analysis.

The outcome

The key findings of the study were that male and female brains develop differently during adolescence, with certain genes and regions of the brain showing more drastic changes in women, which overlap with regions implicated in depression.

The novel method the study used successfully identified gene sets known to cause specific genetic disorders, building confidence in its application to complex disorders like schizophrenia.

The study also identified a cluster of genes highly expressed in brain regions vulnerable to schizophrenia, including known and novel drug targets.

Published papers

Romero-Garcia R, Seidlitz J, Whitaker K, Bullmore E, Vertes P Et Al. Schizotypy-Related Magnetization of Cortex in Healthy Adolescence Is Colocated With Expression of Schizophrenia-Related Genes, Biological Psychiatry, 2019

M.M. Vaghi, M. Moutoussis, F. Váša, R.A. Kievit, T.U. Hauser, P.E. Vértes, Et Al, Compulsivity is linked to reduced adolescent development of goal-directed control and frontostriatal functional connectivity, Proc. Natl. Acad. Sci. U.S.A., 2020

Lena Dorfschmidt et al. Sexually divergent development of depression-related brain networks during healthy human adolescence. Sci. Adv.8,eabm 2022

Talishinsky, A., Downar, J., Vértes, P.E. et al. Regional gene expression signatures are associated with sex-specific functional connectivity changes in depression. Nat Commun 2022

Caroline R Nettekoven, Vértes, P.E. et al Semantic speech networks linked to formal thought disorder in early psychosis, medRxiv 2022

The impact

The findings of Petra’s study reinforce the importance of considering sex differences in psychiatric disorders and the need to consider these in clinical trials and research.

The methodological tools developed for this project are being used to study a wide range of disorders, including autism, Huntington’s disease, depression, epilepsy, and obesity.

Ongoing collaboration with the PSYSCAN consortium and other international partners is advancing neuroimaging-based diagnostics and drug target discovery.