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Neuroscience researchers awarded £2.1 million to study the biological changes that occur in schizophrenia

Press release issued: 17 May 2023

The award from the Medical Research Council will help scientists understand how genetic mutations in multiple different genes lead to common biological and cognitive changes and identify new therapeutic targets.

Schizophrenia is a severe neurodevelopmental disorder, most commonly diagnosed in late teens/early 20s, that affects around 1% of the population. The disorder places a major burden on sufferers, carers and health services with high suicide rates in sufferers (approximately 7%) and consuming roughly 30% of NHS spending on adult mental health. In England alone, the economic cost of schizophrenia is estimated at £12 billion per year. Psychotherapy is not an effective treatment on its own, and although there are some effective medications, those that are licenced are often poorly tolerated. There is therefore a large unmet need to identify new treatments.

The five-year project, led by Professor Jack Mellor from Bristol’s School of Physiology, Pharmacology and Neuroscience in the Faculty of Life Sciences, will use new data from large genetic studies of schizophrenia to identify common biological causes for cognitive changes. These genetic studies point towards changes at synapses, the connections between nerves, and their adaptability – a process that underlies learning and memory.

The project forms a multi-disciplinary and cross-institutional partnership between research teams led by Professor Mellor with Dr Mike Ashby, Professor Jon Hanley and Professor Emma Robinson at Bristol, Professor Jeremy Hall at the University of Cardiff and Professor Dimitri Kullmann at University College London, along with clinical research teams led by Dr Mike Carter and Dr Kasia Sieradzan in Bristol.

Professor Hall said: “This is another exciting development in the growing partnership between Cardiff and Bristol Universities to understand the neurobiology of psychiatric disorders. There have been very few new treatments for the many disorders that affect our mental health, principally because we don’t understand their underlying causes. The new genetic information from large population studies promises to transform our understanding of this field and we aim to turn this knowledge into new treatments.”

The combined expertise of the partnership team will enable investigation of biological changes in mice with genetic mutations in schizophrenia risk genes and, in groundbreaking experiments, to also test the effects of specific genetic mutations on neural networks in human brain tissue.

Professor Mellor said: “This award pulls together expertise from a number of collaborators at the University of Bristol as well as researchers from Cardiff, London and Chicago. The interdisciplinary approach is exciting and we hope will lead to new insight into the common biological changes that occur in schizophrenia. We are also partnering with pharmaceutical companies to develop new drugs to target the processes we identify in what could be a step change in our approach to the diagnosis and treatment of schizophrenia”.

Further information

The five-year, MRC-funded study, entitled ‘Impairment of neural plasticity and adaptive representations by genetic risk factors for schizophrenia’, will begin on 1 October 2023. The multi-disciplinary and cross- institution project is led by Professor Jack Mellor with co-investigators Dr Mike Ashby, Professor Jon Hanley and Professor Emma Robinson from the School of Physiology, Pharmacology and Neuroscience (UoB), Professor Jeremy Hall (University of Cardiff), Professor Dimitri Kullmann (UCL), Dr Mike Carter (University Hospitals Bristol) and Dr Kasia Sieradzan (North Bristol Hospitals), with collaborators Dr Cezar Tigaret (University of Cardiff) and Professor Daniel Dombeck (Northwestern University, USA).

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