This project applies rare variant analysis to drug discovery for depression, explores repurposing heart drugs in psychiatry, and examines public views on genomic research and ethics.

health

Grant

Grant: Strategic
Year awarded: 2025-26
Amount awarded:  £99,803.90

AcademicsProfessor A Floriaan Schmidt, Institute of Cardiovascular Science, Faculty of Population Health Sciences. Professor Jean-Baptiste Pingault, Research Department of Clinical, Educational and Health Psychology, Faculty of Brain Sciences. Dr Helen Knowler, UCL Arena Centre.   Dr José J. Morosoli, Department of Clinical, Educational and Health Psychology. Dr Abi Ter Kulle, Department of Clinical, Educational and Health Psychology.

Project Summary

Mental illnesses rank first in the global burden of disease1. Medications are central to the treatment of mental illnesses, but little progress has occurred in past decades2. Such therapeutic stasis partly stems from inadequate preclinical evidence for drug targets in humans, including a poor understanding of mechanisms of drug action2. This issue is at the core of the Grand Challenge of Mental Health & Wellbeing, which aims to advance the understanding of mechanisms, with the view to accelerate translation into effective interventions. This cross-faculty collaboration across cardiovascular sciences, psychiatry and education is relevant both from a methodological point of view but also because the burden of mental illnesses can materialise through an increased risk of cardiovascular diseases3. For example, people with psychiatric disorders have a four-fold increase of sudden cardiac death4. 

Leveraging genetics for drug discovery is part of the fast-paced development in genetic research and data collection (a recent example being the UK government’s aim to sequence all newborns). This has led to increasing debates around the embedding of genetic testing in healthcare settings5, including in psychiatric genetics. Psychiatric genetic testing spurs public interest6 although most public audiences do not yet fully realise how genetic research may increasingly impact their lives. There is thus a pressing need to involve the public in discussions of the benefits, challenges and ethical concerns around genetic research7. 

The core aims of the project are to: 
1) Implement rare variant analysis into our drug discovery pipeline and apply it to MDD; 
2) Develop pilot data to systematically investigate the repurposing of cardiovascular drugs in psychiatry; 
3) Explore public understanding, attitude, and ethical concerns around genomic research, including for drug discovery; 

References: 
1.    Vigo, D., Thornicroft, G. & Atun, R. Estimating the true global burden of mental illness. Lancet Psychiatry 3, 171–178 (2016).
2.    Kesselheim, A. S., Hwang, T. J. & Franklin, J. M. Two decades of new drug development for central nervous system disorders. Nature Reviews Drug Discovery 14, 815–816 (2015).
3.    Harshfield, E. L. et al. Association Between Depressive Symptoms and Incident Cardiovascular Diseases. JAMA 324, 2396–2405 (2020).
4.    Mujkanovic, J. et al. Nationwide burden of sudden cardiac death among patients with a psychiatric disorder. Heart 110, 1365–1371 (2024).
5.    Andreassen, O. A., Hindley, G. F. L., Frei, O. & Smeland, O. B. New insights from the last decade of research in psychiatric genetics: discoveries, challenges and clinical implications. World Psychiatry 22, 4–24 (2023).
6.    Morosoli, J. J., Colodro-Conde, L., Barlow, F. K. & Medland, S. E. Investigating perceived heritability of mental health disorders and attitudes toward genetic testing in the United States, United Kingdom, and Australia. Am J Med Genet B Neuropsychiatr Genet 186, 341–352 (2021).
7.    Middleton, A. et al. Public engagement with genomics. Wellcome Open Res 8, 310 (2023).

 

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