Using MRI, MEG, and machine learning to better classify severe mental illness

Schizophrenia and bipolar disorder are severe mental health disorders affecting more than 64 million people worldwide. Despite their prevalence, their aetiology is poorly understood and diagnoses still rely on clinical categorisation of symptoms rather than biological markers. This lack of pathophysiological understanding hinders therapeutic progress, with almost no mechanistically novel therapies developed since the introduction of antipsychotics and lithium in the mid-20th century.

This inter-disciplinary PhD project will contribute to the South Wales and South-West England (SW2) Brain and Genomics Hub of the National UKRI Mental Health Platform. The Brain and Genomics Hub will employ deep phenotyping strategies, including advanced magnetic resonance imaging (MRI), magnetoencephalography (MEG), clinical, cognitive, genetic, epigenomic, and immunometabolic evaluations, in 600 people with schizophrenia, bipolar disorder and schizoaffective disorder.

As the PhD student on this project, you will develop advanced machine learning algorithms to meaningfully categorise people with severe mental health disorders, using brain imaging data (e.g. functional and microstructural) that capture features linked to disorders like schizophrenia and bipolar disorder. These categories should be biologically interpretable, repeatable, and generalisable, and provide mechanistic insights to aid future development of personalised treatments and targeted therapies.

You will also work to interpret and understand the biological significance of these categories by exploring additional data from imaging and non-imaging sources as part of the larger Brain and Genomics Hub project. Lastly, you will learn about the processes and challenges associated with bringing neuroimaging biomarkers to real-world clinical settings through hands-on experience at Bioxydyn, a leading start-up in this field.

Preparation phase:

The dataset you will employ in this project allows for a high degree of flexibility. During this phase, you will work with the supervisors to develop the project in line with your academic interests and desired skills training. As part of this preparation phase, you will review recent

literature in advanced clustering algorithms, clinical neuroimaging, psychiatric genetics and psychiatric disorders (specifically, schizophrenia, bipolar disorder and schizoaffective disorder) and suggest novel approaches for improving stratification and classification in psychiatric disorders.

Phase 1: UK Biobank

In this phase, you will develop a clustering algorithm capable of meaningfully categorising people with severe mental health disorders using image-derived phenotypes from the UK Biobank. The UK Biobank includes 157 people with schizophrenia, 602 people with psychotic disorders, and 836 people with bipolar and related disorders, and provides an excellent resource for developing the initial clustering algorithm.

Phase 2: SW2 Brain and Genomics Hub

During this phase, you will determine whether clusters derived from UK Biobank are applicable to the Brain and Genomics Hub project, to identify a robust set of image-derived phenotypes for classification. You will then work to derive biological meaning from clusters through exploration of other imaging (MEG) and non-imaging (genetic, clinical) data collected as part of the Brain and Genomics Hub project.

Phase 3: Broadening Horizons Placement

During the Broadening Horizons Placement, you will develop a comprehensive understanding of the complexities associated with translating research-derived biomarkers into clinical practice, in partnership with Bioxydyn, a leading UK-based imaging start-up pioneering the use of microstructural imaging biomarkers in drug development and clinical trials https://bioxydyn.com.

This project is based at Cardiff University Brain Research Imaging Centre (CUBRIC), in collaboration with researchers at the University of Bath. The project also includes researchers from the University of Bristol, University of Exeter, and Swansea University, as well as experts from Bipolar UK and Adferiad Recovery. Your supervisory team will include experts in neuroimaging, computational modelling, statistical analysis, genetics and psychiatry.

As part of your training, you will be expected to present your work at national and international conferences (e.g., BIC-ISMRM) and publish high-impact peer reviewed papers. In addition, you will participate in research meetings focused on MRI, computer science, genetics and mental health, giving you the opportunity to learn from experts in the field and build lasting relationships with your peers.

This project would be well suited to prospective students with a strong background in coding, computer science and/or neuroimaging who are interested in developing novel algorithms for personalising mental healthcare.

Applications open on Monday 4th September 2024 and close at 5.00pm on Monday 4th November 2024.

The studentships are available to UK and International applicants. Following Brexit, the UKRI now classifies EU students as international unless they have rights under the EU Settlement Scheme. The GW4 partners have agreed to cover the difference in costs between home and international tuition fees. This means that international candidates will not be expected to cover this cost and will be fully funded but need to be aware that they will be required to cover the cost of their student visa, healthcare surcharge and other costs of moving to the UK to do a PhD. Studentships will be competitively awarded and there is a limit to the number of International students that we can accept into our programme.

Applicants for a studentship must have obtained, or be about to obtain, a first or upper second-class UK honours degree, or the equivalent qualification gained outside the UK, in an appropriate area of medical sciences, computing, mathematics or the physical sciences. Applicants with a lower second class will only be considered if they also have a Master’s degree. Please check the entry requirements of the home institution for each project of interest before completing an application. Academic qualifications are considered alongside significant relevant non-academic experience.

If English is not your first language you will need to meet the language requirements of the university that will host your PhD by the start of the programme.

A list of all the projects and how to apply is available on the DTP’s website at gw4biomed.ac.uk. You may apply for up to 2 projects and submit one application per candidate.

Please complete the online application form linked from the DTP’s website by 5.00pm on Monday, 4th November 2024. If shortlisted for interview, you will be notified from Friday, 20th December 2024.

For informal enquiries, please contact GW4BioMed@cardiff.ac.uk

For project related queries, please contact the respective supervisors listed on the project descriptions on the DTP’s website.