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4-year PhD Studentship: Novel immunological mechanisms and treatment targets for depression: evidence from randomised designs

   Faculty of Health Sciences

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  Prof Golam Khandaker, Prof George Davey-Smith, Prof Simon Jones  No more applications being accepted  Self-Funded PhD Students Only

About the Project

Low-grade systemic inflammation represents one promising avenue for new mechanistic explanation and therapeutic development for depression, but success of future trials of immunotherapies will depend of optimum target selection based on evidence of causality. Role of cytokines in depression has been studied extensively in humans and animals, highlighting a potential role of the pleotropic proinflammatory cytokine interleukin 6 (IL-6). However, causal effects of specific IL-6 signalling pathways (classical vs trans signalling) and of key acute phase reactants under control of IL-6, namely hepcidin and serum amyloid A (SAA), in depression are unclear. Evidence for causal effects of specific aspects of IL-6 signalling pathway in depression could inform interventional studies leading to the development of new treatments in future.

Aims and objectives

  1. To provide evidence of causality in the association between IL-6 signalling and depression.
  2. To investigate potential mechanism underlying the association between inflammation and clinical symptoms of depression.


Population and clinical randomised designs testing causal effects of IL-6 signalling on depression. First, two sample Mendelian randomization (MR) analysis testing causal effects of the following exposures on major depressive disorder: genetic variants related to IL-6 trans signalling, hepcidin and SAA. Second, secondary analysis of data from a RCT of anti-IL-6R monoclonal antibody tocilizumab in depression patients, examining whether IL-6 trans signalling, hepcidin and SAA are associated with depression severity at baseline, and with change in depression symptoms severity post intervention.

How to apply for this project

This project will be based in Bristol Medical School - Population Health Sciences in the Faculty of Health Sciences at the University of Bristol.

Please visit the Faculty of Health Sciences website for details of how to apply

Funding Notes

This project is open for University of Bristol PGR scholarship applications (closing date 25th February 2022)
The University of Bristol PGR scholarship pays tuition fees and a maintenance stipend (at the minimum UKRI rate) for the duration of a PhD (typically three years but can be up to four years).
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