Our immune system defends the body against a wide variety of stresses, plays a key role in regulating our mental health and helps mobilise the body’s mechanisms for repairing itself. Immune dysfunction has been shown to be related to symptoms seen across different psychotic disorders, such as difficulties in processing information, lack of pleasure, and poor motivation, which might provide advance warning of an impending threat to our mental health. Evidence suggests that immune dysfunction may be causally linked to psychiatric disorders, particularly in young people at clinical high-risk (CHR) for transition to psychosis, with alterations of immune protein levels (e.g. circulating cytokine concentrations, such as interleukin-6; IL-6) and oxidative stress markers (e.g. glutathione) previously reported in patients with psychotic disorders.
This PhD project will explore whether mediators of innate immune response are associated with changes in brain-related neurobiological mechanistic processes in CHR individuals. Dynamic changes in brain structure and function in the CHR population will be investigated, predicting that elevated IL-6 levels will be associated with cortical volume loss and functional alterations in relevant brain networks, as well as a reduction in glutamatergic-related concentrations (e.g. glutathione) in the brain. Complementary data will investigate whether IL-6 and related cytokines impact on the neurophysiological processes that underpin fundamental cognitive functions, such as attention, working memory, and executive functioning; functions shown to be impaired in CHR individuals. Multivariate data-driven approaches using computational modeling and supervised machine learning methods will help validate clinical and neurobiological markers of CHR transition to psychosis, improving predictive accuracy for clinical and functional outcomes in CHR individuals.
This project will involve recruitment of young people in whom early symptoms indicate that they are at a clinical high-risk (CHR) of developing psychosis. This project will include measuring signs of inflammation by assessing the cells that are involved in innate immune response. The student will also use various non-invasive brain imaging techniques such as magnetic resonance spectroscopy (MRS), magnetic resonance imaging (MRI) and magnetoencephalography (MEG) to target and assess inflammation, antioxidant defences and imbalances, and how these might be linked to structural and functional processes in the brain. Cutting-edge machine learning and computational modeling methods will be used to build analytical models that help predict clinical outcomes in CHR populations. This research will address key questions currently facing the field of neuroimmunology by enhancing our understanding of the innate immune-related and neurobiological mechanisms involved in the early stages of psychosis.
As part of this project the student will develop interdisciplinary skills across neurobiological, clinical and computational interfaces, with the opportunity to learn immuno-phenotyping methods integral to identifying blood-based biomarkers in immune-active CHR individuals. This project will be partnered with Autifony Therapeutics Limited (Autifony Therapeutics), a UK-based SME founded in 2011 utilising pioneering expertise to develop novel treatments for neuropsychiatric disorders, including schizophrenia. The student will undertake a 3-month study placement with Autifony developing mechanistic insights that could lead to novel pharmaceutical treatments for psychosis and other serious disorders of the central and peripheral nervous systems. In addition to an industrial partner, this research project will be leveraged by established national/international networks of early psychosis research and neuroimmunology.
Person Specification
Applicants should have a strong background in psychology or psychiatry, and ideally a background in neuroscience. They should have a commitment to research in mental health and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in a relevant subject.
How to apply
To apply, please download and complete all documentation available at https://more.bham.ac.uk/mrc-aim/phd-opportunities/
Informal enquiries should be directed to Dr Jack Rogers ([Email Address Removed])
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