Exercise for First Episode Psychosis; an opportunity for early intervention

Exercise has been identified as a treatment for psychosis as it has the ability to alter clinical symptoms, rebalance cell health and reset the cellular signals that are altered in psychosis and schizophrenia.

This PhD studentship would comprise two main project elements; an exercise intervention study and a cell study, giving a ‘best of both worlds’ scenario for the PhD student. The proposed exercise intervention in first episode psychosis patients would assess clinical symptoms (primary outcome: symptoms of psychosis), fitness and cellular markers of disease. Informed by our recent feasibility study (Fisher et al, 2019), this exercise intervention would group exercise not by type or mode, but based on intensity, into low, moderate and high to allow participants in the intervention group to choose a mixed programme of exercise. Each week they will undertake some high, some low and some moderate intensity exercise. By grouping exercise in this way we would still allow the choice that is so important for this population, but yet be able to control the intensity of exercise, which we believe is important to affect positive symptoms of psychosis. Alongside assessment of clinical symptoms (using the positive and negative symptom scale; PANSS), measures of cognition and wellbeing would be assessed in addition to physical fitness and markers of inflammation and cell redox status (IL-6, CRP, TNF, Glutathione, lipid oxidation). These outcomes would give insight into the mechanisms by which exercise is effective in altering the symptoms of psychosis.

The cell study would use a brain co-culture model of neurons, astrocytes and microglia which we have successfully developed from induced Pluoripotent Stem Cells (iPSCs). These stem cells are derived from a person with schizophrenia and thus display all the cellular physiology of the disease. This model would allow the mechanisms of change brought about by exercise to be assessed in a controlled system. The different cell types have different roles in the brain. For example, microglia are the brain’s immune cell, and are known to release cytokines like IL-6. The proposed study would assess the effects of stress (using an oxidising agent to mimic the physiological stress of exercise) on factors which are known to be altered and related to the symptoms of psychosis. For example, neurotransmitter action (via characterisation of receptor interaction), neuroplasticity (via BDNF), inflammation (via cytokines) and redox status (via glutathione).

The student will spend time in Orygen, Melbourne, under the supervision of Prof Stephen Wood, where they will have access an ‘at risk for psychosis’ participant population. The student will have the opportunity to run an exercise intervention in this group and assess the effect of exercise on markers of mental and metabolic health. The outcome markers assessed will be informed by the exercise study undertaken first in the UK.

These studies would give the PhD student an enviable skill set. The student would be trained in working from clinic to bench by having the opportunity to work with patients to run an intervention study, and cells to assess mechanism of effect in a controlled system.

Supervisors and environment: Dr Aldred is affiliated to both the School of Sport, Exercise and Rehabilitation Sciences and the Institute for Mental Health. Her research spans brain health across the lifespan from youth mental health to neurodegenerative disease. Dr Aldred’s laboratory comprises 4 other PhD researchers and a post-doctoral fellow all working in the area of exercise and nutrition for brain health. The project fits into the research within Dr Aldred’s lab as she is currently undertaking exercise interventions in first episode psychosis patients, and iPSC work in schizophrenia.
Dr Aldred currently works with both Prof Rachel Upthegrove (Consultant psychiatrist and Professor of Psychiatry and Youth Mental Health) and Prof Stephen Wood (Acting director, Research and Translation, Orygen; Professor of Clinical Translational Neuroscience,University of Melbourne).
Prof Upthegrove would be clinical lead and facilitate patient interaction and Prof Wood would lead on assessment of brain redox status via brain spectroscopy and assessment of cognitive performance following intervention. Aldred and Wood have supervised 2 previous students together (Sahara Rai 2014-2017 and Emily Fisher). Aldred, Wood and Upthegrove are all supervisors of Emily Fisher (2016-2020; MRC IMPACT studentship).