Chronic inflammation and metabolic dysfunction in Severe Mental Illness: Opportunity for new treatments

Host: David Popovic

About the talk:

Numerous avenues of enquiry suggest a potential causal relationship between immune dysfunction and oxidative stress and schizophrenia. Non-resolving elevation of interleukin 6 (IL-6/IL6r) has been implicated, related to development of psychosis, present before the initiation of medication. Chronic inflammation is also a key driver of metabolic dysfunction, common in schizophrenia. Mechanistically, IL6/IL6r and related low molecular weight proteins have the ability to cross the blood-brain barrier and increase its permeability, drawing in further local inflammatory actors including nitric oxide and chemokines. The immune system may be related to structural brain change via complex effects on neuronal development, micro and astrocytic function and synaptic pruning and explain increased grey matter volume loss seen in mental illness. However, whilst it is clear that aberrant immune profiles may be relevant, current evidence is actually mixed. A clear characterisation of a brain signature related to chronic low-level inflammation in schizophrenia, with evidence of related phenotypic profile will help advance our ability to target precision medicines. This presentation will outline recent outputs from the Psychosis Immune Mechanism Stratified Medicine Study (PIMS) and related studies, from genomic, early and later stage populations using multimodal data driven approaches.

Bio:

Rachel Upthegrove is a Professor of Psychiatry in the Department of Psychiatry at the University of Oxford and Chair of the NIHR Mental Health Translational Research Collaboration. She trained in Medicine at the Royal Free Hospital, University of London and completed Psychiatry training in Birmingham. Her research focuses on the identification of novel treatments for early stages of schizophrenia, and she leads the UKRI funded Psychosis Immune Mechanism Stratified Medicine Study (PIMS), a collaborative multi-stage project investigating inflammatory mechanisms of psychosis. Her translational research includes NIHR funded Early Psychosis Informatics into Care (EPICare) platform. She is chief investigator and co-investigator on a number of RCTs for repurposed and targeted treatments.