PEACE
Research type
Research Study
Full title
Psychosis, Excitation/Inhibition Balance And Cognitive Symptoms
IRAS ID
278941
Contact name
Robert A McCutcheon
Contact email
Sponsor organisation
University of Oxford Research Governance, Ethics and Assurance
Duration of Study in the UK
3 years, 6 months, 31 days
Research summary
Schizophrenia accounts for costs of £11.8 billion per year in England. Cognitive impairments inherent to the disorder are a key driver of these costs, yet there are no effective treatments for these symptoms. Recent work has linked these symptoms to altered connectivity of brain networks, as measured using resting state functional MRI (rsfMRI) and electroencephalography (EEG) or magnetoencephalography(MEG). These macroscale functional networks emerge from balanced interactions between excitatory glutamatergic pyramidal cells and inhibitory GABAergic interneurons. Animal and post-mortem work demonstrates a link between disruption of this excitation/inhibition (E/I) balance and cognitive symptoms of schizophrenia, but corroborating this in patients is difficult as measuring E/I balance in living humans is a major methodological challenge.
Recent advances, however, mean that it is now possible to address this challenge by using computational biophysical modelling to infer lower-level E/I mechanisms from macroscale neuroimaging data. Using this modelling approach we will investigate E/I balance in schizophrenia, and investigate the the responsivity of this system to memantine, a compound that may have the potential to alter E/I balance.
Memantine is an approved treatment for Alzheimer’s disease where it benefits cognitive function. Meta-analyses suggest it also has pro-cognitive effects in schizophrenia. Understanding how it affects E/I balance in schizophrenia will increase our understanding of schizophrenia pathophysiology.
In the current study individuals with schizophrenia, and healthy controls will receive brain imaging to measure E/I balance at baseline, and after a period of receiving treatment with placebo, and with memantine. The study has the potential to inform our knowledge about the neurobiology of cognitive symptoms and potentially of mechanisms via which this neurobiology can be adjusted.
REC name
London - Westminster Research Ethics Committee
REC reference
22/PR/1470
Date of REC Opinion
21 Dec 2022
REC opinion
Further Information Favourable Opinion