Energetics and Glutamate in Schizophrenia (EAGLES)
The development of new therapeutics for schizophrenia requires a deeper understanding of the brain processes underlying the illness. These processes are complex, only partially understood, and likely to vary between individuals.
One leading theory is that schizophrenia is related to changes in glutamate, the brain’s main excitatory neurotransmitter. Early evidence suggests that alterations in glutamate may be particularly important in individuals with more severe symptoms and treatment resistance.
Regulation of glutamate release, reuptake and recycling is critical for healthy brain function - and is by far the most energy demanding process in the brain. These energy demands are mainly met by glucose, although when demands are high, lactate can serve as an additional energy source.
While preclinical research has provided considerable insight into glutamate-related energy metabolism, these processes have not been well characterised in the living human brain, either in healthy individuals or in those with schizophrenia.
Aims
The Energetics and Glutamate in Schizophrenia (EAGLES) study explores how glutamate, glucose use, lactate production, and brain activity are related in healthy volunteers and in individuals with schizophrenia, including those with treatment resistant illness.
We are testing the hypothesis that in schizophrenia, the energy demands associated with regulating glutamate are increased, leading to decreased glucose utilisation and increased lactate production. We are also investigating whether these changes are most pronounced in people with more severe symptoms, cognitive difficulties, and treatment resistance.
In addition to providing new insights into the coupling of these fundamental brain processes, the EAGLES study aims to open new directions for research, and ultimately for the development of new therapies for schizophrenia and related conditions.
Funding
The project is funded by the Medical Research Council, UK (Ref: MR/X021696/1).
Principal Investigator: Prof Alice Egerton.
NHS REC reference: 23/LO/0990
Methods
The EAGLES study uses advanced brain imaging, combining PET-MRI and 7 Tesla MRI technologies.
The PET-MRI protocol includes fully quantitative 18F-fluorodeoxyglucose PET (to measure cerebral metabolic rate of glucose utilisation), together with concurrent 3 Tesla MRI (to assess cerebral blood flow, oxygen metabolism, and resting state network activity).
The 7 Tesla MRI protocol includes proton magnetic resonance spectroscopy (1H-MRS) to measure glutamate, glutamine and lactate at rest and during visual stimulation (functional MRS or fMRS).
Imaging is conducted at the King’s College London PET Centre and the London Collaborative Ultra-High field System facility, both located at St Thomas’ Hospital.
Principal Investigator
Professor of Neuropsychopharmacology
Investigators
Professor in Neuroimaging (Analysis & Statistics)
Senior Lecturer
Postdoctoral Research Associate
NIHR Maudsley Biomedical Research Centre PhD Student
Research Assistant