Investigating the role of glutamate in brain function
Research type
Research Study
Full title
Investigating the role of glutamate and the N-methyl-D-aspartate-Receptor (NMDAR) in brain function
IRAS ID
151264
Contact name
Oliver Howes
Contact email
Sponsor organisation
King's College London
Duration of Study in the UK
6 years, 0 months, 1 days
Research summary
Schizophrenia (SCZ) is a severe mental illness with a lifetime risk of 1%. The World Health Organisation (WHO) rates SCZ as one of the top ten causes of disability. For the last 40 years research on drug therapies for SCZ have focussed on the idea that SCZ is caused by problems with the brain chemical dopamine. However, it is unlikely that dopamine dysfunction alone is responsible for all cases of SCZ. There is growing evidence implicating other brain chemicals such as glutamate, particularly involving the glutamate receptor, N-methyl-D-aspartate receptor (NMDAR).
In the 1960s, studies found that drugs such as phencyclidine (PCP) and ketamine could induce the full range of symptoms seen in SCZ. Studies demonstrated that PCP and ketamine work via the NMDAR, suggesting that NMDAR may have a role in SCZ.
A technique called 1H Magnetic resonance spectroscopy (MRS) has been used to measure glutamate levels in the brain. These studies find that brain glutamate levels are raised in early stage SCZ . Another recent study demonstrated increased glutamate in patients with SCZ that were still unwell despite being treated with drugs that work by normalising the dopamine system. MRS studies have also shown that blocking the NMDAR with ketamine increases glutamate levels, suggesting high glutamate levels in SCZ may be caused by reduced NMDAR availability.
PET (Positron Emission Tomography) imaging allows investigation at the level of the molecule and receptor which MRI cannot do.
To further understand the nature of the potential dysfunction in the glutamate system and NMDAR in SCZ we propose to use the PET radiotracer 18F-GE-179 to see if there are differences in NMDAR in schizophrenia compared to healthy controls. This is a radioligand that selectively binds to NMDAR. This information will advance our pathophysiological understanding of SCZ and progression towards finding biomarkers and treatments.REC name
London - West London & GTAC Research Ethics Committee
REC reference
16/LO/0130
Date of REC Opinion
26 Feb 2016
REC opinion
Favourable Opinion