STRESSGAP (FEP) version 1
Research type
Research Study
Full title
Stress and GABA in the pathogenesis of psychosis (first episode study)
IRAS ID
203980
Contact name
Gemma Modinos
Contact email
Sponsor organisation
King's College London
Duration of Study in the UK
4 years, 4 months, 27 days
Research summary
Psychosis is the first leading cause of disability in the developed world. The first symptoms (e.g., hearing voices that aren't there) appear in adolescence, from interactions between genes and environmental risk factors such as psychosocial stress. The treatments that are offered now do not work for about 30-60% of patients, and have little impact on illness prevention. In the brain, psychosis is commonly associated with excessive production of the neurotransmitter dopamine, but little is known about what causes this excess. Research in experimental rats shows that problems in regulating the response to stress lead to the excess production of dopamine through a disruption of another neurotransmitter system: GABA. Furthermore, when these adolescent rats are given a drug that improves GABA function, the response to stress is regulated and the development of excess dopamine at adulthood is prevented.
I propose to use neuroimaging to study the relationship between the response to emotion and psychosocial stress and GABA function in patients with a first-episode of psychosis compared to healthy controls. This will be possible by using simultaneous PET-MRI scanning. The use of the PET radiotracer (C11)RO15-4513 selectively binds to GABAergic receptors in brain regions involved in the pathophysiology of psychosis such as the hippocampus and amygdala. By using it in combination with functional MRI we can examine the relationship between brain function and neurochemistry to advance our pathophysiological understanding of psychosis progression towards finding biomarkers and new treatments aimed at preventing the development of the disorder.
REC name
London - Surrey Research Ethics Committee
REC reference
17/LO/1130
Date of REC Opinion
16 Aug 2017
REC opinion
Further Information Favourable Opinion