Neural mechanisms of positive symptoms in first-episode and prodromal psychosis.

John Grace QC PhD Scholarship 2020 - King's College London

Supervisors: Gemma Modinos, Philip McGuire.

Summary: One in four people will experience a mental health problem in their lifetime. The cost of mental ill health to the economy, NHS and society is estimated to be £105 billion a year. Schizophrenia is a mental health disorder involving psychotic symptoms such as hearing voices that aren't there. Available treatments do not work for about a third of patients and have no impact on prevention. To develop better treatments, we must understand the brain basis of how schizophrenia develops. In the brain, psychosis is associated with excess production of a chemical called dopamine, but we know little about what causes this. Recent research suggests that the dopamine excess is due to oxidative stress. Oxidative stress can lead to deficits in the chemical system GABA. GABA deficits elevate activity in key brain areas such as the hippocampus, leading to increased dopamine and psychotic symptoms. Studies also show that targeting oxidative stress early may be a new way to prevent psychosis. This project will use advanced brain imaging methods to identify the mechanisms linked to psychosis. We will study the relationship between oxidative stress, GABA and psychotic symptoms in people with early psychosis. This will help us understand the brain basis of schizophrenia and inform potential new targets for prevention.



This multimodal in vivo neuroimaging project aims to determine, for the first time:


1. The link between cortical levels of oxidative stress (glutathione) and GABA in patients  with first-episode psychosis (FEP) and CHR individuals, as compared to healthy controls


2. Within the FEP and CHR groups:

        a. The link between glutathione, GABA and hippocampal activity

        b. The relationship between the above imaging measures and levels of positive symptoms.

Research Student: Samuel Knight

I am a PhD student at King’s College London, using multi-modal neuroimaging techniques to study the neural mechanisms of positive symptoms in early psychosis. Before starting my PhD, I completed an Honours degree in Cognitive Psychology studying memory at Victoria University of Wellington in New Zealand. During this time, I also worked as a research assistant studying memory in childhood depression and a longitudinal project on wellbeing in young adults. Most recently I completed a MSc of Neuroscience in Neuroimaging at King’s College London, where I used resting-state fMRI and 5-HT receptor information to investigate MDMA’s influence on the striatum. Since completing my MSc I have been working on a research project using EEG and cortical stimulation to treat childhood epilepsy.