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Title: Neuroinflammation and psychosis : antipsychotic medication
Author: Bloomfield, Peter S.
ISNI:       0000 0004 5989 6630
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2016
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Neuroinflammation is an early feature of a number of nervous system disorders. Inflammation in the brain is primarily mediated via microglial cells, which are active components of circuit development in the central nervous system. Schizophrenia is a psychiatric illness with deficits in perceptual, cognitive and emotional function. Prior to the onset of psychosis, there is a period of attenuated psychotic symptoms, where individuals experience sub threshold features of psychosis. This 'ultra high risk' period can provide unique opportunities to investigate the development of psychosis. It has been demonstrated through translocator protein (TSPO) positron emission tomographic (PET) imaging that microglial activity is elevated in chronic schizophrenia, however it is unknown whether this elevation is present prior to the onset of psychosis. It is also uncertain what effect antipsychotic medication has on microglia in vivo. This thesis is divided between clinical and animal investigation, the results can be split into four findings; Firstly we demonstrate that there is a higher binding of [11C]PBR28 (a novel TSPO PET ligand) in ultra high risk subjects and patients with schizophrenia compared to healthy controls. Symptoms in the ultra high risk subjects also correlate with the level of ligand binding. Secondly, brain volumes are not correlated with [11C]PBR28 binding or inflammatory cytokine levels in peripheral blood samples. The third finding of this thesis is that antipsychotic drug administration does not appear to alter cortical microglial cells in naïve and systemically inflamed animals. The final finding is that brain volume is reduced by antipsychotic medication. Together these findings demonstrate that inflammation is present in subjects experiencing subthreshold psychotic symptoms. The animal experiments suggest medicated patients would not be expected to have higher levels of microglial activity than their un-medicated counterparts. Further investigation is needed to determine the mechanism of cortical volume changes after medication and how this relates to TSPO.
Supervisor: Howes, Oliver ; De Paola, Vincenzo Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral