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Dopaminergic mechanisms underlying psychosis

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Title: Dopaminergic mechanisms underlying psychosis
Authors: Bloomfield, Michael
Item Type: Thesis or dissertation
Abstract: Schizophrenia is a potentially devastating mental illness with a complex aetiology, in which the odds ratios for environmental risk factors for the disorder are greater than the odds ratios of any single gene hitherto identified. Within schizophrenia, striatal dopamine dysfunction has been proposed to underlie the development of psychosis. The Aberrant Salience hypothesis provides an explanatory model based on empirical findings to explain how psychotic symptoms may arise from striatal hyperdopaminergia, whereby multiple risk factors converge to elevate striatal dopamine synthesis capacity as the Final Common Pathway to psychosis. Two important epidemiological risk factors for the disorder are chronic cannabis use and longterm psychosocial stress, both of which have evidence supporting effects on the dopamine system. Environmental risk factors are by their very nature modifiable, and so this thesis examined whether these environmental risk factors were associated with the same dopaminergic abnormalities that have been observed in schizophrenia with 3,4-dihydroxy-6- [18F]-fluoro-l-phenylalanine Positron Emission Tomography. This thesis also examined whether cannabis users exhibit aberrant salience processing using a behavioural task, the Salience Attribution Task. This thesis found that long-term cannabis use was associated with reduced dopamine synthesis capacity and no relationship was found between striatal dopamine synthesis capacity and cannabis-induced psychotic-like symptoms. Whilst cannabis use was not associated with increased aberrant salience processing, there was a relationship between cannabis-induced psychotic-like symptoms and aberrant salience processing. This thesis found that long-term psychosocial stress is associated with reduced dopamine synthesis capacity, although this finding may be due confounding factors. However, a positive relationship was observed between childhood and recent adult stressors and dopamine synthesis capacity. These findings call into question the hypothesis that cannabis increases the risk of psychosis by inducing the same changes observed in schizophrenia, although there some evidence to support the hypothesis that psychosocial stressors do increase risk via this mechanism.
Content Version: Open Access
Issue Date: Sep-2014
Date Awarded: Jan-2016
URI: http://hdl.handle.net/10044/1/44332
DOI: https://doi.org/10.25560/44332
Supervisor: Howes, Oliver
Sponsor/Funder: Kings College London
Medical Research Council (Great Britain)
National Institute of Health Research
Funder's Grant Number: MC-A656-5QD30
Department: Institute of Clinical Science
Publisher: Imperial College London
Qualification Level: Doctoral
Qualification Name: Doctor of Philosophy (PhD)
Appears in Collections:Department of Clinical Sciences PhD Theses



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