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.