Aberrant Salience and the Risk of Psychosis

Student thesis: Doctoral ThesisDoctor of Philosophy


This study unpacks the concept of ‘salience’ as invoked by Kapur and others in
linking dopamine dysregulation to psychotic symptoms. Rather than relying on unidimensional reward based conceptions that have dominated empirical studies thus far it reconsiders the notion from a healthy salience processing point of view. It sets out to then test this model using fMRI and PET scanning in unmedicated subjects at high clinical risk for psychosis in the neural setting of a subcortical and network derived from the MAM animal model of schizophrenia.

To do this I developed a factorial fMRI task that incorporates probes of Novelty and Emotion alongside aspects of Reward. I found behavioural and fMRI main effects and interactions of each aspect in a sample of 29 healthy controls, and used this to advance a multidimensional framework of normal salience processing. We then found several specific departures from this framework in a sample of 29 participants with an At Risk Mental State for psychosis, particularly in the domains of reward and in the interactions with emotion. This resonates with the affectively laden altered motivational states seen in early psychosis and described by early phenomenologists, and fits with cognitive models that emphasise the importance of emotion in producing psychotic symptoms.

Finally, in half of the sample we additionally obtained 18?F?DOPA PET scans and found altered relationships between hippocampal activation to salient stimuli and striatal presynaptic dopamine synthesis in high risk subjects compared to controls. These were as predicted by the MAM model. These findings add support to aberrant salience models of early psychosis and demonstrate that abnormalities in salience processing are present prior to the onset of the first psychotic episode. They also support predictions from the MAM model of schizophrenia that suggests ventral hippocampal overdrive may provoke hyperdopaminergia in psychosis. They therefore also point towards this upstream target for potential new treatments. This will form the basis of ongoing work.

Date of Award2013
Original languageEnglish
Awarding Institution
  • King's College London

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