Freeman, TP; (2013) Salience attribution in addiction and psychosis. Doctoral thesis (PhD), UCL (University College London).

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Abstract

Salience attribution, the process by which particular stimuli come to selectively grab one’s attention, is heightened towards drug-associated cues in substance users and irrelevant cues in psychosis. In Chapter 1 I review this literature. Despite their theoretical link and the substantial co-morbidity of substance use in psychotic disorders, the extent to which these processes overlap is not well understood. The aim of this thesis was to investigate their relationship. The ability of drug cues to impact on associative learning processes was examined in Chapter 2 using a newly developed task. Overshadowing by drug cues was found alongside smoking-related attentional bias in abstinent smokers but not in satiated smokers or controls. This overshadowing effect is replicated in Chapter 3 among frequent ketamine users and polydrug-using controls. Ketamine users showed elevated psychotic-like symptoms, a reduction in associative blocking and a stronger impact of drug cues on blocking compared to polydrug controls. These results are indicative of a shared disruption of salience attribution in addiction and psychosis, which I investigated in Chapter 4 among smokers with a diagnosis of schizophrenia. Associative blocking was reduced in these individuals compared to control smokers but both groups displayed an absence of blocking towards drug cues. The patient group also showed higher drug-cue attentional bias that correlated with positive psychotic symptoms. In Chapter 5 I examined the role of dopamine in salience attribution in smokers. The dopamine D2/D3 agonist pramipexole (0.5mg) reduced urges to smoke and decreased attentional bias towards smoking-related images relative to monetary images when compared to placebo. In Chapter 6 I discuss the theoretical and clinical implications of these findings. The effects of drug cues on associative learning provide a methodological advance, and these findings offer preliminary support for a link between disruptions of salience attribution in addiction and in psychosis.

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