Salience attribution in addiction and psychosis

Salience attribution, the process by which particular stimuli come to selectively grab one’sattention, is heightened towards drug-associated cues in substance users and irrelevant cues inpsychosis. In Chapter 1 I review this literature. Despite their theoretical link and thesubstantial co-morbidity of substance use in psychotic disorders, the extent to which theseprocesses overlap is not well understood. The aim of this thesis was to investigate theirrelationship. The ability of drug cues to impact on associative learning processes wasexamined in Chapter 2 using a newly developed task. Overshadowing by drug cues wasfound alongside smoking-related attentional bias in abstinent smokers but not in satiatedsmokers or controls. This overshadowing effect is replicated in Chapter 3 among frequentketamine users and polydrug-using controls. Ketamine users showed elevated psychotic-likesymptoms, a reduction in associative blocking and a stronger impact of drug cues on blockingcompared to polydrug controls. These results are indicative of a shared disruption of salienceattribution in addiction and psychosis, which I investigated in Chapter 4 among smokerswith a diagnosis of schizophrenia. Associative blocking was reduced in these individualscompared to control smokers but both groups displayed an absence of blocking towards drugcues. The patient group also showed higher drug-cue attentional bias that correlated withpositive psychotic symptoms. In Chapter 5 I examined the role of dopamine in salienceattribution in smokers. The dopamine D2/D3 agonist pramipexole (0.5mg) reduced urges tosmoke and decreased attentional bias towards smoking-related images relative to monetaryimages when compared to placebo. In Chapter 6 I discuss the theoretical and clinicalimplications of these findings. The effects of drug cues on associative learning provide amethodological advance, and these findings offer preliminary support for a link betweendisruptions of salience attribution in addiction and in psychosis.