title: Neural and behavioral correlates of aberrant salience in individuals at risk for psychosis.
abstract: The "aberrant salience" model proposes that psychotic symptoms first emerge when chaotic brain dopamine transmission leads to the attribution of significance to stimuli that would normally be considered irrelevant. This is thought to occur during the prodromal phase of psychotic disorders, but this prediction has not been tested previously. In the present study, we tested this model in 18 healthy volunteers and 18 unmedicated individuals at ultra-high risk of psychosis. Subjects performed the Salience Attribution Test, which provides behavioral measures of adaptive and aberrant motivational salience, during functional magnetic resonance imaging to assess neural responses to relevant and irrelevant stimulus features. On a separate occasion, the same subjects were also studied with [(18)F]fluorodopa positron emission tomography to measure dopamine synthesis capacity. Individuals at ultra-high risk of psychosis were more likely to attribute motivational salience to irrelevant stimulus features (t(26.7) = 2.8, P = .008), and this bias was related to the severity of their delusion-like symptoms (r = .62, P = .008). Ventral striatal responses to irrelevant stimulus features were also correlated with delusion-like symptoms in the ultra-high risk group (r = .59, P = .017). Striatal dopamine synthesis capacity correlated negatively with hippocampal responses to irrelevant stimulus features in ultra-high risk individuals, but this relationship was positive in controls. These data are consistent with the hypothesis that aberrant salience processing underlies psychotic symptoms and involves functional alterations in the striatum, hippocampus, and the subcortical dopamine system.
authors.affiliation: To whom correspondence should be addressed; Institute of Cognitive Neuroscience, University College, 17 Queen Square, London, WC1N 3AR, UK; tel: +44-207-679-1170, fax: +44-207-679-1121, e-mail: j.roiser@ucl.ac.uk.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Roiser
authors.forename: Oliver D
authors.initials: OD
authors.lastname: Howes
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Chaddock
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Joyce
authors.forename: Philip
authors.initials: P
authors.lastname: McGuire
mesh_terms: D000328:Adult; D001479:Basal Ganglia / Q000378:metabolism / Q000503:physiopathology; D054022:Cerebrum / Q000378:metabolism / Q000503:physiopathology*; D003702:Delusions / Q000378:metabolism / Q000503:physiopathology*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D059907:Functional Neuroimaging / Q000295:instrumentation / Q000379:methods*; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D062706:Prodromal Symptoms; D011618:Psychotic Disorders / Q000378:metabolism / Q000503:physiopathology*; D012306:Risk; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D004298:Dopamine