Portal de Periódicos da CAPES

Presynaptic Striatal Dopamine Dysfunction in People at Ultra-high Risk for Psychosis: Findings in a Second Cohort

2013; Elsevier BV; Volume: 74; Issue: 2 Linguagem: Inglês

10.1016/j.biopsych.2012.11.017

1873-2402

Alice Egerton, Christopher A. Chaddock, Toby Winton‐Brown, Michael Bloomfield, Sagnik Bhattacharyya, Paul Allen, Philip McGuire, Oliver Howes,

Parkinson's Disease Mechanisms and Treatments

Background Using positron emission tomography (PET), we previously observed increases in 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (18F-DOPA) uptake in the striatum of subjects at ultra-high risk (UHR) for psychosis, indicating elevated presynaptic dopamine synthesis capacity. The purpose of this study was to test if this finding would be replicated in a second UHR cohort. Methods 18F-DOPA PET was used to estimate dopamine synthesis capacity in the striatum of an entirely new cohort of 26 individuals at UHR for psychosis (14 males, mean±SD age = 22.7±4.7 years) and 20 healthy volunteers matched for age and gender (11 males, mean±SD age = 24.5±4.5 years). Results Dopamine synthesis capacity was elevated in the whole [t(44) = 2.6; p = .01, effect size = .81] and associative striatum [t(44) = 2.6; p = .01, effect size = .73] of UHR compared with control subjects. When the two samples were combined to give a final sample of 32 control and 50 UHR subjects, the higher levels of dopamine synthesis capacity in the UHR group reached significance across the whole [F(1,81) = 11.0; p = .001], associative [F(1,81) = 12.7; p = .001], and sensorimotor [F(1,81) = 4.7; p = .03], but not the limbic [F(1,81) = 2.1; p = .2], striatum. Conclusions The findings indicate that elevated dopamine synthesis capacity in the dorsal striatum is a robust feature of individuals at UHR for psychosis and provide further evidence that dopaminergic abnormalities precede the onset of psychosis. Using positron emission tomography (PET), we previously observed increases in 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (18F-DOPA) uptake in the striatum of subjects at ultra-high risk (UHR) for psychosis, indicating elevated presynaptic dopamine synthesis capacity. The purpose of this study was to test if this finding would be replicated in a second UHR cohort. 18F-DOPA PET was used to estimate dopamine synthesis capacity in the striatum of an entirely new cohort of 26 individuals at UHR for psychosis (14 males, mean±SD age = 22.7±4.7 years) and 20 healthy volunteers matched for age and gender (11 males, mean±SD age = 24.5±4.5 years). Dopamine synthesis capacity was elevated in the whole [t(44) = 2.6; p = .01, effect size = .81] and associative striatum [t(44) = 2.6; p = .01, effect size = .73] of UHR compared with control subjects. When the two samples were combined to give a final sample of 32 control and 50 UHR subjects, the higher levels of dopamine synthesis capacity in the UHR group reached significance across the whole [F(1,81) = 11.0; p = .001], associative [F(1,81) = 12.7; p = .001], and sensorimotor [F(1,81) = 4.7; p = .03], but not the limbic [F(1,81) = 2.1; p = .2], striatum. The findings indicate that elevated dopamine synthesis capacity in the dorsal striatum is a robust feature of individuals at UHR for psychosis and provide further evidence that dopaminergic abnormalities precede the onset of psychosis.