Presynaptic striatal dopamine dysfunction in people at ultra-high risk for psychosis: Findings in a second cohort

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.