Dopamine Synthesis Capacity In Striatum Research Articles

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

Using positron emission tomography (PET), we previously observed increases in 3,4-dihydroxy-6-[(18)F]fluoro-L-phenylalanine ((18)F-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. (18)F-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.

‘Prefrontal’ cognitive performance of healthy subjects positively correlates with cerebral FDOPA influx: An exploratory [18F]‐fluoro‐L‐DOPA‐PET investigation

Dopamine neurotransmission influences those cognitive processes, which are generally regarded as prefrontal cortical functions. In previous positron-emission-tomography (PET) studies, net blood-brain clearance of [18F]-fluoro-l-DOPA (FDOPA) correlated with impaired cognitive performance in patients with Parkinson's disease or schizophrenia. We hypothesized that FDOPA influx also correlates with performance of cognitive tasks associated with prefrontal functioning in healthy volunteers. The net blood-brain clearance of FDOPA (K(in)(app)) was mapped in a group of 11 healthy volunteers and calculated in striatal volumes-of-interest. The Wisconsin-Card-Sorting-Test (WCST), Stroop-Test, Trail-Making-Test (TMT-A/B), and Continuous-Performance-Test (CPT-M) had been administered previously to the same subjects. No correlation of K(in) (app) with perseverative errors in WCST or age could be found. However, there were significant positive correlations between the magnitude of K(in)(app) in caudate nucleus, putamen, and midbrain with performance of the TMT-B, CPT-M, and the Stroop test. Highest correlations were found between the time needed to perform the Stroop interference task and the K(in)(app) of striatal areas (Caudate nucleus: -0.780, P = 0.005; putamen: -0.870, P < 0. 001). Thus, the present findings reveal a strong correlation between dopamine synthesis capacity in striatum of healthy volunteers and performance of cognitive tasks linked to the prefrontal cortex.