Prefrontal cortical dopamine release in clinical high risk for psychosis during a cognitive task: a [¹¹C]FLB457 positron emission tomography study

Research suggests decreased cortical dopamine is a neural correlate of cognitive deficits in schizophrenia. Evidence of impaired cognitive task-induced cortical dopamine release was demonstrated in patients with psychosis. However, whether cortical dopamine release in response to a cognitive task in clinical high risk for psychosis (CHR) is also impaired, is currently unknown. We aimed to test dopamine release in the dorsolateral prefrontal cortex (DLPFC) and the anterior cingulate cortex (ACC) in antipsychotic-free CHR participants and healthy controls (HC) performing the Wisconsin Card Sorting Task (WCST). Two [¹¹C]FLB457 PET scans were conducted for 13 CHR and 15 HC while performing the WCST and the sensorimotor control task (SMCT), respectively. A magnetic resonance image was acquired for anatomical delineation. Percentage change in binding potential (ΔBP_ND) in ACC and DLPFC in WCST were compared with the SMCT between CHR and HC. Mixed model analysis revealed no statistically significant differences in the cognitive task induced ΔBP_ND in any ROIs. There were no main effect of group (F(1, 26) = 0.348; p = 0.560) or ROI (F(1, 26) = 1.080; p = 0.308) and no significant Group x ROI interaction (F(1, 26) = 0.049; p = 0.826). Our findings suggest no statistically significant difference between CHR and HC in cognitive task-induced cortical dopamine release. This is the first in vivo study to illustrate that the cortical hypodopaminergic state observed in schizophrenia may not be present in its putative high-risk state.