Simultaneous measurement of Midbrain and Striatal Dopamine in Schizophrenia using an agonist radiotracer

Imaging studies showing greater amphetamine-induced dopamine release in patients with schizophrenia (SCZ) compared to matched healthy controls (HC) have been repeatedly replicated, but these studies all used radiotracers that were dopamine D2 receptor antagonists. A more recent study using an agonist radiotracer did not detect this increase, raising a question whether the difference in radiotracer pharmacology affected the result. Another study examining the extrastriatal response to the amphetamine challenge with an antagonist tracer observed a blunted effect in SCZ in the midbrain, suggesting mechanisms local to the striatum might have contributed to the striatal imaging results independent of midbrain dopamine availability. Here, we sought to address both of these questions by performing neuroimaging in SCZ and HC with the agonist tracer [11C]-(+)-PHNO that is quantifiable in striatum and extrastriatal brain regions including midbrain.

28 SCZ and 29 HC were scanned at baseline and 3 hours after oral administration of 0.5 mg/kg d-amphetamine. Outcome measures were baseline binding (BP_ND) and the percent change following amphetamine (ΔBP_ND).

There were no significant group differences in any of the outcome measures, but we observed trend level lower BP_ND and ΔBP_ND in SCZ compared to HC. Post-hoc analysis showed this was mainly driven by dorsal striatum subregions. Associations between ΔBP_ND in midbrain and striatal regions were modest in both groups.

Our results are consistent with the prior study using an agonist tracer that did not observe greater ΔBP_ND in SCZ.