Examining endogenous dopamine in treated schizophrenia using [¹¹C]-(+)-PHNO positron emission tomography: A pilot study

Background: Using positron emission tomography (PET) it is possible to estimate endogenous dopamine (DA) occupying D2/3 receptors (D2/3R) in the living human brain. Persons with schizophrenia (SZ) (previously medicated and naïve) have increased endogenous DA occupying D2/3R in the caudate. It is unknown whether currently medicated patients demonstrate increased DA levels at D2/3R. Moreover, DA levels have not been estimated in SZ using agonist radiotracers, which may offer a more sensitive quantification over antagonists.

Methods: Using the agonist radiotracer [(11)C]-(+)-PHNO, DA levels were estimated at D2/3R (ΔBP(ND)) in three patients with SZ (male, mean age=30±16). Patients were currently being treated long-term with Olanzapine (147±88 nmol/L). Results were compared to ten healthy controls (HCs).

Results: Medicated persons with SZ had greater ΔBP(ND) in the left caudate (U=2, Z=-2.20, p=.03) and right putamen (U=2, Z=-2.20, p=.03). No differences were observed in the ventral striatum or globus pallidus.

Conclusions: It is possible to estimate endogenous DA at D2/3R in SZ patients currently taking antipsychotics. Despite medication, patients continue to have increased endogenous DA at D2/3R. This lends more biological support to the clinical observation that relapses in symptoms can occur in the face of complete antipsychotic discontinuation. Future studies with larger samples are warranted.