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The dopamine (DA) D₂ receptors exist in 2 states: a high-affinity state (D₂^high) that is linked to second messenger systems, responsible for functional effects, exhibits high affinity for agonists (e.g., DA), and a low-affinity state that is functionally inert exhibits lower affinity for agonists. The DA D₃ receptor subtype exhibits high agonist affinity, whereas the existence of the multiple affinity states is controversial. Preclinical studies in animal models of psychosis have shown a selective increase of D₂^high as the common factor in psychosis, and the D₃ receptor has been suggested to be involved in the pathophysiology of schizophrenia.

We studied D₂^high and D₃ in people at clinical high risk (CHR) for schizophrenia and in antipsychotic-naive patients with schizophrenia using the novel positron emission tomography radiotracer, [¹¹C]-(+)-PHNO. The binding potential nondisplaceable (BP_ND) was …