Increased baseline occupancy of D ₂ receptors by dopamine in schizophrenia

TLDR

The classical dopamine hypothesis of schizophrenia proposes that hyperactive dopaminergic transmission at D₂ receptors underlies the disorder. In vivo striatal D₂ receptor occupancy was quantified in 18 untreated patients and 18 matched controls by comparing receptor availability before and during pharmacologically induced acute dopamine depletion. Acute dopamine depletion produced a larger increase in striatal D₂ receptor availability in schizophrenia patients (19 ± 11 %) than controls (9 ± 7 %, P = 0.003), with heightened occupancy observed in both first‑episode and chronic patients and correlating with better antipsychotic response, thereby confirming increased dopamine stimulation of D₂ receptors in schizophrenia.

Abstract

The classical dopamine hypothesis of schizophrenia postulates a hyperactivity of dopaminergic transmission at the D 2 receptor. We measured in vivo occupancy of striatal D 2 receptors by dopamine in 18 untreated patients with schizophrenia and 18 matched controls, by comparing D 2 receptor availability before and during pharmacologically induced acute dopamine depletion. Acute depletion of intrasynaptic dopamine resulted in a larger increase in D 2 receptor availability in patients with schizophrenia (19% ± 11%) compared with control subjects (9% ± 7%, P = 0.003). The increased occupancy of D 2 receptors by dopamine occurred both in first-episode neuroleptic-naive patients and in previously treated chronic patients experiencing an episode of illness exacerbation. In addition, elevated synaptic dopamine was predictive of good treatment response of positive symptoms to antipsychotic drugs. This finding provides direct evidence of increased stimulation of D 2 receptors by dopamine in schizophrenia, consistent with increased phasic activity of dopaminergic neurons.