Increased baseline occupancy of D2 receptors by dopamine 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.
