From the cover: increased baseline occupancy
of D2 receptors by dopamine in schizophrenia

by
Abi-Dargham A, Rodenhiser J, Printz D, Zea-Ponce Y,
Gil R, Kegeles LS, Weiss R, Cooper TB,
Mann JJ, Van Heertum RL, Gorman JM, Laruelle M
Departments of Psychiatry and Radiology,
Columbia University College of Physicians and Surgeons,
New York, NY 10032, USA.
aadar@neuron.cpmc.columbia.edu
Proc Natl Acad Sci U S A 2000 Jul 5;97(14):8104-9


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.
D2
Dopamine
Glutamate
Quetiapine
Schizophrenia
Antipsychotics
NMDA antagonists
New antipsychotics
Psychotic depression
Atypical antipsychotics
Bipolars v schizophrenics
Schizophrenia: new drugs
Schizophrenia: neuroleptics
Serotonin hypothesis of schizophrenia
Dopamine hypothesis of schizophrenia
Partial dopamine agonists for psychosis
Atypicals versus traditional antipsychotics


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