Increased baseline occupancy of D2 receptors by dopamine in schizophrenia

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 availabil...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2000-07, Vol.97 (14), p.8104-8109
Main Authors: Abi-Dargham, A, Rodenhiser, J, Printz, D, Zea-Ponce, Y, Gil, R, Kegeles, L S, Weiss, R, Cooper, T B, Mann, J J, Van Heertum, R L, Gorman, J M, Laruelle, M
Format: Article
Language:English
Subjects:
Adult
alpha-Methyltyrosine - pharmacology
Antipsychotic Agents - therapeutic use
Biological Sciences
Chronic Disease
Corpus Striatum - metabolism
Dopamine - metabolism
Female
Humans
Male
Neurology
Neurons
Predictive Value of Tests
Receptors, Dopamine D2 - metabolism
Recurrence
Schizophrenia
Schizophrenia - drug therapy
Schizophrenia - metabolism
Tyrosine 3-Monooxygenase - antagonists & inhibitors
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.97.14.8104