[The dopamine hypothesis of schizophrenia. New findings for an old theory]

The dopamine hypothesis of schizophrenia was based on the neuroleptical blockade of central dopamine D2 receptors. Brain imaging studies, however, generally failed to demonstrate a significant increase in central D2 receptors among schizophrenic patients. Using a novel approach, the group of Laruelle and Abi-Dargham was now able to demonstrate that schizophrenic patients have increased synaptic dopamine concentrations in the striatum. Endogenous dopamine competes with a radioligand for binding at dopamine D2 receptors; compared to healthy control subjects, blockade of dopamine production in neuroleptic-naive schizophrenic patients induced a significantly higher increase in D2 binding of the infused radioligand, indicating higher endogenous synaptic dopamine. A similar increase in D2 binding was also observed in drug-free schizophrenics who had previously been treated with neuroleptics; these patients also showed an increased density of striatal D2 receptors, most likely due to counteradaptive upregulation of D2 receptors during neuroleptic medication. The Columbia study provides an important indication of hyperdopaminergic function in schizophrenia.