Dopamine hypothesis of schizophrenia. New findings support a traditional theory

The dopamine hypothesis of schizophrenia was based on the neuroleptical blockade of central dopamine D-2 receptors. Brain imaging studies, however, generally failed to demonstrate a significant increase in central D-2 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 D-2 receptors; compared to healthy control subjects, blockade of dopamine production in neuroleptic-naive schizophrenic patients induced a significantly higher increase in D-2 binding of the infused radioligand,indicating higher endogenous synaptic dopamine. A similar increase in D-2 binding was also observed in drug-free schizophrenics who had previously been treated with neuroleptics;these patients also showed an increased density of striatal D-2 receptors, most likely due to counteradaptive upregulation of D-2 receptors during neuroleptic medication. The Columbia study provides an important indication of hyper-dopaminergic function in schizophrenia.