Dopamine in the history of the schizophrenic brain: recent contributions of brain-imaging studies

Recent developments in positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging have enabled functional measurements of dopamine (DA) transmission at dopamine D(2) receptors in the living human brain. Studies using these techniques have demonstrated that, in schizophrenia, increased DA stimulation of striatal D(2) receptors is associated with the first episode of illness and subsequent episodes of illness exacerbation. While this dysregulation of DA function is not associated with the severity of positive symptoms per se, increased synaptic DA activity is predictive of good therapeutic response to antipsychotic treatment. Abnormalities of DA function were not detected during periods of illness remission. These findings are integrated into a clinical model proposing that, in schizophrenia, neurodevelopmental abnormalities of cortico-subcortical connectivity result in a vulnerability of the mesolimbic DA system to the development of a process of endogenous sensitization, and that the resulting sustained hyperstimulation of D(2) receptors induces neuroplastic changes within corticostriatal-thalamocortical loops, perturbing information processing and underlying the psychotic experience.