The enduring centrality of dopamine in the pathophysiology of schizophrenia: in vivo evidence from the prodrome to the first psychotic episode

Dopamine has been thought to be central to the pathophysiology of schizophrenia for the last four decades. However, the last decade or so has seen a considerable advance in understanding of dopamine's role in the neurobiology of schizophrenia. This has been informed by advances in neuroimaging, preclinical models, and the study of the prodrome to schizophrenia. Studies using these approaches have identified that the major locus of dopaminergic dysfunction is presynaptic, characterized by elevated dopamine synthesis and release capacity. Moreover, this is seen in the prodrome to the illness, is linked to the symptoms, and increases with the onset of frank symptoms. It has also become clear that there is no marked alteration in dopamine transporter or D2/3 receptor availability in schizophrenia in general, and, similarly, there do not seem to be D2/3 receptor alterations in people at high clinical risk of psychosis. These findings highlight the enduring role of dopamine in the onset of schizophrenia. They suggest that presynaptic dopamine dysregulation underlies the onset of psychosis and are in line with an integrative model accounting for many of the genetic and environmental risk factors for schizophrenia.