The dopamine dysfunction in schizophrenia revisited: New insights into topography and course

Schizophrenia has long been associated with an imbalance in dopamine (DA) neurotransmission, and brain imaging has played an important role in advancing our knowledge and providing evidence for the dopaminergic abnormalities. This chapter reviews the evidence for DA dysfunction in different brain regions in schizophrenia, in particular striatal, extrastriatal, and prefrontal regions, with emphasis on recently published findings. As opposed to the traditional view that most striatal dopaminergic excess, associated with the positive symptoms of schizophrenia, involves the dopaminergic mesolimbic pathway, recent evidence points to the nigrostriatal pathway as the area of highest dysregulation. Furthermore, evidence from translational research suggests that dopaminergic excess may be present in the prodromal phase, and may by itself, as suggested by the phenotype observed in transgenic mice with developmental overexpression of dorso-striatal D₂ receptors, be an early pathogenic condition, leading to irreversible cortical dysfunction.