Dopamine dysfunction in psychosis

The dopamine hypothesis, proposing that aberrant dopamine signaling underlies psychotic symptoms, is one of the longest-standing neurochemical explanations for psychopathology. The efficacy of dopamine antagonists in treating psychotic symptoms provided initial support for the notion that excessive dopamine signaling could underlie the hallucinations and delusions observed in schizophrenia. Postmortem and animal work subsequently provided more mechanistic specificity. More recently in vivo neuroimaging has provided direct evidence of both cortical and subcortical alterations in dopamine signaling in psychotic disorders. This chapter reviews the evidence for dopamine dysfunction in psychotic disorders before considering how genetic and environmental factors may underlie this. We then examine how computational approaches have helped provide models explaining how molecular aberrations may be translated into symptoms. Finally, we consider what this means for treatment, both in terms of optimizing the use of current antipsychotics and for drugs currently in development.