Evidence for reduced and dysregulated turnover of dopamine in schizophrenia

The dopamine (DA) hypothesis of schizophrenia proposes that schizophrenia is related to dopaminergic hyperactivity. To examine this hypothesis, this article reviews studies that have measured levels of DA and its metabolites in schizophrenic patients. From these studies, the following conclusions about schizophrenia emerge: (1) levels of DA and its metabolites can be highly variable; (2) DA turnover appears to be reduced in a subgroup of schizophrenic patients characterized as more chronic and treatment refractory, compared with normal controls; (3) DA turnover has been correlated positively with acute symptomatology and negatively with signs of chronic illness; and (4) central DA levels appear to be elevated. These conclusions support the author's hypothesis that DA turnover may be both reduced and dysregulated in schizophrenia. It is speculated that reduced turnover is primarily due to a deficiency in DA release and that dysregulation may result from the disruption of feedback mechanisms. Acute psychosis may be associated with a relative increase in the release of DA impinging on supersensitive postsynaptic receptors made so by chronic synaptic depletion of the transmitter.