Dopamine as the wind of the psychotic fire: new evidence from brain imaging studies

Abnormalities of dopamine function in schizophrenia are suggested by the co mmon antidopaminergic properties of antipsychotic medications. However, dir ect evidence of a hyperdopaminergic state in schizophrenia has been difficu lt to demonstrate, given the difficulty of measuring dopamine transmission in the living human. brain. This situation is rapidly changing. Recent deve lopments in positron emission tomography and single-photon emission tomogra phic techniques enabled measurement of acute fluctuation of synaptic dopami ne in. the vicinity of D-2 receptors. Using this technique, we, and others, measured the increase in dopamine transmission following acute amphetamine challenge in untreated patients with schizophrenia and matched healthy sub jects. Following a brief overview of these new brain imaging techniques, th e main results derived with this method in patients with schizophrenia are described: (1) amphetamine-induced dopamine release is elevated in patients with schizophrenia, supporting the idea that schizophrenia is associated w ith dysregulation of dopamine transmission; (2) following amphetamine, hype ractivity of dopamine transmission is associated with activation of psychot ic symptomatology; (3) this dysregulation of dopamine release is not a long -term consequence of previous neuroleptic treatment, and is detected in nev er-medicated patients experiencing a first episode of the illness; and (4) in contrast, this exaggerated response of the dopamine system to amphetamin e exposure is not detected in patients studied during a period of illness s tabilization, suggesting that the hyperdopaminergic state associated with s chizophrenia fluctuates over time. In conclusion, a hyperdopaminergic state might be present in schizophrenia during the initial episode and subsequen t relapses, but not during periods of remission. This finding has important consequences for the development of new treatment, strategies for the remi ssion phase.