Dopamine as the wind of the psychotic fire: new evidence from brain imaging studies.
Abnormalities of dopamine function in schizophrenia are suggested by the common antidopaminergic properties of antipsychotic medications. However, direct evidence of a hyperdopaminergic state in schizophrenia has been difficult to demonstrate, given the difficulty of measuring dopamine transmission in the living human brain. This situation is rapidly changing. Recent developments in positron emission tomography and single-photon emission tomographic techniques enabled measurement of acute fluctuation of synaptic dopamine in the vicinity of D2 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 subjects. Following a brief overview of these new brain imaging techniques, the 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 with dysregulation of dopamine transmission; (2) following amphetamine, hyperactivity of dopamine transmission is associated with activation of psychotic symptomatology; (3) this dysregulation of dopamine release is not a long-term consequence of previous neuroleptic treatment, and is detected in never-medicated patients experiencing a first episode of the illness; and (4) in contrast, this exaggerated response of the dopamine system to amphetamine exposure is not detected in patients studied during a period of illness stabilization, suggesting that the hyperdopaminergic state associated with schizophrenia fluctuates over time. In conclusion, a hyperdopaminergic state might be present in schizophrenia during the initial episode and subsequent relapses, but not during periods of remission. This finding has important consequences for the development of new treatment strategies for the remission phase.
Laruelle
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M
Department of Psychiatry, Columbia University College of Physicians and Surgeons, and New York State Psychiatric Institute, New York 10032, USA. laruelle@neuron.cpmc.columbia.edu
Abi-Dargham
A
A
D000818:Animals; D001549:Benzamides / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging* / Q000502:physiology / Q000503:physiopathology*; D004298:Dopamine / Q000502:physiology*; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D011759:Pyrrolidines / Q000493:pharmacokinetics; D011954:Receptors, Dopamine / Q000032:analysis / Q000378:metabolism; D012559:Schizophrenia / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D014055:Tomography, Emission-Computed; D015899:Tomography, Emission-Computed, Single-Photon
D001549:Benzamides; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D011954:Receptors, Dopamine; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D004298:Dopamine