PET study of dopamine D1 and D2 receptors in epilepsy and epileptic psychosis.

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Since the nineteenth century, psychiatrists have been interested in psychotic states in epileptic patients. The characteristics of schizophrenia-like psychosis of epilepsy(SLPE)were reported in the previous clinical description ; (a)schizophrenia-like psychosis is 6-12 times more likely to occur in epileptic patients than in the general population, (b)the onset of psychosis follows some 10-15 years after the onset of the epilepsy, and(c)the risk to occur the psychosis is highest for patients with temporal lobe epilepsy. To study the association between schizophrenia and SLPE, structural and functional neuroimaging techniques are increasingly indispensable. As regards neurochemical abnormalities of psychotic patients with epilepsy, reduced specific binding of Iodine-123 IBZM(dopamine D2 receptor antagonist)to strial D2 receptors have been demonstrated in the psychotic patients compared to those without psychosis. This result support to the "dopamine hypothesis" for schizophrenia. There … More is growing evidence that extrastriatal D2 receptors, in spite of their low density, have pathophysiological significance for schizophrenia. We used the CBA(computerized brain atlas)to explore the extrastriatal distribution of D2 receptors in 13 healthy subjects using[11C]FLB 457, a substituted benzamide with very high affinity for D2 and D3 receptors. The cerebral cortices showed lower levels with significant regional differences. Binding was highest in the temporal cortex and hippocampus followed by the anterior cingulate gyrus, and the parietal and frontal cortices, but was lowest in the occipital cortex. The use of CBA for analysis of[11C]FLB 457 binding makes it possible to build a normal database for the extrastriatal D2 receptors in the living human brain. Further, we aimed to examine the extrastriatal D2 receptors of patients with schizophrenia. Eleven drug-naive male patients with schizophrenia were examined with positron emission tomography using[11C]FLB 457. Comparison was made with 18 healthy controls. Region of interest analysis was performed using the reference tissue method and binding potential(BP)was used for the index of dopamine D2 receptor binding. The BP value was significantly lower in the anterior cingulate cortex about 12% in drug naive patients with schizophrenia than in normal controls. Alteration in D2 receptor function in the extrastriatal region may underlie the positive symptoms of schizophrenia. Finally, we examined a group of SLPE patients and compared them with a group of epileptic patients without psychosis and a normal data base. At the present, we have completed inspective evaluation of[11C]FLB457 PET images and have found no remarkable difference in the distribution of dopamine D2 receptors. Further analysis using sophisticated method such as pixel-by-pixel analysis is need to conclude. Less