Cortical effects of quetiapine in first-episode schizophrenia: a preliminary functional magnetic resonance imaging study.

BACKGROUND: Quetiapine improves both psychotic symptoms and cognitive function in schizophrenia. The neural basis of these actions is poorly understood. METHODS: Three subject groups underwent a single functional magnetic resonance imaging (fMRI) session: drug-naive (n = 7) and quetiapine-treated samples of patients with schizophrenia (n = 8) and a healthy control group (n = 8). The fMRI session included an overt verbal fluency task and a passive auditory stimulation task. RESULTS: In the verbal fluency task, there was significantly increased activation in the left inferior frontal cortex in the quetiapine-treated patients and the healthy control sample compared with the drug-naive sample. During auditory stimulation, the healthy control group and stably treated group produced significantly greater activation in the superior temporal gyrus than the drug-naive sample. CONCLUSIONS: Quetiapine treatment is associated with altered blood oxygen level-dependent responses in both the prefrontal and temporal cortex that cannot be accounted for by improved task performance subsequent to drug treatment.

Is regionally selective D2/D3 dopamine occupancy sufficient for atypical antipsychotic effect? an in vivo quantitative [123I]epidepride SPET study of amisulpride-treated patients.

OBJECTIVE: Atypical antipsychotic drug treatment is clinically effective with a low risk of extrapyramidal symptoms. Explanations for the mechanism underlying this beneficial therapeutic profile of atypical over typical antipsychotic agents include 1) simultaneous antagonism of dopamine D(2) and serotonin 5-HT(2A) receptors or 2) selective action at limbic cortical dopamine D(2)-like receptors with modest striatal D(2) receptor occupancy. Amisulpride is an atypical antipsychotic drug with selective affinity for D(2)/D(3) dopamine receptors and provides a useful pharmacological model for examining these hypotheses. The authors' goal was to evaluate whether treatment with amisulpride results in "limbic selective" D(2)/D(3) receptor blockade in vivo. METHOD: Five hours of dynamic single photon emission tomography data were acquired after injection of [(123)I]epidepride (approximately 150 MBq). Kinetic modeling was performed by using the simplified reference region model to obtain binding potential values. Estimates of receptor occupancy were made relative to a healthy volunteer comparison group (N=6). RESULTS: Eight amisulpride-treated patients (mean dose=406 mg/day) showed moderate levels of D(2)/D(3) receptor occupancy in the striatum (56%), and significantly higher levels were seen in the thalamus (78%) and temporal cortex (82%). CONCLUSIONS: Treatment with amisulpride results in a similar pattern of limbic cortical over striatal D(2)/D(3) receptor blockade to that of other atypical antipsychotic drugs. This finding suggests that modest striatal D(2) receptor occupancy and preferential occupancy of limbic cortical dopamine D(2)/D(3) receptors may be sufficient to explain the therapeutic efficacy and low extrapyramidal symptom profile of atypical antipsychotic drugs, without the need for 5-HT(2A) receptor antagonism.