Effects of clozapine and thiothixene on glucose metabolic rate in schizophrenia.

Twelve patients with schizophrenia received positron emission tomography scans with 18F-deoxyglucose before and after 4 to 6 weeks of treatment with clozapine or thiothixene. Both stereotaxic and magnetic resonance image template methods were used to position regions of interest for metabolic rate analysis. Clozapine increased and thiothixene decreased metabolic rates in the basal ganglia; these effects were most marked on the right side. Within the basal ganglia, a superior to inferior gradient in drug effect was found for thiothixene but not clozapine. This gradient resembled in some respects observations on regional differences in D2 receptors in human autoradiography. Baseline metabolic rates also predicted clinical medication response, with right inferior caudate metabolic rates differentiating clozapine and thiothixene responders. Larger sample studies are needed to replicate and extend these initial findings.

Predicting the posttreatment depressive state of an alcoholic patient.

Seventy-eight patients admitted to an alcohol treatment program were studied to identify variables capable of forecasting a patient's posttreatment depressive state. Factor analysis reduced a large number of items to 12 factors. Pearson correlations showed that Factor VII--Physical and Neurological Complaints and the pretreatment depressive state were both significantly (p = .002) correlated to the posttreatment depressive state. Multiple regression yielded a significant equation (p = .001) confirming that an alcoholic patient who has a high level of pretreatment depression and physical/neurological complaints, and who exhibits little or no irritability or agitation will tend to sustain a high level of posttreatment depression.

EEG alpha photic driving abnormalities in chronic schizophrenia.

Periodic photic stimuli across the entire electroencephalographic (EEG) frequency range were used in an attempt to assess EEG functional differences between chronic schizophrenic patients and control subjects. The EEG responses to these photic stimuli were significantly attenuated in the schizophrenic patients, specifically at the frequencies within the EEG alpha range. The schizophrenic patients also showed an alpha range attenuation in the "no stimulus" EEG alpha measure, such that there was a significant correlation across subjects between the "stimulus" and "no stimulus" EEG alpha range abnormalities. These abnormalities are discussed with reference to possible dysfunctional thalamic mechanisms involved in the pacing of EEG alpha activity and the gating of information through the cerebral cortex.

Positron emission tomography of the cerebellum in autism.

On the basis of neurological evidence that autistic patients have fewer Purkinje and granule cells in the cerebellum as well as vermal cerebellar hypoplasia, the authors tested the hypothesis that autistic patients have cerebellar hypofunctioning. They used positron emission tomography of the cerebellum with 18F-labeled 2-deoxyglucose to study seven autistic patients and eight age-matched control subjects. The results showed no significant difference in mean cerebellar glucose metabolism between the two groups, but all mean glucose rates of the autistic patients were either equal to or greater than those of the control subjects. The implications of these findings are discussed.

High potency neuroleptics and violence in schizophrenics.

In a controlled study, inpatient violence was measured during placebo, high-potency (haloperidol) and low-potency (chlorpromazine or clozapine) neuroleptics. Some patients had a marked increase in violent behavior with the moderately high-dose haloperidol, but not with low-potency neuroleptics. The authors discuss reasons for the increased violence with haloperidol, including akathisia and drug-induced behavioral toxicity.

Exacerbation of psychosis after discontinuation of carbamazepine treatment.

Carbamazepine alone or carbamazepine plus neuroleptic was administered to 20 chronic schizophrenic patients. Upon abrupt discontinuation two of the 20 patients had exacerbations of their psychoses characterized by paranoia, hostility, and agitation. The authors discuss the possibility of a carbamazepine withdrawal syndrome.

Neuroleptic-induced hypothermia associated with amelioration of psychosis in schizophrenia.

Body temperature is a regulatory function of the hypothalamus. Recently, DeMet et al. (Society for Neuroscience Abstracts Vol 12, 1986) reported that apomorphine stimulation of dopamine autoreceptors caused a significant decrease in metabolic rate in the posterior heat-conserving area of the hypothalamus. The logical hypothesis to follow is that apomorphine administration should induce a decrement in body temperature; this in fact was demonstrated by Cutler et al. (Commun Psychopharmacol 3:375-382, 1979) in humans. It is well known that neuroleptics also disrupt thermoregulation (Clark: Neurosci Biobehav Rev 3:179-231, 1979) and affect dopamine autoreceptors. Therefore, eight chronic treatment-resistant schizophrenics underwent a 6-week single-blind trial of haloperidol and then a subsequent 6-week double-blind trial of clozapine. Both haloperidol and clozapine significantly lowered oral body temperatures relative to baseline washout temperatures. More interestingly, clozapine relative to haloperidol was found to induce a greater decrement in body temperature and was associated with greater clinical improvement. Possible confounding variables are discussed, as is the possible neurochemical basis for the amelioration of psychosis associated with hypothermia.