Aberrant judgmental pattern of schizophrenic patients in weight discrimination.

Sixteen chronic schizophrenics and 16 normal controls were tested on a weight discrimination task in various categories and hand conditions. Schizophrenics made significantly more errors than normals when the 'equal' category was included, whereas schizophrenics' performance could approximate the normals' discriminations when the 'equal' category was excluded. In the former condition, the more inaccurate performance of schizophrenics was ascribed to the selective increase in the errors by the 'equal' judgments, which was not due to an increase in 'doubtful' judgments. These findings were assumed to reflect schizophrenics' preference to equal judgments, which seemed to be their fundamental cognitive attitude, because the same tendency was found on the various discrimination tasks of other sensory modalities. Furthermore, the present results supported neither left hemisphere dysfunction nor interhemispheric transfer deficit in schizophrenia, because schizophrenics failed to show consistently more errors in the right hand and the bimanual conditions.

Mapping epileptic foci by the dipole tracing method in a brain tumor patient with olfactory seizures: comparison with intraoperative electrocorticograms.

We estimated the position of the epileptic foci in a case of brain tumor with olfactory seizures using the Dipole Tracing Method (DTM) and compared the results with electrocorticograms (ECoGs) recorded during surgical resection. The case was a 24-year-old male. Electroencephalograms (EEG) showed frequent focal spikes in the right temporal area. Magnetic resonance imaging revealed a tumor in the right hippocampus region. We analyzed the spikes using DTM with a CDT-1000 EEG analyzer. The locations of two independent foci were analyzed; one was thought to be in the right hippocampus and the other in the right superior temporal gyrus. When the ECoG was taken, the results were in very close correlation with those of DTM, demonstrating the accuracy of DTM in the estimation of the location of epileptic foci in epileptic seizures with brain lesions.

Circadian variation in R-THBP-induced enhancement of the ambulation-increasing effect of methamphetamine on mice.

6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-THBP), a co-factor for tyrosine hydroxylase and tryptophan hydroxylase, induces the enhancement of ambulation-increasing effect of methamphetamine on mice. In this study, we investigated the circadian variation in the interaction between R-THBP and methamphetamine by changing the time-of-day of both methamphetamine administration and pretreatment with R-THBP. The mouse's ambulatory activity was measured by a tilting-type activity cage for 4 hr. In the daytime, but not in the nighttime, the ambulation-increasing effect of methamphetamine (1 and 2 mg/kg, s.c.) was significantly enhanced by the pretreatment with R-THBP (100 mg/kg, s.c., 2 or 6 hr before). These data indicate the possibility that peripherally administered R-THBP increases the biosynthesis of catecholamine especially in the daytime.

Chronic methamphetamine intoxication model of schizophrenia in animals.

The chronic methamphetamine (MAP) intoxication model of schizophrenia in animals is outlined. The idea originated from the clinical and neurochemical similarities between MAP psychosis and schizophrenia that were found during the decade immediately after World War II when MAP abuse occurred in epidemic proportions in Japan. The chronic intoxication model is produced by daily injections of a small dose of MAP into animals for several weeks or months. Behavioral studies with various species of animals from guinea pigs to monkeys produced essentially the same disorders as those observed in human abusers. Specifically, monkeys manifest psychotic behaviors, which appear to result from perceptual-cognitive disturbances, as well as enduring autistic behavior disorders that resemble the defect symptoms in chronic schizophrenia. Furthermore, the psychotic behaviors were found to have a high relapse liability; they recurred readily after the readministration of the drug or under nonspecific stress conditions. The difference and relationship between the chronic MAP intoxication model and the amphetamine stereotypy (acute intoxication) model are discussed.

[Characteristics of antagonism between ceruletide and various central-acting drugs: investigation by means of ambulatory activity in mice].

Behavioral characteristics of ceruletide, a cholecystokinin-like decapeptide, were investigated by means of ambulatory activity in mice. Ceruletide at 100 and 300 micrograms/kg, i.p. slightly but significantly decreased the mouse's activity for 20 min. Therefore, 100 micrograms/kg of ceruletide was used in the experiment of combined administration with the central-acting drugs. Ceruletide reduced the increased activity which was produced by methamphetamine (2 mg/kg, s.c.), ephedrine (80 mg/kg, i.p.), methylphenidate (4 mg/kg, s.c.), cocaine (20 mg/kg, s.c.), mazindol (2.5 mg/kg, s.c.), apomorphine (0.5 mg/kg, s.c.), bromocriptine (8 mg/kg, i.p.), scopolamine (0.5 mg/kg, s.c.), caffeine (10 mg/kg, s.c.) and morphine (20 mg/kg, s.c.) with different potencies and durations. The mice that had experienced ceruletide at 3 micrograms/kg for 5 times at intervals of 3-4 days demonstrated a significant increase in the sensitivity to methamphetamine, although the same treatment with 10-300 micrograms/kg of ceruletide was without effect. On the other hand, when 3-300 micrograms/kg of ceruletide was combined with 2 mg/kg of methamphetamine, the development of reverse tolerance to the ambulation-increasing effect of methamphetamine was inhibited dependently on the doses of ceruletide. However, the reverse tolerance to methamphetamine once established was scarcely modified by ceruletide when it was administered afterwards.

An epidemiological study of tics.

We devised a questionnaire for estimation of each tic, and used a two-step investigation procedure, first by a parent questionnaire with 1,218 responses and second by a confirmatory telephone interview for 197 positive responses. The average estimated values were 11.3% for boys and 5.2% for girls. The prevalences were--blinking: 4.2%, head-jerking: 1.6%, shrugging: 1.2%, mouth-twitching: 0.6%, face-distortion: 0.5%, mouth-opening: 0%, throat-clearing: 2.7%, sniffing: 0.6%, and vocalization: 0.2%. According to the criteria in DSM-III-R, 5.1% of 1,218 had TTD, 2.2% had CMVTD, and 0.5% had Tourette disorder.

Schizophrenic disorders and HLA-DR antigens.

HLA-A, -B, and -DR antigens, including supertypic specificities (MT antigens), were studied in Japanese schizophrenic patients. Although frequencies of HLA-A, -B, and MT antigens did not differ significantly between the schizophrenic patients and controls, the frequency of DRw8 in DR locus showed a statistically significant increase in the patients. The authors conclude that DRw8 is a genetic marker of susceptibility to schizophrenia. Inconsistencies in previous reports of antigens could be resolved by examination of the DR locus.

Frequency of criteria-defined borderline patients among the first-visit patients at a psychiatric clinic.

Five trained psychiatrists evaluated 330 first-visit patients aged from 12 to 30 at a psychiatric outpatient facility using the DSM-III criteria (Axis-I and Axis-II). Seven cases were diagnosed as definite Borderline Personality Disorder and six cases as definite Schizotypal Personality Disorder. Hence, we had a total of 13 criteria-defined borderline patients (3.9%). Discussions were held on some methodological problems involved in collecting information and making diagnostic judgments.

Mathematical approaches to the evaluation of the flux of gamma-aminobutyrate in brain tissue in vitro.

In the preceding paper (Balázs, Machiyama, Hammond, Julian & Richter, 1970) the flux of gamma-aminobutyrate (GABA) was found, in guinea-pig brain-cortex slices incubated in glucose-saline medium, to represent about 10% of the total tricarboxylic acid cycle flux, as opposed to other estimates, which are as high as 40%. However, the latter value was deduced from experimental results by methods that made no allowance for the metabolic compartmentation of glutamate: a mathematical investigation was therefore undertaken to show that this omission necessarily leads to an overestimation of GABA flux. The magnitude of this over-estimation was shown by computer simulation methods to be of such an order as to bring the corrected value into agreement with the lower value. Computer simulation methods were also used to evaluate the GABA flux from the experimental results presented by Balázs et al. (1970) and a value of 0.0315mumol/min per g wet wt. was obtained. This value was also shown to be consistent, in the simulated system, with the experimentally observed time-courses for the radioactivity and quantity of aspartate. Since there is now evidence that GABA is itself a metabolically compartmented intermediate this possibility was considered mathematically, but it was found that in this case the assumption of compartmentation had little effect upon the value of GABA flux deduced on the basis of GABA homogeneity.

The operation of the gamma-aminobutyrate bypath of the tricarboxylic acid cycle in brain tissue in vitro.

1. Cerebral-cortex slices prelabelled with gamma-amino[1-(14)C]butyrate (GABA) were incubated in a glucose-saline medium. After the initial rapid uptake there was no appreciable re-entry of (14)C into the GABA pool, either from the medium or from labelled metabolites formed in the tissue. The kinetic constants of GABA metabolism were determined by computer simulation of the experimental results by using mathematical procedures. The GABA flux was estimated to be 0.03mumol per min/g, or about 8% of the total flux through the tricarboxylic acid cycle. It was found that the assumption of compartmentation did not greatly affect the estimates of the GABA flux. 2. The time-course of incorporation of (14)C into amino acids associated with the tricarboxylic acid cycle was followed with [1-(14)C]GABA and [U-(14)C]-glucose as labelled substrates. The results were consistent with the utilization of GABA via succinate. This was confirmed by determining the position of (14)C in the carbon skeletons of aspartate and glutamate formed after the oxidation of [1-(14)C]GABA. These results also indicated that under the experimental conditions the reversal of reactions catalysed by alpha-oxoglutarate dehydrogenase and glutamate decarboxylase respectively was negligible. The conversion of [(14)C]GABA into gamma-hydroxybutyrate was probably also of minor importance, but decarboxylation of oxaloacetate did occur at a relatively slow rate. 3. When [1-(14)C]GABA was the labelled substrate there was evidence of a metabolic compartmentation of glutamate since, even before the peak of the incorporation of (14)C into glutamate had been reached, the glutamine/glutamate specific-radioactivity ratio was greater than unity. When [U-(14)C]glucose was oxidized this ratio was less than unity. The heterogeneity of the glutamate pool was indicated also by the relatively high specific radioactivity of GABA, which was comparable with that of aspartate during the whole incubation time (40min). The rates of equilibration of labelled amino acids between slice and medium gave evidence that the permeability properties of the glutamate compartments labelled as a result of oxidation of [1-(14)C]GABA were different from those labelled by the metabolism of [(14)C]glucose. The results showed therefore that in brain tissue incubated under the conditions used, the organization underlying metabolic compartmentation was preserved. The observed concentration ratios of amino acids between tissue and medium were also similar to those obtaining in vivo. These ratios decreased in the order: GABA>acidic acids>neutral amino acids>glutamine. 4. The approximate pool sizes of the amino acids in the different metabolic compartments were calculated. The glutamate content of the pool responsible for most of the labelling of glutamine during oxidation of [1-(14)C]GABA was estimated to be not more than 30% of the total tissue glutamate. The GABA content of the ;transmitter pool' was estimated to be 25-30% of the total GABA in the tissue. The structural correlates of metabolic compartmentation were considered.

The metabolism of gamma-aminobutyrate and glucose in potassium ion-stimulated brain tissue in vitro.

1. The metabolism of gamma-aminobutyrate (GABA) was investigated in cerebral-cortex slices incubated in glucose-saline medium with [1-(14)C]GABA and [U-(14)C]-glucose as labelled substrates. 2. A rapid release of GABA from the tissue, amounting to 25-30% of the total, was observed on addition of 66m-equiv. of K(+)/1 to the medium; the liberation of other amino acids was relatively small. The effect was apparently specific for K(+); GABA was not released on addition of equivalent amounts of Na(+) or on increasing the respiration rate with 10mm-ammonium chloride. The results show that GABA behaves like the transmitter compounds (acetylcholine, catecholamines) on K(+) stimulation, and therefore now satisfies certain of the criteria required for a transmitter in mammalian brain. 3. The release of GABA from the tissue on addition of K(+) was followed by a slow re-uptake. The rate of uptake of GABA in a medium containing 5.9m-equiv. of K(+)/1 was more than four times that in a medium containing 66m-equiv. of K(+)/1. 4. The concentration of GABA in brain tissue incubated for 1h in a medium containing 66m-equiv. of K(+)/1 was about 50% higher than that observed under normal conditions. 5. There was evidence that exogenous [(14)C]GABA mixed with the endogenous pool(s), since the proportion of the total GABA released on K(+) stimulation was the same, and the specific radioactivity of the liberated GABA was close to that remaining in the tissue, whether the GABA was labelled by [1-(14)C]GABA from the medium or generated in the tissue from [(14)C]glucose. 6. On the basis of these findings and the observations outlined in the preceding papers it was possible to calculate the kinetic constants of GABA metabolism by computer simulation of the results. K(+) stimulation led to a 2.5-fold increase in the flux through the tricarboxylic acid cycle, whereas the flux in the GABA bypath was little affected; as a result the flux through the GABA bypath, which under normal conditions was 8% of that through the tricarboxylic acid cycle, decreased to 3-5%. 7. The metabolism of glutamine was greatly affected by K(+)-stimulation. The ratio of the concentration of glutamine in the slices to that in the medium, which under normal conditions was the smallest among the amino acids investigated, increased from about 17 to 63 in 1h. This effect was attributable partly to an uptake of glutamine from the medium (1.8mumol/h per g) and partly to a net increase in the total amount of glutamine (2.6mumol/h per g). At 1h after the addition of K(+) the net gain of glutamine could be accounted for by the decrease of glutamate. 8. Metabolic compartmentation was evident when brain-cortex slices were incubated in glucose-saline medium and the labelled substrate was [(14)C]GABA, since the specific radioactivity of glutamine exceeded that of glutamate. On addition of K(+) the signs of metabolic compartmentation promptly disappeared: this effect was apparently associated with an increase in the permeability of the compartments containing labelled metabolites derived from [(14)C]GABA. The change in the permeability, however, did not affect all the compartments; when the labelled substrate was [(14)C]glucose the equilibration of labelled amino acids between tissue and medium was similar under normal conditions and in the presence of high concentrations of K(+). 9. The metabolism of [(14)C]glucose was followed by measuring oxygen uptake, respiratory (14)CO(2), and incorporation of (14)C into amino acids. The results showed that K(+) stimulation increased the flux of glucose carbon, both in the glycolytic pathway and in the tricarboxylic acid cycle.