Harry Freeman

The effects of daily administration of carphenazine on attention in the schizophrenic patient

SummaryChronic schizophrenic patients on daily administrations of carphenazine were clinically rated by two separate methods and measured by two types of performance tests. One was an attention test (CPT) and one a cognitive or associative test (DSST). Before medication the subjects performed poorly on the attention test but showed significant improvement during the course of medication. They showed no similar improvement on the cognitive test. Clinical improvement was also manifested and this correlated positively with improvement on the attention test. No such significant correlation existed between the DSST scores and the clinical ratings.The results of the study were discussed in light of the hypothesis that schizophrenic patients are hyperaroused. The fact that patients showed improvement on the CPT and not the DSST gave further evidence to support the hypothesis that phenothiazines have an effect on the selective areas of the brain and that these areas may be inherently related to the underlying factors in schizophrenia.

The effect of ethanol ingestion on serotonin-C14 metabolism in man.

Abstract Low doses of ethanol ingested prior to serotonin-C 14 in man significantly decreased formation of urinary 5-HIAA-C 14 . The decreased formation of 5-HIAA-C 14 was dependent upon the dose and time of administration of ethanol and was related to the blood alcohol level. It was suggested that ethanol increased NADH and decreased NAD such that 5-hydroxyindoleacetaldehyde-C 14 derived from the serotonin-C 14 was preferentially converted to 5-hydroxytryptophol-C 14 with a concomitant decrease in 5-HIAA-C 14 .

A HUMAN PLASMA FACTOR INDUCING BEHAVIORAL AND ELECTROPHYSIOLOGICAL CHANGES IN ANIMALS: II. CHANGES INDUCED IN ANIMALS *

The historical background and methods of preparation of biologically active plasma and serum protein extracts, including the procedure currently used to prepare the extracts used in our laboratory, have been presented in the previous paper. We wish now to discuss the biological effect produced by these substances in animals. Blood samples were supplied by acutely ill psychotics within three days after hospitalization and before diagnosis has been established or drug therapy begun, or from chronic schizophrenics not on drug therapy. Usually two psychotics and one nonpsychotic subject were bled a t the same time into ion exchange blood packs (Fenwal). After separation of the cells a t the Protein Foundation Laboratories, Jamaica Plain, Mass., simultaneous processing of the three plasmas was performed by the aforementioned techniques. Using the Winter and Flataker rat climbing test‘ estimates of biological activity were made on samples equivalent to 5 ml. of original plasma injected intraperitoneally into 5 rats each unless otherwise stated. Values for the degree of impairment of climbing ability are listed as climbing-time delay CTD in units termed minute-seconds. Statistical significance of the results was evaluated by an analysis of variance. In our initial experiments we examined the effect produced in trained rats by injections of serum and plasma from nonpsychotic subjects and schizophrenic patients (TABLE 1) . Each sample was injected into 3 to 5 rats depending on the amount available. The first experiment with serum showed no elevation in CTD produced by 1-ml. samples from 19 schizophrenic patients over effects produced by equivalent samples from nonpsychotic subjects. The mean change of the CTD value produced by the psychotics’ serum from the nonpsychotics’ serum was -5.0 mine-sec., an effect that is not significant. Repetition of this experiment a t a later date compared effects on rat CTD produced by sera from 13 schizophrenics with an equal number of nonpsychotics’ samples. No consistent differences between the 2 groups were observed. Plasma samples, however, produced effects which clearly differentiated between the two groups. Whole plasma samples were compared under conditions similar to those employed using serum samples. In this series, usually 2 schizophrenics’ and 1 nonpsychotic’s plasma were tested simultaneously. Injections of plasma from schizophrenics increased the climbing time delay scores of the rats more than 100 per cent over the delay produced by the plasma from the non-psychotic persons. This difference is highly significant (p = <0.001). * The work described in this study was supported in part by Grant MY-2967 of the National Institutes of Health, Public Health Service, Bethesda, Md., by the Ford Foundation, New York, N.Y., and by the Scottish Rite Fund for Dementia Praecox Research, through the National Association for Mental Health, New York, N.Y.

Studies of Plasma Protein Factors that may be Involved in Psychoses

During the last five years work has been reported from four independent groups indicating the existence of a protein factor in human plasma that may be involved in psychotic behavior. In contrast to many investigations, these studies refreshingly tend to confirm each other.

A short‐acting monoamine oxidase inhibitor, Ro 5‐1025

A clinical, physiologic, and biochemical study was made of Ro 5‐1025, a short‐acting MAO inhibitor. Ro 5‐1025 did not show antidepressant properties and did not lower blood pressure at 20 to 60 mg. per day. The radioactioe serotonin test for MAO showed that Ro 5‐1025 was a weak MAO inhibitor without accumulative effects at the doses indicated.