Ferris N. Pitts

Affective disorder *: IV. Mania

Summary In this paper 31 patients with a diagnosis of manic depressive, manic are matched for age, sex and socioeconomic status with 31 patients with a diagnosis of manic depressive, depressed. The study shows that hospitalized manics contain a higher percentage of men than hospitalized depressives and the manics are hospitalized at an earlier age. It is also noted that the first symptoms are seen at an earlier age. There were no significant differences in the family histories of manics and depressives. Turning to the clinical picture of mania, cuphoria, overactivity and push of speech were seen in almost all patients studied. Objective confusion was seen in 18 of the 31 (58 per cent) patients. Eighteen of 24 patients (58 per cent), in whom information about depressive symptoms was recorded, reported a depression immediately preceding the onset of the mania. Special attention was given to those patients who exhibited schizophrenic symptomatology in their index admission. Seven patients with passivity feelings were personally interviewed approximately 2 years after their index admission. It was found that in none had classical schizophrenia with deterioration developed. Their cases histories are presented.

THE ENZYMIC MEASUREMENT OF γ ‐AMINOBUTYRIC‐α ‐OXOGLUTARIC TRANSAMINASE

PREVIOUS reports from this laboratory have detailed the fluorimetric measurement of glutamate decarboxylase (GDC) (LOWE, ROBINS and EYERMAN, 1958) and the enzymic fluorimetric measurement of y-aminobutyric acid (GABA) (HIRSCH and ROBINS, 1962) in 3-5 pg lyophilized sections of the layers of cerebellar and cerebral cortex. This report is of the development of a sensitive and specific fluorimetric enzymic assay for y-aminobutyric-cr-oxoglutaric transaminase (GABA-T) activity applicable to 0-2-2-0 pg sections of lyophilized neural tissue, and of the levels obtained in various neural regions in several mammalian species. This method demonstrates small, but appreciable, GABA-T rates in white matter, where it was previously reported as not present. The development of this method is one portion of a larger project to study the biochemistry and physiological significance of the GABA pathway in single cells of the nervous system. EXPERIMENTAL

Brain succinate semialdehyde dehydrogenase. I. Assay and distribution.

SUCCINATE semialdehyde dehydrogenase catalyses the terminal step of the y-aminobutyrate pathway which is of significance in mammals only in neural tissues because of the unique localization of the initial catalyst, glutamate decarboxylase AWAPARA, LANDUA, FUERST and SEALE, 1950). The y-aminobutyrate pathway provides both a probable oxidative shunt around a-oxoglutarate dehydrogenase (ROBERTS, 1956) and the source of the potent neural inhibitor y-aminobutyrate (BAZEMORE, ELLIOTT and FLOREY, 1956). An enzymic analytical method for y-aminobutyrate-a-oxoglutarate transaminase (PITTS, QUICK and ROBINS, 1965) is available and demonstrates rates supporting the results of in vivo and in vitro studies with labelled substrates which have demonstrated that as much as half of a-oxoglutarate in brain may be oxidized by the y-aminobutyrate pathway ( MCKHANN, ALBERS, SOKOLOFF, MICHELSEN and TOWER, 1960). ALBERS and SALVADOR (1 958) demonstrated succinate semialdehyde dehydrogenase activities in the range of 3 m-moles per kg protein per hr after 150-fold purification of a particulate fraction from monkey brain. This report is of the measurement of brain succinate semialdehyde dehydrogenase by means of the fluorescence of NADH. The analytical method is sensitive enough to allow assay of succinate semialdehyde dehydrogenase in as little as 0.05 pg freeze-dried brain. Maximal brain succinate semialdehyde dehydrogenase activities are in the range of those of the major metabolic pathways, and specific rates are detailed for various neural regions of several mammalian species. The purification, kinetics and protein characteristics of brain succinate semialdehyde dehydrogenase will be the subjects of subsequent reports.

BRAIN SUCCINATE SEMIALDEHYDE DEHYDROGENASE—II. CHANGES IN THE DEVELOPING RAT BRAIN

A METHOD for measurement of brain succinate semialdehyde dehydrogenase was reported (PITTS and QUICK, 1965) which is sensitive enough to allow assay of 0.01 pg freeze-dried brain samples. This method, based on the fluorescence of NADH, was highly reproducible over a wide range of brain concentrations. In freshly reconstituted freeze-dried whole brain homogenates, succinate semialdehyde dehydrogenase activities for adults of various species were: rat 2000, guinea pig 1400, mouse 1400, and rabbit 750-m-moles per kg dry wt. per hr. Succinate semialdehyde dehydrogenase rates for cerebellar layers, white tracts, and regions of spinal cord of rabbit and monkey were also reported. Brain succinate semialdehyde dehydrogenase has high substrate specificity (PITTS and QUICK, 1965); the nonspecific aldehyde dehydrogenase of brain probably does not oxidize succinate semialdehyde and has a maximal activity with other substrates less than 0.01 that of succinate semialdehyde dehydrogenase (ERVIN and DEITRICH, 1966). A systematic study of succinate semialdehyde dehydrogenase in developing rat brain is the subject of this report. The data include enzymic rates for whole brain and cerebellar layers at various ages. Whole brain succinate semialdehyde dehydrogenase rates were measured at every day of age from birth to 30 days, and less frequently thereafter until day 90. Succinate semialdehyde dehydrogenase was assayed in the layers of the developing rat cerebellum. The data are analysed statistically and correlated with development, dry wt., and total brain protein.