[Monoamines (2): reduced monoamine levels in senile dementia. Relation between monoamine levels, age and grade of dementia].
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Biomedical subjects
Publications and source records attributed to B E Roos.
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Four patients with chronic schizophrenia of stationary character were studied in order to titrate the lowest dose of thioridazine necessary for symptomatic control when the drug is given in combination with the inhibitor of catecholamine synthesis, metyrosine. The study showed 15% to 50% of the pretrial dose level of thioridazine hydrochloride was effective. In the present trial, the 779704 combination was maintained without any alterations in dosage for six months, and the therapeutic effect persisted unchanged. This treatment period was terminated by a double-blind crossover design, and the activity of metyrosine was corroborated in all cases. Plasma drug concentrations and cerebrospinal fluid amine metabolites were measured. The data indicate that schizophrenic symptoms can be profoundly influenced by changes in catecholamine synthesis. Catecholamine-carrying neurons thus seem to be fundamentally involved in those brain functions that are disturbed in schizophrenia. The clinical usefulness of metyrosine in combination with neuroleptic agents deserves more extensive investigation.
Different nuclei and regions of the brain from patients who had committed suicide and from controls were analysed for their content of monoamine and monoamine metabolites. There was a post mortem breakdown of 5-hydroxyindoleacetic acid (5-HIAA) which could be correlated to the time elapsed between the occurrence of death and autopsy. Homovanillic acid (HVA) and the monoamines did not decrease post mortem during the time observed (6-148 hours). There was no significant correlation between age and chemical variables in this investigation. There were no significant group differences between suicides and controls concerning dopamine, noradrenaline, 5-hydroxytryptamine, and HVA, 5-HIAA levels were significantly lower in the suicide group in six out of eight parts of the brain investigated. It was, however, also demonstrated that there was a longer time elapse between the occurrence of death and autopsy in the suicide group. The suicides came on average 48 hours later to autopsy than the controls. As there was a post mortem decrease of 5-HIAA, this time variable had to be kept constant when group differences were analysed. When the influence of this time variable was eliminated there were no longer any differences between suicides and controls. According to this investigation, there seem to be no differences in levels of monoamines and their metabolites between suicides and controls.
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Twenty-three rabbits were exposed with 60Co irradiation over the skull. Nineteen of the animals received 29.6 Gy over the right hemisphere and 4 animals received 20 Gy over both hemispheres. Six months after the exposure the cncentrations of 5-hydroxyindolacetic acid (5-HIAA) and homovanillic acid (HVA) in seven different brain regions were assayed. No significant differences in the levels of these monoamine metabolites as compared to nonirradiated control animals were found. In contrast to discrete biochemical changes, a relatively marked parenchymal destruction was demonstrated by means of light microscopy, microangiography and scanning electron microscopy of the vessels, which exhibited telangiectases, fibrinoid necroses and thrombosis due to the late effects of irradiation.
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Newborn mice were inoculated with attenuated Coxsackie type B4 virus. Three-to-4-day old mice were infected with yellow fever virus vaccine. A number of mice survived the acute infections. Some of these demonstrated residual neurological symptoms, some showed recovery from symptoms while others survived the infection without revealing symptoms of disease. Determinations of dopamine, noradrenaline, 5-hydroxytryptamine, homovanillic acid and 5-hydroxyindoleacetic acid in the inoculated brains indicated an imparied turnover of neurotransmitters. Subnormal concentrations of catecholamines and homovanillic acid were encountered in the acutely-infected mice as well as among the survivors. Failure to synthesize catecholamines was observed not only in mice demonstrating symptoms of disease or in animals which recovered from their infection but also among a proportion of the mice which never demonstrated neurological symptoms. In contrast, 6-week-old Swiss albino mice infected with West Nile virus showed no effect on the turnover of brain monoamines either in acutely infected mice or in animals which survived the acute infection. Herpes simplex virus infection of 3-week-old mice induced during the acute infection an increased release of neurotransmitters. When these mice were "cured" of the infection by increasing the environmental temperature the elevated turnover of monoamine metabolism was normalized. Two months later there were no differences in concentrations of catecholamines or homovanillic acid between infected animals or uninfected controls. Thus, persistent impairment of brain monoamine metabolism was induced in mice infected when very young. The possible importance of the observations, in particular the findings of an impaired turnover after subclinical infection, is discussed.
5HIAA and HVA were determined in successive samples of CSF withdrawn at the lumbar and cisternal levels in connection with gas myelographic examinations in 16 patients. The mean of 5-HIAA in the first cisternal samples were 83 ng/ml (n equal to 8) and of HVA 143 NG/ML (N equal to 7). A sharp increase in the concentration of both metabolites, but particulary of HVA, was seen in successive lumbar samples. The ratio of cisternal/lumbar 5-HIAA was 3/1, and of HVA 10/1 in one patient in whom lumbar and cisternal CSF were obtained with 2 weeks' interval. The concentrations of monoamine metabolites in CSF obtained at lumbar puncture are thus highly dependent on the amount of fluid withdrawn. This fact should be taken into consideration when different materials are compared.
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