Dopamine and its metabolites homovanillic acid and dihydroxyphenylacetic acid, noradrenaline, serotonin and its metabolite 5-hydroxyindoleacetic acid, and tryptophan and its metabolite kynurenine have been assayed in 9 schizophrenic and 10 control brains, together with the monoamine-related enzymes tyrosine hydroxylase monoamine oxidase, dopamine-beta-hydroxylase, and catechol-o-methyl-transferase. In schizophrenic brains dopamine, noradrenaline and serotonin were significantly increased in some areas of corpus striatum, but there were no significant changes in enzyme activity or monoamine metabolite concentrations in any of the brain areas examined. The findings are not consistent with theories that serotonin or noradrenaline stores are grossly depleted or noradrenaline neurones have degenerated, or that monoamine oxidase activity is abnormal, in schizophrenia, and provide no direct support for the hypothesis that dopamine neurones are overactive.
Serotonin (5HT), its chief metabolite 5-hydroxyindoleacetic acid (5 HIAA), its precursor tryptophan, and kynurenine, another metabolite of tryptophan, have been measured in post mortem human brain samples. Concentrations of these metabolites were not found to be significantly different in putamen, hippocampus or temporal cortex from 23 normal subjects compared with 15 subjects in whom a diagnosis of schizophrenia could be restrospectively confirmed. The results have been analysed with respect to cause of death, medication and post mortem changes. Post mortem increases in tryptophan and kynurenine were observed. Some interrelationships between the variables measured within and between the different areas studied are discussed. It is concluded that there is no evidence for a generalised deficit of 5HT in the brain in schizophrenia, nor for gross changes in turnover along the serotonin or kynurenine pathways of tryptophan metabolism in brain.
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