Tryptophan Metabolism in Psychoses

Multiple biochemical correlates of manic-depressive illness

“…Previous studies of IAA excretion in psychiatric illness have involved primarily schizophrenic subpopulations. Both normal and increased IAA excretion in schizophrenics have been reported [14], and nonspecific influences such as dietary intake of tryptophan have been outlined [10]. Increased IAA excretion has been correlated with increased intensity of psychotic activity in schizophrenics [14].…”

“…Both the schizophrenic patients in Brune and Himwich's study [14,15] and our manic-depressive patients were maintained on a constant 100 g protein per day diet, thereby minimizing dietary influence on changes in IAA excretion. In spite of a constant tryptophan intake, our patients evidenced considerable variability in daily excretion values during both manic and depressive periods.…”

Negative Findings with Nicotinic Acid in the Treatment of Schizophrenias

“…At first, Brune and Himwich (1963) found that there is a decrease in vV-methylnicotinamide excretion together with an increase in tryptamine, 3-indoleactic acid and 5-hydroxyindoleacetic acid excretion in acute or exacerbated schizo phrenics. On the basis of these findings Brune (1967) suggested that at least in some schizophrenic patients there is a blockage within the kynurenine pathway of tryptophan metabolism, yielding to a reduction in the biological formation of nicotinic acid, which in turn leads to increased tryptophan metabolism along the other two possible pathways: the tryptamine pathway and the serotonin path way. Furthermore, it was speculated that interference with the biological forma tion of nicotinic acid may be responsible, at least in part, for the excess of available methyl groups, and that the reaction of these methyl groups with the increase in indoleamine metabolites results in the formation of dimethylated psychotoxic metabolic products.…”

The Use of Nicotinic Acid and Pyridoxine in the Treatment of Schizophrenia

“…Deficiencies of pyridoxine, in addition to reducing the formation of nicotinic acid, could lead to diversion of tryptophan metabolism from the kynurenine pathway to the indoleamine [Brune, 1967], The end products of this pathway are methylated and dimethylated compounds with psycho toxic properties. Since nicotinic acid is a methyl acceptor substance, its reduced formation could produce an excess availability of methyl groups, and consequently an increase in the formation of dimethylated psychotoxic metabolites [Heller et al, 1970].…”