Tryptophan metabolism in depression

SUMMARY Psychiatric patients suffering from endogenous depression and a control group without endogenous depression were given oral loads of L-tryptophan and urinary excretion determined of the tryptophan metabolites on the pyrrolase pathway: kynurenine, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid. Female endogenously depressed subjects excreted significantly more kynurenine and 3-hydroxykynurenine but not the subsequent metabolite 3-hydroxyanthranilic acid than did female control subjects. Variability of excretion of kynurenine and 3-hydroxykynurenine at different times by the same subject was much greater in the endogenously depressed than in the control group. There was no consistent temporal relationship between excretion of metabolites and severity of the depressive illness. The possible significance of the findings in relation to defective tryptophan metabolism in the brain in endogenous depression is commented upon. The considerable efficacy of physical treatments in patients with affective illnesses has encouraged research into the implied physical abnormalities present. A relatively specific indication of the presence of a biochemical disturbance is provided by the therapeutic effectiveness of monoamine oxidase inhibitor (MAOI) and tricyclic antidepressants, which influence monoamine metabolism. The extent to which amines derived from tryptophan, such as 5-hydroxytryptamine (5HT), and those derived from tyrosine, such as the catecholamines, play a part in the regulation of mood has been the subject of much controversy and has been discussed by Schildkraut (1965) and by Brodie and Reid (1968). There is considerable evidence that tryptophan metabolism is disturbed in affective illnesses. Thus the therapeutic activity of MAOI compounds was found by Coppen, Shaw, Herzberg, and Maggs (1967) to be enhanced by oral tryptophan, suggesting that depression may be associated with insufficient cerebral 5HT. In addition, depressed subjects re-sponding to iproniazid were found by Pare an