Tryptophan and serotonin in schizophrenia: a clue to biochemical defects?

Abstract

There have been many reports implicating abnormalities of tryptophan metabolism in the pathogenesis of schizophrenic diseases; Gilka (1975) has reviewed much of this evidence. Pollin, Cardon and Kety (1961) showed that administration of tryptophan and a monoamine oxidase inhibitor to chronic schizophrenics led to an exacerbation of symptoms in some cases. This was followed by an apparent ‘rebound’ period, during which the patients were somewhat better than prior to the trial. This finding was confirmed by Alexander and co-workers (1963). However, relatively less attention has been paid to the results of tryptophan administration observed by these two groups of workers than to their observation that administration of methionine under the same conditions had the same effect in some patients. This effect of methionine (and other methyl group donors such as betaine) was interpreted as suggesting that an abnormal methyl derivative of a normal brain metabolite might be an endogenous psychotogen, and hence a major biochemical factor in the pathogenesis of schizophrenia. One compound that has been proposed for such a role is dimethyltryptamine, which is known to induce hallucinations when administered to normal subjects. In view of the reports from Pollin and co-workers and from Alexander’s group, cited above, dimethyltryptamine is an especially interesting compound, since it can be regarded as a derivative of both tryptophan and methionine.