Behavioral and Biochemical Alterations in Schizophrenic Patients

A Review of Nicotinic Acid, N-Methylated Indoleamines and Schizophrenia

“…Psychotic symptoms have been reported also in nonschizophrenics given large doses of methionine with an MAOI . Similar effects in schizophrenics have been reported for both betaine , another methyl donor, and cysteine (Spaide et al, 1968), a sulfur con taining amino acid when given along with an MAOI. As well, a schizophrenic-like psychosis appears with an unexpectedly high frequency in patients with homocystinuria (and in their families), an inborn error of metabolism, that is usually associated with a deficiency of cystathionine synthetase and high circulating levels of methionine (Freeman et al, 1975).…”

“…The only other studies touching on this question were carried out with cysteine and MAOI, not methionine. Spaide et al (1968) administered to four chronic schizophrenics, first methionine, then cysteine, next tranylcypromine and finally an MAOI and cysteine. Using rather nonspecific techniques, they found that with either amino acid alone, the amount of urinary bufotenine was very small (less than 1 mg daily), but with the addition of the MAOI it rose (2-5 mg daily).…”

“…The work of Fischer et al (1961), was replicated using paper chromatography by Spatz (1967) andSiri ex andMarini (1969). Bufotenine was also found in the urine of schizophrenics given a MAOI alone (Heller, 1966) or in conjunction with betaine , or cysteine (Spaide et al, 1968). However, other workers could not find bufotenine in the urine of schizophrenics (Rodnight, 1956;Sprince et al, 1963;Siegel, 1965;Nishimura and Gjessing, 1965;Kakimoto et al, 1967), or could find it only in medicated and not in unmedicated schizophrenics (Runge et al, 1966).…”

Transmethylation Hypothesis of Schizophrenia: Methionine and Nicotinic Acid

“…In favor of this proposal are the findings of Park et al (1965), that both MAOI drugs tested (iproniazid and isocarboxazid), but not placebo, elevated the ratio of tryptamine:indoleacetic acid in the urine of schizophrenic patients. In another series of experiments, it was found that when methionine loading was combined with a MAOI the increase in excretion of tryptamine in the urine of schizophrenic patients was much greater than the increase produced by the MAOI alone Berlet et al, 1965a;Spaide et al, 1968Spaide et al, , 1969. This effect can be interpreted as the result of a breakdown of body protein or as an inhibition of the tryptophan pyrrolase pathway.…”

“…A third amino acid, cysteine, has also produced effects similar to those of methionine and betaine when given to schizophrenic patients (Brune and Him wich, 1963;Spaide et al, 1968). These findings are not easily interpreted because cysteine is not a methyldonor.…”