The effects of L-methionine (without MAOI) in schizophrenia

Abstract

IN 1961 POLLIN, CARDON and KETY’ reported that a proportion of chronic schizophrenic patients who received methionine given in conjunction with a monoamine oxidase inhibitor showed an acute psychosis followed in some cases by an amelioration of their chronic schizophrenic symptoms. These authors were undecided whether the psychosis was a non-specific ‘toxic’ reaction or whether the methionine, being a methyl donor, was acting on the same biochemical mechanism at fault in the illness as suggested by OSMOND and SMYTHIES (1952)2. This finding was confirmed by BRUNE and HIMWICH~, ALEXANDER CURTIS and SPRINCE,~ and by Kety’s group again5 without, however, answering this question. Himwich reported that the same effect could be obtained by giving betaine or cysteine.6 In 1967 KAKIMOTO and SANO~ reported the same clinical effects with methionine and MAO1 but again were not able to confirm the nature of the reaction. They measured NMN + MN* in the urine of these patients and found no increase in the levels of these 0-methylated metabolites of noradrenaline and adrenaline on methionine loading. Thus, the mechanism still remains quite obscure. Catecholamines are metabolized by deamination and 0-methylation with either step preceding the other.8 L-methionine through its active form, S-Adenosyl methionine,g provides the methyl group for 0-methylation by the enzymelO COMT.* .The methylated metabolites of adrenaline and noradrenaline are MN, NMN, VMA and MHPG. VMA is the major methylated metabolite in the bodyl’ and MHPG the major methylated metabolite in the brain.12-14 The present study was designed to assess firstly the nature of the clinical reaction produced by methionine administration to schizophrenic patients without MAO1 cover, since the latter can produce worsening of symptoms in schizophrenic patients; secondly whether the clinical effects of methionine are associated with an increase in 0-methylated