Homocysteinemia and schizophrenia as a case of methylation deficiency.

A 27-year-old woman is described whose disorder meets the DSM-III-R criteria for a diagnosis of schizophrenia and who was found to have a significantly increased serum level of homocysteine. Repeatedly, she improved on frequent cobalamin injections and deteriorated in periods without treatment. The effects of prolonged weekly treatment appeared to diminish as time went on, suggesting that the abnormality was not wholly cobalamin-dependent. It was found that methylenetetrahydrofolate reductase (MR) activity in cultured skin fibroblasts was reduced to a magnitude that is found among people with heterozygous deficiency. A defect in MR activity indicates a deficiency in methyltetrahydrofolate (MTHF), with a consequent reduction of the remethylation of homocysteine to methionine. Thus, reduced methylation may explain the increased levels of homocysteine and the transient effects of cobalamin treatment in the patient. Theoretically, MTHF should be the optimal treatment for her. The case reported highlights the importance of assessing the serum homocysteine level in order to detect methylation deficiency in patients with schizophrenia.