Homocysteine, folate, methylation, and monoamine metabolism in depression

Objectives-Previous studies suggest that folate deficiency may occur in up to one third of patients with severe depression, and that treatment with th e vitamin may enhance recovery of the mental state. There are, however, dif ficulties in interpreting serum and red cell folate assays in some patients , and it has been suggested that total plasma homocysteine is a more sensit ive measure of functional folate (and vitamin B12) deficiency. Other studie s suggest a link between folate deficiency and impaired metabolism of serot onin, dopamine, and noradrenaline (norepinephrine), which have been implica ted in mood disorders. A study of homocysteine, folate, and monoamine metab olism has, therefore, been undertaken in patients with severe depression. Methods-In 46 inpatients with severe DSM III depression, blood counts, seru m and red cell folate, serum vitamin B12, total plasma homocysteine, and, i n 28 patients, CSF folate, S-adenosylmethionine, and the monoamine neurotra nsmitter metabolites 5HIAA, HVA, and MHPG were examined. Two control groups comprised 18 healthy volunteers and 20 patients with neurological disorder s, the second group undergoing CSF examination for diagnostic purposes. Results-Twenty four depressed patients (52%) had raised total plasma homocy steine. Depressed patients with raised total plasma homocysteine had signif icant lowering of serum, red cell, and CSF folate, CSF S-adenosylmethionine and all three CSF monoamine metabolites. Total plasma homocysteine was sig nificantly negatively correlated with red cell folate in depressed patients , but not controls. Conclusions-Utilising total plasma homocysteine as a sensitive measure of f unctional folate deficiency, a biological subgroup of depression with folat e deficiency, impaired methylation, and monoamine neurotransmitter metaboli sm has been identified. Detection of this subgroup, which will not be achie ved by routine blood counts, is important in view of the potential benefit of vitamin replacement.