Abnormalities of one-carbon metabolism in psychiatric disorders: Study of methionine adenosyltransferase kinetics and lipid composition of erythrocyte membranes

Two independent lines of inquiry have implicated some disturbance of one-carbon cycle metabolism in affective disorders. (1) Folic acid deficiency commonly leads to depression, and S-adenosylmethionine has been reported to have antidepressant properties. (2) Methionine adenosyltransferase has been reported to be underactive in depression and schizophrenia and over active in mania. This study reports the effects on erythrocyte methionine adenosyltransferase (MAT) kinetics (V_max) of a 2-week treatment in a population of patients housed on a psychiatric research ward. The drug-free schizophrenic patients and depressives had, upon admission, low V_max values, and the drug-free manic patients had high V_max values on admission. After 2 weeks of appropriate treatment, the values for all three patient samples showed significant normalization (i.e., the levels rose in schizophrenics and depressives and fell in manies). We have further shown that pretreatment low levels of erythrocyte membrane phosphatidylcholine in depressives and high levels in manies show statistically significant normalization following 2 weeks of pharmacotherapy. The significance of these results is discussed.