The role of one-carbon metabolism in schizophrenia and depression.
OBJECTIVE
Physicians often check folate and cobalamin levels in patients with schizophrenia and depression. The reasons for this practice are reviewed, as well as implications for treatment.


METHODS
The physiology of the one-carbon cycle, involving folate, cobalamin, homocysteine, S-adenosyl-methionine, and methylene tetrahydrofolate reductase (MTHFR) is first reviewed, and then the particular contributions of folate and B12 are reviewed. PubMed was searched for studies of the association between folate, cobalamin, homocysteine, and MTHFR polymorphisms and schizophrenia and depression.


RESULTS
The recent key studies from the large literature addressing these topics are summarized. Treatment implications are discussed.


CONCLUSIONS
It is important to check folate and B12 levels in certain situations, such as alcoholism, malnutrition, malabsorption, and the concurrent use of some medications. Checking homocysteine and methylmalonic levels might be useful. With respect to treatment, folate and cobalamin deficiencies should be corrected. Cobalamin supplementation is probably not helpful. Folate supplementation is indicated in pregnancy but may exacerbate the effects of cobalamin deficiency. SAMe may prove to be a useful antidepressant. In the future, screening for MTHFR polymorphisms might be useful.
Department of Psychiatry, Harvard Medical School, and Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA 01730, USA. frances.frankenburg@med.va.gov
Frances Rachel
FR
Frankenburg
D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism*; D005492:Folic Acid / Q000378:metabolism / Q000627:therapeutic use; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000378:metabolism; D019875:One-Carbon Group Transferases / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*; D014805:Vitamin B 12 / Q000378:metabolism / Q000627:therapeutic use
D006710:Homocysteine; D012436:S-Adenosylmethionine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D019875:One-Carbon Group Transferases; D014805:Vitamin B 12