The role of one-carbon metabolism in schizophrenia and depression

Harv Rev Psychiatry. 2007 Jul-Aug;15(4):146-60. doi: 10.1080/10673220701551136.


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.

Method: 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.

Conclusion: 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.

Publication types

  • Review

MeSH terms

  • Depressive Disorder / drug therapy
  • Depressive Disorder / metabolism*
  • Folic Acid / metabolism
  • Folic Acid / therapeutic use
  • Homocysteine / metabolism
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2) / metabolism
  • One-Carbon Group Transferases / metabolism*
  • S-Adenosylmethionine / metabolism
  • Schizophrenia / drug therapy
  • Schizophrenia / metabolism*
  • Vitamin B 12 / metabolism
  • Vitamin B 12 / therapeutic use


  • Homocysteine
  • S-Adenosylmethionine
  • Folic Acid
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • One-Carbon Group Transferases
  • Vitamin B 12