One-carbon metabolism and schizophrenia: current challenges and future directions

Trends Mol Med. 2009 Dec;15(12):562-70. doi: 10.1016/j.molmed.2009.10.001. Epub 2009 Nov 5.


Schizophrenia is a heterogeneous disease generally considered to result from a combination of heritable and environmental factors. Although its pathophysiology has not been fully determined, biological studies support the involvement of several possible components including altered DNA methylation, abnormal glutamatergic transmission, altered mitochondrial function, folate deficiency and high maternal homocysteine levels. Although these factors have been explored separately, they all involve one-carbon (C1) metabolism. Furthermore, C1 metabolism is well positioned to integrate gene-environment interactions by influencing epigenetic regulation. Here, we discuss the potential roles of C1 metabolism in the pathophysiology of schizophrenia. Understanding the contribution of these mechanisms could yield new therapeutic approaches aiming to counteract disease onset or progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbon / metabolism*
  • DNA Methylation
  • Environment
  • Epigenesis, Genetic
  • Folic Acid Deficiency / complications
  • Folic Acid Deficiency / metabolism
  • Folic Acid Deficiency / physiopathology
  • Genetic Predisposition to Disease
  • Homocysteine / metabolism
  • Humans
  • Metabolic Networks and Pathways
  • Methionine / metabolism
  • Mitochondrial Diseases / complications
  • Mitochondrial Diseases / metabolism
  • Mitochondrial Diseases / physiopathology
  • Receptors, Glutamate / metabolism
  • Schizophrenia / etiology
  • Schizophrenia / metabolism*
  • Schizophrenia / physiopathology
  • Time Factors


  • Receptors, Glutamate
  • Homocysteine
  • Carbon
  • Methionine