One-carbon metabolism and schizophrenia: current challenges and future directions.
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.
Krebs
M O
MO
INSERM, Pathophysiology of Psychiatric Disorders, CPN, U894, Sainte-Anne Hospital, Paris F-75014, France. Marie-Odile.krebs@inserm.fr
Bellon
Alfredo
A
Mainguy
Gaell
G
Jay
T M
TM
Frieling
Helge
H
D002244:Carbon / Q000378:metabolism*; D019175:DNA Methylation; D004777:Environment; D044127:Epigenesis, Genetic; D005494:Folic Acid Deficiency / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D053858:Metabolic Networks and Pathways; D008715:Methionine / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D017470:Receptors, Glutamate / Q000378:metabolism; D012559:Schizophrenia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors
D017470:Receptors, Glutamate; D006710:Homocysteine; D002244:Carbon; D008715:Methionine