Abstract
This paper reviews our present knowledge of the role of the one-carbon cycle in mood disorder and schizophrenia with particular attention to S-adenosyl methionine (SAM). After an historical introduction the clinical data is first reviewed of the anti-depressant action of SAM, in particular a survey of double blind placebo-controlled trials. Then follows an account of the biochemical parameters of the action of SAM, in particular the role of folic acid and 5-methyltetrahydrofolate (vitamin B9), polyamines, homocysteine, together with epigenetic studies. In schizophrenia the effect of oral l-methionine on worsening the symptoms of some chronic schizophrenics has been known since 1961. Recent epigenetic research covered has addressed the mechanism of this reaction. This includes the role of SAM in modulating DNA methyltransferase-1 mRNA activity, cytosine 5-methylation, spine numbers and the expression of mRNAs encoding for reelin and GAD67 in GABAergic neurons in the frontal cortex in schizophrenia. There is also evidence that marker D8S542 located within the methionine sulfoxide reductase (MSRA) gene may be involved in schizophrenia as well as 677C > T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene. The possible roles of homocysteine and methionine S-adenosyl transferase kinetics are also discussed.
Highlights
The question of whether some abnormality in the one-carbon cycle might be related to psychiatric disease was first raised by Osmond and Smythies [1] in 1953
There is evidence that marker D8S542 located within the methionine sulfoxide reductase (MSRA) gene may be involved in schizophrenia as well as 677C > T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene
There is evidence that marker D8S542 located within the methionine sulfoxide reductase (MSRA) gene is involved in schizophrenia [19]
Summary
The question of whether some abnormality in the one-carbon cycle might be related to psychiatric disease was first raised by Osmond and Smythies [1] in 1953. The process of methylation has been liked to schizophrenia, depression and bipolar disorder in another way—in relation to the universal methyl group donor, Sadenosyl methionine (SAM). During the transmethylation SAM is converted to homocysteine in a two-enzyme step needing vitamin B6 (pyridoxyl phosphate). Homocysteine is converted to cystathionine in a reaction that needs vitamin B6 (pyridoxyl phosphate). S-adenosylmethionine is involved in numerous methylation reactions involving proteins, phospholipids, DNA, and neurotransmitter metabolism. Both folate and vitamin B12 deficiency may cause similar neurologic and psychiatric disturbances including depression, dementia, and demyelinating myelopathy [2]
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