From trans-methylation to cytosine methylation: Evolution of the methylation hypothesis of schizophrenia
Epigenetics April 30, 2009 Dennis R. Grayson, Ying Chen, Erbo Dong et al. 54 citations
The transmethylation hypothesis, proposed when chlorpromazine was first synthesized, suggested that abnormal metabolism in schizophrenia patients leads to methylation of brain amines, producing hallucinogenic compounds that cause positive symptoms. Methionine was given to patients to test this, but no endogenous psychotropic compound was found. Current understanding suggests methionine may disrupt epigenetic regulation in susceptible patients. This review focuses on coordinate regulation of multiple neuronal promoters through methylation. The methionine mouse model may help identify genes regulated by epigenetic perturbations. Studies with reelin and GAD67 promoters show additional neuronal promoters are similarly affected by methionine, potentially expanding knowledge of global methylation changes in brain regions.