Le rôle de l'épigenèse dans la schizophrénie

Role of epigenetics in schizophrenia Although the propensity to develop schizophrenia has long been attributed in part to a “genetic” component, this component does not follow Mendelian laws and may be primarily epigenetic. Studies have shown that several schizophrenia candidate genes are especially susceptible to changes in transcriptional activity as a result of histone modifications and DNA methyl ation. Increased expression of epigenetic enzymes which generally reduce transcription, such as DNA methyltransferase (DNMT) family, have been reported in schizophrenia postmortem brain samples. An abnormal chroma tin state leading to reduced candidate gene expression can be explained by aberrant coordination of epigenetic mechanisms in schizophrenia. The GABAergic neurotransmission deficit associated with schizophrenia is probably mediated by hypermethylation of the glutamic acid decarboxylase 67 (GAD67), reeling and other GABAergic promoters, which leads to downregulation of transcription and protein production. An experimental pharmacological strategy to reduce hypermethylation of GABAergic pro moters is to induce DNAcytosine demethylation by altering chromatin remodelling.