Epigenetic mechanisms in schizophrenia.
Epidemiological research suggests that both an individual's genes and the environment underlie the pathophysiology of schizophrenia. Molecular mechanisms mediating the interplay between genes and the environment are likely to have a significant role in the onset of the disorder. Recent work indicates that epigenetic mechanisms, or the chemical markings of the DNA and the surrounding histone proteins, remain labile through the lifespan and can be altered by environmental factors. Thus, epigenetic mechanisms are an attractive molecular hypothesis for environmental contributions to schizophrenia. In this review, we first present an overview of schizophrenia and discuss the role of nature versus nurture in its pathology, where 'nature' is considered to be inherited or genetic vulnerability to schizophrenia, and 'nurture' is proposed to exert its effects through epigenetic mechanisms. Second, we define DNA methylation and discuss the evidence for its role in schizophrenia. Third, we define posttranslational histone modifications and discuss their place in schizophrenia. This research is likely to lead to the development of epigenetic therapy, which holds the promise of alleviating cognitive deficits associated with schizophrenia.
Roth
Tania L
TL
Department of Neurobiology and Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, 35294, USA.
Lubin
Farah D
FD
Sodhi
Monsheel
M
Kleinman
Joel E
JE
D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D019175:DNA Methylation; D004777:Environment; D044127:Epigenesis, Genetic; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005968:Glutamate Decarboxylase / Q000235:genetics; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics; D000091042:Reelin Protein; D012559:Schizophrenia / Q000209:etiology / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D044402:Receptor, Serotonin, 5-HT2A; D000091042:Reelin Protein; D002394:Catechol O-Methyltransferase; D012697:Serine Endopeptidases; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1