Journal
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
Volume 1790, Issue 9, Pages 869-877Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbagen.2009.06.009
Keywords
Schizophrenia; Environment; Epigenetic; DNA methylation; Histone; HDAC; DNMT; Cognition
Categories
Funding
- National Institutes of Health
- National Alliance for Research on Schizophrenia and Depression
- Civitan International
- Evelyn F. McKnight Brain Research Foundation
- NATIONAL INSTITUTE OF MENTAL HEALTH [ZIAMH002399, R00MH082106, ZICMH002903] Funding Source: NIH RePORTER
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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. (C) 2009 Elsevier B.V. All rights reserved.
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