Schizophrenia Bulletin Advance Access published online on August 21, 2007
Schizophrenia Bulletin, doi:10.1093/schbul/sbm093
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Aberrant Epigenetic Regulation Could Explain the Relationship of Paternal Age to Schizophrenia
2 Department of Psychiatry, School of Medicine, New York University, New York, NY
3 New York State Psychiatric Institute, New York, NY
4 Department of Psychiatry, Columbia University, New York, NY
1 To whom correspondence should be addressed; Dolores Malaspina, Department of Psychiatry, New York University School of Medicine, 550 Ist Avenue, MLH323, New York, NY 10016; tel: 212-263-6214, fax: 212-263-5717, e-mail: Dolores.Malaspina{at}NYUMC.ORG.
The causal mechanism underlying the well-established relation between advancing paternal age and schizophrenia is hypothesized to involve mutational errors during spermatogenesis that occur with increasing frequency as males age. Point mutations are well known to increase with advancing paternal age while other errors such as altered copy number in repeat DNA and chromosome breakage have in some cases also been associated with advancing paternal age. Dysregulation of epigenetic processes may also be an important mechanism underlying the association between paternal age and schizophrenia. Evidence suggests that advancing age as well as environmental exposures alter epigenetic regulation. Errors in epigenetic processes, such as parental imprinting can have serious effects on the offspring both pre- and postnatally and into adulthood. This article will discuss parental imprinting on the autosomal and X chromosomes and the alterations in epigenetic regulation that may lead to such errors.
Keywords: methylation / imprinting / X-chromosome inactivation / schizophrenia
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