Skip to main content Accessibility help
×
Hostname: page-component-586b7cd67f-rcrh6 Total loading time: 0 Render date: 2024-11-26T15:05:02.546Z Has data issue: false hasContentIssue false

10 - Schizophrenia, neurodevelopment, and epigenetics

Published online by Cambridge University Press:  04 August 2010

Arturas Petronis
Affiliation:
Centre for Addiction and Mental Health, Toronto, Canada
Matcheri S. Keshavan
Affiliation:
University of Pittsburgh
James L. Kennedy
Affiliation:
Clarke Institute of Psychiatry, Toronto
Robin M. Murray
Affiliation:
Institute of Psychiatry, London
Get access

Summary

The neurodevelopmental theory of schizophrenia is based on the hypothesis that early brain insults affect brain development and eventually cause dysfunction of the mature brain, predisposing to schizophrenia. A large group of putative etiological factors has been suggested, investigated, and categorized into environmental and genetic groups. The first group includes various obstetric complications such as birth trauma, maternal viral infection during pregnancy, pre-eclampsia, and deficiencies in nutrition. The second group provokes emphasis on DNA sequence variation in the genes that may play a role in neurodevelopment. This chapter suggests the idea that developmental changes in schizophrenia can be caused and/or mediated by epigenetic factors. It argues that shifting the emphasis from the traditional gene-environment dichotomy to epigenetics may provide a cohesive theoretical framework for a myriad of fragmented phenomenological and molecular findings in schizophrenia and lead to a series of new molecular strategies, designs, and approaches.
Type
Chapter
Information
Publisher: Cambridge University Press
Print publication year: 2004

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bestor, T. H., (2000). The DNA methyltransferases of mammals. Hum Mol Genet 9: 2395–2402CrossRefGoogle ScholarPubMed
Cardno, A. G., Gottesman, I. I. (2000). Twin studies of schizophrenia: from bow-and-arrow concordances to Star Wars Mx and functional genomics. Am J Med Genet 97: 12–173.0.CO;2-U>CrossRefGoogle ScholarPubMed
Chen, Y., Sharma, R. P., Costa, R. H., Costa, E., Grayson, D. R. (2002). On the epigenetic regulation of the human reelin promoter. Nucl Acids Res 30: 2930–2939CrossRefGoogle ScholarPubMed
El-Osta, A. (2002). FMR1 silencing and the signals to chromatin: a unified model of transcriptional regulation. Biochem Biophys Res Commun 295: 575–581CrossRefGoogle ScholarPubMed
El-Osta, A., Baker, E. K., Wolffe, A. P. (2001). Profiling methyl-CpG specific determinants on transcriptionally silent chromatin. Mol Biol Rep 28: 209–215CrossRefGoogle ScholarPubMed
Gottesman, I., Shields, J. (1982). Schizophrenia: The Epigenetic Puzzle. Cambridge, UK: Cambridge University Press
Gottlicher, M., Minucci, S., Zhu, P.et al. (2001). Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J 20: 6969–6978CrossRefGoogle ScholarPubMed
Henikoff, S., Matzke, M. A. (1997). Exploring and explaining epigenetic effects. Trends Genet 13: 293–295CrossRefGoogle ScholarPubMed
Holliday, R. (1994). Epigenetics: an overview. Dev Genet 15: 453–457CrossRefGoogle ScholarPubMed
Holliday, R. (1996). DNA methylation in eukaryotes: 20 years on. In Epigenetic Mechanisms of Gene Regulation, ed. V. Russo, R. Martienssen, A. Riggs. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, pp. 5–27
Holliday, R., Pugh, J. E. (1975). DNA modification mechanisms and gene activity during development. Science 187: 226–232CrossRefGoogle ScholarPubMed
Jablonka, E., Lamb, M. (1995). Epigenetic Inheritance and Evolution. Oxford: Oxford University Press
Jackson-Grusby, L., Beard, C., Possemato, R.et al. (2001). Loss of genomic methylation causes p53-dependent apoptosis and epigenetic deregulation. Nat Genet 27: 31–39CrossRefGoogle ScholarPubMed
Jenuwein, T., Allis, C. D. (2001). Translating the histone code. Science 293: 1074–1080CrossRefGoogle ScholarPubMed
Kolb, B. (1995). Brain Plasticity and Behavior. Mahwah, NJ: Lawrence Erlbaum Associates
Kraepelin, E. (1919). Dementia Praecox and Paraphrenia. Edinburgh: Livingstone
Lewis, D. A., Levitt, P. (2002). Schizophrenia as a disorder of neurodevelopment. Annu Rev Neurosci 25: 409–432CrossRefGoogle ScholarPubMed
Li, E. (2002). Chromatin modification and epigenetic reprogramming in mammalian development. Nat Rev Genet 3: 662–673CrossRefGoogle ScholarPubMed
Litt, M. D., Simpson, M., Gaszner, M., Allis, C. D., Felsenfeld, G. (2001). Correlation between histone lysine methylation and developmental changes at the chicken beta-globin locus. Science 293: 2453–2455CrossRefGoogle ScholarPubMed
Maynard Smith, J. (1990). Models of a dual inheritance system. J Theor Biol 143: 41–53CrossRefGoogle ScholarPubMed
McClintock, B. (1951). Chromosome organization and genic expression. Genes and Mutations. Cold Spring Harb Symp Quant Biol XVI: 13–47CrossRefGoogle Scholar
Mertineit, C., Yoder, J. A., Taketo, T.et al. (1998). Sex-specific exons control DNA methyltransferase in mammalian germ cells. Development 125: 889–897Google ScholarPubMed
Morgan, T. H. (1934). Embryology and Genetics. New York: Columbia University Press
Petronis, A. (2000). The genes for major psychosis: aberrant sequence or regulation?Neuropsychopharmacology 23: 1–12CrossRefGoogle ScholarPubMed
Petronis, A. (2001). Human morbid genetics revisited: relevance of epigenetics. Trends Genet 17: 142–146CrossRefGoogle ScholarPubMed
Petronis, A., Paterson, A. D., Kennedy, J. L. (1999). Schizophrenia: an epigenetic puzzle?Schizophr Bull 25: 639–655CrossRefGoogle Scholar
Petronis, A., Popendikyte, V., Kan, P. X., Sasaki, T. (2002). Major psychosis and chromosome 22: genetics meets epigenetics. CNS Spectrums 7: 209–214CrossRefGoogle ScholarPubMed
Petronis, A., Gottesman, I. I., Kan, P. X.et al. (2003). Monozygotic twins exhibit numerous epigenetic differences: clues to twin discordance?Schizophr Bull 29: 169–178CrossRefGoogle ScholarPubMed
Phiel, C. J., Zhang, F., Huang, E. Y.et al. (2001). Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem 276: 36734–36741CrossRefGoogle ScholarPubMed
Rakyan, V. K., Blewitt, M. E., Druker, R., Preis, J. I., Whitelaw, E. (2002). Metastable epialleles in mammals. Trends Genet 18: 348–351CrossRefGoogle ScholarPubMed
Razin, A., Shemer, R. (1999). Epigenetic control of gene expression. Results Probl Cell Differ 25: 189–204CrossRefGoogle ScholarPubMed
Reik, W., Dean, W., Walter, J. (2001). Epigenetic reprogramming in mammalian development. Science 293: 1089–1093CrossRefGoogle ScholarPubMed
Rideout, III, W. M., Eggan, K., Jaenisch, R. (2001). Nuclear cloning and epigenetic reprogramming of the genome. Science 293: 1093–1098CrossRefGoogle Scholar
Riggs, A., Xiong, Z., Wang, L., LeBon, J. M. (1998). Methylation dynamics, epigenetic fidelity and X chromosome structure. In Epigenetics, Vol. Novartis Foundation Symposium 214: Epigenetics, ed. A. Wolffe. Chichester, UK: Wiley, pp. 214–227
Riggs, A. D. (1975). X inactivation, differentiation, and DNA methylation. Cytogenet Cell Genet 14: 9–25CrossRefGoogle ScholarPubMed
Robertson, K. D., Wolffe, A. P. (2000). DNA methylation in health and disease. Nat Rev Genet 1: 11–19CrossRefGoogle ScholarPubMed
Schumacher, A. (2001). Mechanisms and brain specific consequences of genomic imprinting in Prader–Willi and Angelman syndromes. Gene Funct Dis 1: 7–253.0.CO;2-N>CrossRefGoogle Scholar
Seeman, M. V. (1997). Psychopathology in women and men: focus on female hormones. Am J Psychiatry 154: 1641–1647CrossRefGoogle ScholarPubMed
Siegfried, Z., Eden, S., Mendelsohn, M.et al. (1999). DNA methylation represses transcription in vivo. Nat Genet 22: 203–206CrossRefGoogle ScholarPubMed
Singal, R., Ginder, G. D. (1999). DNA methylation. Blood 93: 4059–4070Google ScholarPubMed
Slack, J. M. (2002). Conrad Hal Waddington: the last Renaissance biologist?Nat Rev Genet 3: 889–895CrossRefGoogle ScholarPubMed
Stancheva, I., Meehan, R. R. (2000). Transient depletion of xDnmt1 leads to premature gene activation in Xenopus embryos. Genes Dev 14: 313–327Google ScholarPubMed
Torrey, E. F., Bowler, A. E., Taylor, E. H., Gottesman, I. I. (1999). Schizophrenia and Manic Depressive Disorder. The Biological Roots of Mental Illness as Revealed by the Landmark Study of Identical Twins. New York: Basic Books
Tremolizzo, L., Carboni, G., Ruzicka, W. B.et al. (2002). An epigenetic mouse model for molecular and behavioral neuropathologies related to schizophrenia vulnerability. Proc Natl Acad Sci USA 99: 17095–17100CrossRefGoogle ScholarPubMed
Veyver, I. B., Zoghbi, H. Y. (2001). Mutations in the gene encoding methyl-CpG-binding protein 2 cause Rett syndrome. Brain Dev 23(Suppl. 1): S147–S151CrossRefGoogle ScholarPubMed
Walsh, C. P., Bestor, T. H. (1999). Cytosine methylation and mammalian development. Genes Dev 13: 26–34CrossRefGoogle ScholarPubMed
Warnecke, P. M., Clark, S. J. (1999). DNA methylation profile of the mouse skeletal alpha-actin promoter during development and differentiation. Mol Cell Biol 19: 164–172CrossRefGoogle ScholarPubMed
Wolffe, A. P. (1994). Inheritance of chromatin states. Dev Genet 15: 463–470CrossRefGoogle ScholarPubMed
Wolffe, A. P., Barton, M. C. (2000). Developmental regulation of chromatin function and gene expression. In Chromatin Structure and Regulation, ed. S. C. R. Elgin, J. L. Workman. Oxford: Oxford University Press, pp. 182–202
Wolffe, A. P., Matzke, M. A. (1999). Epigenetics: regulation through repression. Science 286: 481–486CrossRefGoogle ScholarPubMed
Woods, B. T. (1998). Is schizophrenia a progressive neurodevelopmental disorder? Toward a unitary pathogenetic mechanism. Am J Psychiatry 155: 1661–1670CrossRefGoogle Scholar
Woolf, C. M. (1997). Does the genotype for schizophrenia often remain unexpressed because of canalization and stochastic events during development?Psychol Med 27: 659–668CrossRefGoogle ScholarPubMed
Yeivin, A., Razin, A. (1993). Gene methylation patterns and expression. In DNA Methylation: Molecular Biology and Biological Significance, ed. J. Jost, H. Saluz. Basel: Birkhauser Verlag, pp. 523–568CrossRef

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×