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Decanalization, brain development and risk of schizophrenia

McGrath, J J, Hannan, A J, Gibson, G·2011·Translational Psychiatry

Abstract

Waddington's original description of canalization refers to the ability of an organism to maintain phenotypic fidelity in the face of environmental and/or genetic perturbation. Development of the human brain requires exposure to a 'wild-type' environment-one that supports the optimal set of instructions for development. Recently derived brain structures in our species, such as the expanded neocortex, may be more vulnerable to decanalization because there has been insufficient time to evolve buffering capacity. On the basis of modern notions of decanalization, we provide perspectives on selected environmental and genetic risk factors for schizophrenia, and we discuss strengths and weaknesses of this conceptual framework. We argue that if we are to build a solid foundation for translational psychiatry, we must explore models that attempt to capture the complexity of the interaction between genetic and non-genetic risk factors in mediating and modulating brain development.

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Figures

Figure 1 The distribution of quantitative brain phenotypes. The upper panel (a) shows a population with a small proportion of deviant outcomes (shown in red and blue). The lower panel (b) shows how decanalization of a brain phenotype can leave the mean value unaffected but result in a greater proportion of deviant outcomes (shown in red and blue). Note that the increase in variance need not be symmetric for decanalization to occur.
Figure 1 The distribution of quantitative brain phenotypes. The upper panel (a) shows a population with a small proportion of deviant outcomes (shown in red and blue). The lower panel (b) shows how decanalization of a brain phenotype can leave the mean value unaffected but result in a greater proportion of deviant outcomes (shown in red and blue). Note that the increase in variance need not be symmetric for decanalization to occur.CC BY-NC-ND · PubMed Central
Figure 2 The epigenetic landscape. The upper panel (a) shows an optimal developmental trajectory, with a range of expected instructions (red and green arrows) contributing over time to maintain the desired trajectory. The middle panel (b) shows how the absence of expected instructions during early development (unbalanced arrows in the top of the figure) can decanalize development. The lower panel (c) shows how an unexpected instruction (large blue arrow) can also lead to decanalization of development.
Figure 2 The epigenetic landscape. The upper panel (a) shows an optimal developmental trajectory, with a range of expected instructions (red and green arrows) contributing over time to maintain the desired trajectory. The middle panel (b) shows how the absence of expected instructions during early development (unbalanced arrows in the top of the figure) can decanalize development. The lower panel (c) shows how an unexpected instruction (large blue arrow) can also lead to decanalization of development.CC BY-NC-ND · PubMed Central

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Metadata

Authors
McGrath, J. J., Hannan, A. J., & Gibson, G.
Venue
Translational Psychiatry
Published
2011-06-28
Volume
1
Issue
6
Pages
e14-e14
ISSN
2158-3188
Cited by
45
References
55
Language
en

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CoChat. (2026). Citation check: Decanalization, brain development and risk of schizophrenia. https://app.cochat.ai/papers/10.1038/tp.2011.16
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McGrath, J. J., Hannan, A. J., & Gibson, G. (2011). Decanalization, brain development and risk of schizophrenia. Translational Psychiatry. https://doi.org/10.1038/tp.2011.16

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