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Correlation analysis between genome-wide expression profiles and cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders

Molecular Psychiatry volume 15, pages 326–336 (2010)Cite this article

Abstract

Cytoarchitectural abnormalities have been described in the prefrontal cortex of subjects with schizophrenia, bipolar disorder and depression. However, little is known about the gene expression profiles associated with these abnormalities. Genome-wide expression profiling technology provides an unbiased approach to identifying candidate genes and biological processes that may be associated with complex biological traits such as cytoarchitecture. In this study, we explored expression profiles associated with the abnormalities by using publicly available microarray metadata and cytoarchitectural data from post-mortem samples of the frontal cortex from 54 subjects (schizophrenia, n=14; bipolar disorder, n=13; depression, n=12 and controls n=15). Correlation analysis between genome-wide expression levels and cytoarchitectural traits revealed that 818 genes were significantly correlated with a decrease in the number of perineuronal oligodendrocytes across all subjects. A total of 600 genes were significantly correlated with a decrease in density of calbindin-positive interneurons across all subjects. Multiple biological processes including cellular metabolism, central nervous system development, cell motility and programmed cell death were significantly overrepresented in both correlated gene lists. These findings may provide novel insights into the molecular mechanisms that underlie the cytoarchitectural abnormalities of perineuronal oligodendrocytes and calbindin-containing GABAergic interneurons in the prefrontal cortex of the major psychiatric disorders.

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Acknowledgements

We thank all the investigators generating original data in the SMRIDB, in particular Drs S Hossein Fatemi, Natalya Uranova, Gavin Reynolds, Erminio Costa, David Cotter, Husseini K Manji, Paul Harrison, M Kerry O'Banion, C Anthony Altar and Pamela Sklar, along with their many collaborators, who made this study possible.

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  1. Stanley Brain Research Laboratory, Stanley Medical Research Institute, Rockville, MD, USA

    S Kim & M J Webster

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  1. S Kim
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Correspondence to M J Webster.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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Kim, S., Webster, M. Correlation analysis between genome-wide expression profiles and cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders. Mol Psychiatry 15, 326–336 (2010). https://doi.org/10.1038/mp.2008.99

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