Transcriptomes in schizophrenia: assessing altered gene expression with microarrays

doi:10.1017/CBO9780511735103.014

12 - Transcriptomes in schizophrenia: assessing altered gene expression with microarrays

Published online by Cambridge University Press: 04 August 2010

David A. Lewis,

Karoly Mirnics and

Pat Levitt

Edited by

Matcheri S. Keshavan,

James L. Kennedy and

Robin M. Murray

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David A. Lewis: Affiliation:
University of Pittsburgh, Pittsburgh, USA
Karoly Mirnics: Affiliation:
University of Pittsburgh, Pittsburgh, USA
Pat Levitt: Affiliation:
Vanderbilt University, Nashville, USA
Matcheri S. Keshavan: Affiliation:
University of Pittsburgh
James L. Kennedy: Affiliation:
Clarke Institute of Psychiatry, Toronto
Robin M. Murray: Affiliation:
Institute of Psychiatry, London

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Summary

This chapter reviews the current status of the technology to assess transcriptomes, its associated strengths and limitations, and initial findings resulting from the use of the approaches to study schizophrenia. Two types of microarray platform have been used in studies of schizophrenia: complementary DNA (cDNA) microarrays and synthetic oligonucleotide probe arrays. The study of gene expression in human brain tissue, the area of interest in schizophrenia, requires the use of postmortem human brain specimens. In postmortem brain specimens from subjects with schizophrenia, a difference in the expression level of one or a cluster of genes may have several different meanings. The application of transcriptome-based methods to studies of the molecular neuropathology of schizophrenia is clearly in their infancy, and like newborns they offer great promise for the future. However, careful rearing is essential to fulfill this promise.

Keywords

altered gene expression DNA microarrays transcriptomes synthetic oligonucleotide probe arrays schizophrenia

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Type: Chapter
Information: Neurodevelopment and Schizophrenia , pp. 210 - 223
DOI: https://doi.org/10.1017/CBO9780511735103.014 [Opens in a new window]
Publisher: Cambridge University Press
Print publication year: 2004

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References

Akbarian, S., Kim, J. J., Potkin, S. G.et al. (1995). Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Arch Gen Psychiatry 52: 258–266CrossRef Google Scholar PubMed

Arnold, S. E., Trojanowski, J. Q., Gur, R. E.et al. (1998). Absence of neurodegeneration and neural injury in the cerebral cortex in a sample of elderly patients with schizophrenia. Arch Gen Psychiatry 55: 225–232CrossRef Google Scholar

Berman, K. F., Zec, R. F., Weinberger, D. R. (1986). Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia. II. Role of neuroleptic treatment, attention and mental effort. Arch Gen Psychiatry 43: 126–135CrossRef Google Scholar

Branca, M. (2003). Genetics and medicine: putting gene arrays to the test. Science 300: 238CrossRef Google Scholar PubMed

Brown, P. O., Bottenstein, D. (1999). Exploring the new world of the genome with DNA microarrays. Nat Genet 21S: 33–37CrossRef Google Scholar

Brzustowicz, L. M., Hodgkinson, K. A., Chow, E. W. C., Honer, W. G., Bassett, A. S. (2000). Location of a major susceptibility locus for familial schizophrenia on chromosome 1q21–q22. Science 288: 678–682CrossRef Google Scholar

Buchsbaum, M. S., Haier, R. J., Potkin, S. G.et al. (1992). Frontrostriatal disorder of cerebral metabolism in never-medicated schizophrenics. Arch Gen Psychiatry 49: 935–942CrossRef Google Scholar

Burrone, J., O'Byren, M., Murthy, V. N. (2002). Multiple forms of synaptic plasticity triggered by selective suppression of activity in individual neurons. Nature 420: 414–418CrossRef Google Scholar PubMed

Cheung, V. G., Morley, M., Aguilar, F.et al. (1999). Making and reading microarrays. Nat Genet 21S: 20–32Google Scholar

Chowdari, K. V., Mirnics, K., Semwal, P.et al. (2002). Association and linkage analyses of RGS4 polymorphisms in schizophrenia. Hum Mol Genet 11: 1373–1380CrossRef Google Scholar

DeRisi, J., Iyer, V. R., Brown, P. O. (1997). Exploring the metabolic and genetic control of gene expression on a genomic scale. Science 278: 680–686CrossRef Google Scholar PubMed

DeRisi, J., Penland, L., Brown, P. O.et al. (1996). Use of a cDNA microarray to analyse gene expression patterns in human cancer. Nat Genet 14: 457–460Google Scholar PubMed

Vries, L., Zheng, B., Fischer, T., Elenko, E., Farquhar, M. G. (2000). The regulator of G protein signaling family. Annu Rev Pharmacol Toxicol 40: 235–271CrossRef Google Scholar PubMed

Duggan, D. J., Bittner, M., Chen, Y., Meltzer, P., Trent, J. M. (1999). Expression profiling using cDNA microarrays. Nat Genet 21S: 10–14CrossRef Google Scholar

Eastwood, S. L., McDonald, B., Burnet, P. W. J.et al. (1995). Decreased expression of mRNAs encoding non-NMDA glutamate receptors GluR1 and GluR2 in medial temporal lobe neurons in schizophrenia. Mol Brain Res 29: 211–223CrossRef Google Scholar

Glantz, L. A., Lewis, D. A. (1997). Reduction of synaptophysin immunoreactivity in the prefrontal cortex of subjects with schizophrenia: regional and diagnostic specificity. Arch Gen Psychiatry 54: 943–952CrossRef Google Scholar PubMed

Glantz, L. A., Lewis, D. A. (2000). Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch Gen Psychiatry 57: 65–73CrossRef Google Scholar

Hakak, Y., Walker, J. R., Li, C.et al. (2001). Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc Natl Acad Sci USA 98: 4746–4751CrossRef Google Scholar PubMed

Harrison, P. J., Heath, P. R., Eastwood, S. L.et al. (1995). The relative importance of premortem acidosis and postmortem interval for human brain gene expression studies: selective mRNA vulnerability and comparison with their encoded proteins. Neurosci Lett 200: 151–154CrossRef Google Scholar PubMed

Hashimoto, T., Volk, D. W., Buchheit, S. E., Lewis, D. A. (2002). Expression of BDNF and trkB mRNAs in prefrontal cortex of subjects with schizophrenia. Soc Neurosci Abstr 28: 703. 7Google Scholar

Hashimoto, T., Volk, D. W., Eggan, S. M.et al. (2003). Gene expression deficits in a subclass of GABA neurons in the prefrontal cortex of subjects with schizophrenia. J Neurosci 23: 6315–6326CrossRef Google Scholar

Hemby, S. E., Ginsberg, S. D., Brunk, B.et al. (2002). Gene expression profile for schizophrenia: discrete neuron transcription patterns in the entorhinal cortex. Arch Gen Psychiatry 59: 631–640CrossRef Google Scholar PubMed

Hof, P. R., Haroutunian, V., Friedrich, V. L. Jr.et al. (2003). Loss and altered spatial distribution of oligodendrocytes in the superior frontal gyrus in schizophrenia. Biol Psychiatry 53: 1075–1085CrossRef Google Scholar

Huttenlocher, P. R. (1979). Synaptic density in human frontal cortex: developmental changes and effects of aging. Brain Res 163: 195–205Google Scholar PubMed

Kamme, F., Salunga, R., Yu, J.et al. (2003). Single-cell microarray analysis in hippocampus CA1: demonstration and validation of cellular heterogeneity. J Neurosci 23: 3607–3615CrossRef Google Scholar PubMed

Lewis, D. A. (2002). The human brain revisited: opportunities and challenges in postmortem studies of psychiatric disorders. Neuropsychopharmacology 26: 143–154CrossRef Google Scholar PubMed

Lewis, D. A., Levitt, P. (2002). Schizophrenia as a disorder of neurodevelopment. Annu Rev Neurosci 25: 409–432CrossRef Google Scholar PubMed

Lewis, D. A., Lieberman, J. A. (2000). Catching up on schizophrenia: natural history and neurobiology. Neuron 28: 325–334CrossRef Google Scholar PubMed

Lidow, M. S., Goldman-Rakic, P. S., Rakic, P., Innis, R. B. (1989). Dopamine D(2) receptors in the cerebral cortex: distribution and pharmacological characterization with [(3)H]raclopride. Proc Natl Acad Sci USA 86: 6412–6416CrossRef Google Scholar

Lipshutz, R. J., Fodor, S. P. A., Gingeras, T. R., Lockhart, D. J. (1999). High density synthetic oligonucleotide arrays. Nat Genet 21S: 20–24CrossRef Google Scholar

Lockhart, D. J., Barlow, C. (2001). DNA arrays and gene expression analysis in the brain. In Methods in Genomic Neuroscience, ed. H. R. Chin, S. Moldin. New York: CRC Press, pp. 143–170CrossRef

Lockhart, D. J., Dong, H., Byrne, M. C.et al. (1996). Expression monitoring by hybridization to high-density oligonucleotide arrays. Nat Biotechnol 14: 1675–1680CrossRef Google Scholar PubMed

Luo, L., Salunga, R. C., Guo, H.et al. (1999). Gene expression profiles of laser-captured adjacent neuronal subtypes. Nat Med 5: 117–122CrossRef Google Scholar PubMed

Middleton, F. A., Mirnics, K., Pierri, J. N., Lewis, D. A., Levitt, P. (2002). Gene expression profiling reveals alterations of specific metabolic pathways in schizophrenia. J Neurosci 22: 2718–2729CrossRef Google Scholar

Mimmack, M. L., Ryan, M., Baba, H.et al. (2002). Gene expression analysis in schizophrenia: reproducible up-regulation of several members of the apolipoprotein L family located in a high-susceptibility locus for schizophrenia on chromosome 22. Proc Natl Acad Sci USA 99: 4680–4685CrossRef Google Scholar

Mirnics, K., Middleton, F. A., Marquez, A., Lewis, D. A., Levitt, P. (2000). Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex. Neuron 28: 53–67CrossRef Google Scholar PubMed

Mirnics, K., Middleton, F. A., Stanwood, G. D., Lewis, D. A., Levitt, P. (2001a). Disease-specific changes in regulator of G-protein signaling 4 (RGS4) expression in schizophrenia. Mol Psychiatry 6: 293–301CrossRef Google Scholar

Mirnics, K., Middleton, F. A., Lewis, D. A., Levitt, P. (2001b). Analysis of complex brain disorders with gene expression microarrays: schizophrenia as a disease of the synapse. Trends Neurosci 24: 479–486CrossRef Google Scholar

Pongrac, J., Middleton, F. A., Lewis, D. A., Levitt, P., Mirnics, K. (2002). Gene expression profiling with DNA microarrays: advancing our understanding of psychiatric disorders. Neurochem Res 27: 1049–1063CrossRef Google Scholar PubMed

Rakic, P., Bourgeois, J. P., Eckenhoff, M. F., Zecevic, N., Goldman-Rakic, P. S. (1986). Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex. Science 232: 232–235CrossRef Google Scholar PubMed

Schena, M., Davis, R. W. (1999). Microgenes, genomes and chips. In DNA Microarrays: A Practical Approach, ed. M. Schena. Oxford: Oxford University Press, pp. 1–16

Schena, M., Shalon, D., Davis, R. W., Brown, P. O. (1995). Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270: 467–470CrossRef Google Scholar PubMed

Schena, M., Shalon, D., Heller, R.et al. (1996). Parallel human genome analysis: microarray-based expression monitoring of 1000 genes. Proc Natl Acad SciUSA 93: 10614–10619CrossRef Google Scholar PubMed

Schneider, A., Montague, P., Griffiths, I.et al. (1992). Uncoupling of hypomyelination and glial cell death by a mutation in the proteolipid protein gene. Nature 358: 758–761CrossRef Google Scholar PubMed

Sklar, P. (2001). Microarray analysis of the Stanley brain collection. Abstract. In 7th Symposium on the Neurobiology and Neuroimmunology of Schizophrenia and Bipolar Disorder. Washington, DC: Stanley Foundation

Southern, E., Mir, K., Shchepinov, M. (1999). Molecular interactions on microarrays. Nat Genet 21: 5–9CrossRef Google Scholar PubMed

Vawter, M. P., Barrett, T., Cheadle, C.et al. (2001). Application of cDNA microarrays to examine gene expression differences in schizophrenia. Res Bull 55: 641–650CrossRef Google Scholar

Vawter, M. P., Crook, J. M., Hyde, T. M.et al. (2002). Microarray analysis of gene expression in the prefrontal cortex in schizophrenia: a preliminary study. Schizophr Res 58: 11–20CrossRef Google Scholar PubMed

Volk, D. W., Austin, M. C., Pierri, J. N., Sampson, A. R., Lewis, D. A. (2000). Decreased GAD67 mRNA expression in a subset of prefrontal cortical GABA neurons in subjects with schizophrenia. Arch Gen Psychiatry 57: 237–245CrossRef Google Scholar

Waterworth, D. M., Bassett, A. S., Brzustowicz, L. M. (2002). Recent advances in the genetics of schizophrenia. Cell Mol Life Sci 59: 331–348CrossRef Google Scholar

Weickert, C. S., Hyde, T. M., Lipska, B. K.et al. (2003). Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia. Mol Psychiatry 8: 592–610CrossRef Google Scholar PubMed

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