Abstract
The molecular basis of complex neuropsychiatric disorders most likely involves many genes. In recent years, specific genetic variations influencing risk for schizophrenia and other neuropsychiatric disorders have been reported. We have used custom DNA microarrays and qPCR to investigate the expression of putative schizophrenia susceptibility genes and related genes of interest in the normal human brain. Expression of 31 genes was measured in Brodmann’s area 10 (BA10) in the prefrontal cortex of 72 postmortem brain samples spanning half a century of human aging (18–67 years), each without history of neuropsychiatric illness, neurological disease, or drug abuse. Examination of expression across age allowed the identification of genes whose expression patterns correlate with age, as well as genes that share common expression patterns and that possibly participate in common cellular mechanisms related to the emergence of schizophrenia in early adult life. The expression of GRM3 and RGS4 decreased across the entire age range surveyed, while that of PRODH and DARPP-32 was shown to increase with age. NRG1, ERBB3, and NGFR show expression changes during the years of greatest risk for the development of schizophrenia. Expression of FEZ1, GAD1, and RGS4 showed especially high correlation with one another, in addition to the strongest mean levels of absolute correlation with all other genes studied here. All microarray data are available at http://www.ncbi.nlm.nih.gov/geo/ (accession #: TBA).
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Acknowledgments
This research was supported by funding solely provided by the Intramural Research Program of the National Institute of Mental Health. The authors would also like to thank Llewellyn B. Bigelow, MD., Vesna Imamovic, Yeva Snitkovsky, and Jewell King for their contributions to the collection and diagnosis of the brain specimens used in this research, the Offices of the Chief Medical Examiner of Washington DC and of Northern Virginia, as well as families of the deceased whose donation of this tissue made this research possible.
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We, the authors declare that, except for income received from our primary employer, no financial support or compensation has been received from any individual or corporate entity over the past three years for research or professional service and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest.
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An erratum to this article can be found at http://dx.doi.org/10.1007/s00429-008-0188-y
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Colantuoni, C., Hyde, T.M., Mitkus, S. et al. Age-related changes in the expression of schizophrenia susceptibility genes in the human prefrontal cortex. Brain Struct Funct 213, 255–271 (2008). https://doi.org/10.1007/s00429-008-0181-5
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DOI: https://doi.org/10.1007/s00429-008-0181-5