Gene expression profiling in postmortem prefrontal cortex of major depressive disorder

Jung Kang Hyo, David H. Adams, Arthur Simen, Birgitte B. Simen, Grazyna Rajkowska, Craig A. Stockmeier, James C. Overholser, Herbert Y. Meltzer, George J. Jurjus, Lisa C. Konick, Samuel S. Newton, Ronald S. Duman

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

Investigations of the molecular mechanisms underlying major depressive disorder (MDD) have been hampered by the complexity of brain tissue and sensitivity of gene expression profiling approaches. To address these issues, we used discrete microdissections of postmortem dorsolateral prefrontal cortex (DLPFC) (area 9) and an oligonucleotide (60mer) microarray hybridization procedure that increases sensitivity without RNA amplification. Mixed-effects statistical methods were used to rigorously control for medication usage in the subset of medicated depressed subjects. These analyses yielded a rich profile of dysregulated genes. Two of the most highly dysregulated genes of interest were stresscopin, a neuropeptide involved in stress responses, and Forkhead box D3 (FOXD3), a transcription factor. Secondary cell-based analysis demonstrated that stresscopin and FoxD3 are increased in neurons of DLPFC gray matter of MDD subjects. These findings identify abnormal gene expression in a discrete region of MDD subjects and contribute to further elucidation of the molecular alterations of this complex mood disorder.

Original languageEnglish (US)
Pages (from-to)13329-13340
Number of pages12
JournalJournal of Neuroscience
Volume27
Issue number48
DOIs
StatePublished - Nov 28 2007

Keywords

  • Corticotrophin releasing hormone
  • Fibroblast growth factor
  • FoxD3
  • Microarray
  • Stress
  • Stresscopin
  • Urocortin III

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Hyo, J. K., Adams, D. H., Simen, A., Simen, B. B., Rajkowska, G., Stockmeier, C. A., Overholser, J. C., Meltzer, H. Y., Jurjus, G. J., Konick, L. C., Newton, S. S., & Duman, R. S. (2007). Gene expression profiling in postmortem prefrontal cortex of major depressive disorder. Journal of Neuroscience, 27(48), 13329-13340. https://doi.org/10.1523/JNEUROSCI.4083-07.2007