St John's wort and imipramine-induced gene expression profiles identify cellular functions relevant to antidepressant action and novel pharmacogenetic candidates for the phenotype of antidepressant treatment response

M. L. Wong, F. O'Kirwan, J. P. Hannestad, K. J.L. Irizarry, D. Elashoff, J. Licinio

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Both the prototypic tricyclic antidepressant imipramine (IMI) and the herbal product St John's wort (SJW) can be effective in the treatment of major depressive disorder. We studied hypothalamic gene expression in rats treated with SJW or IMI to test the hypothesis that chronic antidepressant treatment by various classes of drugs results in shared patterns of gene expression that may underlie their therapeutic effects. Individual hypothalami were hybridized to individual Affymetrix chips; we studied three arrays per group treatment. We constructed 95% confidence intervals for expression fold change for genes present in at least one treatment condition and we considered genes to be differentially expressed if they had a confidence interval excluding 1 (or -1) and had absolute difference in expression value of 10 or greater. SJW treatment differentially regulated 66 genes and expression sequence tags (ESTs) and IMI treatment differentially regulated 74 genes and ESTs. We found six common transcripts in response to both treatments. The likelihood of this occurring by chance is 1.14 × 10-23. These transcripts are relevant to two molecular machines, namely the ribosomes and microtubules, and one cellular organelle, the mitochondria. Both treatments also affected different genes that are part of the same cell function processes, such as glycolytic pathways and synaptic function. We identified single-nucleotide polymorphisms in the human orthologs of genes regulated both treatments, as those genes may be novel candidates for pharmacogenetic studies. Our data support the hypothesis that chronic antidepressant treatment by drugs of various classes may result in a common, final pathway of changes in gene expression in a discrete brain region.

LanguageEnglish
Pages237-251
Number of pages15
JournalMolecular Psychiatry
Volume9
Issue number3
DOIs
Publication statusPublished - 1 Mar 2004

Keywords

  • Antidepressants
  • Hypericum
  • Imipramine
  • Major depression
  • Microarray
  • Treatment

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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