Alteration in estrogen receptor α mRNA levels in frontal cortex and hippocampus of patients with major mental illness

William R. Perlman, Eva Tomaskovic-Crook, Deidra M. Montague, Maree J. Webster, David R. Rubinow, Joel E. Kleinman, Cynthia Shannon Weickert

Research output: Contribution to journalArticlepeer-review


Background: Gender differences have been described in major mental illnesses (MMI). The dorsolateral prefrontal cortex (DLPFC) and hippocampus are estrogen-sensitive brain regions structurally and functionally altered in patients with MMI. We hypothesized that gender-specific alterations in DLPFC and hippocampus estrogen receptor α (ERα) mRNA levels may exist in MMI patients. Methods: We used Northern blot analysis to survey the expression of ERα mRNA transcripts in brain and body, detected by our human ERα riboprobe and in situ hybridization, to examine the expression pattern and quantify ERα mRNA levels in DLPFC and anterior hippocampus of patients with major depressive disorder (MDD), schizophrenia, and bipolar disorder compared with normal control subjects. Results: Northern blotting revealed brain-region-specific differences in expression levels of a 5 kb ERα mRNA transcript. By in situ hybridization, ERα mRNA was detected in all layers of DLPFC and all hippocampal subfields in all subjects. We detected greater DLPFC ERα mRNA expression in male compared with female MDD subjects and reduced ERα mRNA levels in the dentate gyrus of schizophrenics compared with control subjects. Conclusions: Our results suggest that alterations in ERα mRNA levels exist in distinct telencephalic regions in male and female MDD patients, and in both genders in schizophrenia.

Original languageEnglish (US)
Pages (from-to)812-824
Number of pages13
JournalBiological psychiatry
Issue number10
StatePublished - Nov 15 2005
Externally publishedYes


  • Age of onset
  • Bipolar disorder
  • Gender difference
  • Major depression
  • Psychosis
  • Schizophrenia

ASJC Scopus subject areas

  • Biological Psychiatry


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