Dysregulation in the Suicide Brain

mRNA Expression of Corticotropin-Releasing Hormone Receptors and GABAA Receptor Subunits in Frontal Cortical Brain Region

Zul Merali, Lisheng Du, Pavel Hrdina, M. Palkóvits, G. Faludi, Michael O. Poulter, Hymie Anisman

Research output: Contribution to journalArticle

278 Citations (Scopus)

Abstract

Corticotropin-releasing hormone (CRH) and GABA have been implicated in depression, and there is reason to believe that GABA may influence CRH functioning. The levels of CRH, and mRNA for CRH-binding protein, CRH 1, and CRH2 receptors, as well as various GABA A receptor subunits (α1, α2, α3, α4, α5, δ, and γ2), were determined in several frontal cortical brain regions of depressed suicide victims and nondepressed individuals who had not died by suicide. Relative to the comparison group, CRH levels were elevated in frontopolar and dorsomedial prefrontal cortex, but not in the ventrolateral prefrontal cortex of suicide victims. Conversely, using quantitative PCR analyses, it was observed that, in frontopolar cortex, mRNA for CRH 1, but not CRH2, receptors were reduced in suicide brains, possibly secondary to the high levels of CRH activity. In addition, mRNA of the α1, α3, α4, and δ receptor subunits was reduced in the frontopolar region of suicide victims. Interestingly, a partial analysis of the GABAA receptor functional genome revealed high cross-correlations between subunit expression in cortical regions of nondepressed individuals, suggesting a high degree of coordinated gene regulation. However, in suicide brains, this regulation was perturbed, independent of overall subunit abundance. These findings raise the possibility that the CRH and GABAA receptor subunit changes, or the disturbed coordination between these GABAA receptor subunits, contribute to depression and/or suicidality or are secondary to the illness/distress associated with it.

Original languageEnglish
Pages (from-to)1478-1485
Number of pages8
JournalJournal of Neuroscience
Volume24
Issue number6
DOIs
Publication statusPublished - Feb 11 2004

Fingerprint

Corticotropin-Releasing Hormone Receptors
Corticotropin-Releasing Hormone
GABA-A Receptors
Suicide
Messenger RNA
Brain
Prefrontal Cortex
gamma-Aminobutyric Acid
Depression
Genome
Polymerase Chain Reaction

Keywords

  • Cortex
  • CRF
  • Depression
  • GABA
  • Human suicide
  • Prefrontal
  • QPCR

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Dysregulation in the Suicide Brain : mRNA Expression of Corticotropin-Releasing Hormone Receptors and GABAA Receptor Subunits in Frontal Cortical Brain Region. / Merali, Zul; Du, Lisheng; Hrdina, Pavel; Palkóvits, M.; Faludi, G.; Poulter, Michael O.; Anisman, Hymie.

In: Journal of Neuroscience, Vol. 24, No. 6, 11.02.2004, p. 1478-1485.

Research output: Contribution to journalArticle

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abstract = "Corticotropin-releasing hormone (CRH) and GABA have been implicated in depression, and there is reason to believe that GABA may influence CRH functioning. The levels of CRH, and mRNA for CRH-binding protein, CRH 1, and CRH2 receptors, as well as various GABA A receptor subunits (α1, α2, α3, α4, α5, δ, and γ2), were determined in several frontal cortical brain regions of depressed suicide victims and nondepressed individuals who had not died by suicide. Relative to the comparison group, CRH levels were elevated in frontopolar and dorsomedial prefrontal cortex, but not in the ventrolateral prefrontal cortex of suicide victims. Conversely, using quantitative PCR analyses, it was observed that, in frontopolar cortex, mRNA for CRH 1, but not CRH2, receptors were reduced in suicide brains, possibly secondary to the high levels of CRH activity. In addition, mRNA of the α1, α3, α4, and δ receptor subunits was reduced in the frontopolar region of suicide victims. Interestingly, a partial analysis of the GABAA receptor functional genome revealed high cross-correlations between subunit expression in cortical regions of nondepressed individuals, suggesting a high degree of coordinated gene regulation. However, in suicide brains, this regulation was perturbed, independent of overall subunit abundance. These findings raise the possibility that the CRH and GABAA receptor subunit changes, or the disturbed coordination between these GABAA receptor subunits, contribute to depression and/or suicidality or are secondary to the illness/distress associated with it.",
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