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Association between treatment-emergent suicidal ideation with citalopram and polymorphisms near cyclic adenosine

Roy H Perlis1, Shaun Purcell, Maurizio Fava

  • 1Massachusetts General Hospital, Boston, MA 02114, USA. rperlis@partners.org

Archives of General Psychiatry
|June 6, 2007
PubMed
Abstract

Insights

Certain CREB1 gene variations are linked to increased suicidality risk in men with depression. This finding may help identify individuals needing closer monitoring during antidepressant treatment.

Area of Science:

  • Neuroscience
  • Genetics
  • Psychiatry

Background:

  • A small subset of patients with depression experience increased suicidal thoughts or behaviors when treated with antidepressants.
  • The cyclic adenosine monophosphate response element binding (CREB) protein is involved in antidepressant mechanisms and suicide, making the CREB1 gene a candidate for influencing treatment-emergent suicidality.

Purpose of the Study:

  • To investigate the association between CREB1 gene polymorphisms and new or worsening suicidal behavior in patients with major depressive disorder.
  • To build upon previous findings linking CREB1 to anger expression in men with depression.

Main Methods:

  • A nested case-control study using data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial.
  • Examined 5 single nucleotide polymorphisms (SNPs) within the CREB1 gene in individuals with nonpsychotic major depressive disorder treated with citalopram.
  • Suicidality was defined as a score of 2 or higher on a specific suicide item post-baseline.

Main Results:

  • No overall significant association was found between CREB1 polymorphisms and treatment-emergent suicidality across all participants.
  • A significant gene-by-sex interaction was observed; 2 SNPs and 2 haplotypes within CREB1 were significantly associated with new-onset suicidality in men.
  • Out of 1447 participants, 124 (8.6%) reported suicidality during the study.

Conclusions:

  • CREB1 gene polymorphisms are associated with treatment-emergent suicidality in men with depression.
  • These findings align with prior research on male anger expression and CREB1.
  • Pharmacogenetic testing of CREB1 may help identify at-risk individuals for closer monitoring during antidepressant therapy.

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