Monoamine oxidase a and catechol-o-methyltransferase functional polymorphisms and the placebo response in major depressive disorder

Andrew F. Leuchter, James T. McCracken, Aimee M. Hunter, Ian A. Cook, Jonathan E. Alpert

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

The placebo response shows pronounced interindividual variability. Placebos are postulated to act through central reward pathways that are modulated by monoamines. Because monoaminergic signaling is under strong genetic control, we hypothesized that common functional polymorphisms modulating monoaminergic tone would be related to degree of improvement during placebo treatment of subjects with major depressive disorder. We examined polymorphisms in genes encoding the catabolic enzymes catechol-O-methyltransferase and monoamine oxidase A. Subjects with monoamine oxidase A G/T polymorphisms (rs6323) coding for the highest activity form of the enzyme (G or G/G) had a significantly lower magnitude of placebo response than those with other genotypes. Subjects with ValMet catechol-O-methyltransferase polymorphisms coding for a lower-activity form of the enzyme (2 Met alleles) showed a statistical trend toward a lower magnitude of placebo response. These findings support the hypothesis that genetic polymorphisms modulating monoaminergic tone are related to degree of placebo responsiveness in major depressive disorder.

Original languageEnglish (US)
Pages (from-to)372-377
Number of pages6
JournalJournal of Clinical Psychopharmacology
Volume29
Issue number4
DOIs
StatePublished - Aug 1 2009
Externally publishedYes

Keywords

  • Catechol-O-methyltransferase (COMT)
  • Dopamine
  • Genetic polymorphisms
  • Major depressive disorder
  • Monoamine oxidase A (MAO-A)
  • Norepinephrine
  • Placebo response

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)

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