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

TitleMonoamine oxidase a and catechol-o-methyltransferase functional polymorphisms and the placebo response in major depressive disorder.
Publication TypeJournal Article
Year of Publication2009
AuthorsLeuchter, AF, McCracken JT, Hunter AM, Cook IA, Alpert JE
JournalJournal of clinical psychopharmacology
Volume29
Issue4
Pagination372-7
Date Published2009 Aug
ISSN1533-712X
KeywordsAdult, Antidepressive Agents, Catechol O-Methyltransferase, Depressive Disorder, Major, Double-Blind Method, Female, Genotype, Humans, Male, Middle Aged, Monoamine Oxidase, Phenotype, Placebo Effect, Polymorphism, Single Nucleotide, Randomized Controlled Trials as Topic, Severity of Illness Index, Treatment Outcome
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.

DOI10.1111/j.1460-9568.2012.08134.x
Alternate JournalJ Clin Psychopharmacol