Monoamine oxidase a and catechol-o-methyltransferase functional polymorphisms and the placebo response in major depressive disorder.
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.
Leuchter
Andrew F
AF
Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA,760 Westwood Plaza, Rm 37-452, Los Angeles, CA 90024-1759, USA. afl@ucla.edu
McCracken
James T
JT
Hunter
Aimee M
AM
Cook
Ian A
IA
Alpert
Jonathan E
JE
D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D015990:Placebo Effect; D020641:Polymorphism, Single Nucleotide; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000928:Antidepressive Agents; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase