期刊
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
卷 29, 期 4, 页码 372-377出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/JCP.0b013e3181ac4aaf
关键词
major depressive disorder; placebo response; genetic polymorphisms; catechol-O-methyltransferase (COMT); monoamine oxidase A (MAO-A); dopamine; norepinephrine
资金
- NIH [R01 AT002479]
- Eli Lilly Company
- Pfizer, Inc.
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 Val(158)Met 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.
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