Catechol-O-methyltransferase polymorphism alters hypothalamic-pituitary- adrenal axis responses to naloxone: A preliminary report

Research output: Contribution to journalArticle

Abstract

Background: A common polymorphism in the catechol-O-methyltransferase gene involves a valine to methionine mutation that results in a threefold to fourfold decrease in enzyme activity. This polymorphism has been associated with altered μ-opioid receptor binding potential and prefrontal cognitive performance, as well as risk for several neuropsychiatric conditions. We hypothesized that subjects homozygous for the low-activity allele would have greater hypothalamic-pituitary-adrenal axis responses to opioid blockade than subjects with the high-activity allele. Methods: Forty-six healthy adults were genotyped and underwent a procedure in which adrenocorticotropin hormone and cortisol responses to the opioid antagonist naloxone were examined. Results: Findings showed that adrenocorticotropin hormone and cortisol responses were greater in subjects with the methionine/methionine genotype compared to subjects homozygous or heterozygous for the valine allele. Conclusions: These findings suggest that individual differences in catecholamine metabolism may impact hypothalamic-pituitary-adrenal axis function and may play a pharmacogenetic role in responses to naloxone.

Original languageEnglish (US)
Pages (from-to)102-105
Number of pages4
JournalBiological Psychiatry
Volume55
Issue number1
DOIs
StatePublished - Jan 1 2004

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Catechol O-Methyltransferase
Naloxone
Methionine
Alleles
Valine
Adrenocorticotropic Hormone
Hydrocortisone
Hormones
Narcotic Antagonists
Pharmacogenetics
Opioid Receptors
Individuality
Opioid Analgesics
Catecholamines
Genotype
Mutation
Enzymes
Genes

Keywords

  • Adrenocorticotropin
  • Catecholamine
  • Cortisol
  • Genetics
  • Human
  • Hypertension
  • Naloxone
  • Neuroendocrine

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

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title = "Catechol-O-methyltransferase polymorphism alters hypothalamic-pituitary- adrenal axis responses to naloxone: A preliminary report",
abstract = "Background: A common polymorphism in the catechol-O-methyltransferase gene involves a valine to methionine mutation that results in a threefold to fourfold decrease in enzyme activity. This polymorphism has been associated with altered μ-opioid receptor binding potential and prefrontal cognitive performance, as well as risk for several neuropsychiatric conditions. We hypothesized that subjects homozygous for the low-activity allele would have greater hypothalamic-pituitary-adrenal axis responses to opioid blockade than subjects with the high-activity allele. Methods: Forty-six healthy adults were genotyped and underwent a procedure in which adrenocorticotropin hormone and cortisol responses to the opioid antagonist naloxone were examined. Results: Findings showed that adrenocorticotropin hormone and cortisol responses were greater in subjects with the methionine/methionine genotype compared to subjects homozygous or heterozygous for the valine allele. Conclusions: These findings suggest that individual differences in catecholamine metabolism may impact hypothalamic-pituitary-adrenal axis function and may play a pharmacogenetic role in responses to naloxone.",
keywords = "Adrenocorticotropin, Catecholamine, Cortisol, Genetics, Human, Hypertension, Naloxone, Neuroendocrine",
author = "Oswald, {Lynn Marie} and McCaul, {Mary Elizabeth} and Leena Choi and Xiaoju Yang and Wand, {Gary S}",
year = "2004",
month = "1",
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doi = "10.1016/j.biopsych.2003.07.003",
language = "English (US)",
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pages = "102--105",
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T1 - Catechol-O-methyltransferase polymorphism alters hypothalamic-pituitary- adrenal axis responses to naloxone

T2 - A preliminary report

AU - Oswald, Lynn Marie

AU - McCaul, Mary Elizabeth

AU - Choi, Leena

AU - Yang, Xiaoju

AU - Wand, Gary S

PY - 2004/1/1

Y1 - 2004/1/1

N2 - Background: A common polymorphism in the catechol-O-methyltransferase gene involves a valine to methionine mutation that results in a threefold to fourfold decrease in enzyme activity. This polymorphism has been associated with altered μ-opioid receptor binding potential and prefrontal cognitive performance, as well as risk for several neuropsychiatric conditions. We hypothesized that subjects homozygous for the low-activity allele would have greater hypothalamic-pituitary-adrenal axis responses to opioid blockade than subjects with the high-activity allele. Methods: Forty-six healthy adults were genotyped and underwent a procedure in which adrenocorticotropin hormone and cortisol responses to the opioid antagonist naloxone were examined. Results: Findings showed that adrenocorticotropin hormone and cortisol responses were greater in subjects with the methionine/methionine genotype compared to subjects homozygous or heterozygous for the valine allele. Conclusions: These findings suggest that individual differences in catecholamine metabolism may impact hypothalamic-pituitary-adrenal axis function and may play a pharmacogenetic role in responses to naloxone.

AB - Background: A common polymorphism in the catechol-O-methyltransferase gene involves a valine to methionine mutation that results in a threefold to fourfold decrease in enzyme activity. This polymorphism has been associated with altered μ-opioid receptor binding potential and prefrontal cognitive performance, as well as risk for several neuropsychiatric conditions. We hypothesized that subjects homozygous for the low-activity allele would have greater hypothalamic-pituitary-adrenal axis responses to opioid blockade than subjects with the high-activity allele. Methods: Forty-six healthy adults were genotyped and underwent a procedure in which adrenocorticotropin hormone and cortisol responses to the opioid antagonist naloxone were examined. Results: Findings showed that adrenocorticotropin hormone and cortisol responses were greater in subjects with the methionine/methionine genotype compared to subjects homozygous or heterozygous for the valine allele. Conclusions: These findings suggest that individual differences in catecholamine metabolism may impact hypothalamic-pituitary-adrenal axis function and may play a pharmacogenetic role in responses to naloxone.

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KW - Cortisol

KW - Genetics

KW - Human

KW - Hypertension

KW - Naloxone

KW - Neuroendocrine

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