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 mu-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.
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 mu-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.
Authors: Christopher C Conway; Constance Hammen; Patricia A Brennan; Penelope A Lind; Jake M Najman Journal: Depress Anxiety Date: 2010-08 Impact factor: 6.505
Authors: Deborah J Walder; Hanan D Trotman; Joseph F Cubells; Joy Brasfield; Yi-Lang Tang; Elaine F Walker Journal: Psychiatr Genet Date: 2010-08 Impact factor: 2.458
Authors: Jonathan Evans; Ke Xu; Jon Heron; Mary-Anne Enoch; Ricardo Araya; Glyn Lewis; Nic Timpson; Simon Davies; David Nutt; David Goldman Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2009-03-05 Impact factor: 3.568
Authors: Lauren D Hill; Margaret S Lorenzetti; Sarah M Lyle; Ana I Fins; Aurélien Tartar; Jaime L Tartar Journal: Brain Behav Date: 2018-01-18 Impact factor: 2.708