Journal
BIOLOGICAL PSYCHIATRY
Volume 55, Issue 1, Pages 102-105Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2003.07.003
Keywords
catecholamine; naloxone; cortisol; adrenocorticotropin; neuroendocrine; hypertension; genetics; human
Categories
Funding
- NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR000052] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [R01AA010158, R37AA012303] Funding Source: NIH RePORTER
- NCRR NIH HHS [M01RR00052] Funding Source: Medline
- NIAAA NIH HHS [AA10158, AA12303] Funding Source: Medline
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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 V-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. (C) 2004 Society of Biological Psychiatry.
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