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Catechol-O-methyltransferase polymorphism alters hypothalamic-pituitary-adrenal axis responses to naloxone: a
Lynn M Oswald1, Mary McCaul, Leena Choi
1Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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.
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