TY - JOUR
T1 - Cortisol Stress Response in Men and Women Modulated Differentially by the Mu-Opioid Receptor Gene Polymorphism OPRM1 A118G
AU - Lovallo, William R.
AU - Enoch, Mary Anne
AU - Acheson, Ashley
AU - Cohoon, Andrew J.
AU - Sorocco, Kristen H.
AU - Hodgkinson, Colin A.
AU - Vincent, Andrea S.
AU - Glahn, David C.
AU - Goldman, David
N1 - Funding Information:
This work was supported by Department of Veterans Affairs Medical Research Service; NIH Grants NIRR M01 RR014467, NIAAA R01AA019691 and R01 AA012207; and the NIAAA Intramural Research Program. The content is solely the view of the authors and does not necessarily represent the official view of the National Institutes of Health or the Department of Veterans Affairs. Dr Vincent receives income from the University of Oklahoma Department of Psychology, the University of Oklahoma Health Sciences Center Department of Psychiatry and Behavioral Sciences, and the Cognitive Science Research Center at the University of Oklahoma. None of these sources involves producing a product that is used or featured as a result of this research. The authors declare no conflict of interest.
PY - 2015/10/12
Y1 - 2015/10/12
N2 - Differences in stress reactivity may affect long-term health outcomes, but there is little information on how these differences arise. The stress axis is regulated by, in part, the endogenous opioid, beta-endorphin, acting on mu-opioid receptors. Persons carrying one or two copies of the G allele of the mu-opioid receptor gene (OPRM1 A118G) may have higher receptor binding for beta-endorphin compared with AA homozygotes that may contribute to individual differences in cortisol reactivity to stress, leading to a relative blunting of cortisol stress reactivity in G allele genotypes. We measured cortisol in 251 young adults (69 GA/GG vs 182 AA genotypes) exposed to mental arithmetic plus public speaking stress relative to a resting control day. Women had smaller cortisol responses than men (F=10.2, p=0.002), and women with GA or GG genotypes (N=39) had an absence of cortisol response relative to AA carriers (N=110) (F=18.4, p<0.0001). Male genotypes had no such difference in response (F=0.29). Cortisol response following mu-opioid receptor blockade using naltrexone in 119 of these subjects unmasked a greater tonic opioid inhibition of cortisol secretion in women (N=64), consistent with their blunted stress reactivity. Compared with men, women may have cortisol stress responses that are more heavily regulated by endogenous opioid mechanisms, and the OPRM1 GA/GG genotypes may affect females differentially relative to males. Diminished cortisol responses to stress may have consequences for health behaviors in women with GA/GG genotypes.
AB - Differences in stress reactivity may affect long-term health outcomes, but there is little information on how these differences arise. The stress axis is regulated by, in part, the endogenous opioid, beta-endorphin, acting on mu-opioid receptors. Persons carrying one or two copies of the G allele of the mu-opioid receptor gene (OPRM1 A118G) may have higher receptor binding for beta-endorphin compared with AA homozygotes that may contribute to individual differences in cortisol reactivity to stress, leading to a relative blunting of cortisol stress reactivity in G allele genotypes. We measured cortisol in 251 young adults (69 GA/GG vs 182 AA genotypes) exposed to mental arithmetic plus public speaking stress relative to a resting control day. Women had smaller cortisol responses than men (F=10.2, p=0.002), and women with GA or GG genotypes (N=39) had an absence of cortisol response relative to AA carriers (N=110) (F=18.4, p<0.0001). Male genotypes had no such difference in response (F=0.29). Cortisol response following mu-opioid receptor blockade using naltrexone in 119 of these subjects unmasked a greater tonic opioid inhibition of cortisol secretion in women (N=64), consistent with their blunted stress reactivity. Compared with men, women may have cortisol stress responses that are more heavily regulated by endogenous opioid mechanisms, and the OPRM1 GA/GG genotypes may affect females differentially relative to males. Diminished cortisol responses to stress may have consequences for health behaviors in women with GA/GG genotypes.
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U2 - 10.1038/npp.2015.101
DO - 10.1038/npp.2015.101
M3 - Article
C2 - 25881118
AN - SCOPUS:84941314933
VL - 40
SP - 2546
EP - 2554
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
SN - 0893-133X
IS - 11
ER -