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Neuropsychopharmacology. 2015 Oct;40(11):2546-54. doi: 10.1038/npp.2015.101. Epub 2015 Apr 16.

Cortisol Stress Response in Men and Women Modulated Differentially by the Mu-Opioid Receptor Gene Polymorphism OPRM1 A118G.

Author information

1
VA Medical Center, Oklahoma City, OK, USA.
2
Department of Psychiatry and Behavioral Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
3
Laboratory of Neurogenetics, NIH, NIAAA, Bethesda, MD, USA.
4
Department of Psychiatry, University of Texas Health Sciences Center at San Antonio, San Antonio, TX, USA.
5
Research Imaging Institute, UTHSCSA, San Antonio, TX, USA.
6
Donald W. Reynolds Department of Geriatric Medicine, OUHSC, Oklahoma City, OK, USA.
7
Cognitive Science Research Center, University of Oklahoma, Norman, OK, USA.
8
Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA.
9
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.

Abstract

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.

PMID:
25881118
PMCID:
PMC4569944
DOI:
10.1038/npp.2015.101
[Indexed for MEDLINE]
Free PMC Article

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