Send to

Choose Destination
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

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


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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center