Journal
NEUROPSYCHOPHARMACOLOGY
Volume 40, Issue 11, Pages 2546-2554Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2015.101
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Funding
- Department of Veterans Affairs Medical Research Service
- NIH [NIRR M01 RR014467, NIAAA R01AA019691, R01 AA012207]
- NIAAA Intramural Research Program
- University of Oklahoma Department of Psychology
- University of Oklahoma Health Sciences Center Department of Psychiatry and Behavioral Sciences
- Cognitive Science Research Center at the University of Oklahoma
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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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