title: Cortisol Stress Response in Men and Women Modulated Differentially by the Mu-Opioid Receptor Gene Polymorphism OPRM1 A118G.
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.
authors.affiliation: VA Medical Center, Oklahoma City, OK, USA.|Department of Psychiatry and Behavioral Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Lovallo
authors.affiliation: Laboratory of Neurogenetics, NIH, NIAAA, Bethesda, MD, USA.
authors.forename: Mary-Anne
authors.initials: MA
authors.lastname: Enoch
authors.affiliation: Department of Psychiatry, University of Texas Health Sciences Center at San Antonio, San Antonio, TX, USA.|Research Imaging Institute, UTHSCSA, San Antonio, TX, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Acheson
authors.affiliation: VA Medical Center, Oklahoma City, OK, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Cohoon
authors.affiliation: VA Medical Center, Oklahoma City, OK, USA.|Donald W. Reynolds Department of Geriatric Medicine, OUHSC, Oklahoma City, OK, USA.
authors.forename: Kristen H
authors.initials: KH
authors.lastname: Sorocco
authors.affiliation: Laboratory of Neurogenetics, NIH, NIAAA, Bethesda, MD, USA.
authors.forename: Colin A
authors.initials: CA
authors.lastname: Hodgkinson
authors.affiliation: Cognitive Science Research Center, University of Oklahoma, Norman, OK, USA.
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Vincent
authors.affiliation: Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA.|Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Glahn
authors.affiliation: Laboratory of Neurogenetics, NIH, NIAAA, Bethesda, MD, USA.
authors.forename: David
authors.initials: D
authors.lastname: Goldman
mesh_terms: D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D055641:Mathematical Concepts; D009271:Naltrexone / Q000008:administration & dosage; D009292:Narcotic Antagonists / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D011897:Random Allocation; D017450:Receptors, Opioid, mu / Q000235:genetics*; D012463:Saliva / Q000187:drug effects / Q000378:metabolism; D012727:Sex Characteristics; D012938:Social Perception; D013315:Stress, Psychological / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D009292:Narcotic Antagonists; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D009271:Naltrexone; D006854:Hydrocortisone