William R Lovallo1, Mary-Anne Enoch, Kristen H Sorocco, Andrea S Vincent, Ashley Acheson, Andrew J Cohoon, Colin A Hodgkinson, David Goldman. 1. From the VA Medical Center (Lovallo, Sorocco); Department of Psychiatry and Behavioral Sciences (Lovallo, Cohoon), University of Oklahoma Health Sciences Center, Oklahoma City; Laboratory of Neurogenetics (Enoch, Hodgkinson, Goldman), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland; Donald W. Reynolds Department of Geriatric Medicine (Sorocco), University of Oklahoma Health Sciences Center, Oklahoma City; Cognitive Science Research Center (Vincent), University of Oklahoma, Norman; Department of Psychiatry (Acheson), University of Texas Health Sciences Center at San Antonio; and Research Imaging Institute (Acheson), San Antonio, Texas.
Abstract
OBJECTIVE: Exposure to stress during critical periods of development can diminish stress reactivity by the hypothalamic-pituitary-adrenocortical axis. Genetic characteristics may further modify this effect of early adversity, leading to a gene by environment (G × E) interaction on stress reactivity in adulthood. Val-allele carriers of a common polymorphism of the COMT gene (Val158Met, rs4680) have rapid removal of catecholamines in the prefrontal cortex, limbic system, and reward centers. Carriers of the Val and Met alleles may therefore respond differently to the environment and differ in the long-term impact of exposure to early life adversity (ELA). METHODS: We measured saliva cortisol reactivity to public speaking and mental arithmetic stress in 252 healthy young adults exposed to low, medium, and high levels of ELA and who were genotyped for the Val158Met polymorphism. RESULTS: Cortisol responses showed a G × E interaction (F(4,243) = 2.78, p = .028); simple effects tests showed that Met/Met carriers had progressively smaller cortisol responses with greater levels of ELA. In comparison, Val/Val homozygotes had blunted responses that did not vary with ELA exposure. CONCLUSIONS: Met/Met homozygotes seem sensitive to stressful events in childhood and adolescence, leading to environmental programming of the stress axis. Glucocorticoid responsivity may represent a common pathway revealing targeted genetic vulnerabilities to the long-term effects of early life stress. The results suggest that further G × E studies of ELA are warranted in relation to health behaviors and health outcomes in adulthood.
OBJECTIVE: Exposure to stress during critical periods of development can diminish stress reactivity by the hypothalamic-pituitary-adrenocortical axis. Genetic characteristics may further modify this effect of early adversity, leading to a gene by environment (G × E) interaction on stress reactivity in adulthood. Val-allele carriers of a common polymorphism of the COMT gene (Val158Met, rs4680) have rapid removal of catecholamines in the prefrontal cortex, limbic system, and reward centers. Carriers of the Val and Met alleles may therefore respond differently to the environment and differ in the long-term impact of exposure to early life adversity (ELA). METHODS: We measured saliva cortisol reactivity to public speaking and mental arithmetic stress in 252 healthy young adults exposed to low, medium, and high levels of ELA and who were genotyped for the Val158Met polymorphism. RESULTS:Cortisol responses showed a G × E interaction (F(4,243) = 2.78, p = .028); simple effects tests showed that Met/Met carriers had progressively smaller cortisol responses with greater levels of ELA. In comparison, Val/Val homozygotes had blunted responses that did not vary with ELA exposure. CONCLUSIONS: Met/Met homozygotes seem sensitive to stressful events in childhood and adolescence, leading to environmental programming of the stress axis. Glucocorticoid responsivity may represent a common pathway revealing targeted genetic vulnerabilities to the long-term effects of early life stress. The results suggest that further G × E studies of ELA are warranted in relation to health behaviors and health outcomes in adulthood.
Authors: William R Lovallo; Andrew J Cohoon; Kristen H Sorocco; Andrea S Vincent; Ashley Acheson; Colin A Hodgkinson; David Goldman Journal: Alcohol Clin Exp Res Date: 2019-05-31 Impact factor: 3.455
Authors: Anne L Ersig; Debra L Schutte; Jennifer Standley; Elizabeth J Leslie; Bridget Zimmerman; Kirsten Hanrahan; Jeffrey C Murray; Ann Marie McCarthy Journal: Biol Res Nurs Date: 2019-01-30 Impact factor: 2.522