Joint Impact of Early Life Adversity and COMT Val158Met (rs4680) Genotypes on the Adult Cortisol Response to Psychological Stress

William R. Lovallo, Mary Anne Enoch, Kristen H. Sorocco, Andrea S. Vincent, Ashley Acheson, Andrew J. Cohoon, Colin A. Hodgkinson, David Goldman

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)631-637
Number of pages7
JournalPsychosomatic Medicine
Issue number6
StatePublished - Jul 1 2017


  • AIMS = ancestry-informative markers
  • C-DIS-IV = computerized diagnostic interview system for Diagnostic and Statistical Manual IV diagnosis of psychiatric disorders
  • COMT = catechol-O-methyltransferase
  • ELA = early life adversity
  • HPA = hypothalamic-pituitary-adrenocortical
  • HR = heart rate
  • Key words/Abbreviations
  • OFHP = Oklahoma Family Health Patterns project
  • SNP = single-nucleotide polymorphism
  • catechol-O-methyltransferase
  • cortisol
  • dopamine
  • early life adversity
  • genotype
  • stress

ASJC Scopus subject areas

  • Applied Psychology
  • Psychiatry and Mental health


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