When grief makes you sick: Bereavement induced systemic inflammation is a question of genotype

Christian R. Schultze-Florey, Otoniel Martínez-Maza, Larry Magpantay, Elizabeth Crabb Breen, Michael R. Irwin, Harald Gündel, Mary Frances O'Connor

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


Although bereavement is associated with increased morbidity and mortality in the surviving spouse, some widow(er)s remain healthy. Genetic variability in expression of inflammatory markers in response to stress may be the key to this observation. The present study compares bereaved vs. married/partnered older adults, investigating the impact of bereavement status, pro-inflammatory cytokine single nucleotide polymorphisms (SNPs) on circulating markers of inflammation and hypothesizing a gene by environment (GxE) effect. The study sample included 64 older adults, of which 36 were widow(er)s. Circulating levels of inflammatory markers IL-6, IL-1RA and sTNFRII were measured. Participants were genotyped for SNPs in the IL-6 gene (IL-6 -174 and -572), the IL-1β gene (IL-1β -511), and TNF-α gene (TNF-α -308). Grief severity was assessed with the Inventory of Complicated Grief. Bereaved participants had higher circulating levels of IL-1RA and IL-6. This increase could not be explained by pro-inflammatory genotype frequency differences, or Complicated Grief diagnosis. However, a GxE effect with the IL-6 -174 SNP moderated individual vulnerability to higher circulating levels of inflammation resulting from bereavement exposure. These results suggest a possible mechanism for the increase in morbidity and mortality in the surviving spouse. Genetic variability interacts with an environmental stressor, leading to increased inflammatory markers in genetically susceptible subjects only. For these patients, clinical interventions for bereavement-related stressor reduction might be crucial for overall health.

Original languageEnglish (US)
Pages (from-to)1066-1071
Number of pages6
JournalBrain, Behavior, and Immunity
Issue number7
StatePublished - Oct 2012


  • Aging
  • Bereavement
  • Cytokines
  • Gene
  • Gene by environment
  • Grief
  • IL-1
  • IL-6, TNF-a
  • Inflammation

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience


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