TY - JOUR
T1 - When grief makes you sick
T2 - Bereavement induced systemic inflammation is a question of genotype
AU - Schultze-Florey, Christian R.
AU - Martínez-Maza, Otoniel
AU - Magpantay, Larry
AU - Breen, Elizabeth Crabb
AU - Irwin, Michael R.
AU - Gündel, Harald
AU - O'Connor, Mary Frances
N1 - Funding Information:
This research was supported by the National Institute of Aging (K01-AG028404), UCLA Older Americans Independence Center Inflammatory Biology Core (NIH/NIA Grant P30-AG028748) and the UCLA Cousins Center for Psychoneuroimmunology. We would like to thank Richard Olmstead for his comments on the statistical analyses, and Ryan Sadakane and Susanne Yoon for their technical assistance.
PY - 2012/10
Y1 - 2012/10
N2 - 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.
AB - 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.
KW - Aging
KW - Bereavement
KW - Cytokines
KW - Gene
KW - Gene by environment
KW - Grief
KW - IL-1
KW - IL-6, TNF-a
KW - Inflammation
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U2 - 10.1016/j.bbi.2012.06.009
DO - 10.1016/j.bbi.2012.06.009
M3 - Article
C2 - 22735772
AN - SCOPUS:84865623134
SN - 0889-1591
VL - 26
SP - 1066
EP - 1071
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
IS - 7
ER -