Targeted rejection predicts decreased anti-inflammatory gene expression and increased symptom severity in youth with asthma

Abstract

Although responses to different stressors are sometimes assumed to be similar, recent research has demonstrated that certain types of stress, such as targeted rejection, are particularly potent. To test such associations in a chronic-disease model, we examined how noninterpersonal, interpersonal, and targeted-rejection major life events predicted changes in gene expression and symptom severity in 121 youths with asthma who were assessed every 6 months for 2 years. Youths who had recently experienced targeted rejection had lower messenger RNA expression for signaling molecules that control airway inflammation and obstruction (specifically, the glucocorticoid receptor and β2-adrenergic receptor) than youths who had not experienced targeted rejection. These associations were specific to targeted rejection and stronger for youths higher in subjective social status. Higher-status youths exposed to targeted rejection (but not other types of stress) also reported more asthma symptoms. These data demonstrate stressor-specific associations with molecular-signaling pathways and the severity of asthma, and they suggest that threats to the social self may be particularly deleterious.

Keywords: asthma; gene expression; health; social rejection; social status.

Figure 1

Regression-based point estimates of the differences in messenger RNA (mRNA) expression for glucocorticoid receptor (GR) following the experience of a recent targeted rejection major life event (n = 17) for participants reporting different levels of subjective social status (SSS). At visits when participants had experienced a recent targeted rejection major life event, they exhibited less mRNA for GR, p = .01, d = −.42. Moreover, this association was moderated by SSS, p = .02, with a simple slopes analysis revealing that youth higher in SSS showed the steepest declines in expression of GR following targeted rejection, p = .004, d = −.59. Individual bars represent the point estimate (not observed means) for GR mRNA based on the multilevel model regression coefficients (N = 121).

Figure 2

Regression-based point estimates of the differences in messenger RNA (mRNA) expression for β2-adrenergic receptor (β2-AR) following the experience of a recent targeted rejection major life event (n = 17) for participants reporting different levels of subjective social status (SSS). At visits when participants had experienced a recent targeted rejection major life event, they exhibited less mRNA for β2-AR, p = .006, d = −.51. Moreover, this association was moderated by SSS, p = .05, with a simple slopes analysis revealing that youth higher in SSS showed the steepest declines in expression of β2-AR following targeted rejection, p = .001, d = − .64. Individual bars represent the point estimates (not observed means) for β2-AR mRNA based on the multilevel model regression coefficients (N = 121).

Figure 3

Regression-based point estimates of the differences in self-reported asthma symptoms following the experience of a recent targeted rejection major life event (n = 17) for participants reporting different levels of subjective social status (SSS). As a group, at visits when participants had experienced a recent targeted rejection major life event, they did not report an increase in asthma symptoms, p = .48, d = .11. However, this association was moderated by SSS, p < .001, with a simple slopes analysis revealing that youth higher in SSS showed a significant increase in asthma symptoms following targeted rejection, p = .008, d = .47, whereas youth with lower or average SSS did not. Individual bars represent the point estimates (not observed means) for asthma symptoms based on the multilevel model regression coefficients (N = 121).